Herbal remedies for oral and dental health: a comprehensive review of their multifaceted mechanisms including antimicrobial, anti-inflammatory, and antioxidant pathways

Article type: Review Article

Keywords: Nanotechnology, Dental care, Anti-inflammatory, Herbal remedies, Complementary medicine, Oral health

Authors: Mohamed A. Anwar, Ghadir A. Sayed, Dina M. Hal, Mohamed S. Abd El Hafeez, Abdel-Aziz S. Shatat, Aya Salman, Nehal M. Eisa, Asmaa Ramadan, Riham A. El-Shiekh ⚬, Shymaa Hatem, Shaza H. Aly

Affiliations: https://ror.org/03q21mh05grid.7776.10000 0004 0639 9286Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562 Egypt; https://ror.org/029me2q51grid.442695.80000 0004 6073 9704Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr, Cairo, 11829 Egypt; https://ror.org/02m82p074grid.33003.330000 0000 9889 5690Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522 Egypt; https://ror.org/0520xdp940000 0005 1173 2327Department of Pharmacy, Kut University College, Al Kut, Wasit, 52001 Iraq; https://ror.org/029me2q51grid.442695.80000 0004 6073 9704Department of Pharmacognosy, Faculty of Pharmacy, Egyptian Russian University, Cairo-Suez Road, Badr , 11829 Egypt; https://ror.org/05fnp1145grid.411303.40000 0001 2155 6022Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt; https://ror.org/04f90ax67grid.415762.3Clinical Research Department at Giza Health Affairs Directorate, MOHP, Giza, Egypt; https://ror.org/0481xaz04grid.442736.00000 0004 6073 9114Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; https://ror.org/03s8c2x09grid.440865.b0000 0004 0377 3762Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Future University in Egypt, Cairo, Egypt; https://ror.org/04tbvjc27grid.507995.70000 0004 6073 8904Department of Pharmacognosy, Faculty of Pharmacy, Badr University in Cairo (BUC), Cairo, 11829 Egypt

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Article links: DOI: 10.1007/s10787-024-01631-8  |  PubMed: 39907951  |  PMC: PMC11914039

Relevance: Moderate: mentioned 3+ times in text

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Introduction

Oral diseases remain a significant global health issue, with dental caries and periodontal diseases being among the most critical challenges in oral health. Additionally, conditions like oral and pharyngeal cancers, as well as lesions of oral tissues, are also serious concerns. Oral health is essential for overall well-being and impacts quality of life in ways that go beyond the functions of the craniofacial structure (Anushri et al. ref. 2015). Although some conditions, like cleft palate, cannot be prevented, there are effective strategies to reduce the risk of oral cancer and more prevalent Adental problems, such as gingivitis, pericoronitis (inflammation of the tissue around wisdom teeth), and severe periodontal disease, all of which can result in tooth loss. Moreover, inadequate oral hygiene has been linked to a higher risk of heart disease, underscoring the connection between oral health and overall well-being (Laudenbach and Kumar ref. 2020; Odell ref. 2024). Gingivitis and periodontal disease can be further aggravated by underlying medical conditions such as diabetes, making regular oral health monitoring crucial. Daily brushing and flossing provide an opportunity to inspect the mouth, tongue, and gums for any changes, and it is important to communicate any concerns to a healthcare professional. Early detection and intervention significantly enhance the likelihood of preventing complications and achieving favorable treatment outcomes (Dubey and Mittal ref. 2020). Even seemingly minor issues, such as teeth grinding, can escalate into serious problems. Chronic grinding can lead to significant wear on tooth surfaces, jaw pain, and damage to teeth, including chips and fractures (PeaceHealth and a Bill, 2023). Dentists can offer guidance and solutions to help maintain dental health throughout one’s life. Moreover, advancements in drug delivery systems, such as niosomes, phytosomes, cubosomes, and transdermal patches, present improved opportunities for enhancing the bioavailability, solubility, and permeability of natural plant constituents used in the treatment of dental diseases (Das ref. 2022).

The anatomy of the mouth develops during the early stages of embryonic growth and serves multiple essential functions. The oral cavity is not only vital for communication and food intake, but also plays a critical role in the digestive process (Sterzenbach et al. ref. 2020). It comprises various structures, including the hard and soft palates, mucosal tissues lining the upper and lower mouth, gingiva (gums), tongue, uvula, tonsils, and openings of the salivary glands, all of which contribute to its complex functionality (Shyam and Cohen ref. 2021). Tooth brushing is a fundamental aspect of oral hygiene, and indigenous populations around the world utilize natural toothbrushes made from healing plants. These primitive twig "brushes" are surprisingly effective, providing disposable brushes with natural bristles that contain healing properties inherent to the plants themselves. Twigs possess volatile oils that stimulate blood circulation, tannins that tighten and cleanse gum tissue, and other beneficial substances like vitamin C that promote healthy gums. Plants such as bay, eucalyptus, oak, fir, and juniper are particularly effective for this purpose (Kumar et al. ref. 2013).

Throughout history, humans have turned to nature for remedies to various ailments, and in recent years, herbal medicine has gained significant popularity in a variety of applications, including dietary supplements, energy drinks, multivitamins, massage therapies, and weight management products (Akter et al. ref. 2021). This growing interest has not only expanded the field of herbal medicine, but has also enhanced its credibility and acceptance in modern healthcare.

In dentistry, herbal compounds are increasingly being utilized to address common issues such as tooth pain, gum inflammation, and oral lesions. Dental diseases rank among the most prevalent health concerns globally, with oral health being closely linked to overall quality of life, extending beyond mere functionality of the craniofacial complex (Kumar et al. ref. 2022).

Herbal agents with antiseptic, antibacterial, antimicrobial, antifungal, antioxidant, antiviral, and analgesic properties are becoming essential tools in dental care (Dalir Abdolahinia et al. ref. 2023). Conditions such as dental caries, periodontal disease, and endodontic infections are primarily caused by well-known bacterial and fungal pathogens, including Streptococcus mutans, Porphyromonas gingivalis, and Candida albicans (Singh et al. ref. 2022). Preventive dental care predominantly focuses on maintaining oral hygiene to minimize bacterial biofilm formation. While chemical agents such as chlorhexidine, hyaluronic acid, and fluoride are commonly used in mouth rinses and toothpaste, they may come with clinical drawbacks, such as tooth discoloration, altered taste, dry mouth, and irritation of the oral mucosa (Hernández et al. ref. 2022).

Research indicates that numerous herbs possess antibacterial, anti-inflammatory, and analgesic properties, making them valuable in managing conditions such as gingivitis, periodontitis, and toothaches (Rani et al. ref. 2022). Commonly used herbs in dentistry include clove, known for its analgesic effects; aloe vera, which aids in healing and reducing inflammation; and peppermint, often used for its soothing properties and freshening breath. Other herbs such as myrrh, sage, and turmeric also contribute significantly to oral health by promoting gum health and reducing plaque formation (Dick et al. ref. 2020).

Despite the historical use of these herbs, there remains a need for more rigorous scientific studies to fully understand their mechanisms of action and potential side effects. This exploration into herbal medicine not only highlights the importance of traditional practices, but also encourages a more comprehensive approach to oral healthcare, integrating both herbal and conventional methods for optimal patient outcomes.

Search strategy

The search strategy involved a systematic approach utilizing multiple databases, including PubMed, Scopus, Web of Science, and Google Scholar. Key search terms such as "herbal remedies," "oral health," "dental health," "antimicrobial properties," "anti-inflammatory effects," and "antioxidant activity" were employed to maximize relevant literature retrieval. Inclusion criteria encompassed peer-reviewed articles published in English that focused on the effects of herbal remedies related to oral health and explored at least one of the main properties: antimicrobial, anti-inflammatory, or antioxidant. A total of 500 articles were retrieved and evaluated according to the inclusion criteria (in vitro, in vivo, ex vivo, and clinical studies). Following a thorough screening process, 358 research articles were selected for the review. Studies were excluded if they were a review article, letter, or conference abstract lacking sufficient details.

Herbal remedies in dental care

Recent trends indicate that more people are opting to buy herbal products rather than consulting their doctors. Consequently, traditional healthcare providers may need to respond to the rising demand for herbal remedies driven by market changes. However, consumers who lack proper knowledge could encounter serious risks from the misuse of these products. Therefore, health educators must take on the responsibility of ensuring that individuals are well informed and engaged in their decisions about herbal medicine to protect public health (Sharif ref. 2002). Oral diseases remain a significant global health concern, with dental caries and periodontal diseases being among the most pressing oral health challenges worldwide. Additionally, conditions like oral and pharyngeal cancers and lesions of the oral tissues are also serious issues. Oral health is essential to overall well-being and impacts quality of life in ways that go beyond the functions of the craniofacial structure (Anushri et al. ref. 2015).

For centuries, herbs have been utilized to prevent and manage dental diseases. Herbal extracts are effective due to their interaction with particular chemical receptors in the body. Although herbal medicines typically have fewer side effects than conventional medications, they can still cause adverse reactions. It is crucial to recognize that the strength of herbal products can differ significantly (Buggapati ref. 2016).

The worldwide demand for safe, effective, and affordable alternative prevention and treatment options for oral diseases has arisen due to several factors. These include the rising incidence of such diseases—especially in developing countries—the growing resistance of pathogenic bacteria to existing antibiotics and chemotherapeutics, the prevalence of opportunistic infections in immunocompromised individuals, and economic constraints faced by developing nations (Jena et al. ref. 2021). Although various chemical agents are available on the market, they can disrupt oral microbiota and lead to unwanted side effects, including vomiting, diarrhea, and tooth discoloration. As a result, the quest for alternative products persists, with natural phytochemicals derived from plants used in traditional medicine viewed as promising substitutes for synthetic chemicals (Ege and Ege ref. 2021).

Herbal products are increasingly utilized as sedatives, agents for reducing plaque, and for promoting healthy gums. These natural remedies present a promising way to support oral health while reducing the disadvantages linked to conventional treatments (Pandey et al. ref. 2011).

Herbal compounds are being increasingly suggested for the treatment of serious conditions, including purulent gingivitis, mucositis, superficial periodontitis, catarrhal inflammation of the tongue, toxic oral cavity inflammation, mucosal infections, and difficult postoperative wound healing. Furthermore, herbal medications are also used to relieve oral symptoms related to systemic diseases (Szyszkowska et al. ref. 2010). Plant-based compounds can be highly effective, especially in addressing inflammation caused by local irritants. Herbal medications are characterized by their anti-inflammatory, antiseptic, analgesic, astringent, edema-reducing, soothing, and wound-healing properties. The therapeutic benefits of these herbs stem from the biologically active compounds they contain. Many of these compounds have been isolated or extracted through bio-guided methods that identify the specific activities of different plant parts. Notable biologically active compounds in herbs include flavonoids, coumarins, iridoid glycosides, phenolic acids, resins, triterpenes, phytoesters, choline, carotenoids, tannins, vitamins, and mineral salts such as magnesium, iron, and lithium, as well as essential oils. Flavonoids and essential oils are particularly recognized for their healing properties and are commonly used in herbal treatments for oral health (Sinha and Sinha ref. 2014).

