Introduction

The periodontal term consists of the teeth which are supported by Gum and bone. Such teeth are affected due to poor oral hygiene and it causes the inflammation and formation of bacterial plaque which eventually losses the tooth. Gingivitis is one of the mildest forms of it.¹ Periodontitis based on specific etiology: chronic and aggressive. Sometimes it can be occurance by manifestation of systemic disease.² The main bacteria involved in the development of dental caries are Streptococcus mutans and Lactobacillus acidophilus.³ Treatment for periodontitis seeks to lower the number of pathogenic bacteria in the mouth, eradicate diseased pockets, and heal inflammatory tissue.¹ For that treatment options may vary from cost-effective and costly surgical & non-surgical involving various antimicrobials, mouth rinsers, mouthwashes, antiseptic formulations, gels, and oral antibiotics prescribed by a periodontist. Surgeries are also available for periodontitis depending on the severity e.g flap surgery, guided tissue regeneration (GTR), tissue-stimulating proteins, soft tissue, and bone grafts.⁴

More severe periodontitis with bone loss and pocket formation, which could eventually lead to losing the tooth if not treated appropriately, may impact 40% to 45% of India’s population, according to a report by the National Commission on Macroeconomics.⁵ Traditional medicine has been used worldwide for centuries. Traditional herbal medicine is used by near about 70% of the total population in India and up to 90% of the population in Africa using for medical treatment.⁴ Naturally occurring herbal components which having multiple bioactive constituents possess enormous medicinal value with few side effects and most important is maximum they are safe. The other synthetic antibiotics and antimicrobials have the disadvantages of being drug-resistant and numerous side effects. So, the natural phytoconstituent is a good and safest proven alternative for such oral diseases.⁶ Various herbs are patented and have proven study for oral disease. In this review, introducing various herbal remedies that are useful for periodontitis. The following Fig.1 are shown comparison between Synthetic and Herbal drugs.

Figure 1: The comparison between Synthetic drugs and Herbal drugs. Click here to view figure

Commonly Used Herbs: Overview

Due to the anti-plaque and anti-inflammatory properties of herbal medicine, they are strongly recommended in dentistry.⁶ Some of them also act as precautionary, helping to prevent it from arising.  Antimicrobial resistance and severe side effect are the disadvantages of synthetic drugs used in infection. Instead of them, phytoconstituents are the safe alternatives to control infections.⁷ When applied to the gums, the aloe vera gel has been observed to reduce gum tissue irritation and pain. Clove oil lowers infection and relieves discomfort from pain. The methanolic extract of clove shows activity against anaerobic Gram-negative oral bacteria which cause tooth infection and periodontitis. From the literature, it is reported that Myricetin & Kaempferol have significant inhibitory activity against periodontal pathogens. Echinacea and goldenseal also have been reported to reduce inflammation and relief infection. A natural supplement of Coenzyme Q-10 promotes a healthy blood supply to the gums by increasing oxygen transport in the body. Clinical research data have shown that daily use of Coenzyme Q-10 improves plaque and calculus counts in patients with periodontal disease. Some nutraceutical product such as bioflavonoids along with Vitamin C helps to accelerate the healing process in oral issues. Some herbal components are patented for their action and uses. Among them are patented herbs like oral administration of a dried extract of Vinca rosea for reducing plaque. Which is a good oral hygiene method for the treatment of periodontal diseases. Acacia catechu has been used to remove tartar, plaque, and stains, as well as to cleanse and polish the tooth surface, which helps to enhance the condition.¹

Miswak (Salvadora persica) 

