Plant-Based Antimicrobials against Periodontitis: Comparison
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eriodontal diseases and dental caries are the most common infectious oral diseases impacting oral health globally. Oral cavity health is crucial for enhancing life quality since it serves as the entranceway to general health. The oral microbiome and oral infectious diseases are strongly correlated. Gram-negative anaerobic bacteria have been associated with periodontal diseases. Due to the shortcomings of several antimicrobial medications frequently applied in dentistry, the lack of resources in developing countries, the prevalence of oral inflammatory conditions, and the rise in bacterial antibiotic resistance, there is a need for reliable, efficient, and affordable alternative solutions for the prevention and treatment of periodontal diseases. Several accessible chemical agents can alter the oral microbiota, although these substances also have unfavorable symptoms such as vomiting, diarrhea, and tooth discoloration. Natural phytochemicals generated from plants that have historically been used as medicines are categorized as prospective alternatives due to the ongoing quest for substitute products. This review concentrated on phytochemicals or herbal extracts that impact periodontal diseases by decreasing the formation of dental biofilms and plaques, preventing the proliferation of oral pathogens, and inhibiting bacterial adhesion to surfaces. Investigations examining the effectiveness and safety of plant-based medicines have also been presented, including those conducted over the past decade.

  • herbal medicine
  • plant extracts
  • periodontal diseases

1. Acacia arabica (Babul)

A commonly used chewing stick in India is Acacia arabica, known as “Babul” or “Kikar” datun. Many societies use Acacia arabica gum to maintain oral hygiene [56][1]. The main ingredient is arabica, a complex blend of Arabic acid’s calcium, magnesium, and potassium salts. In addition, tannins, cyanogenic glycosides, oxidases, peroxidases, and pectinases with antibacterial properties are present [57][2]. Acacia arabica’s antibacterial and antiprotease abilities have been established in vitro [58][3]. Clinical studies comparing Acacia arabica gum to CHX have demonstrated its comparable effectiveness in preventing plaque, lowering bacteria counts, and treating gingivitis without any of CHX’s side effects [59,60][4][5]. As a result, long-term Acacia arabica use is advised.

2. Acacia nilotica

The tree Acacia nilotica, also known in Sudanese folk medicine as “Garad or Sunt”, is found in this country’s central and northern regions. Tannin [61][6], gallic acid, catechin, epigallocatechin-7-gallate, catechin derivatives [62[7][8],63], ellagic acid, kaempferol, and quercetin [64][9] have all been found in the leaves and bark of A. nilotica. Additionally, numerous investigations have demonstrated that it possesses a variety of pharmacological effects, such as anti-HIV-1 protease [65][10], antibacterial [66][11], antioxidant, anticarcinogenic [67][12], and anti-inflammatory characteristics [68][13]. According to evidence, A. nilotica bark has antibacterial potential and inhibitory activity. Moreover, it can be utilized as an adjuvant antioxidant in mouthwashes and to develop future treatment options for periodontal diseases [69][14].