The purpose of this review is to highlight recent examples of traditional medicinal plant extracts or phytochemicals that have demonstrated the ability to inhibit the growth of oral pathogens, reduce the development of dental plaque, and alleviate the symptoms of oral diseases. These natural products offer a promising alternative to conventional treatments, particularly in light of the increasing resistance to synthetic antimicrobials.

Natural products in the management of gingivitis, ulcers, mucositis, and periodontitis

Gingivitis is an inflammatory disorder that impacts the gingival tissue, characterized by irritation and erythema of the gingiva. It primarily results from bacterial infection owing to deposits of plaque (Kurgan and Kantarci ref. 2018). Certain plant-based components, such as tea tree oil, aloe vera, lemongrass and cloves, posses antibacterial and anti-inflammatory characteristics that may assist in alleviating gingivitis symptoms (Mosaddad et al. ref. 2023). Mouth ulcers, referred to as canker sores or aphthous ulcers, are tiny, painful lesions that arise on the mucous membranes of the oral cavity. These ulcers may manifest on the inner cheeks, lips, tongue, gums, and the palate (Philipone and Yoon ref. 2016). Another condition is known as mucositis, which is a prevalent adverse effect of cancer treatment, especially chemotherapy and radiation therapy, marked by inflammation and ulceration of the mucous membranes in the digestive tract, oral cavity, and pharynx. It may induce pain and discomfort, and impede eating and speaking (Naidu et al. ref. 2004). Periodontitis represents a more advanced phase of periodontal disease than gingivitis. It entails inflammation surrounding the tooth, impacting the supporting tissues, including the gums, periodontal ligament, and alveolar bone. If neglected, periodontitis may result in tooth loss and other severe health complications (Lang et al. ref. 2009; Slots ref. 2017).

Natural products provide a more comprehensive and potentially safer alternative to synthetic pharmaceuticals, as they may serve as supplements to conventional therapies or as preventive strategies for sustaining optimal oral health (Abdelazim et al. ref. 2024; Aly et al. ref. 2023). Specifically, they are particularly accessible and cost-effective, rendering them available to a broad demographic (Herman et al. ref. 2005). Natural products provide an abundant supply of vital nutrients and bioactive metabolites such as flavonoids, alkaloids, phenolics, steroids, volatile oils and vitamins, minerals, and fiber, which are crucial for sustaining optimal health and maintaining antioxidant and anti-inflammatory properties (Aly et al. ref. 2024; Cusumano et al. ref. 2024; Goher et al. ref. 2024; Zengin et al. ref. 2024). Natural products they have received considerable interest in the treatment of numerous oral health conditions, including gingivitis, ulcers, mucositis, and periodontitis, owing to their potential therapeutic advantages (Ferreira et al. ref. 2022a; Kumar et al. ref. 2022; Salehi et al. ref. 2019). For example, crocin is a carotenoid metabolite in the blooms of crocus and gardenia (Pfister et al. ref. 1996). Crocin is recognized for its capacity to diminish oxidative stress and inflammation, which are major factors in periodontal disease. It may suppress the synthesis of pro-inflammatory cytokines, thereby mitigating tissue damage linked to periodontitis. Also, it regulates osteoclast–osteoblast equilibrium and promotes type 1 collagen accumulation in teeth and bone (Pfister et al. ref. 1996). Figure 1 shows how natural products can play a role in the management of these conditions as indicated by in vitro, in vivo studies, and clinical trials (Fig. 1).

MK615 is an extract rich in triterpenoids derived from Ume, the Japanese apricot, which has served as a traditional Japanese medicine for centuries and is widely consumed as food (Nakagawa et al. ref. 2007). In vitro investigations have examined MK615’s effects on cell survival, migration, and inflammatory response in human gingival fibroblasts. The generation of pro-inflammatory indicators including interleukin (IL)-6 and IL-8 by gingival fibroblasts stimulated by LPS was reduced in a dose-dependent manner by MK615 by modulating cytokine production (Morimoto-Yamashita et al. ref. 2015).

Another study aimed to assess the antigingivitis efficacy of Lentinula edodes extract, known as shiitake mushroom, by evaluating its efficiency against common bacterial infections linked to gingivitis. The shiitake mushroom extract exhibited considerable antibacterial efficacy against many bacterial strains, especially reducing the numbers of Fusobacterium nucleatum typically linked to gingivitis. The extract’s efficacy was similar to conventional antiseptic chemicals employed in oral hygiene as chlorhexidine, suggesting its viability as a natural substitute (Ciric et al. ref. 2011).

A recent investigation is focused on evaluating the potential of extracting beneficial chemicals from chestnut shells (Castanea sativa) for use in products for the treatment of oral mucositis. The extract showed superior antioxidant and antiradical properties, with scavenging efficiency against HOCl and ROO with IC₅₀ values of 4.47 µg/mL and 0.73 µmol TE/mg DW, respectively. The antioxidant potential was associated with the phenolic profile of the chestnut extract, which was abundant in gallic acid, protocatechuic acid, epicatechin, catechin, and rutin. It demonstrated antibiotic activity against several oral bacteria present in the oral cavity during oral mucositis, particularly Staphylococcus, Enterococcus, Streptococcus, and Escherichia. Moreover, the chestnut shells revealed the lowest IC₅₀ values of 1325.03 and 468.15 µg/mL against two human oral cancer cell lines, namely, HSC3 and TR146, respectively (Ferreira et al. ref. 2022b).

Another study examines the therapeutic efficacy of ethanol extracts from Alpinia katsumadai seeds in the prevention and treatment of periodontitis, specifically targeting their impact on dental plaque bacteria including Porphyromonas gingivalis and inflammation. The extract suppressed RANKL-induced osteoclast development, resulting in reduced bone resorption, reduced COX-2 levels, and at concentrations ranging from 1 to 10 µg/mL the extract suppressed P. gingivalis growth on agar plates (Shin and Hwang ref. 2021).

An Ayurvedic herbal extract consisting of a mixture of clove, ginger, Aleppo oak galls, black pepper, heartwood of cutch tree, Spanish cherry bark, pongame oil tree root, and myrobalan fruit was investigated for its potential as anti-inflammatory responses associated with gingivitis and periodontitis. It markedly suppressed IL-8 expression in telomerase-immortalized gingival keratinocytes (TIGK) in response to all evaluated stimuli, either Fusobacterium nucleatum or pro-inflammatory cytokines (IL-1β and TNF-α), exhibiting a dose-dependent action that was not attributable to cytotoxicity (Chang et al. ref. 2020).

An in vivo study examined the therapeutic efficacy of Kouyanqing Granule (KYQG) in the treatment of mouth ulcers induced by phenol and aggravated by sleep deprivation. KYQG markedly diminished inflammation and enhanced the healing of oral ulcers, as evidenced by reduced levels of inflammatory markers including COX-2, MMP-9, and TNF-α. The KYQG influences many pathways, notably through the suppression of inflammatory responses and the modulation of immunological function.

The TNF signaling pathway and HIF-1 signaling pathway are key involved signaling pathways (Chen et al. ref. 2020). The UPLC–MS analysis of the KYQG indicated a high concentration of phenolics and flavonoids, with chlorogenic acid identified as the predominant component in the extract (Chen et al. ref. 2020).

Another study developed a sustainable hydrogel composition with liquorice extract to enhance the healing of oral ulcers in rats, utilizing eco-friendly methods. The results revealed that liquorice extracts at a concentration of 30% in the hydrogel composition demonstrated enhanced wound healing results, comprising faster re-epithelialization, augmented collagen synthesis (27.8%), raised growth factor expression (23.24%), and diminished inflammation (88%). Liquorice possesses anti-inflammatory and antibacterial characteristics that enhance its efficacy in facilitating tissue repair and alleviating symptoms related to mouth ulcers. The efficacy is ascribed to glycyrrhizic acid, which constitutes the principal constituent of the extract (34.85 ± 2.77%) (Moussa et al. ref. 2023).

The therapeutic efficacy of Ficus deltoidea leaf extract at a dose of 500 mg/kg in the treatment of oral ulcers was examined using an animal model. It diminished the dimensions of the oral ulcer and augmented the proportion of the inhibitory area (Ahmad and Amin ref. 2017).

Individuals with cleft lip and palate frequently encounter distinct obstacles in sustaining oral hygiene due to anatomical variations and orthodontic interventions, rendering proficient oral care essential (Gaggl et al. ref. 1999; Wong and King ref. 1998). The study comprised 50 patients aged 9–16 years, categorized into two groups. Group A utilized toothpaste combined with propolis, tea tree oil, menthol, and rosemary oil vs. Group B as a placebo group. Gingival bleeding and oral hygiene indices were measured before and after 35 days. The findings demonstrated substantial enhancements in oral hygiene, evidenced by a decrease in the oral hygiene index (OHI-T) and a marked reduction in the gingival bleeding index (GBI) for both overall scores and particular tooth types (incisors and molars) in Group A, indicating improved gingival health. This outcome is ascribed to the antibacterial properties of propolis against oral infections, aiding in the reduction of plaque buildup and inflammation. Furthermore, combining it with essential oils aids in diminishing gum inflammation (Machorowska-Pieniążek et al.).

A study conducted by Zhang et al. evaluated the effectiveness of various mouthwashes in preventing oral mucositis (OM), a common and painful side effect of cancer treatments such as chemotherapy and radiotherapy. The study is based on utilizing a Bayesian network meta-analysis approach. The analysis indicated that honey mouthwash exhibited the greatest efficacy in preventing oral mucositis, followed by chamomile, curcumin, and benzydamine.

These mouthwashes demonstrated markedly greater efficacy than the placebo and exhibited superior outcomes relative to chlorhexidine, sucralfate, and povidone-iodine (Zhang et al. ref. 2020).

The efficacy of honey on OM may be attributed to its hygroscopic properties, viscosity, or acidic pH, which inhibits bacterial proliferation on the mucosa, alongside tissue-nourishing minerals and vitamins that facilitate direct tissue repair. Moreover, honey is readily accessible, simple to gargle, mildly sweet, non-irritating, and is generally more palatable for patients, particularly children (Kocot et al. ref. 2018; Ramsay et al. ref. 2019). Besides, the effectiveness of chamomile may be attributed to its antimicrobial, anti-inflammatory, antioxidant, and anticancer properties (Sebai et al. ref. 2014).