Miswak belongs to the Salvadoraceae family & also known as a chewing stick. Since ancient times miswak has been used for maintaining oral hygiene.⁸ Researchers have suggested that miswak has over ten naturally occurring elements that are important for good dental, oral, and overall health like Fluoride, Silica, Benzyl isothiocynate, Essential oils, salvadorine, Salvadoraside, 1,8-Cineole, linalool, Piperidine, Isoterpinolene, Myrcenol, and sabiene.^6,9 In medicinal component Benzyl isothiocyanate shown in Fig 2 is a major volatile oils component of Salvadora persica which show bactericidal effect against many bacteria.⁴ The important chemical constituent of miswak and their actions are shown in Fig 3. Another antimicrobial constituents & prophylactic components include alkaloids, fluoride, Sulphur compounds & glucosinolates, Methyl chavicol, etc.⁵ Miswak is scientifically proven for its effectiveness against tooth decay and it is recommended to use as a successful oral hygiene tool by World Health Organization. It is a unique remarkable dental stick and cost‑effective solution for common people.  Report from miswak users is that there is less gingival bleeding, better periodontal health, and interproximal bone loss when especially in comparison with common toothbrush users.^10,11.

Figure 2: The Structure of Benzyl Isothiocynate Click here to view figure

Figure 3: The bioactive components of Miswak Click here to view figure

Neem (Azadirachata indica) 

The Neem tree is primarily grown in Asia and Africa’s southern regions and because of its therapeutic characteristics, Asians have long utilized neem to treat a variety of ailments. The chemical composition includes Nimbin, nimbidin, azadirachtin, nimbolide, epicatechin, catechin, gallic acid, and margolone.⁶ The bioactive compound of neem is shown in Fig 4. We found clinical study data showing the effect of Neem in the literature. In this study, 50 individuals with confirmed gingivitis were chosen, 40 of whom had significant bleeding and pustular discharges from their gums. Eight out of ten patients exhibited considerable improvement after brushing twice a day with a paste containing neem leaf extracts just for three weeks. The patients also experienced a decrease in bacterial populations as well as the removal of halitosis, all with no negative side effects.⁸ Insoluble glucan production is prevented by aqueous extract of Neem, leading to bacterial aggregation. As a result, streptococci’s ability to colonize tooth surfaces and the oral cavity will be reduced. It has been recommended that it be used to treat tooth plaque. The mucoadhesive dental gel has a composition of neem extract Compared to chlorhexidine gluconate mouthwash, it was found to be more effective at reducing bacterial count and plaque index.¹²

Figure 4: List of bioactive compounds in A. indica. Click here to view figure

Water-soluble extracts of the Azadirachata indica affect some bacterial properties which may alter bacterial adhesion and also affect the growing ability to the colonization of tooth surfaces by streptococci. The most important thing is among the oral streptococci studied, neem has a broad bacterial aggregating effect.¹³ Formulation of gel with neem extract combined with a mucoadhesive polymer can greatly shorten the time it takes to cure oral infections and manage the microorganisms that cause tooth problems.¹⁴ Adyanthaya et.al¹⁵ studied the antimicrobial effect of methanol extract of neem twig. They discovered that neem extract was effective in lowering cariogenic and periodontal disease-causing bacteria, and they proposed utilizing methanolic extracts of neem twig in oral care products. Following a daily dosage of 25, 50, or 100 mg/kg for 6 weeks, nimbidin caused subacute toxicity in adult rats; a hypoglycemia effect was also reported after administering nimbidin to fasting rabbits and on another side, when nimbolide and nimbic acid are injected intravenously or intraperitoneally they are found to be harmful to mice; however, these chemicals are less dangerous to rats.¹⁶ Fig 5 shows the structure of Nimbolide. Fig 6 structure of Nimbidin. 

Figure 5: The Structure of Nimbolide. Click here to view figure

Figure 6: The Structure of Nimbidin. Click here to view figure

Guava (Psidium guajava) 

