Table 2.
In vitro and in vivo investigations of plant-based antimicrobials in periodontal diseases.
| Natural Compound | Study Type | Samples Studied | Methods | Result(s)/Conclusion(s) | Ref./Year |
|---|---|---|---|---|---|
| Acacia nilotica | In vivo | Albino rabbits with ligature-induced periodontitis | G1: Distilled water G2: Positive control group G3: A. nilotica aqueous extract (dosage 300 mg/kg) G4: A. nilotica aqueous extract (dosage 500 mg/kg) G5: Amoxicillin (15 mg/kg) [CBC, ESR, serum creatinine, ALT, and AST were measured after 14 days] |
A. nilotica extract significantly cured periodontitis to a great extent after 14 consecutive days of oral administration. | [292]/2019 |
| Allium sativum | In vitro | P. gingivalis, F. nucleatum, A. a. | Gs: An aqueous extract of Allium sativum [Disc diffusion technique, microspindle dilution method, and assessment of MIC and MBC were performed] |
Allium sativum extract at 55.2% w/v produced inhibition zones of 17.3 ± 1.0, 30.3 ± 1.7, and 21.2 ± 2.3 mm with A. a, F. nucleatum, and P. gingivalis, respectively. MIC of 17.2, 1.1, and 4.3 mg/mL was obtained for A. a, F. nucleatum, and P. gingivalis, respectively. The MBC was 34.4, 1.1, and 8.6 mg/mL, respectively. Allium sativum aqueous extract may be a therapeutic alternative for treating periodontal disease based on the results obtained in this study. |
[293]/2021 |
| In vitro | L. acidophilus, S. aureus, S. sanguis, S. mutans, S. salivarius | Gs: Allium sativum bulb [MIC and MBC were measured] |
A. sativum bulbs are effective in treating periodontitis and dental caries. MBC value ranged from 60 ± 5 to 215 ± 7 mg/mL and MIC value ranged between 20 ± 2 and 120 ± 6 mg/mL. | [80]/2020 | |
| In vitro | P. gingivalis | G1: Aqueous garlic extract G2: 0.2% CHX [Groups were compared regarding MIC and MBC] |
A significant difference was observed between G1 and G2 (0.29 ± 0.1 μL; p < 0.001) regarding the MIC (1.21 ± 0.37 μL) and MBC (1.44 ± 0.67 μL) against P. gingivalis. As compared to G1 (20.1 ± 1.4 mm), G2 (27.3 ± 1.8 mm) showed a significantly larger inhibitory zone against P. gingivalis (p < 0.000). Garlic extracts performed well as antimicrobial agents against P. gingivalis; however, they were not superior to CHX as antimicrobial agents. | [294]/2019 | |
| Aloe barbadensis Miller | In vitro | C. albicans, S. mutans, L. acidophilus, E. faecalis, P. intermedia, P. anaerobius | G1: Aloe vera tooth gel G2: Pepsodent toothpaste G3: Colgate toothpaste [Zone of inhibition was measure] |
In preliminary tests, Aloe vera tooth gel and other toothpastes had similar antibacterial effects. S. mitis benefited from an enhanced antibacterial impact by Aloe vera tooth gel (p = 0.034). | [295]/2009 |
| Amphipterygium adstringens | In vitro | S. mutans, P. gingivalis, A. a, E. coli, C. albicans, C. dubliniensis | Gc: 0.12% CHX Gs: A methanolic extract of A. Adstringens [MIC, MBC, and total growth inhibition were measured] |
All microbial strains tested with methane extracts of A. adstringens exhibited antimicrobial activity between 0.125 and 63 mg/mL. MIC of S. mutans was 0.125 mg/mL, and MBC was 0.31 mg/mL, making it the most sensitive strain. The MIC and MFC of Candida strains were 0.4 and 1.6 mg/mL, respectively. An MIC/MBC of 37 mg/mL was observed for both P. gingivalis and E. coli. With an inhibitory concentration of 63 mg/mL, A. a and E. coli also exhibited similar results. An MBC of 2.4 mg/L was found for chlorhexidine. | [296]/2015 |
| Azadirachta indica, Syzygium aroticum, and Cinnamomum zeylanicum | Ex vivo | Actinobacillus sp. | Gc: Tetracycline and azithromycin (30 mcg/mL) Gs: Neem, clove, and cinnamon in aqueous and acetone solvents (2%, 4%, 6%, 8%, and 10%) [Zone of inhibition was measured] |