A comparative controlled randomized trial studied the use of a mouthwash containing Terminalia chebula fruit extract compared to chlorhexidine in reducing plaque accumulation and gingival inflammation. The extract of T. chebula fruit is recognized for its antibacterial and astringent characteristics, containing elevated levels of tannins (Bag et al. ref. 2009). The findings indicated that both mouthwashes substantially diminished plaque index (PI) and gingival index (GI) scores following 4 weeks of use. The T. chebula extract mouthwash showed similar efficacy to chlorhexidine in managing plaque and alleviating gingival inflammation with fewer side effects such as staining of teeth and altered taste sensation (Gupta et al. ref. 2015).

A clinical trial assessed the efficacy of aged garlic extract (AGE) in diminishing probing pocket depth (PPD) and enhancing gingival health over an 18-month duration. The average PPD for the AGE group dramatically declined from 1.89 ± 0.74 mm at baseline to 1.06 ± 0.49 mm at 18 months (p < 0.001) (Zini et al. ref. 2020). AGE comprises sulfur compounds, including S-allylcysteine, S-1-propenylcysteine, and S-allylmercaptocysteine, which exhibit antioxidant properties that enhance the efficacy of AGE in addressing periodontitis. It also improves peripheral circulation, diminishes inflammation, and augments immunological abilities (Ushijima et al. ref. 2018; Xiao et al. ref. 2012).

A further study administered AGE to dogs with mild gingivitis at a dosage of 18 mg/kg/day for 8 weeks. The results indicated that the dogs with improved gingival index scores did not demonstrate an increase in volatile sulfur compounds (VSCs), typically linked to bad breath and periodontal disease, whereas the placebo group exhibited elevated levels at 8 weeks. The outcomes are ascribed to the anti-inflammatory and antibacterial characteristics of AGE, possibly aiding in the reduction of inflammation and bacterial presence in the oral cavity (Takahashi et al. ref. 2023).

Another investigation attempted to evaluate the effectiveness of a mouth rinse derived from Azadirachta indica, known as neem leaves in diminishing clinical manifestations of gingivitis, particularly probing depth and gingival inflammation. Results showed that individuals utilizing the neem mouthrinse exhibited notable decreases in gingival index scores and probing depth relative to those utilizing the placebo owing to the antimicrobial characteristics of the neem mouthwash that enhance oral hygiene and diminish irritation. It also has the advantage of being well accepted by participants, with negligible side effects observed during the trial (Botelho et al. ref. 2008).

Spirulina (Spirulina platensis) is a photosynthetic cyanobacterium possessing various biological activities. It comprises different chemical compounds such as phenolic compounds, tocopherols, beta-carotenes, and phycocyanins that exhibit antioxidant effects.

Phycocyanin, a principal component of spirulina, exists as a complex mixture of trimers and hexamers. It also has antioxidant properties, elucidating its potent anti-inflammatory impact (Mahendra et al. ref. 2013; Nuhu ref. 2013). Participants receiving spirulina supplementation demonstrated notable decreases in inflammatory markers linked to chronic periodontitis. Clinical indicators, including probing depth and gingival index, demonstrated improvements, signifying increased periodontal health. Spirulina augments the function of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which are essential for mitigating oxidative damage in periodontal tissues (Kaipa et al. ref. 2022).

A study by Howshigan et al. examined the effectiveness of an Ayurvedic toothpaste containing nine medicinal plants in treating persistent gingivitis in comparison to a placebo. The nine herbal components in the Ayurvedic toothpaste known as Sudantha® are Zingiber officinale Rosce, Syzygium aromaticum L., Piper nigrum L., Terminalia chebula Retz., Mimusops elengi L., Pongamia pinnata (L.) Pirerre, Acacia chundra Willd., Adhatoda vasica Nees., and Quercus infectoria Olivier. Participants utilizing the Ayurvedic toothpaste exhibited substantial decreases in plaque index, bleeding on probing, and probing pocket depth relative to the placebo group (p < 0.0001). Microbiological evaluations revealed a notable reduction in total salivary anaerobic bacterial counts in the Ayurvedic toothpaste group vs the placebo (p < 0.05). The enhancements in clinical indicators progressed throughout time, signifying enduring advantages from the use of the Ayurvedic formulation (Howshigan et al. ref. 2016).

A controlled, randomized study examined the therapeutic effects of a mouthwash containing a Mexican Sanguinaria extract (Polygonum aviculare) on individuals with gingivitis. It demonstrated substantial enhancements in clinical indicators, including decreased gingival bleeding and inflammation relative to the placebo group. Additionally, antibacterial and anti-inflammatory properties enhanced its efficacy in the management of gingivitis (Begné et al. ref. 2001). Research involving sanguinarine, an alkaloid derived from Sanguinaria canadensis, has indicated that this extract may be very beneficial for the prevention of plaque and gingivitis (Croaker et al. ref. 2016).

A randomized controlled study involving individuals who chewed sugar-free gum with magnolia bark extract showed a reduction in dental cavities and gingival irritation compared to regular gum (Campus et al. ref. 2011). It also showed antibacterial capabilities that reduced the levels of oral microorganisms linked to caries and gingivitis. The primary components of the bark are magnolol and honokiol, which exhibit antibacterial and anti-inflammatory properties that may aid in diminishing bacterial load and inflammation in periodontal tissues (Teng et al. ref. 1990).

A recent research study examined the impact of a chewing gum formulation including extracts from Scutellaria lateriflora and Cistus × incanus on symptoms of gingivitis in a double-blind, placebo-controlled clinical trial for 3 months. Results revealed that the modified gingival index (MGI), quantitative gingival bleeding index (QGBI), and Oral Health 15 items (OH-15) were reduced by the 3rd month of treatment as compared to placebo (Di Minno et al. ref. 2024).

DiSilvestro et al. conducted a study aimed to assess the impact of pomegranate (Punica granatum L.) extract rinse on salivary indicators related to dental health and the risk of gingivitis. The research included 32 young adult participants who gargled with a pomegranate extract diluted in water three times daily for 4 weeks. The results revealed that the participants exhibited a major decrease in total protein levels in saliva, which coincides with a reduction in plaque-forming bacteria.

A significant reduction in AST and α-glucosidase activity was observed, suggesting less cellular damage and a decline in sucrose breakdown, respectively. Also, elevations in ceruloplasmin activity and radical scavenging capacity were noted, indicating improved antioxidant defense against oxidative stress. These findings indicate the incorporation of pomegranate extracts as a potent and effective candidate for oral hygiene products (DiSilvestro et al., 2009).

Natural products in the management of xerostomia, caries, and oral carcinoma

In recent years, there has been a notable increase in the exploration of alternative and natural therapies for managing xerostomia. These natural remedies not only address the symptoms of dry mouth, but also mitigate complications associated with the condition, such as dental caries xerostomia and oral tumors (Motallaei et al. ref. 2021; Nieuw Amerongen and Veerman ref. 2003).

Xerostomia, commonly referred to as dry mouth, is a clinical condition characterized by a significant reduction in saliva production, leading to discomfort and increased susceptibility to oral infections, including dental caries. This condition can result in dysphagia (difficulty swallowing) and is associated with various etiological factors, such as medications that induce xerostomia, radiation therapy targeting the head and neck, and autoimmune disorders like Sjögren’s syndrome (Kontogiannopoulos et al. ref. 2023). Among the most extensively studied natural products are thyme honey, apigenin, ethanolic extracts of Ixeris dentata (IXD), Lycium barbarum polysaccharides (LBP), green tea, fermented lingonberry juice, coconut oil, ginger, aloe vera, peppermint, glucosylceramide from pineapple, linseed, Malva sylvestris, Alcea digitata, pilocarpine, and lycopene-enriched virgin olive oil (Ibrahim et al. ref. 2023). In this context, thyme honey has emerged as a promising remedy for severe dry mouth, particularly in older adults with end-stage kidney disease. Clinical studies indicate that thyme honey oral rinses can stimulate salivary flow without adverse effects. Furthermore, it has shown efficacy in alleviating dry mouth symptoms associated with radiation therapy in patients with head and neck cancer (Kontogiannopoulos et al. ref. 2023) (Ibrahim et al. ref. 2023). Virgin olive oil, recognized for its health benefits, has been utilized as a spray enriched with lycopene—a carotenoid beneficial for xerostomia patients undergoing treatment. Although this intervention did not significantly increase saliva output, it provided relief from dry mouth discomfort (Navarro Morante et al. ref. 2017). In addition, the ethanolic extract of Ixeris dentata has been investigated in diabetic xerostomic rat models. Results indicated improved salivary production and enzyme levels alongside reduced blood glucose concentrations. This suggests a potential therapeutic role for IXD extract in managing xerostomia (Kontogiannopoulos et al. ref. 2023). Research on Lycium barbarum (Goji Berry) highlights its ability to promote salivation in Sjögren’s syndrome models. Low doses of LBP have been shown to stimulate salivary flow and reduce inflammatory responses, positioning it as a viable treatment option for xerostomia. (Kontogiannopoulos et al. ref. 2023). Green tea (Camellia sinensis) is rich in polyphenols such as epigallocatechin-3-gallate (EGCG), which may aid in managing dry mouth symptoms. A specialized formulation known as MighTeaFlow has demonstrated effectiveness in alleviating xerostomia symptoms through the supplementation of green tea catechins (Kontogiannopoulos et al. ref. 2023). Fermented lingonberry juice (FLJ) has attracted attention for its ability to enhance salivary pH and stimulate salivation. Its antioxidant and anti-inflammatory properties contribute to its potential utility in treating dry mouth symptoms; however, further research is warranted to confirm these findings (Kontogiannopoulos et al. ref. 2023). Coconut oil (Cocos nucifera) has proven effective for patients experiencing dry mouth due to radiation therapy. Its unique surface-active properties help retain moisture within the oral cavity (Kontogiannopoulos et al. ref. 2023). Ginger (Zingiber officinale) stimulates salivation by activating the parasympathetic nervous system through its action on M3 muscarinic receptors. This herbal remedy has long been employed for managing dry mouth symptoms (Kontogiannopoulos et al. ref. 2023). Preparations combining Aloe vera and peppermint have been developed into gels that alleviate dry mouth symptoms while reducing plaque accumulation and improving overall oral health (Kontogiannopoulos et al. ref. 2023). Glucosylceramide, derived from pineapple (Ananas comosus), enhances mucosal cell proliferation and ceramide production within the oral cavity, presenting itself as a natural alternative to conventional moisturizers (Kontogiannopoulos et al. ref. 2023). Linseed (Linum usitatissimum L.) extract and specifically Salinum®—a viscous polysaccharide containing liquid—was used for the prevention of dry mouth caused by radiation therapy. The use of this extract by patients has led to improvements in oral hygiene and the health of the mucosa (Kontogiannopoulos et al. ref. 2023). Traditional Persian medicine recognizes the anti-inflammatory and moisturizing properties of Malva sylvestris and Alcea digitata, which have been effective in treating radiation-induced xerostomia by promoting hydration and stimulating salivary gland function (Kontogiannopoulos et al. ref. 2023). Pilocarpine, a plant-derived sialagogue commonly prescribed for xerostomia—especially in Sjögren’s syndrome—acts via M3 muscarinic receptors to enhance salivation (Kontogiannopoulos et al. ref. 2023). Lastly, apigenin, a flavonoid found in various plants, has garnered interest due to its potential role in stimulating salivary gland function through estrogen receptor modulation (Kontogiannopoulos et al. ref. 2023). In summary, an increasing body of research underscores the efficacy of natural products in managing xerostomia. These alternative therapies present attractive options for patients seeking less invasive treatments with favorable effects on saliva secretion and oral health while minimizing side effects associated with conventional pharmacological interventions.

