The Role of Phytochemicals in the Management of Periodontal Diseases

Areej Aldhaher

doi:10.69923/pn5fgs58

Authors

Areej Aldhaher University of Basrah, College of Dentistry Author https://orcid.org/0000-0002-8319-2022

DOI:

https://doi.org/10.69923/pn5fgs58

Keywords:

Periodontal diseases, Natural products, Herbal medicine, Phytotherapy Periodontitis

Abstract

According to the World Health Organization (WHO), about 10%-15% of the population is affected by periodontitis. This complex infectious condition arises from the aggressive growth of bacteria on the teeth. Both surgical and nonsurgical treatment options are available to manage MB formation. Consistent daily care and regular professional intervention can prevent the condition from worsening and lead to significant improvements in oral health. However, these conventional treatments often face restrictions due to adverse effects and antibiotic resistance, prompting the exploration of alternative therapies. This review evaluated the therapeutic effect of phytochemicals in managing periodontal disease and highlighted the mechanisms by which compounds exhibit anti-inflammatory, antimicrobial, and antioxidant effects. Some promising herbal agents, such as Baccharis Dracunculifolia, Piper nigrum, Punica grtiatum, and Scrophularia Striata, have been reported to be effective in reducing plaque accumulation and other periodontitis indications, sometimes comparable to standard treatments. In addition, natural products can modulate the oral microbiome and enhance tissue enhancement. In addition, the review explained the crucial role of PROs, satisfaction, and QoL in contemporary health care. Although the patient’s perceptions of its benefits are often favorable, clinical evidence by the absence of large-scale trials. The significant challenges of using natural NPation include a lack of product standardization and inconsistent study designs with short follow-up periods. Future research will require standardized, long-term randomized test guidelines to establish the success and safety of herbal interventions in the management of periodontitis.

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Author Biography

Areej Aldhaher, University of Basrah, College of Dentistry

Dr. Areej Hasan S. Aldhaheris is an Associate Professor at the College of Medicine, University of Basrah. She built her academic foundation in Biology at the University of Basrah, earning both her Bachelor's and Master's degrees. She then pursued and obtained her PhD in Biology with a specialization in the Phytochemistry of natural products from the University of Surrey in the United Kingdom. Her primary research expertise lies in the field of natural products, focusing on the purification and identification of pure compounds from natural sources and evaluating their biological activity through various bioassays. Dr. Aldhaher has actively contributed to her field, authoring several scientific papers that have been presented at national and international conferences and published in reputable journals. Her email address is areej.saleem@uobasrah.edu.iq.

References

[1] P. Dubey and N. Mittal, “Periodontal diseases- A brief review,” International Journal of Oral Health Dentistry, vol. 6, no. 3, pp. 177–187, Oct. 2020, doi: 10.18231/j.ijohd.2020.038.

[2] M. S. Tonetti, H. Greenwell, and K. S. Kornman, “Staging and grading of periodontitis: Framework and proposal of a new classification and case definition,” J. Periodontol., vol. 89, pp. S159–S172, Jun. 2018, doi: 10.1002/JPER.18-0006.

[3] D. F. Kinane, P. G. Stathopoulou, and P. N. Papapanou, “Periodontal diseases,” Jun. 22, 2017, Nature Publishing Group. doi: 10.1038/nrdp.2017.38.

[4] G. Hajishengallis, “Periodontitis: From microbial immune subversion to systemic inflammation,” Jan. 01, 2015, Nature Publishing Group. doi: 10.1038/nri3785.

[5] T. Dietrich et al., “Periodontal diagnosis in the context of the 2017 classification system of periodontal diseases and conditions – Implementation in clinical practice,” Br. Dent. J., vol. 226, no. 1, pp. 16–22, Jan. 2019, doi: 10.1038/sj.bdj.2019.3.

[6] J. G. Caton et al., “A new classification scheme for periodontal and peri-implant diseases and conditions – Introduction and key changes from the 1999 classification,” J. Clin. Periodontol., vol. 45, 2018, doi: 10.1111/jcpe.12935.

[7] J. Slots, “Periodontitis: facts, fallacies and the future,” Oct. 01, 2017, Blackwell Munksgaard. doi: 10.1111/prd.12221.