Actinobacillus sp. were inhibited at 10% concentration by aqueous extracts of clove and neem (24 and 22 mm, respectively). At the same concentration, aqueous cinnamon extracts displayed only a moderate inhibition zone (16 mm). Acetone extracts of neem and clove showed effective inhibition of Actinobacillus sp. (20 and 18 mm, respectively) compared with cinnamon, which showed a moderate inhibition zone (14 mm). Neem, clove, and cinnamon extracts could be used as an alternative treatment for chronic periodontitis. | [297]/2020 |
| Berberis vulgaris | In vivo | Rats with ligature-induced periodontitis | Gc: Cholisal gel Gs: A dental gel containing barberry extract. [Histopathology and ultrasound dopplerography were performed] |
Periodontitis can be effectively treated with a dental gel containing 0.015 mg/g of barberry root extract. | [130]/2020 |
| Cinnamomum burmanii | In vitro | An A. a. or E. coli LPS-stimulated macrophage model | Gs: Cinnamon bark aqueous extract [Cytokine production, binding of LPS cells, and PPAR-γ binding were studied] |
IL-6, TNF-α, and IL-8 secretion was reduced by the cinnamon fraction in a dose-dependent manner. A cinnamon fraction may have anti-inflammatory properties by reducing LPS binding to monocytes. A natural PPAR-γ ligand may exist in the cinnamon fraction as well. A cinnamon fraction has been shown to contain anti-inflammatory properties that can be used to treat periodontal disease due to its anti-inflammatory properties. | [298]/2021 |
| Cinnamomum zeylanicum | In vitro | P. gingivalis | Gs: Different concentrations of cinnamon with oil solvent (10, 50, 100, 250, 500, 750, and 1500 mg/mL) Gc: Amoxicillin, metronidazole, ciprofloxacin, amikacin, and gentamycin [MBC and MIC were evaluated] |
Cinnamon at an MIC value of 750 mg/mL inhibited bacteria, while cinnamon at an MIC value of 1500 mg/mL killed them. The antibacterial activity was, however, much weaker than that of common antibiotics (p < 0.001). The antimicrobial activity of cinnamon against the pathogen P. gingivalis was demonstrated in patients with chronic periodontitis with deep pockets. | [299]/2018 |
| In vitro | A. a, F. nucleatum, P. gingivalis, S. salivarius, S. mitis, and S. mutans | Gs: EO from cinnamon tree bark + cinnamaldehyde [MIC was measured] |
An MIC of 0.21–0.63 mg/mL was observed for cinnamon oil and 0.8–0.15 mg/mL for cinnamaldehyde against the tested bacteria. Changes in cell membranes were observed after two hours of exposure to the oil. Bacterial infections of the oral cavity can be prevented by cinnamon bark oil. | [300]/2013 | |
| Citrus sinensis | In vitro | P. gingivalis | Gs: Citrus sinensis [MIC, SI, and IC50 were measured] |
Citrus sinensis exhibited low cytotoxicity and good antibacterial activity. It demonstrated an IC50 value of 512 μg/mL. | [155]/2020 |
| Coffea canephora | In vitro | P. gingivalis | Gs: Coffee extract and chlorogenic acid [The inhibitory effect, protease activity, and viability of P. gingivalis were evaluated] |
Chlorogenic acid had an MIC of 4 mg/mL and an MBC of 16 mg/mL. When chlorogenic acid is applied above the MIC, the viability of P. gingivalis is inhibited for a longer period of time and the activity of the associated protease is significantly reduced. Different roast levels of coffee had no effect on the antibacterial activity of the extract. | [206]/2019 |
| Coptidis rhizoma | In vitro | A. naeslundii A. a, P. gingivalis, P. nigrescens, P. intermedia | Gs: C. rhizoma extract. [MIC and IC50 were measured] |
MICs of 0.031–0.25 mg/mL inhibited the growth of the mentioned bacteria, while MICs of 0.5–2 mg/mL inhibited the growth of Lactobacillus and Streptococcus. C. rhizoma extract inhibited periodontopathogenic bacteria. Clinical application of these results may be possible for treating periodontal diseases. | [126]/2000 |
| Curcuma longa | In vivo | Rats with induced periodontitis | Gs: Curcumin-loaded nanoparticles | The μCT analysis demonstrated significant attenuation of NF-kB activation and p38 MAPK activity resulting from curcumin local administration. Inflammatory bone resorption, osteoclast counts, and inflammation infiltrates were significantly reduced. Experimental periodontal disease was effectively treated with curcumin-loaded nanoparticles. | [301]/2018 |