Tooth decay, also reckoned as caries, is an infectious disease of the tooth that destroys the enamel and dentin layers of the tooth (Wilson et al. ref. 2021). The process of decay begins with the activity of bacteria found in the mouth that use the sugars present and produce acids which then attack the teeth. Treatment strategies mainly involve improvement of oral care habits, spitting out, and reducing the use of sugar-containing beverages (Yadav and Prakash ref. 2017). Several studies have reported effective remedy for dental caries using various medicinal herbs such as Lespedeza cuneata, Sambucus williamsii var. coreana, Glycyrrhiza uralensis, Vaccinium macrocarpon, Uva-fugi apple, Vitis vinifera (red grape seeds), Myristica fragrans nutmeg, ajwain Trachyspermum ammi, Coffea arabica and Coffea robusta, Hordeum vulgare (barley coffee), Myrtus communis, Allium sativum (garlic), Theobroma cacao (cocoa), propolis, and Camellia sinensis (tea). Lespedeza cuneata is included in mouthwash products and has been reported to lower the acid-producing activity of oral bacteria responsible for dental caries. This helps to lower the microbial load in the oral cavity, hence preventing any chances of dental caries. This mouthwash extract serves as an excellent protective measure against the development and progression of dental cariesdue to the absence of harmful chemical ingredients (Kim and Nam ref. 2022c). A clinical trial demonstrated that mouth rinsing with a preparation containing Sambucus williamsii var. coreana extract is effective in fighting dental caries as it reduces the proportion of Streptococcus mutans in the mouth. The results showed that after 5 days of continuous treatment with mouthwash, the number of bacteria rapidly decreased. Moreover, there were no side effects after the treatment including any increase in corrosive agents, suggesting its potential in the prevention of tooth cavities (Kim and Nam ref. 2022c). Research on Glycyrrhiza uralensis confirms its capacity to inhibit cariogenic bacteria, particularly Streptococcus mutans, making it a valuable component in mouthwashes and sugar-free lollipops designed to mitigate bacterial activity (He et al. ref. 2006; Kim and Nam ref. 2021, ref. 2022a; Sidhu et al. ref. 2020). The polyphenols found in cranberries, especially A-type proanthocyanidins, have been shown to influence key virulence factors of caries-related microbes by inhibiting acid production and bacterial adhesion to tooth surfaces (Philip and Walsh ref. 2019). Additionally, compounds from apples have demonstrated the ability to suppress water-insoluble glucan production essential for bacterial retention on teeth, thus highlighting their potential in caries prevention (Gazzani et al. ref. 2012). Extracts from red grape seeds exhibit significant antibacterial activity, with minimum inhibitory concentrations as low as 0.5 mg/ml, effectively inhibiting oral bacteria (Gazzani et al. ref. 2012). Additionally, nutmeg (Myristica fragrans) extracts, and particularly the compound macelignan can be considered a potent anticaries ingredient. Macelignan has been reported to kill Streptococcus mutans at low concentrations and to inhibit its biofilm formation, thus being an effective substance against tooth decay (Gazzani et al. ref. 2012). Similarly, the extract of ajowan caraway (Trachyspermum ammi) contains naphthalene derivative which is a high anticaries agent. This agent inhibits the adherence of bacteria as well as the formation of biofilm and acid production, thereby becoming a useful natural product in caries management (Gazzani et al. ref. 2012). Roasted coffee, especially because of its α-dicarbonyl compounds, exhibited inhibitory activity toward Streptococcus mutans. Moreover, both extracts of roasted and unroasted coffee were found to possess antiadhesive properties, preventing the attachment of bacteria onto the tooth surface and thus minimizing caries development (Gazzani et al. ref. 2012). Barley coffee has been found to possess the ability to prevent the adherence of bacteria and the formation of their biofilms. Research suggests that at concentrations below those that inhibit bacterial growth, barley coffee is capable of decreasing formation of biofilms induced by Streptococcus mutans, making it a candidate for a natural treatment agent for dental caries (Gazzani et al. ref. 2012). Myrtle (Myrtus communis) leaf extract is found to be used as a folk remedy in Mediterranean regions. Ethanol extracts of myrtle leaves have shown a significant antibacterial effect, reducing the microbial load in the oral cavity after a single application which can probably be attributed to the flavonoids present in the extracts (Gazzani et al. ref. 2012). Seven days of garlic-containing mouthwash was sufficient to lower the levels of Streptococcus mutans in salivary samples. This shows that oral healthcare products containing garlic raw material are feasible and efficacious (Gazzani et al. ref. 2012). Cocoa, in particular husk’s extract, has exhibited potent antibacterial activity. It has been revealed that cocoa polyphenols help inhibit the formation of plaque as well as acid production, which are contributory factors to the occurrence of dental caries. In clinical studies, mouthwash using cocoa bean husk extract showed a marked decrease in plaque accumulation and bacteria count (Gazzani et al. ref. 2012). Propolis has been fully characterized as an antimicrobial agent against Streptococcus mutans in vitro and in vivo. Its flavonoids and sesquiterpenes help in the reduction of biofilm and bacteria attachment, and when propolis is administered together with fluoride it had been effective in preventing dental caries (Gazzani et al. ref. 2012). The association of tea, black and green, with oral in healthy possesses beneficial influence has been a widespread practice for quite a long time. EGCG, one of the green tea catechins, was specifically found to inhibit glucosyltransferase enzyme activity. Studies show that caries rate is decreased by green tea. In addition, black tea’s higher polymerized polyphenol content and fluoride levels further enhance its anticariogenic properties (Gazzani et al. ref. 2012). In summary, these natural substances, through their antibacterial, antiadhesive, and biofilm-reducing properties, offer promising alternatives to traditional chemical treatments for the prevention and management of dental caries (Bagan et al. ref. 2010).

Oral carcinoma, commonly referred to as oral cancer, is a malignant condition characterized by the destruction of tissues in the mouth and throat. Key risk factors for this disease include tobacco use, excessive alcohol consumption, and infections with human papillomavirus (HPV). Early diagnosis is crucial for effective treatment and significantly influences the prognosis and survival rates of affected individuals (Zygogianni et al. ref. 2011). Recent studies have highlighted the potential of various natural compounds in the management of oral carcinoma. These compounds not only exhibit anticancer properties, but also possess additional benefits that may enhance oral health. Research indicates that zinc oxide is encapsulated using cinnamic acid, as a stabilizing agent, and exhibits significant antioxidant and antimicrobial activities. Furthermore, these nanoparticles demonstrate dose-dependent cytotoxicity against human oral epidermal carcinoma KB cells by modulating apoptotic pathways involving critical proteins such as BCL-2, BAX, and P53 (Ravikumar et al., ref. 2024). Another formulation combines curcumin with zinc oxide nanoparticles. Evaluated for its antioxidant, antimicrobial, and anticancer properties, the formula has shown promising results in apoptosis assays and gene expression studies against KB oral squamous carcinoma cells. This dual-action approach addresses both infectious agents and cancerous cells (Tayyeb et al. ref. 2024). Essential oils derived from various plants within the Zingiberaceae family such as Curcuma mangga, Curcuma xanthorrhiza, Kaempferia galanga, and Curcuma aeruginosa have demonstrated antibacterial activity against specific oral pathogens. For instance, Curcuma xanthorrhiza oil exhibits activity against Streptococcus mitis and Streptococcus sanguinis, while Curcuma mangga oil inhibits Streptococcus mutans. Additionally, these oils show moderate cytotoxic effects against oral cancer cells, suggesting their potential utility in natural oral care products (Amil et al. ref. 2024). Probiotic strains such as Saccharomyces boulardii and Saccharomyces cerevisiae have been identified as effective agents against dental caries caused by the interaction between Streptococcus mutans and Candida albicans. These probiotics not only inhibit fungal growth but also help maintain a balanced pH in the oral cavity, thereby protecting dental enamel. Notably, S. boulardii has been shown to downregulate key genes expressed in S. mutans, enhancing its potential for caries prevention (Yousif et al. ref. 2024). Extracts from European spruce needles are rich in biologically active compounds (BACs), particularly phenolic and flavonoid components. Luteolin, a prominent flavonoid within these extracts, exhibits significant antitumor activity against squamous carcinoma cells in vitro (Tylkowski et al. ref. 2022). Innovative formulations incorporating mucoadhesive patches that utilize hydroxypropyl methylcellulose (HPMC) combined with ethanol extract of Usnea barbata have been developed. These patches demonstrate anticancer properties by inducing oxidative stress and inhibiting DNA synthesis in cancer cells while also exhibiting antimicrobial activity against pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Candida parapsilosis. The dual functionality of these patches positions them as viable candidates for both prophylactic and therapeutic applications in oral diseases (Popovici, Violeta et al., 2022).