3. Allium sativum (Garlic)

As a medicine, garlic (Allium sativum) has been recognized for centuries as having antibacterial, antifungal, and antiviral properties [70,71][15][16]. Allium sativum is traditionally used in treating infection, diabetes, and cardiac disease. Fresh raw garlic are composed mainly of water (66%), carbohydrates (27%), proteins (2.5%), amino acids (1.3%), fiber (1.6%), phenols, and trace minerals (2.4%) [72][17]. Garlic extract (GE) may benefit health because of its phytochemicals, including alliin, methiin, and sodium acetate [73][18]. Alliinase converts garlic alliin into allicin, an antibacterial compound that shows promise for treating periodontal disease, dental caries, and oral cancer [74][19]. Innovative concepts have emerged with fresh discoveries, such as aged garlic extract (AGE), which has been applied as medicine since 3000 BC. Researchers found that AGE lowered patients’ periodontitis levels more effectively than a placebo [75][20]. It is widely known that garlic can prevent inflammation, attack bacteria, viruses, and fungi, and prevent mutagenesis [76,77][21][22]. Numerous oral microbial diseases may be treated with garlic. Several novel garlic-based products, such as gels, gums, toothpaste, and pharmaceutical strips, have been reported as cost-effective and consumer-friendly solutions for improving oral health [78][23]. Figure 41 demonstrates the antimicrobial effects of GE against oral microorganisms. Allicin takes 1000 times longer than antibiotics to acquire resistance. Alcohol dehydrogenases and cysteine proteases (vital for tissue destruction) are among the thiol-containing enzymes inhibited by allicin’s antibacterial chemical [73][18]. A study discovered that taking GE orally reduced both the gingival (GI) and the bleeding index (BI), demonstrating that GE can also reduce periodontal conditions [79][24]. Tannins, flavonoids, and alkaloids are responsible for GE’s antibacterial activities [80][25]. As a result, periodontal diseases and dental caries can be successfully treated using garlic bulbs. When administered directly, garlic irritates the mucosa and so must be used carefully [81][26]. DAS, a sulfur-containing amino acid found in AGE, was shown to suppress the development of periodontal bacteria and reduce the P. gingivalis-induced inflammatory responses in human gingival fibroblast cells [82][27]. Taking AGE tablets helped prevent and enhance periodontal diseases in the long term [83][28]. According to studies, gingival inflammation and bleeding are reduced when AGE is consumed regularly for at least four months [79][24]. In recent investigations, garlic has been discovered to have anti-proteolytic properties against P. gingivalis protease, as evidenced by AGE’s intense bacteriostatic activity against P. gingivalis and gelatin liquefaction after 250 μL/mL dose administration [84][29]. In 200 individuals with good health, the effectiveness and effects of AGE on periodontitis were examined. Compared to the baseline value (1.50 ± 0.46), the mean PD for AGE after ten months was 1.06 ± 0.49, showing that AGE might help prevent or decrease periodontitis. Garlic’s bioactive components may suppress oral infections and some proteases, which may benefit patients with periodontitis [83][28].
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Figure 41. Different mechanisms of action through which garlic extract’s compounds assert antibacterial, antifungal, and antiviral effects [78][23].

4. Aloe barbadensis Miller (Aloe Vera)

Therapeutic uses of Aloe vera date back thousands of years. In addition to treating bruising, X-ray burns, skin infections, hemorrhoids, sinusitis, gastrointestinal pain [85][30], and insect bites, this medicinal plant is also an anti-helminthic, somatic, and anti-arthritic [86,87][31][32]. Among the 75 constituents of Aloe vera are minerals, enzymes, sugars, anthraquinone, and salicylic acid [88][33]. Approximately 99.5% of Aloe vera leaves contain water and 0.0013% protein [87][32]. Figure 52 shows the primary constituents of an Aloe vera plant. Aloe vera gel has been shown to have pharmacokinetic activities that include anti-inflammatory, antibacterial, antioxidant, immune-stimulating, and hypoglycemic effects [89,90][34][35]. Aloe vera has antimicrobial effects on Streptococcus pyogenes and Enterococcus faecalis [91,92][36][37]. Isorabaichromone, feruoylaloesin, and p-coumaryl aloesin, three aloesin derivatives, have demonstrated the potential to scavenge radicals and superoxide anions [93,94][38][39]. It is perfect for treating gingivitis and periodontitis due to having an anti-inflammatory compound (C-glucosyl chromone), inhibiting the COX pathway, reducing PGE2, and breaking down the bradykinin inflammatory agent responsible for pain generation [93,95,96][38][40][41]. Edema, bleeding, and irritation of the gingival tissues are reduced by using it. It is beneficial in deep pockets where routine cleansing is challenging, and its antifungal properties also help treat denture stomatitis, aphthous ulcers, and angular cheilitis [97][42]. Using it after extractions is a powerful healer [98][43]. In root canal therapy, it has been used as a sedative dressing and file lubricant [99][44]. Many studies have been performed to determine if Aloe vera effectively cures gingivitis. In a double-blinded trial, 120 volunteers were requested to skip two weeks of tooth brushing. After being separated into three groups, 100% Aloe vera, distilled water as a placebo, and 0.2% CHX were given to the patients. The Aloe vera mouthwash was beneficial in lowering plaque and gingivitis, although when compared to CHX, its effects were not as noticeable [100][45]. Another study investigated how toothpaste with a high Aloe vera content affected the remission of plaque and gingivitis. The subjects were observed over three six-month periods using either Aloe vera toothpaste or a regular one. After the clinical experiment, the plaque and gingivitis indices decreased by roughly 20%, with no significant difference between the two study groups. Individuals motivated to improve their dental hygiene practices did not experience extra anti-plaque or -gingivitis when using an Aloe vera toothpaste [101][46]. Using Aloe vera as a medication in periodontal pockets was highlighted in a study performed by Geetha et al. [85][30].
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Figure 52. The main phenolic compounds of the Aloe vera plant and their chemical structures [102].
The main phenolic compounds of the Aloe vera plant and their chemical structures [47].
In Ajmera et al.’s study, Aloe vera mouthwash reduced plaque-induced gingivitis inflammation. Three months of Aloe vera mouthwash (BID) were administered to Group 1. Group 2 was scaled only. Group 3 received Aloe vera mouthwash and scaling. In contrast to the other two groups, Aloe vera mouthwash and scaling were more effective in reducing gingival inflammation. Consequently, Aloe vera was found to be anti-inflammatory, and combined with mechanical therapy, it helped treat plaque-induced gingivitis (Figure 63) [103][48].
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Figure 63. Results of a study on beneficial anti-inflammatory effects of Aloe vera + scaling treatment [(a) baseline; (b) one-month post-op; and (c) three-month post-op] to reduce plaque-induced gingivitis [103][48].