| In vivo | Wistar rats with ligature-induced periodontitis | G1: Placebo G2: Resveratrol G3: Curcumin G4: Resveratrol + curcumin [Morphometric analysis of bone loss was performed histologically; TNF-α, IL-4, IFN-γ, and IL-1β were studied] |
As compared with the other groups, G1 showed greater bone loss than the other groups based on intergroup comparisons (p < 0.05). G2, G3, and G4 did not have different bone-loss values (p > 0.05). In G4, IL-1 β levels were lower than in G1 based on the immunoenzymatic assay of gingival tissue (p < 0.05). In comparison with G1, G2, and G3, G4 showed higher IL-4 values (p < 0.05). The levels concerning IFN-γ were only reduced by G2 (p < 0.05). Among the four groups, the TNF-α concentrations did not differ (p > 0.05). There was a reduction in alveolar bone loss due to resveratrol and curcumin. It was not found that these agents combined or synergized in any way. |
[302]/2017 | |
| Cymbopogon citratus | In vitro | S. mutans, S. epidermidis, Lactobacillus | Gc: Tetracycline Gs: Lemongrass EO [Inhibition zone measurement] |
The minimal inhibitory concentration of lemongrass EO was estimated to be 10 μL. A statistically significant zone of inhibition, and the antibacterial zone was more marked in Gs than Gc for S. mutans and S. epidermis (p < 0.001). Tetracycline had less antibacterial activity than lemongrass. Therefore, the herbal EO may be an adjunctive treatment for periodontitis or an alternative to tetracycline. |
[303]/2019 |
| In vitro | A. naeslundii, P. gingivalis | Gs: Cymbopogon citratus EO [MIC was measured] |
Based on the results, EO had MIC values of 0.44 and 0.22 mg/mL against A. naeslundii and P. gingivalis. Both reference strains and most clinical isolates, especially the tetracycline-resistant strains, are sensitive to Cymbopogon citratus EO. | [239]/2009 | |
| Eucalyptus globulus | In vitro | P. gingivalis, F. nucleatum, A. a | Gs: Eucalyptus globulus EOs [Their antioxidant capacity and MIC were measured] |
In the analyzed oils, the antioxidant activity was weak, although the antibacterial activity was significant, especially against F. nucleatum (MIC = 1.14 mg/mL) and P. gingivalis (MIC = 0.28 mg/mL). A potential therapeutic application for E. globulus EOs may be periodontal disease treatment. | [304]/2015 |
| Garcinia mangostana | In vivo | Wistar rats with administered A. a | G1: Tetracycline gel (0.7%) G2: Mucoadhesive patch G2: An extract of mangosteen peel applied to a mucoadhesive patch [Histopathological examinations were performed to quantify osteoblasts and osteoclasts] |
Osteoclasts and osteoblasts were significantly reduced in all groups by G3 (p < 0.05). Mangosteen peel extract inhibited osteoclasts and stimulated osteoblasts, thus preventing alveolar bone damage in periodontitis. | [305]/2021 |
| Glycyrrhiza uralensis | In vitro | P. gingivalis | Gs: Glycyrrhiza uralensis root extract [MIC and MBC were evaluated] |
It was found that the licorice root extract had antimicrobial activity against P. gingivalis at an MIC value of 62.5 μg/mL and an MBC value of 25 μg/mL. Biofilms of P. gingivalis were also affected by licorice root extract. A potential therapeutic application of licorice root extract could be for periodontal disease. | [306]/2017 |
| In vivo | GCF samples from patients with mild–moderate periodontitis | G1: Doxycycline G2: Licorice G3: Placebo [MMP-8 concentration was measured] |
There was a statistically significant difference between G1 and G2 and G3 in the mean MMP-8 concentrations (p < 0.001). A statistically significant difference was not detected between G2 and G1 in the mean MMP-8 concentration. Licorice extract is a powerful natural remedy for periodontitis and inflammation, as well as preventing MMPs from being released by the host cells. There were no side effects associated with the use of licorice extract. | [261]/2013 | |
| Glycyrrhiza glabra | In vitro | Pathogens responsible for plaque colonization and periodontitis | Gs: Glycyrrhiza uralensis bark extract [Zone of inhibition was measured] |