Natural products in miscellaneous dental disorders

Oral lichen planus (OLP) is a chronic autoimmune condition primarily affecting middle-aged women, characterized by painful lesions in the buccal mucosa. Conventional treatments, often involving corticosteroids, can lead to side effects, prompting interest in alternatives like curcumin from turmeric. Curcumin exhibits anti-inflammatory, antioxidant, and antimicrobial properties, with clinical trials showing its efficacy in alleviating OLP symptoms through high doses and topical formulations. Despite challenges with bioavailability, nano-curcumin formulations have improved absorption. While corticosteroids remain standard treatment, curcumin’s potential as a safe alternative for managing OLP is promising and warrants further research (Khosrojerdi et al. ref. 2023). This randomized double-blind study evaluated the effectiveness of topical aloe vera (AV) for treating oral lichen planus (OLP). Patients applying AV three times daily reported significant improvements in pain levels, lesion severity, and overall quality of life, particularly in psychological disability and total Oral Health Impact Profile (OHIP-49) scores. Although the AV group showed greater pain relief compared to the placebo group, these differences were not statistically significant. Notably, 61.29% of the AV group achieved complete recovery by the study’s end, compared to 41% in the placebo group, with no adverse effects reported. The findings suggest that AV may serve as a safe alternative treatment for OLP, highlighting the need for further research to confirm its efficacy and explore its preventive applications (Salazar‐Sánchez et al., 2010). This study evaluated the clinical efficacy of topical chamomile gel compared to a placebo in treating OLP in 60 patients. Participants received either 2% chamomile gel or a placebo three times daily for 4 weeks. Results showed significant improvements in pain, burning sensation, itching, and overall oral health in the chamomile group, with 92% experiencing partial or total responses versus 17% in the placebo group. No adverse effects were reported. The findings suggest that chamomile gel may be an effective alternative treatment for OLP, offering a low-cost and accessible option with minimal side effects compared to traditional therapies. Further long-term studies are recommended to confirm these results (Lopez Jornet and Aznar‐Cayuela, 2016).

Oral submucous fibrosis (OSF) is a chronic disease primarily caused by areca nut chewing, leading to inflammation and fibrosis of the oral mucosa. This study investigates the combined use of curcumin, an anti-inflammatory polyphenol, with intralesional dexamethasone and hyaluronidase for treating OSF. A 12-week randomized clinical trial with 34 patients showed that curcumin significantly improved mouth opening, and reduced symptoms compared to standard treatment. The findings suggest curcumin’s potential as an effective adjunct therapy for OSF, warranting further research (Adhikari et al. ref. 2022).

Recurrent aphthous stomatitis (RAS) affects 5%–25% of the population, presenting as painful oral ulcers categorized into minor, major, and herpetiform forms. Minor ulcers are the most common, typically healing within 10–14 days, but causing significant discomfort. The exact cause of RAS is unclear, with factors like hypersensitivity, nutritional deficiencies, and stress implicated. Current treatments focus on pain relief, but no single therapy is fully effective. This study explored the efficacy of myrtle (Myrtus communis) extract in a randomized trial involving 45 participants. Results showed that myrtle significantly improved ulcer healing and pain relief compared to placebo, with no adverse effects reported. The findings suggest that myrtle extract could be a safe and effective treatment for RAS, warranting further research into its preventive applications during the prodromal phase of ulcer development (Babaee et al. ref. 2010).

Oral submucous fibrosis (OSMF) is a chronic and debilitating condition characterized by fibrosis in the oral cavity, leading to stiffness and reduced mouth opening. Defined by Pindborg and Sirsat, OSMF can affect any part of the oral cavity and sometimes the pharynx, often associated with inflammation and epithelial atrophy (More et al. ref. 2020). This condition is considered precancerous and can progress to oral cancer if untreated. Symptoms include difficulty eating, burning sensations, and potential malnutrition. Increased awareness and research are essential for effective management and treatment strategies to improve patient outcomes and quality of life (Xu et al. ref. 2021). A study developed a herbal muco-adhesive gel containing 1% curcumin and licorice to treat OSMF in a rat model induced by bleomycin injections. Histological analysis confirmed the model’s fibrotic features. Treatment with the gel significantly improved mouth opening and reduced fibrosis, especially in weeks 12 and 16, attributed to the anti-inflammatory and antifibrotic properties of curcumin and licorice. The findings suggest that this herbal gel could be a therapeutic alternative for managing OSMF, warranting further research for clinical applications (Ejaz et al. ref. 2022).

Denture stomatitis (DS), also referred to as denture sore mouth or stomatitis prosthetica, is a prevalent condition among denture wearers, particularly those with inadequate oral hygiene. Characterized by localized or widespread erythema in the oral mucosa beneath dentures, it is more frequently observed in women and affects the maxillary arch. While discomfort is often minimal, DS has a prevalence ranging from 11 to 72%, making it a significant concern for denture users. Ill-fitting dentures can cause mucosal trauma, increasing the risk of colonization by opportunistic microorganisms, particularly Candida species (Gorji et al. ref. 2024). A study explored the antifungal properties of betel quid and its components, particularly focusing on its effectiveness against DS. A clinical trial compared nystatin mouthwash and garlic extract, finding both effective in treating DS, but nystatin led to faster recovery with more side effects and lower patient satisfaction due to its bitter taste. The research highlighted garlic extract as a viable alternative, supported by its antimicrobial properties attributed to allicin. Overall, the findings suggest that garlic extract could serve as an effective adjunct or alternative therapy for oral fungal infections, warranting further clinical investigation (Bakhshi et al. ref. 2012).

The role of herbal extracts in dental treatment

Natural products exhibit a wide range of bioactive compounds, including flavonoids, terpenoids, alkaloids, and phenolic compounds, which have demonstrated antimicrobial, wound healing, anti-inflammatory, and antioxidant activities. These properties are crucial in combating periodontal pathogens such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and others that contribute to periodontal disease progression (López-Valverde et al. ref. 2023).

Several pathogens, such as Staphylococcus mutans, Staphylococcus aureus, Enterococcus faecalis, and Candida albicans, represent main causative agents of different oral diseases (Ravikumar et al., ref. 2024). S. mutans is a Gram-positive, facultatively anaerobic bacterium, mostly reside in fissures and pits. It is an opportunistic commensal bacterium that causes dental caries (the most common chronic disease worldwide) especially the early childhood caries (Falsetta et al. ref. 2014; Morrison et al. ref. 2023). C. albicans is a commensal yeast fungus of the human skin and oral, gastrointestinal, as well as genital mucous membranes (Lopes and Lionakis ref. 2022). It accounts for up to 95% of oral candidiasis infection (Vila et al. ref. 2020). In vitro and in vivo models revealed that the co-infection with S. mutans and C. albicans enhanced the pathogenesis of dental caries. This symbiotic relationship enhances the biofilm formation as C. albicans induce exopolysaccharides and support the viability of S. mutans than single-species biofilm (Falsetta et al. ref. 2014). As S. mutans enhance its biofilm formation by the aid of C. albicans, the oral streptococci reinforce C. albicans’s invasive characters (Radaic and Kapila ref. 2021). Periodontal diseases are complex, polymicrobial inflammatory infections characterized by tooth-supporting tissues destruction. The disease begins as acute inflammation of the gingiva (gingivitis) and, if untreated, proceeds to form teeth pockets, and eventually teeth loss. Porphyromonas gingivalis, a Gram-negative anaerobe, is the major contributor to chronic periodontitis (How et al. ref. 2016). Prevotella are Gram-negative, anaerobic bacteria that normally colonize the oral cavity. The species of this genus, viz., P. dentalis, P. fusca, P. enoeca, P. denticola, P. melaninogenica, P. intermedia 17, and P. intermedia 17–2, induce inflammatory cytokine production that contributes also to periodontal diseases (Morrison et al. ref. 2023). Another dental issue is halitosis which is a condition characterized by oral malodor. Bacteria such as Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, Porphyromonas endodontalis, Fusobacterium nucleatum, and Solobacterium moorei contribute in this case (Prabhu et al. ref. 2022). This bad breath is caused by volatile sulfur compounds (VSCs) that resulted from protein degradation by halitosis bacteria (Liu et al. ref. 2022). All these mentioned microbes with other ones (up to a total of 1000 species) belong to bacteria, fungi, protozoa, archaea, and viruses comprising the oral microbiota which is a community of microorganisms residing in the oral cavity. The microbiota of healthy hosts in normal conditions maintains balanced symbiotic/commensal relationships which we refer to as eubiosis or microbial homeostasis (Radaic and Kapila ref. 2021). Changes or insults such as tobacco smoking, immunosuppression, and diet alteration may shift this eubiosis to what is called dysbiosis, which is a state of parasitic/pathogenic relationship that promote diseases like dental caries and periodontitis, among others (Lamont et al. ref. 2018; Radaic and Kapila ref. 2021). New drug delivery technologies such as nano systems may aid in diagnosis, prevention, and care of dentistry diseases (Agnihotri et al. ref. 2020). Nanomaterials can enhance the performance of various dental hygiene products such as toothpastes, mouthwashes, and polishing pastes. They range from 1 to 100 nm in size and their extraordinary surface-to-volume ratio increases their bioavailability toward cells and tissues (Carrouel et al. ref. 2020). Nanoparticles of metals have been incorporated into the dental materials to enhance the regenerative, mechanical, and antimicrobial properties. For example, Zn, Ag, Au, Cu, and Ti have antibacterial activity (Agnihotri et al. ref. 2020). Another technique is photodynamic therapy that uses a combination of light of specific wavelength and photosensitizer drug in the presence of oxygen to form toxic oxygen species that interfere with pathogens’ cellular components and damage them (Konopka and Goslinski ref. 2007). Integration between these technologies and natural products has been showing promising results for oral health (Lima et al. ref. 2024; Ravikumar et al., ref. 2024). Many herbal extracts have shown efficacy against periodontal pathogens. The efficacy of these herbal extracts is summarized in Table 1.

Herbal remedies are widely recognized for their traditional applications due to their soothing properties, which have significantly contributed to advancements in dental practice. Numerous plant-based products have been identified for their substantial anti-inflammatory effects. Research in this area has varied, with some studies focusing on single-ingredient formulations, while others have explored the efficacy of more complex combinations. This diversity in approach underscores the potential of herbal remedies to enhance dental treatments and improve patient outcomes (Moghadam et al. ref. 2020). A study evaluated the efficacy of Nigella sativa essential oil (NSEO) in enhancing oral health by targeting periodontal pathogens, inflammation, and oxidative stress. NSEO demonstrated significant antioxidant properties, effectively reducing DPPH radicals and exhibiting high free radical-scavenging activity. The oil also showed anti-inflammatory effects by inhibiting protein denaturation and stabilizing red blood cell membranes. Notably, NSEO displayed antimicrobial activity against key periodontal pathogens, including Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, as well as antifungal effects against Candida albicans. Cytocompatibility tests confirmed its safety for oral care formulations, maintaining over 82% cell viability at concentrations up to 100 µg/mL (Bhavikatti et al. ref. 2024). Another study which was the first scientific evaluation of Multidentia crassa for its potential dental health benefits, reinforcing its traditional use in developing plant-based treatments for dental pain and inflammation. The research highlights the analgesic and anti-inflammatory properties of M. crassa extracts, which may provide effective solutions for oral health issues, especially in low-resource settings. Using gas chromatography–mass spectrometry (GC–MS) and Fourier transform infrared (FT-IR) analysis, 58 active compounds were identified, including phenols and carboxylic acids. Molecular docking studies revealed that stigmastan-3,5-diene shows strong binding potential to oral health-related proteins, indicating its promise as a natural analgesic and anti-inflammatory agent, despite some toxicity concerns for certain compounds (Chikowe et al. ref. 2024).