Guava primarily rich in Vitamin C (Ascorbic acid) shows an excellent antioxidant property. This ascorbic acid alters the fibroblast differentiation and modulates procollagen gene expression by the effect on the extracellular matrix, following collagen formation. Ascorbic acid, in combination with bioflavonoids, assists in the healing process.¹⁷ Phytoconstituent of guava mainly shows multifunctional effects like carotenoids, quercetin, and polyphenols which exhibit its antioxidant action, the antibacterial effect of guava is mainly associated to flavonoids, guaijaverin, and quercetin. One of the major flavanol quercetin has demonstrated good antimicrobial activity against periodontal pathogens Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Fusobacterium nucleatum, etc. and this activity of quercetin is thought to be related to the formation of irreversible complexes that disrupt the membrane and inactivate extracellular proteins. The structure and MOA of quercetin are shown in Fig 7. Guava essential oils and leaf extracts can scavenge hydrogen peroxide and superoxide anion, as well as reduce the generation of hydroxyl radicals. The decoction of leaves can be used as a gargle for bleeding gums, while the decoction of roots and bark can be used as a mouthwash.^18,19 Quercetin’s anti-inflammatory properties are due to its involvement in the NF-κB, JNK, and Nrf2 signaling pathways. NF-κB is a transcription factor that can influence the transcription of cell genes and thereby regulate the inflammatory response.²⁰ The existence of several essential oil compounds, such as monoterpenes, 1.8-cineol, and acetate of α-Terpenil along with guaijaverin and psidiolic acid contributes to P. guajava’s antimicrobial activity.

Figure 7: The Structure of Quercetin with its various effect. Click here to view figure

According to the literature, most of these medicinal plant extracts or their combinations could be used as herbal alternatives to chlorhexidine.²¹ The second most important constituent is Guaijaverin which is a promising antiplaque component due to its bacteriostatic property by preventing the growth of S. mutans and S. aureus. Guaijaverin reduces the hydrophobicity of oral pathogenic bacteria, which is one of the most critical components in their ability to attach to the tooth surface. This activity could be due to guava extracts binding to cell surface proteins, lowering total cell hydrophobicity, and so guava could be developed as a natural antiplaque agent. The structure of guaijaverin is shown in Fig 8. Guava extract has been shown to suppress the growth, adhesion, and co-aggregation of dental plaque bacteria in in-vitro. Guava leaf extracts may reduce plaque bacteria formation without altering oral cavity balance.¹⁹ From the literature author found that there was a significant reduction in full-mouth scores of plaque index (1.36 ± 0.04), gingival index (1.29 ± 0.047), gingival bleeding index (47.5±1.162), and PPD (0.71 ± 0.024mm) and gain in CAL (0.72 ± 0.052mm), at various time intervals. Thus, these indicated an overall improvement in gingival and periodontal health.¹⁷ The presence of catechol at the B ring may have attributed to the flavanol compound guaijaverin which demonstrated growth-inhibitory effect against the test microorganisms. The bioactive compound in the extract of the guava leaf, such as flavonoids and tannins, are responsible for the prevention of bacterial adhesion. Flavonoids have anti-GTase properties. This enzyme is capable of converting sucrose to viscous insoluble glucan, which encourages S. mutans to stay firmly attached to the tooth’s surface.²²

Figure 8: The Structure of Guaijaverin Click here to view figure

Green Tea (Camellia sinensis) 

Green tea is made from Camellia sinensis leaves that have been processed with minimal oxidation. It has the highest percentages of polyphenols, which are antioxidants in nature and categorized as catechins. Green tea has 6 major catechin components. : Catechin, gallocatechin, epicatechin, epigallocatechin, epicatechin gallate (ECg), and epigallocatechin gallate (EGCg). Among all the other chemicals, EGCg has been the subject of much research, and it is a particularly powerful antioxidant in action. Green tea is also found in tocopherols, selenium, carotenoids, ascorbic acid, chromium, and zinc as well as a variety of phytochemical substances. Catechins in green tea have demonstrated potential antibacterial activity on periodontal infections, as shown in Fig 9. The principal etiological agents in periodontitis are anaerobic bacteria such as Porphyromonas gingivalis and Prevotella spp. The in-vitro experiment demonstrated that these herbal medicinal compounds prevent the growth of P. gingivalis, and Prevotella nigrescens. This further inhibits P. gingivalis from adhering to human buccal epithelial cells.²³

Figure 9: Cell membrane associated effect and bacterial cell function effect of catechin. Click here to view figure