5. Amphipterygium adstringens

A Mexican endemic species of the Julianaceae family called “Cuachalalate” is Amphipterygium adstringens [104][49]. Anacardic acid [105][50], which has antioxidant, anti-inflammatory [106][51], anticancer [107][52], antiulcer, and antibacterial effects [105[50][53],108], is the primary ingredient responsible for the plant’s capabilities, according to recent studies.

6. Azadirachta indica [109]

6. Azadirachta indica [54]

A member of the Meliaceae family of mahogany trees, the neem tree (Azadirachta indica) is an evergreen that grows naturally in India and Myanmar’s subcontinent [110,111][55][56]. It has been found that extracts from various portions of this tree contain a variety of polyphenols, such as tannins, lignins, and flavonoids, that are potent antioxidants, antibacterials, anti-inflammatory agents, and immunomodulators [110,111,112,113,114,115,116,117,118,119,120][55][56][57][58][59][60][61][62][63][64][65]. The chewing sticks produced from twigs of the tree may play a role in oral care due to their mechanical cleansing properties, stimulation of saliva secretion, and antibacterial and antioxidant properties [121][66]. Aqueous preparations of neem have shown antimicrobial properties by reducing the surface adhesion of specific bacteria, destructing bacterial cell membranes, and inhibiting bacterial growth [115,116,122,123][60][61][67][68]. The plaque buildup and bacterial counts were significantly reduced after oral neem extract therapy [124][69]. With antioxidant properties, a neem extract may reduce the oxidative stress associated with periodontal disease and have anti-inflammatory potential [110,111,125][55][56][70]. Neem may have anti-inflammatory properties by suppressing prostaglandin E and 5 HT, reducing inflammation [123][68].

7. Berberis vulgaris

Extracts of Berberis vulgaris (Berberidaceae family) root exhibit antibacterial activity against periodontal bacteria due to berberine, the principal active ingredient. The growth of P. gingivalis and A. a has been shown by researchers to be inhibited by berberine [126,127,128][71][72][73]. P. intermedia, Actinomyces naeslundii, and Prevotella nigrescens do not grow due to the bacteriostatic properties of berberine [126,129][71][74]. The microbiological activity of a dental gel containing barberry root extract was investigated [130][75]. It was demonstrated that the protoberberine alkaloids had a synergistic antibacterial action, which can be used to explain why P. gingivalis growth was suppressed at 0.015 mg/g [130][75]. The plaque index (PI) was found to have decreased in a trial of the efficacy of a dental gel containing 1% berberine. Comparatively, applying a 5% gel reduced the growth of invading bacteria [129][74].

8. Camellia sinensis (Green Tea)

Camellia sinensis belongs to the Theaceae family and has small perennial shrubs widely used to produce green and black teas [131][76]. Its beneficial properties are attributed to green tea’s polyphenol components (catechins). Epicatechin-3-gallate and epigallocatechin-3 gallate are the two significant catechins. Compared to black tea, green tea contains higher polyphenols (30–40% vs. 3–10%), with enhanced antioxidant capacity and strong anti-inflammation, antibacterial, antiviral, antimutagenic, and anti-aging activities [132,133,134][77][78][79]. Inflammation and periodontitis are positively affected by green tea. Thus, research supports green tea as a curative and preventive agent for periodontal disease [135][80].