A potential antibacterial effect was observed for G. glabra against primary plaque colonizers and periodontal pathogens (ZOI = 9.2 ± 1.09 and 10.6 ± 0.54 mm, respectively). Statistically, there was no significant difference between G. glabra and standard antibiotics for periodontal pathogens. | [307]/2016 |
| Juglans regia | In vitro | G. adiacens, S. sciuri, Kocuria spp. | Gc: Ciprofloxacin (5 μg/mL) + cefotaxime (30 μg/mL) Gs: Crude aqueous extracts from Juglans regia (100 mg/mL, 250 mg/mL, 500 mg/mL). [Measurement of zone of inhibition] |
Compared to the other extracts, the 250 mg/mL extract was more effective. The extract showed the greatest impact on Kocuria spp. The extract’s active components increased biological activities, thus aiding in fighting bacterial infections. | [308]/2021 |
| In vitro | P. gingivalis | G1: Immature fruit ethanol extraction G2: Immature fruit methanol extraction G3: Woody parts ethanol extraction G4: Woody stems ethanol extraction G5: Woody stems methanol extraction [MIC, SI, and IC50 were measured] |
The MIC and SI of the five extracts of J. regia studied were as follows: G5 (MIC 64 μg/mL, SI > 16), SI > 16), G4 (MIC 64 μg/mL, SI > 16), G3 (MIC 32 μg/mL, SI > 32), G2 (MIC 32 μg/mL, SI > 32), and G1 (MIC 64 μg/mL. | [155]/2020 | |
| In vitro | S. mutans, S. salivarius, S. sanguis, S. aureus | Gc(+): Erythromycin 15 μg + tetracycline 30 μg Gc(-): Water Gs: Aqueous and ethanolic extracts of Juglans regia bark [MIC was measured] |
Aqueous and ethanolic extracts were found to be the most potent against S. sanguis and S. mutans, respectively. All strains of bacteria tested were significantly inhibited by the ethanolic extract. An antibacterial effect was not observed on S. mutans in the aqueous extract in comparison with the ethanolic extract. In comparison with the control, the aqueous extract significantly inhibited S. sanguis, S. salivarius, and S. aureus (p < 0.0001), In comparison with erythromycin, it did not affect S. mutans. The growth of oral bacteria was significantly inhibited by ethanolic and aqueous bark extracts of Juglans regia. | [290]/2013 | |
| Lippia sidoides | In vivo | Wistar rats with ligature-induced periodontitis | Gc(+): Diethylammonium diclofenac gel at 10 mg/g Gc(-): Saline gel Gs: Thymol gel [Histopathological analyses were performed] |
Compared with a control of saline gel, Gs reduced histopathological lesions in gingival tissue and reduced myeloperoxidase activity (p < 0.05). | [309]/2016 |
| Manuka honey | In vitro In vivo |
E. nodatum, S. mutans, C. rectus, S. sangiunis, A. a, P. gingivalis | In vitro section (G1: 0.2% CHX, G2: honey mouthwash, G3: saline) [MIC was measured] In vivo section: Plaque regrowth was simulated for four days. Four days after baseline, PI was measured |
Among the six microorganisms tested, honey mouth rinses inhibited their growth effectively. All test species showed the lowest MICs with CHX rinses over honey and saline rinses. As a result of in vivo testing, CHX and honey rinses inhibited or reduced plaque formation. Testing showed honey to be antibacterial and antiplaque. | [310]/2012 |
| Myristica fragrans | In vitro | Ten tissue samples from patients with chronic periodontitis undergoing a flap surgery | Gc: Doxycycline Gs: Myristica fragrans [Zone of inhibition and antiprotease activity were measured] |
Myristica fragrans, when added to the tissue sample, showed no zone of clearance compared to a significant zone of clearance of the tissue sample alone. Doxycycline demonstrated a small zone of clearance. Myristica fragrans possesses a better antiprotease activity as compared to doxycycline in vitro. | [311]/2016 |
| Myristica fragrans | In vitro | P. gingivalis | Gs: Myristica fragrans extract [Zone of inhibition was measured] |
A 13.5 mm inhibitory zone was found in nutmeg extract. Myristica fragrans inhibited Porphyromonas gingivalis | [312]/2016 |