The catechin from green tea had a bactericidal action against black-pigmented Gram-negative anaerobic rods (BPR), and the combination of mechanical therapy and green tea catechin application using a local drug delivery system improved periodontal condition. Green tea catechin was tested for its minimum inhibitory concentration (MIC) and bactericidal action against BPR. As a method of slow-release local delivery, the hydroxy propyl cellulose patches containing catechin were placed in dental pockets of the patients. Dosing like once in a week for eight weeks. The clinical, enzymatic, and microbiological effects of catechin were investigated. Green tea catechin demonstrated a bactericidal effect against Porphyromonas gingivalis and Prevotella spp. in the investigation, with MIC was found to be1.0 mg/ml reported by in-vitro method.²⁴ The structure of catechin shown in Fig 10.

Figure 10: The structure of Catechin Click here to view figure

The goal of this study was to see how epigallocatechin gallate (EGCg) affected developed biofilms and it’s development through Porphyromonas gingivalis, a common periodontal disease pathogenic bacteria. The primary polyphenolic component of tea, (-) epigallocatechin-3-gallate (EGCg), has the greatest bactericidal and biological effects among catechins. EGCg inhibited the growth of P. gingivalis in a dose-dependent manner and shown bactericidal action on P. gingivalis at 500 mg l1 (99.9% decrease) and 1 g l1 (100% decrease).²⁵ The antibacterial action of green tea extract on the periodontic pathogen examine by standard agar disk diffusion (ADD) test was found to be, the P. gingivalis, P. intermedia and A. actinomycetemcomitans were sensitive at 12.5, 25, and 50 mg/ml concentrations and zone of inhibition found in the rang from 10 to 30 mm in diameter. The most antioxidant component like epigallocatechin-3-gallate (EGCG) has been found to diminish acid generation in dental plaques by inhibiting S. mutans proliferation, interfering with bacterial attachment to the enamel, and suppressing glucosyltransferase and amylase activities.²⁶.

Garlic (Allium sativum) 

Allicin, is the main phytochemical chemical constituent, has antibacterial activity against various Gram-negative and Gram-positive bacteria, including Mycobacterium tuberculosis, Escherichia, pneumonia, Lactobacilli, Helicobacter pylori, Pseudomonas aeruginosa and Klebsiella as well as antifungal action, specifically against Candida albicans and also exhibit some antiparasitic activity and antiviral activity.²⁶ Garlic is the plant materials that had a lot of research done on it because of its composition and therapeutic properties. The antibacterial activity of allicin, structure shown in Fig11 is due to a main compound called allicin (diallyl thiosulfinate). It is, however, exceedingly thermo-labile, and when heated, it forms a variety of disulfide compounds.²⁷ The advantage of allicin shown in Fig 12.

Figure 11: The structure of Allicin. Click here to view figure

Figure 12: Various Advantages of Allicin Click here to view figure

The many inhibitory effects that allicin shows on diverse thiol dependent enzymatic systems account for allicin’s broad antibacterial spectrum. Allicin’s principal antimicrobial impact is owing to its interacting with key thiol containing enzymes, specifically its capacity to interact with a model thiol molecule (L-cysteine) to produce the S-thiolation product which is S-allylmercaptocysteine.²⁸ The extract of garlic was found to be potent against all bacterial strains tested. Unfortunately, pharmaceutical companies have shown little interest in converting garlic into a medicine and conducting clinical studies. The important fact is, because of allicin’s for so long presence in the public domain, no patents may be filed on it.²⁹ Limitation of allicin shown in Fig 13. Because of its powerful efficacy, garlic extract could be a viable periodontitis treatment and having effective action against both P. gingivalis and A. actinomycetemcomitans and also on the proteases of P. gingivalis. However, therapeutic medicines for periodontitis should preferably to be effective against biofilms rather than only planktonic cells in order to transfer into effective in vivo therapies. Garlic extract, on the other hand, has been shown to prevent Staphylococcus epidermidis from forming biofilms, even at sub-MIC levels.⁷ 

Figure 13: Limitations of Allicin Click here to view figure

Aloe vera (Aloe barbadensis) 

The Aloe barbadensis plant, also known as Aloe vera, is a member of the Lily family. It’s a xerophyte type plant means that can adapt to less or erratic water availability with the ability to store a large amount of water. Aloin, Aloe emodin, barbaloin, aloetic acid, isobarbaloin, chrysophanic acid, anthracine, ethereal oil, anthranol, cinnamonic acid esters & resistannol are some of the plant’s natural anthraquinones that have antimicrobial properties.⁶ Structure of aloe emodin and its action shown in Fig 14.