[8] F. Barutta, S. Bellini, M. Durazzo, and G. Gruden, “Novel Insight into the Mechanisms of the Bidirectional Relationship between Diabetes and Periodontitis,” Jan. 01, 2022, MDPI. doi: 10.3390/biomedicines10010178.

[9] I. S. Gomes-Filho et al., “Periodontitis and respiratory diseases: A systematic review with meta-analysis,” Oral Dis., vol. 26, no. 2, pp. 439–446, Mar. 2020, doi: 10.1111/odi.13228.

[10] J. Wu, Q. Li, and X. Fu, “Fusobacterium nucleatum Contributes to the Carcinogenesis of Colorectal Cancer by Inducing Inflammation and Suppressing Host Immunity,” Jun. 01, 2019, Neoplasia Press, Inc. doi: 10.1016/j.tranon.2019.03.003.

[11] M. G. Newman and H. H. Takei, “Newman and Carranza’s Clinical Periodontology THIRTEENTH EDITION.”

[12] C. Erbe et al., “Comparative assessment of plaque removal and motivation between a manual toothbrush and an interactive power toothbrush in adolescents with fixed orthodontic appliances: A single-center, examiner-blind randomized controlled trial,” American Journal of Orthodontics and Dentofacial Orthopedics, vol. 155, no. 4, pp. 462–472, Apr. 2019, doi: 10.1016/j.ajodo.2018.12.013.

[13] P. James et al., “Chlorhexidine mouthrinse as an adjunctive treatment for gingival health,” Mar. 31, 2017, John Wiley and Sons Ltd. doi: 10.1002/14651858.CD008676.pub2.

[14] F. Poppolo Deus and A. Ouanounou, “Chlorhexidine in Dentistry: Pharmacology, Uses, and Adverse Effects,” Jun. 01, 2022, Elsevier Inc. doi: 10.1016/j.identj.2022.01.005.

[15] F. Cieplik, N. S. Jakubovics, W. Buchalla, T. Maisch, E. Hellwig, and A. Al-Ahmad, “Resistance toward chlorhexidine in oral bacteria-is there cause for concern?,” 2019, Frontiers Media S.A. doi: 10.3389/fmicb.2019.00587.

[16] I. Sanz, B. Alonso, M. Carasol, D. Herrera, and M. Sanz, “Nonsurgical Treatment of Periodontitis,” Journal of Evidence Based Dental Practice, vol. 12, no. 3, pp. 76–86, Sep. 2012, doi: 10.1016/S1532-3382(12)70019-2.

[17] S. Peeran et al., Essentials of Periodontics and Oral Implantology, 1st ed. India: Dr. Syed Wali Peeran and Dr. Karthikeyan Ramalingam @ Saranraj JPS Publication, 2021.

[18] P. Bidault, F. Chandad, and D. Grenier, “Systemic antibiotic therapy in the treatment of periodontitis,” J. Can. Dent. Assoc. (Tor)., vol. 73, no. 6, 2007.

[19] P. Bidault, F. Chandad, and D. Grenier, “Risk of bacterial resistance associated with systemic antibiotic therapy in periodontology,” J. Can. Dent. Assoc. (Tor)., vol. 73, no. 8, 2007. PMID: 17949540

[20] F. G. Everett, J. Waerhaug, and A. Widman, “Leonard Widman: Surgical Treatment of Pyorrhea Alveolaris,” J. Periodontol., vol. 42, no. 9, 1971, doi: 10.1902/jop.1971.42.9.571.

[21] J. Durham, H. M. Fraser, G. I. McCracken, K. M. Stone, M. T. John, and P. M. Preshaw, “Impact of periodontitis on oral health-related quality of life,” J. Dent., vol. 41, no. 4, pp. 370–376, 2013, doi: https://doi.org/10.1016/j.jdent.2013.01.008.

[22] D. J. Newman and G. M. Cragg, “Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019,” 2020. doi: 10.1021/acs.jnatprod.9b01285.

[23] M. A. Anwar et al., “Herbal remedies for oral and dental health: a comprehensive review of their multifaceted mechanisms including antimicrobial, anti-inflammatory, and antioxidant pathways,” Mar. 01, 2025, Springer Science and Business Media Deutschland GmbH. doi: 10.1007/s10787-024-01631-8.