9. Cinnamomum zeylanicum (Ceylon Cinnamon)

Cinnamon has been utilized as a culinary herb in traditional medicine. Cinnamon has been researched in pregnancy, diabetes management [136][81], and gynecological disorders [137][82]. It has anti-inflammatory, cardioprotective, antioxidative, and antibacterial activities and anti-inflammatory capabilities [138][83]. Cinnamon refers to a collection of around 250 evergreen trees belonging to the Lauraceae family [139][84]. Several species have been studied, including those linked to oral medicine. Cinnamomum verum and Cinnamomum zeylanicum are two of the most studied cinnamon types. Cassia cinnamon, often known as Chinese cinnamon or Cinnamomum aromaticum, is a well-studied spice. Cinnamomum burmannii and Cinnamomum loureiroi are two more major cinnamon species [138,140][83][85]. The EO of Cinnamomum bark (CBEO) contains many aromatic compounds and high concentrations of cinnamaldehyde and eugenol. CBEO and cinnamaldehyde have antibacterial, antifungal, anti-inflammatory, and anticancer properties [141,142,143][86][87][88]. According to Wang et al., the cinnamaldehyde in C. zeylanicum bark EO works against P. gingivalis [144][89]. According to reports, cinnamaldehyde is responsible for CBEO’s antibacterial effect [144][89]. The relative mechanism of cinnamaldehyde was uncovered by examining the cell microstructure, membrane integrity, and membrane properties [145][90]. CBEO and cinnamaldehyde may irreversibly damage bacterial membranes, thus compromising membrane integrity. The metabolism will err when the cell membrane depolarizes, and the bacteria will die [144][89]. As determined by propidium iodide uptake tests, the CBEO and cinnamaldehyde treatments interrupted the integrity of the bacterial membranes. The confocal microscopy analysis of P. gingivalis detected PI incorporation, indicating a cell membrane disruption [144][89]. Microorganisms can be killed by this principal mechanism, which is known as membrane damage [146][91]. P. gingivalis may therefore be susceptible to membrane permeabilization caused by CBEO and cinnamaldehyde.
Eugenol, a compound more commonly associated with clove, is also a potent component of cinnamon EO [147][92]. Due to its powerful antibacterial properties and abundance in cinnamon EO and extracts, it has been demonstrated to be beneficial to periodontal health. In addition to having antibacterial properties, eugenol has multiple mechanisms of action [148][93] through the destruction of the cell membrane in a dose-dependent fashion and reducing the presence and formation of the biofilm [148][93]. Cinnamaldehyde has also been declared safe and non-toxic by the FDA. Cinnamaldehyde can be absorbed quickly by the gastrointestinal system [149][94]. Nearly no residues are left when the body removes the metabolites [150][95].

10. Citrus sinensis

In the Rutaceae family, oranges are classified as Citrus sinensis, a sweet and juicy fruit. Orange trees are often grown in tropical and subtropical climates because of their medicinal properties and sweet juice. Aside from preventing and treating vitamin deficiency, colds, flu, and scurvy, it also fights bacterial and viral infections [151][96]. Antibacterial properties have also been reported for orange peel [152][97]. Dubey et al. demonstrated the robust antibacterial properties of orange peel extracts against different bacteria using the disk diffusion method [153][98]. The effectiveness of orange peel extract against Klebsiella pneumoniae has been demonstrated by Jabuk et al. [154][99]. Numerous studies [109,151,152,155][54][96][97][100] have revealed that Citrus sinensis can also treat periodontal disease.

11. Coffea canephora (Coffee)

The primary phenolic acid in coffee, chlorogenic acid, acts on human health due to its various effects, such as its antioxidant, anti-inflammatory, and antibacterial properties [199,200,201,202,203][101][102][103][104][105]. The safety of chlorogenic acid in rats and dogs is well documented, although there are no reports about humans, except for a potential allergic reaction [204][106]. Green coffee extract’s chlorogenic acid reduced the quantity of the oral bacteria S. mutans in a clinical experiment [205][107]. There is evidence that coffee extract is antibacterial and inhibits the activity of proteases produced by periodontitis-causing organisms, such as P. gingivalis [206][108].

12. Copaifera pubiflora

Copaifera pubiflora (Fabaceae-Caesalpinioideae) plants are indigenous to tropical areas of Western Africa and Latin America. Copaiba is the common name given to these plants in Brazil. The plants produce oléoresin as a byproduct of their secondary metabolism to protect themselves against animals, fungi, and bacteria [207,208,209,210,211,212,213,214,215][109][110][111][112][113][114][115][116][117]. Numerous studies have suggested that Copaifera can act against the bacteria responsible for endodontic infections and dental caries [208,209,210,213][110][111][112][115]. The antibacterial and antivirulence activity was tested against P. gingivalis and A. a by Abrão et al. These compounds were helpful as antimicrobials against periodontal pathogens [216][118].

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