Figure 14: The structure of Aloe Emodin and its action Click here to view figure

Aloe vera mouth rinse was found to be effective for the reduction of gingivitis and accumulation of plaque in clinical study.²⁶ Polysaccharides from aloe vera have also been linked to direct bacterial activity via phagocytic leukocyte activation, which kills bacteria.⁵ The cyclooxygenase pathway is inhibited by aloe vera, which lowers the formation of prostaglandin E2 from arachidonic acid. Structure of aloin and its action shown in Fig 15. C-glucosyl chromone, a novel anti-inflammatory component isolated from gel extracts, was recently discovered. Lupeol, urea nitrogen, salicylic acid, cinnamonic acid, sulphur & phenolsare six antiseptic compounds found in aloe vera that fight fungi, bacteria, and viruses.³⁰ Aloe vera shows several properties like anti-inflammatory, analgesic, wound healing, stomatitis, gingival health, immunostimulant and also effective against varicella-zoster virus & herpes simplex types 1 and 2.^30,31

Figure 15: The structure of Aloin and its action Click here to view figure

Clove (Syzygium aromaticum) 

Clove is a highly valuable spice which has been utilised in the food industry as a preservative and for a variety of therapeutic uses for ages. Oil that is highly volatile (16-21) % likely Phenols. In which particularly Eugenol near about (80-88) %, acetyl eugenol (10-15) %, α and β -Caryophyllene, Pyrogallol tannins (10-13) %, Methyl furfural and dimethyl furfural are important compounds. Clove oil is most commonly used in dental and oral care. The oil’s germicidal characteristics make it ideal for treating dental pain, toothaches, mouth ulcers and sore gums. Clove oil majorly contains eugenol, a substance that has long been utilised in dentistry since many years.³² The extract showed potential activity against Actinobacillus Sp. In an in-vitro antibacterial study, with show an effective zone of inhibition in the aqueous extract compared to a moderate zone of inhibition in the acetone extract.³³ Antioxidant polyphenolic substances kaempferol and myricetin have been shown to be bacteriostatic against periodontal infections. Structure of Kaempferol shown in Fig 16.

Figure 16: The structure of Kaempferol Click here to view figure

Table 1: List of some important herbal remedies with their active component and pharmacological actions

Conclusion

As demonstrated by various traditional herbal remedies the in given review, they are found to be a wide range of biological & medicinal properties like antibacterial, antioxidant, and anti-inflammatory effects and are useful in the prophylactic purpose or maintenance of various dental diseases like periodontitis condition. Herbal remedies are also called ancient medicines hence those having high patient acceptance. Diseases like periodontitis are less aware to common people and because of unawareness it may create several health problems. Synthetic drugs like painkillers and antibiotics are not advised to take for a longer period, they are more preferred in chronic conditions or an emergency condition or at the time of surgery. Hence from the literature, it was found that there are several herbal remedies having potent medicinal components which are useful for the prevention, treatment, and maintainance of dental diseases like periodontitis.  Likewise, this is one of the thrust areas for researcher to develop novel drug delivery by using herbal components or making a combinatorial formulation that shows highly effectiveness over synthetic medicines.

Acknowledgment

Authors are thankful to M.E.T.’s Bhujbal Knowledge City, Institute of Pharmacy, Adgaon, Nashik, Maharashtra, India for support and providing necessary facilities.

Conflict of Interest

There is no any conflict of interest.

Funding Sources

There is no funding Sources

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