Additionally, a study was conducted to investigate the effectiveness of Phyllanthus emblica (PE) fruit extract in managing halitosis and reducing inflammation caused by oral bacteria. PE demonstrated dose-dependent inhibition of halitosis-related bacteria, including Fusobacterium nucleatum and Porphyromonas gingivalis, while significantly lowering VSCs in clinical trials with a 5% mouthwash. Additionally, PE exhibited anti-inflammatory effects by reducing markers like IL-6 and IL-8 in oral epithelial cells. Rich in polyphenols, PE has the potential to modulate inflammatory pathways and bacterial growth, suggesting its promise as a natural ingredient for oral health and advocating for further clinical trials (Lu et al. ref. 2024).

This study by Pan et al. investigated the effects of green tea extracts on oral inflammation and microbiome balance in mice with acetic acid-induced oral inflammation. The researchers aimed to assess whether green tea extract could serve as a natural remedy to reduce inflammation and restore microbial diversity in the oral cavity. Results showed that green tea extract significantly lowered inflammatory markers such as IL-1β and TNF-α, indicating its anti-inflammatory potential. Additionally, it promoted balanced oral microbiota by reducing harmful bacteria and aiding mucosal tissue repair. The bioactive polyphenols in green tea, particularly catechins, contributed to these protective effects. The findings suggest that green tea extract may be a promising natural therapeutic agent for managing oral inflammation and dysbiosis, warranting further clinical exploration (Pan et al. ref. 2023).

Moreover, the study by Zhou et al. investigated the effects of Liubao tea extract on oral tissue regeneration, inflammation reduction, and microbiome balance. The research highlighted Liubao tea’s potential as a natural treatment for improving oral health, particularly in repairing tissue damage and managing inflammation from oral infections. Results showed that the tea extract significantly promoted healing, reduced inflammatory markers like IL-6 and TNF-α, and helped restore a healthy oral microbiome by decreasing harmful bacteria. These findings suggest that Liubao tea extract may be an effective natural agent for enhancing oral health outcomes (Zhou et al. ref. 2023).

Another research investigated the use of traditional medicinal plants for managing oral diseases, particularly focusing on their anti-inflammatory properties. Traditional medicine, relied upon by 80% of the global population, is increasingly applied in dentistry for conditions like tooth pain and gum inflammation. The study examined four plants: Azadirachta indica (Neem), Terminalia chebula (Haritaki), Camellia sinensis (Green Tea), and Piper nigrum (Black Pepper). The extracts showed significant protease inhibition, indicating their effectiveness as anti-inflammatory agents, while molecular docking studies revealed their active compounds bind well to the trypsin enzyme, suggesting potential mechanisms for their therapeutic effects in oral health (Assiry et al. ref. 2022).

Furthermore, research examined the potential of a natural product mixture (NPM-8) in fluoride toothpaste for its antibacterial and anti-inflammatory effects, addressing the rise in oral diseases. NPM-8, derived from eight herbal extracts, demonstrated superior antibacterial performance against pathogens like Streptococcus mutans and Porphyromonas gingivalis, outperforming conventional fluoride toothpaste and chlorhexidine. It effectively disrupted biofilms and reduced pro-inflammatory cytokines, indicating its safety and efficacy for daily use. The findings suggest that NPM-8 could enhance oral health by combining antibacterial, anti-biofilm, and anti-inflammatory properties in dental care products (Qi et al. ref. 2022).

In addition, another study investigated the antimicrobial and anti-inflammatory properties of Pistacia lentiscus L. essential oil (PLL-EO), derived from wild plants in Northern Sardinia, as a potential treatment for infections and inflammation, particularly in periodontal disease. PLL-EO demonstrated significant antimicrobial efficacy against key pathogens and high biocompatibility, with minimal cytotoxicity observed in oral cell lines. The oil effectively inhibited COX-2 and LOX enzymes, suggesting its potential to reduce inflammatory responses. The study concludes that PLL-EO could be a promising natural treatment option for periodontal diseases, warranting further research on its mechanisms and interactions with biofilm development (Milia et al. ref. 2020).

Also, a study evaluated the effects of two mouthwash tinctures on oral hygiene and inflammation in orthodontic patients with dental deformities over 10 days, comparing "Octenidol" with a tincture from Georgian legume crop extract (GLCE). Results showed significant improvements in oral hygiene and a greater reduction in gingival inflammation for the GLCE group, with a 41.3% decrease in the PMA index compared to 27.8% in the control group. Additionally, GLCE increased IL-10 levels in saliva, indicating enhanced anti-inflammatory effects. The findings suggest that GLCE may be a more effective alternative to "Octenidol" for managing oral health during orthodontic treatment (Chkhikvishvili et al. ref. 2020).

In this context, another study investigated the effects of aqueous extract (AE) from Larrea divaricata on oxidative stress in the submandibular glands of female rats induced by streptozotocin (STZ). The administration of STZ resulted in significant oxidative stress, marked by increased serum glucose, nitric oxide, and malondialdehyde levels. Treatment with AE restored antioxidant balance, primarily due to its major compound, nordihydroguaiaretic acid (NDGA). The AE significantly reduced oxidative damage markers and improved gland health without cytotoxic effects, suggesting its potential therapeutic applications for managing oxidative stress-related conditions, particularly in diabetes (Peralta et al. ref. 2019).

The inhibitory effects of Lactobacillus salivarius WB21 was investigated on Streptococcus mutans and Porphyromonas gingivalis. Results showed that L. salivarius WB21 completely inhibited the growth of two S. mutans strains after 40 h, with significant reductions in insoluble glucan production. Additionally, it inhibited P. gingivalis growth within 6 h, likely due to the acidic environment it creates. The study also explored the synergistic effects of L. salivarius WB21 and EGCG on P. gingivalis, finding that EGCG enhances the antimicrobial action of L. salivarius. The findings suggest that a combined product could improve oral health by reducing pathogens and inflammation, warranting further clinical trials for managing oral malodor and enhancing overall oral hygiene (Higuchi et al. ref. 2019).

The immunomodulatory effects of a propolis-containing mouthwash (P/CHX) was studied on human monocytes. Propolis was found to be non-cytotoxic, while chlorhexidine (CHX) exhibited cytotoxicity at higher concentrations. Treatment with P/CHX increased Toll-like receptor 4 (TLR-4) expression and enhanced interleukin-10 (IL-10) production, which may inhibit co-stimulatory molecules like CD80. The combination also slightly activated the NF-κB signaling pathway and improved monocytes’ bactericidal activity against Streptococcus mutans, potentially through reactive oxygen species generation. Additionally, P/CHX reduced TNF-α production from CHX, indicating anti-inflammatory potential. Overall, the findings suggest that P/CHX could be beneficial for managing periodontal diseases due to its enhanced microbicidal and anti-inflammatory properties (Santiago et al. ref. 2016).

The antioxidant and cytoprotective activities of betel quid and its components were investigated, where the study highlighted their potential health benefits in the oral cavity. Using an aqueous extraction method, gambir was found to have superior antioxidant activity compared to areca nut, with effects similar to ascorbic acid. Betel quid containing calcium hydroxide showed reduced antioxidant capacity due to higher alkalinity. The total phenolic content in gambir correlated positively with antioxidant activity and cytoprotection against oxidative stress in human gingival fibroblasts. Key compounds like quinic acid and quercetin contributed to these effects, while the stability of phenolics was influenced by pH levels. The findings suggest that betel quid may improve oral health, warranting further clinical investigation into its bioactive compounds for periodontal disease prevention (Nur Sazwi et al. ref. 2013).

The endocannabinoid system (ECS) plays a crucial role in cognitive functions, inflammation, and immune response, particularly during periodontal disease, where inflammatory mediators can elevate pro-inflammatory cytokines. Recent studies on plant cannabinoids (pCBs) revealed that while they showed limited activity at the CB1 receptor, compounds like CBG and CBVN acted as agonists at the CB2 receptor, promoting anti-inflammatory effects. pCBs enhanced the viability of human gingival fibroblasts and modulated cytokine production, suggesting their potential as therapeutic agents for managing periodontal inflammation and pain while reducing harmful bacteria (Abidi et al. ref. 2022).

As is known, cigarette smoke contains over 5,300 chemicals, including nicotine and carcinogens, which generate free radicals that cause oxidative damage to lipids, proteins, and DNA. This oxidative stress triggers an inflammatory response through the activation of IκB kinase (IKK) and the degradation of NF-κB inhibitors, leading to increased expression of pro-inflammatory genes. Smoking significantly raises the risk of oral diseases like gingivitis and periodontitis. A study investigated candy lozenges containing extracts from Moringa oleifera and Cyanthillium cinereum, hypothesizing that their antioxidant and anti-inflammatory properties may alleviate oral inflammation in smokers (Luetragoon et al. ref. 2021).

Another epidemiological research has linked polyphenols in black tea, particularly theaflavins, to various health benefits, including potential protective effects against oral diseases. This study evaluated the antibacterial efficacy of black tea extract and its theaflavin derivatives against key periodontopathogens like Porphyromonas gingivalis and Prevotella intermedia. The findings showed that black tea extract and theaflavins effectively inhibited these pathogens and enhanced the antibacterial effects of conventional antibiotics. Additionally, black tea extract reduced IL-8 production, potentially lowering inflammation in periodontal diseases. The study suggested that incorporating black tea bioactive compounds into oral hygiene products could be a cost-effective strategy for improving periodontal health (Lombardo Bedran et al. ref. 2015).

A comprehensive list of several herbal remedies utilized to enhance oral health is presented in Table 2. These remedies have been recognized for their therapeutic properties and potential benefits in dental care, contributing to the prevention and management of various oral conditions.

Toothpastes containing various components

Zinc-containing drugs have gained popularity in dental treatments due to their potent antibacterial characteristics and capacity to stimulate mucosal healing (Uwitonze et al. ref. 2020). Zinc citrate, zinc oxide, zinc chloride, and zinc gluconate are common ingredients in dental care regimens. Zinc citrate is commonly found in toothpaste and mouthwashes, where it inhibits bacterial development and so helps to minimize the development of plaque and gingivitis. Zinc oxide, which is extensively used in dental cements and fillings, has both antibacterial and remineralizing properties (Moradpoor et al. ref. 2021). Zinc chloride, found in mouthwashes and topical gels, helps to manage oral infections and speeds up wound healing after dental treatments. Zinc gluconate is also helpful at reducing unpleasant breath and inhibiting bacterial proliferation (Pushpalatha et al. ref. 2022).