| In vitro | P. gingivalis | Gs: Isolated malabaricone C from nutmeg (Myristica fragrans) [MIC was measured] |
Arg-gingipain was irreversibly inhibited by malabaricone C at 0.7 μg/mL, and P. gingivalis was selectively inhibited. | [313]/2014 | |
| Ocimum sanctum | In vitro | A. a, P. intermedia, P. gingivalis | Gc(+): Doxycycline Gc(-): Dimethyl formamide Gs: Ethanolic extract of Tulsi leaves (0.5%, 1%, 2%, 5%, and 10%) [Zone of inhibition was measured] |
It was found that Tulsi extracts showed similar inhibition zones to doxycycline at concentrations of 5% and 10%, with similar antimicrobial activity against A. a (p > 0.05). However, P. gingivalis and P. intermedia resisted Tulsi extract, showing significantly smaller inhibition zones (p < 0.05). Due to its antimicrobial properties, Tulsi may be used as a complementary therapy to standard periodontal care. |
[314]/2016 |
| In vivo | Wistar albino rats with ligature-induces periodontitis | G1: Control G2: Plain gel G3: 2% O. sanctum gel. [GI, PD, and morphometric analysis were performed] |
Inhibition of edema by 2% Tulsi (O. sanctum) gel was 33.66% at 24 h. The GI and PD demonstrated statistical significance. No significant differences were found between the groups based on the morphometric analysis. Tulsi extract 2000 mg/kg was not found to have any toxic effects when administered orally. The O. sanctum gel was effective in treating experimental periodontitis. | [315]/2015 | |
| Pistacia atlantica Kurdica | In vitro In vivo |
P. gingivalis Wistar rats |
Gs: EO extracted from the gum of Pistacia atlantica Kurdica [MIC and MBC were measured; histological analyses were performed] |
The experimental gel produced adequate wound healing and exhibited inhibitory and bactericidal activity against P. gingivalis. | [316]/2019 |
| Salvadora persica | In vitro | P. gingivalis and HSV-1 | Gs: Miswak raw extract [MIC, IC50, and MTT antiviral assays were measured] |
An MIC of 62.5 μg/mL was determined against P. gingivalis. A therapeutic index of 11.3 μg/mL was observed against HSV-1. A concentration of 18.6 μg/mL was calculated as the IC50. A concentration of 210 μg/mL caused cytotoxicity in 50% of Vero cells. The SP films significantly inhibit P gingivalis and the HSV-1. | [317]/2020 |
| In vitro | S. mutans, S. mitis, Candida albicans, L. acidophilus, P. intermedia, and Peptostreptococcus | Gc(+): CHX Gc(-): Distilled water Gs: Aqueous and alcoholic extracts of SP (200 μg/mL and 400 μg/mL) [MIC was measured] |
No significant results were obtained when Salvadora persica’s water extracts were tested, except for the minimum inhibitory effect against bacteria. Salvadora persica alcoholic extract exhibited relatively significant inhibitory effects. On all tested pathogens, alcoholic extract from SP showed antimicrobial activity. | [318]/2016 | |
| Satureja hortensis | In vitro |
A. a, P. gingivalis, P. micra, T. forsythia, F. nucleatum, P. Intermedia, P. nigrescens |
Gc: CHX Gs: Satureja hortensis EO [MIC and antibiofilm effects were measured] |
All tested bacteria were inhibited by S. hortensis EO, despite its low MIC value. All strains of bacteria tested showed inhibition of proliferation at 0.125 µL/mL. In tests against periodontal bacteria, S. hortensis EO had limited antibiofilm activity (0.01 µL/mL), inhibiting only P. nigrescens biofilm formation. | [319]/2009 |
| Syzygium aromaticum | In vitro | A. a, F. nucleatum, and P. intermedia | G1: Hydro-ethanolic extracts G2: Delipidated hydro-ethanolic extracts G3: Fresh extract [MIC, MBC, and zone of inhibition were measured] |
According to the MIC values, the tested organisms were antibacterial when tested at 6.25–25 mg/mL. On all bacteria subjected to the extract, the non-delipidated dry extract had a bactericidal effect. F. nucleatum was also shown to be bactericidal by delipidated extracts, as well as A. actinomycetemcomitans by fresh extracts. | [320]/2021 |