Recent research has demonstrated the efficacy of zinc-containing medications in dental treatments, particularly in reducing bacterial development and boosting mucosal healing. For example, a study on the development of an injectable zinc-containing hydrogel with a double dynamic bond proved its efficacy in treating periodontitis. The hydrogel demonstrated outstanding osteogenic capabilities, self-healing ability, and broad-spectrum antibacterial activity, making it a viable local drug delivery system (Yang et al. ref. 2024). Another study examined the development of zinc-containing chitosan/gelatin coatings with immunomodulatory properties for soft tissue sealing around dental implants. These coatings were reported to successfully induce pro-regenerative macrophage polarization while also increasing gingival fibroblast adhesion, proliferation, and collagen secretion (Han et al. ref. 2024).

Furthermore, studies on the integration of zinc oxide nanoparticles displayed their ability to hinder acid generation by Streptococcus mutans and Lactobacillus in dental plaque, indicating their potential for avoiding dental caries and treating oral infections (El Shahawi ref. 2023). Another study examined the use of zinc oxide nanoparticles in a variety of dental applications, including endodontics, restoratives, periodontics, implantology, orthodontics, and prosthodontics. These nanoparticles exhibited increased cytotoxicity, high selectivity, biocompatibility, and ease of manufacturing, making them useful in dental materials (Zeidan et al. ref. 2022).

Meanwhile, a pilot randomized controlled trial assessed the efficacy of CAREDYNE Shield, an advanced zinc-containing desensitizer, in treating dentin hypersensitivity. The study discovered that CAREDYNE Shield effectively reduced the intensity of pain in response to air stimuli, which was comparable to other desensitizers (Matsuura et al. ref. 2022). Further research explored the efficacy of dentifrice containing arginine and zinc in reducing dental plaque both in vitro and in vivo. The combination of these active chemicals was shown to be beneficial in eradicating dental plaque (Gloag et al. ref. 2023).

In addition, salicylate-containing medications, such as aspirin (acetylsalicylic acid) and topical NSAIDs as diclofenac sodium and methyl salicylate, are often utilized in dental treatments owing to their analgesic and anti-inflammatory effects. These drugs can help treat oral pain, inflammation, and temporomandibular diseases (Jeske ref. 2024).

Research findings have been conflicting, with some suggesting a decrease in the severity of pain and others pointing to a limited level of efficacy when compared to placebo treatments. When employing salicylate-containing drugs in dental care, it is essential to consider the response of each patient as well as possible adverse effects, like gastrointestinal discomfort (Panchanadikar et al. ref. 2021). According to a systematic review, for example, although several topical therapies demonstrated promise, the limited number of studies and possible biases indicate that the total evidence is still equivocal. To confirm these results and provide precise recommendations for the use of drugs containing salicylate in dental procedures, more investigation is required (Wiśniewska et al. ref. 2023). It is important to note that a previous study demonstrated the employment of choline salicylate and lidocaine hydrochloride in a new dental gel as a promising anti-inflammatory approach in various dental treatments (Maslii et al. ref. 2021).

Furthermore, fluoride-containing medications play an important role in dental therapies since they can prevent dental caries and promote tooth remineralization. These drugs comprise many forms, including toothpastes, mouth rinses, gels, varnishes, and silver diamine fluoride (Sun et al. ref. 2020). For example, fluoride toothpaste is commonly advised for daily usage to strengthen tooth enamel and lower the incidence of cavities. Professionally administered fluoride treatments, including varnishes and gels, contain a higher concentration of fluoride and are especially effective for individuals who are at high risk of dental caries (Saad et al. ref. 2022). Additionally, community water fluoridation is a public health practice that raises the fluoride content of the water to appropriate levels to prevent tooth decay. These fluoride treatments have been recognized for their safety and efficacy in maintaining oral health (Jurasic et al. ref. 2022). Several studies have demonstrated the use of topical fluoride solutions, namely silver diamine fluoride, in dental treatment as an anti-hypersensitivity agent and putative caries-preventing formulation (Gao et al. ref. 2021; Horst ref. 2018; Mei et al. ref. 2016; Zheng et al. ref. 2022).

Besides, a previous study investigated the efficacy of a localized sustained fluoride release from personalized 3D printed mouthguards at the device enamel interface which proved to enhance the integration of fluoride inside the tooth matrix and avoid lesion progression (Berger et al. ref. 2022). Further, the dual action of fluoride and nitric oxide-releasing hydrogels was reported with enhancement in combating dental caries (Estes Bright et al. ref. 2022). Also, topical application of casein phosphopeptide–amorphous calcium phosphate comprising fluoride proved to be an effective treatment approach for children with caries combating dysbiotic oral microbiome which contributes to dental caries pathogenesis in children (Widyarman et al. ref. 2021).

Dental medications containing salicylate have been reported to offer anti-inflammatory and analgesic effects, especially in cases of periodontal diseases (Kotowska-Rodziewicz et al. ref. 2023). However, long usage can present complications such as local inflammation as well as various hypersensitivity reactions in some patients (Nagi et al. ref. 2015). Various toothpaste containing different types of fluoride act effectively in preventing dental caries through aspects of enamel depositional rebinding and bacterial suppression (Mahmoud et al. ref. 2020). Several research studies have also shown that fluoride in alloys with zinc or bioactive glass nanoparticles widened the positive impact of bacterium eradication and decreased the number of oral bacteria and plaques compared with fluoride alone (Cui et al. ref. 2023; Satpathy et al. ref. 2023). Nevertheless, excessive use of fluorides in the form of oral products results in dental fluorosis particularly in children and therefore needs close monitoring (Toumba et al. ref. 2019).

Applications of herbal products in dentistry

Herbal extracts are concentrated substances derived from plants, containing active compounds that can offer therapeutic benefits (Ashfaq et al. ref. 2023). However, many herbal extracts face challenges with solubility and bioavailability, which limit their effectiveness in treatment of several orodental disorders. To enhance these properties, several strategies were employed (Hani et al. ref. 2023), among which were nanotechnology-based formulations. Nanotechnology-based delivery systems, such as lipid nanoparticles, polymeric nanoparticles, and hybrid nanoparticles can significantly enhance the solubility, stability, and extend the release of herbal extracts, promoting effective absorption across biological membranes (Wassif et al. ref. 2024). Additionally, using permeability enhancers, enteric coatings, bioenhancers, and solubilizing agents such as cyclodextrins can further boost the solubility and bioavailability of these herbal extracts (Sodeifian and Usefi ref. 2023).

Consequently, several reports revealed the formulation of phytochemicals into nano-based systems to foster their therapeutic efficiency for treatment of orodental disorders (Nsairat et al. ref. 2023). This will be listed in the following.

Periodontitis and dental caries are the most prevalent oral infections. It was discovered that invasion by pathogenic bacteria is the primary cause of these conditions. These bacteria sequester inside the extracellular matrix, preventing the penetration of antibacterial agents and forming biofilms. Essential oils possess the functionality to be quite beneficial for the management of dental infections (Di Stefano et al. ref. 2022). Though, a challenge occurs as bacterial cells are surrounded by a hydrophilic extracellular matrix which is impervious to essential oils. To overcome the development of resistance, the approach of nanotechnology has been effectively applied, with a remarkable increase in antibacterial action (Mubeen et al. ref. 2021).

In a previous study, Poly (D, L-lactide-co-glycolide) (PLG) nanoparticles laden with Harungana madagascariensis extract were synthesized and investigated for their antimicrobial effects against Gram-negative and Gram-positive strains that inhabit the oral cavity. The nanoformulations demonstrated a significantly lower minimum bactericidal concentration (1.875 × 102 mg/L) relative to extracts in ethyl acetate (5–7 × 102 mg/L). The bioadhesive characteristic of the PLG polymer enabled nanoparticles to adhere to bacterial cells, resulting in the extract’s sustained release while preserving the concentration (Kumar et al. ref. 2022).

Similarly, biofilms are hydrophilic in nature, therefore lipophilic essential oils can be transformed into nanoemulsions of size smaller than 300 nm, allowing substances to penetrate the biofilm matrix. A study displayed that cinnamon oil and grapefruit seed extract encapsulated in nanoemulsions reduced the biofilm of Streptococcus mutans by 86% relative to 60% for the oil solution in ethanol (Choi et al. ref. 2023).

In parallel, studies have proposed that nano/microemulsions provide superior outcomes in terms of resistance to bacteria (Subbiah et al. ref. 2019). The combination of the nanosize feature and surfactants in the formulation supplied the delivery system with a high wetting ability and surface tension. This permitted fusion with the microbes’ cell membranes, ultimately leading to their mortality.

Meanwhile, Aloa vera-loaded nanomaterials showed enduring antibacterial action in endodontic infections, a condition in which standard irrigation solutions and intracanal treatments used in root canal therapy are unable to completely eradicate the germs from the root canal (Beigoli et al. ref. 2021). Additionally, the fabrication of silver, gold and bimetallic (gold and silver) nanoparticles allowed for substantial use of neem leaf extract (Borah et al. ref. 2018). In the process of creating neem leaf extract loaded silver nanoparticles, the extract reduced and capped the adherence and growth of oral infections while also preventing secondary caries.

Similarly, in oral drug delivery systems, green tea catechin derivative nanoparticles demonstrated promising results. The maximum growth inhibition of oral Fusobacterium, Actinomyces, Prevotella, Lactobacillus, Streptococcus, Propionibacterium species was demonstrated by gallic acid loaded-PLG nanoparticles, indicating their efficacy in treating various bacterial infections that cause orodental diseases (Dalir Abdolahinia et al. ref. 2023).

In another trial, the Chinese herbal remedy icariin—which was exploited to prevent osteopenia—was shown to prevent peri-implantitis and inflammation as well. The process of sequestering it into nanoparticles significantly sped up the incorporation of dental implants, increasing their efficiency (Liang et al. ref. 2021). Additionally, Mangifera indica-loaded nanoparticles had shown encouraging antibacterial activity and had been propitiously applied in several dental applications, enhancing the hardness and mechanical bonding of the glass ionomer dental cement (Soesanto et al. ref. 2023).

Meanwhile, Moringa oleifera-loaded casein phosphopeptide nanoparticles were also utilized to treat white spots, erosion, and dentin hypersensitivity. This new mixture displayed antimicrobial activity and dentin remineralization (Shafiq and Mahdee ref. 2023). Furthermore, in another study, the manufacture of nano-hydroxyapatite with Moringa oleifera leaf extract showed remarkable nonlinear properties, including reducing and stabilizing action (Anwar et al. ref. 2024).

Curcumin exhibits strong anti-inflammatory properties; yet, due to its hydrophobic nature, it experiences minimal oral absorption when utilized as a powder or in other traditional carriers. As a result, nanomicelles were developed encapsulating curcumin in a hydrophobic core. The delivery approach improved curcumin’s solubility, rendering it effective in lowering inflammation in mild periodontitis and gingivitis (Bapat et al. ref. 2023).

Nanotechnology has been shown to improve the stability of plant extracts against hydrolysis, oxidation, and photo or thermal degradation, as well as minimize volatility (Antunes Filho et al. ref. 2023). Curcumin was reported to be photoreactive, reducing its activity by 70%. Therefore, Onoue et al. (Onoue et al. ref. 2013) created curcumin loaded solid dispersions with enhanced physical stability, in which only 17% degradation was detected, hence increasing its effectiveness in gingivitis and mucositis treatment.

Moreover, Tonglairoum et al. (Tonglairoum et al. ref. 2016) also demonstrated that complexing betel oil and clove oil with cyclodextrins increased their solubility. They were then integrated into nanofibers that developed rapid oil release and boosted antifungal efficacy against oral Candida species, demonstrating their potential for treating denture stomatitis.

In another study, researchers created microspheres loaded with zedoary oil derived from turmeric. It was shown that the small size of the carrier permitted greater in-vivo absorption, increasing bioavailability by 135.6% (Pandey et ref. al.2022). Furthermore, the prolonged release of the employed oil minimized the undesirable side effects and lowered dose frequency. Also, baicalein was synthesized as a nanocrystal in another attempt, and the outcomes showed 1.67-fold increase in solubility and bioavailability (Dhaval et al. ref. 2020). Both delivery systems showed enhanced therapeutic efficacy against periodontitis.

A variety of herbal extracts have been incorporated into nanosystems to treat periodontitis. Kaempferol nanoparticles loaded with calcium sulphate composite beads were recently developed and shown to exert antibacterial action against Escherichia coli and Staphylococcus aureus, indicating their usefulness in periodontal treatment to lower the level of bacteria at the area of infection (Narang and Narang ref. 2015).

Previously, additional research carried out on dogs with periodontal abnormalities and treated with luteolin-loaded nanoparticles demonstrated high absorption across the junctional epithelium (Zhu et al. ref. 2024). Additionally, a unique strategy involved sequestering apigenin-loaded polycaprolactone nanofibers for periodontal tissue regeneration at the gum interface. The researchers proved that encapsulating apigenin-loaded nanofibers with submicron diameters into the nanofibers’ network reduced the release of apigenin from the nanoparticles, resulting in its extended release inside the periodontal pocket throughout the duration of the therapy. Initial investigations on human mesenchymal stem cells revealed cell survival up to 5 days after culture, hence suggesting the potential of these nanofibers in treating periodontal diseases (Mohammadinejad et al. ref. 2020).

One of the most major implications of nanotechnology-based treatments is cancer therapy, which might otherwise cause numerous side effects and be prohibitively expensive. Recently, various novel revolutionary drug delivery systems have been discovered imparting nanoparticles laden with resveratrol, which could be an important advancement in avoiding periodontal disease development (Sharifi-Rad et al. ref. 2021). Peppermint oil has been shown to provide considerable anticancer capabilities against oral cancer; yet its low solubility hinders its use. Lopes et al. (Lopes et al. ref. 2022) established peppermint oil-loaded nanoemulsions with droplet size around 100 nm and then incorporated into the internal hydrophobic core with an external aqueous compartment, rendering them soluble in aqueous media.

In addition, herbal extracts from Trypterygium wilfordii showed promising results as oral chemotherapy treatments, although being water-insoluble and having limited intestinal absorption. A study reported that lipid-based nanocarriers as lipid nanospheres (Wagh et al. ref. 2021) and lipid nanoparticles (Guo et al. ref. 2021), laden with Trypterygium wilfordii were developed to improve its solubility and diffusivity into tumor cells. Moreover, phytosomes loaded with protamine and integrated into chitosan sponges were developed. This carrier system exhibited mucoadhesive attributes along with improved penetration across the buccal mucosa, resulting in a 90% increment in bioavailability for the management of numerous forms of oral malignancies (Lagoa et al. ref. 2020).

Furthermore, researchers introduced the herbal shotgun strategy, in which synergistic mixtures of virgin coconut oil and peppermint oil loaded into nanoemulsions demonstrated tremendous cytotoxic functions towards oral squamous cancer cell lines (Kumar et al. ref. 2022).

In parallel, silica nanoparticles laden with curcumin showed greater cellular uptake and cytotoxicity in oral squamous cell carcinoma cells relative to free curcumin dispersion. Curcumin-loaded nanoparticles proved to be more cytotoxic compared to free curcumin forms, promoting apoptosis in cancer cells (Pecorini et al. ref. 2023).

Furthermore, naringenin-loaded nanoparticles possessing a cationic copolymer increased the solubility of naringenin (Budi and Farhood ref. 2023). In a dimethoxybenzaldehyde-induced oral squamous cell carcinoma hamster model, they showed significant reduction in proliferation of tumor while increasing antioxidant levels. A further study displayed that the employment of chitosan-coated nanoemulsions encapsulating genistein that were incorporated into buccal tablet forms. Cytotoxicity studies on these cell lines demonstrated that the employed nanoemulsions constituted remarkable cytotoxic effectiveness than genistein conventional formulations (Umapathy et al. ref. 2023).

Furthermore, the dried root of Saliva miltiorrhiza was previously employed in conventional Chinese medicine for the treatment of a variety of ailments, particularly cancer, and its loading into transfersomes demonstrated effectiveness to inhibit the proliferation of oral precancerous as well as oral squamous cell carcinoma cell lines (Qin and Wu ref. 2023). Moreover, another study reported that Bacillus subtilis, Escherichia coli, Candida albicans, Staphylococcus aureus, and Bacillus cerevisiae from oral squamous cell cancer cell lines showed absence of resistance to flower extract of Carthamus tinctorius-loaded silver nanoparticles (Vyas et al. ref. 2023).

Meanwhile, Dendropanax morbifera Le’veille, an ancient medicinal plant prevalent in South Korea, was employed for treatment of several types of cancers including oral ones. Fortunately, silver nanoparticles loading this plant extract was employed as carriers for its delivery to manage oral cancer, showing potent superior results as well as non-cytotoxicity to normal cells (Talukdar et al. ref. 2023).

A further study reported that various plant extracts such as Tamarix gallica, Terminalia chebula, Dendropanax mobifera Le´veille, and ginseng aqueous leaf extract with reported antitumor action were additionally loaded into the environmentally friendly crystalline gold and silver nanoparticles with proven functionality against several types of oral cancers (Manikkath et al. ref. 2023). Additionally, a number of green nanoparticles have been shown to exhibit potent antimetastatic, cytotoxicity and anticancer activities against a variety of oral cancer cell lines (Karnjana et al. ref. 2023). These include gold nanoparticles encompassing the edible mushroom Pleurotus florida, Erythrina suberosa, Couroupita zizanioides ethanolic extract, Dysosma pleiantha rhizome aqueous extract, Polygala senega ethanolic extract nanoencapsulated form, and gold nanoparticles laden with Siberian ginseng.

Simultaneously, Pluchea indica extract-loaded nanoparticles increased both the migration of oral squamous carcinoma cells and cytotoxicity at low concentrations, and their oral nanoformulations improved the extract’s colloidal stability (Mali ref. 2023). Furthermore, green synthesized metal nanoparticles have shown tremendous effectiveness in the management of oral cancer and oral microbial infections. Copper oxide nanoparticles loaded with an aqueous bean extract were reported to promote mitochondrial apoptosis, decrease HeLa cell growth, and demonstrate in vitro chemotherapeutic action against oral squamous cell carcinoma (Sharma et al. ref. 2024).

Besides, coriander sativum-loaded silver nanoparticles were found to possess increased antibacterial action towards common oral pathogenic organisms (Peng et al. ref. 2023). Furthermore, artichoke extract loaded nanoparticles displayed significant reduction in oral premalignant lesions (Imbesi Bellantoni et al. ref. 2023). Meanwhile, nanoparticles generated from guava leaves demonstrated effectuality to suppress the proliferation of oral cancer cells, eliminating up to 80% of them (Nsairat et al. ref. 2023).

In addition, hydroxyapatite has been proven to demonstrate bone-forming features and is thus employed in several dental implants as a bone substitute. In one study, it was observed that hydroxyapatite-sequestered nanocrystals induced bone remineralization, yet only in the enamel’s outer layer (Angellotti et al. ref. 2023). Moreover, Imran et al. (Imran et al. ref. 2023) discovered that combining both Gallachinensis extracts and nanohydroxyapatite improved bone deposition and remineralization on teeth relative to single procedures.

Further, nanocomposites have found widespread utilization in dentistry. They could create a more robust and natural contact between the hard mineralized tissues of the tooth and the small filler particles employed by improving consistency between the structure of the tooth and these proficient regenerative materials. These nanofillers showed their potential to provide flexural strength, superior hardness, translucency, elasticity, exemplary handling characteristics as well as a 50% reduction in filling shrinkage (Aktas et al. ref. 2024).

Fortunately, nanotechnology was also projected to contribute to significant advancements in digital dental imaging procedures in addition to its therapeutic properties. High-quality images could be obtained with a reduced radiation dosage in digital radiographies that employ nanophosphor scintillators (Haidar ref. 2023).

Several approved oral medications used in dentistry are listed as follows:

Conclusion and future perspectives

Incorporating herbal dentifrice into daily oral hygiene can greatly benefit individuals with oral problems by effectively reducing plaque, mouth ulcers, oral carcinoma, and inflammation. Their anti-inflammatory properties help to reduce the gum inflammation, which is essential for managing periodontal diseases. Many herbs possess antibacterial effects that can inhibit the growth of periodontal pathogens, including antibiotic-resistant strains, thus preventing plaque formation and gum infections. Additionally, the antioxidant activity of various plants combats oxidative stress in oral tissues, promoting overall gum health. Herbal remedies offer notable advantages, including accessibility, cost-effectiveness, prolonged effects, and lower toxicity compared to conventional treatments.

Although many plants demonstrate low toxicity and promising pharmacological effects, there is a lack of comprehensive studies on their dental applications. Comprehensive preclinical and clinical studies are essential to ensure the safety and biocompatibility of these treatments. The demand for innovative substances to inhibit bacterial growth and biofilm formation in dental treatments underscores the necessity for additional research to validate these natural products’ efficacy and safety in clinical settings.

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