| In vitro | P. gingivalis | Gc(+): Tinidazole Gs: Syzygium aromaticum leaf essential oil (CLEO)-derived eugenol [MIC, MBC, CFU count, SEM, PI uptake, nucleic acid and protein leakage, biofilm quantification, and PCR were performed] |
The amount of eugenol in CLEO, 90.84%, was found to have antibacterial activity against P. gingivalis at a concentration of 31.25 μM. The presence of eugenol at different concentrations inhibited the formation of biofilms and reduced the preformed ones of P. gingivalis. | [148]/2017 | |
| Terminalia chebula | In vitro | S. mutans, A. a | Gc: Dimethyl sulfoxide (0.01%) Gs: Ethanol extract of Terminalia chebula (EETC) [MIC, susceptibility test, cytotoxicity assay, PGE2 assay, PCR, inflammation antibody array, protease array, ECM degradation, osteoclast formation, and pit formation were studied] |
By inhibiting the growth of bacteria, EETC also inhibited the stimulation of PGE2, COX-2, and inflammatory cytokines. In the osteoblasts, EETC stimulated lipopolysaccharide derived from dental plaque to inhibit bone resorption and inhibit osteoclast formation. | [321]/2017 |
| Vaccinium macrocarpon | In vitro | P. gingivalis | Gc: Phosphate-buffered saline Gs: Cranberry juice concentrate prepared as a non-dialysable material [Growth, adherence properties, and biofilm formation of P. gingivalis were studied] |
With cranberry concentrations exceeding 62.5 mg/mL, significant inhibition was observed (p < 0.05). With cranberry, P. gingivalis could not adhere effectively to collagen-, fibrinogen- or human serum-coated surfaces. Cranberry constituents may help prevent and treat periodontitis by preventing P. gingivalis from colonizing periodontal sites. | [322]/2006 |
| Vicia faba | In vitro | P. gingivalis | Gs: Vicia faba ethanolic and methanolic extracts [MIC, SI, and IC50 were measured] |
Vicia faba exhibited low cytotoxicity and antibacterial activity. | [155]/2020 |
| Vitis vinifera | In vivo | Rats with ligature-induced periodontitis | G1: Laboratory diet G2: GSE for eight weeks G3: GSE for six weeks G4: GSE for two weeks [Histopathological studies were performed to determine ICN, CAL, OD, IL-10, and TGF-β] |
GSE groups had lower ICN, higher CAL, and lower OD (p < 0.05). In the GSEs and GEs, IL-10 levels were higher (p < 0.05). In group B, periodontal ligament IL-10 levels were highest (p < 0.05). All groups had higher levels of TGF-ß in the gingival epithelium (p < 0.017). | [323]/2017 |
| Zingiber officinale | In vitro | P. gingivalis, P. endodontalis, P. intermedia | Gs: Ethanol and n-hexane extracts of ginger [MIC and MBC were measured] |
The two alkylated gingerols, [10]-gingerol and [12]-gingerol, inhibited oral pathogen growth at MICs of 6–30 μg/mL. At an MBC range of 4–20 μg/mL, these ginger compounds also killed oral pathogens, but not 5-acetoxy-[6]-gingerol, galanolactone, or 3,5-diacetoxy-[6]-gingerdiol. | [324]/2008 |
CBC: Complete Blood Count; ESR: Erythrocyte Sedimentation Rate; ALT: Alanine Transaminase; AST: Aspartate Transaminase; Gs: Study Group; Gc: Control Group; MBC: Minimum Bactericidal Concentration; EPS: Extracellular Polysaccharides; MFC: Minimum Fungicidal Concentration; MIC: Minimum Inhibitory Concentrations; CBEO: Cinnamomum zeylanicum Bark Essential Oil; PI: Propidium Iodide; SI: Selectivity Index; IC50: Half MIC; MAPK: Mitogen-Activated Protein Kinase; EO: Essential Oil; MEC: Ethanol Extracts of Garcinia mangostana Peel and Propolis; ZOI: Zone of Inhibition; SEM: Scanning Electron Microscope; GCF: Gingival Crevicular Fluid; CFU: Colony-Forming Units; PI: Plaque Index; MSE: M. alba Stem Extract; LPS: Lipopolysaccharide; hPDL: Human Periodontal Ligament; GI: Gingival Index; PD: Pocket Depth; PYC: Pycnogenol®; SP: Salvadora persica; HSV: Herpes Simplex Virus; MTT: (3-[4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide); CLEO: Syzygium aromaticum Leaf Essential Oil; EETC: Ethanol Extract of Terminalia chebula; PGE2: Prostaglandin E2; AC-PACs: A-Type Cranberry Proanthocyanidins; GSE: Grape Seed Extract; ICN: Inflammatory Cell Number; CAL: Connective Tissue Attachment Level; OD: Osteoclast Density.