[24] S. Prasad and A. K. Tyagi, “Curcumin and its analogues: a potential natural compound against HIV infection and AIDS,” Food Funct., vol. 6, no. 11, 2015, doi: 10.1039/c5fo00485c.

[25] G. Malcangi et al., “Effectiveness of Herbal Medicines with Anti-Inflammatory, Antimicrobial, and Antioxidant Properties in Improving Oral Health and Treating Gingivitis and Periodontitis: A Systematic Review,” Mar. 01, 2025, Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/nu17050762.

[26] S. Pfister, P. Meyer, A. Steck, and H. Pfander, “Isolation and Structure Elucidation of Carotenoid−Glycosyl Esters in Gardenia Fruits (Gardenia jasminoides Ellis) and Saffron (Crocus sativus Linne),” J. Agric. Food Chem., vol. 44, pp. 2612–2615, 1996, doi:10.1021/jf950713e. [Online]. Available: https://api.semanticscholar.org/CorpusID:85324418

[27] S. G. Moussa et al., “Sustainable Treatment of Oral Traumatic Ulcers with Licorice Containing Hydrogels: Integrating Computational Modeling, Quality by Design, Green Synthesis, and Molecular Biological Evaluation,” Pharmaceutics, vol. 15, no. 12, 2023, doi: 10.3390/pharmaceutics15122734.

[28] F. C. Groppo, J. C. Ramacciato, R. H. Motta, P. M. Ferraresi, and A. Sartoratto, “Antimicrobial activity of garlic against oral streptococci.,” Int. J. Dent. Hyg., vol. 5, no. 2, 2007, doi: 10.1111/j.1601-5037.2007.00230.x.

[29] M. A. Botelho et al., “Efficacy of a mouthrinse based on leaves of the neem tree (Azadirachta indica) in the treatment of patients with chronic gingivitis: A double-blind, randomized, controlled trial,” Journal of Medicinal Plants Research, vol. 2, no. 11, 2008.

[30] K. N. Kontogiannopoulos et al., “A Review of the Role of Natural Products as Treatment Approaches for Xerostomia,” 2023. doi: 10.3390/ph16081136.

[31] M. Khosrojerdi, E. Gumpricht, T. Jamialahmadi, P. Kesharwani, and A. Sahebkar, “Is Curcumin a Safe and Effective Therapeutic in the Treatment against Oral Lichen Planus?,” Curr. Med. Chem., vol. 30, no. 15, 2022, doi: 10.2174/0929867330666221202150727.

[32] R. S. A. Shinkai, C. L. Azevedo, T. T. de Campos, E. Michel-Crosato, and M. G. H. Biazevic, “Importance of phytotherapy for oral health care and quality of life in adults: A scoping review,” Apr. 01, 2024, Association for Dental Sciences of the Republic of China. doi: 10.1016/j.jds.2024.01.002.

[33] K. Sharma, S. Acharya, E. Verma, D. Singhal, and N. Singla, “Efficacy of chlorhexidine, hydrogen peroxide and tulsi extract mouthwash in reducing halitosis using spectrophotometric analysis: A randomized controlled trial,” J. Clin. Exp. Dent., vol. 11, no. 5, pp. e457–e463, May 2019, doi: 10.4317/jced.55523.

[34] G. D. Slade, “Communify Dentistiy and Oral Epidemiology Derivation and validation of a short-form oral health impact profile,” Cotnmunity Detit Oral Epidemiol, vol. 25, pp. 284–90, 1997.

[35] M. Ekor, “The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety,” 2014. doi: 10.3389/fphar.2013.00177.

[36] S. A. Al-Maweri et al., “Efficacy of aloe vera mouthwash versus chlorhexidine on plaque and gingivitis: A systematic review,” Int. J. Dent. Hyg., vol. 18, no. 1, pp. 44–51, 2020, doi: 10.1111/idh.12393.

[37] S. Kumar and A. K. Pandey, “Chemistry and biological activities of flavonoids: An overview,” 2013. doi: 10.1155/2013/162750.

[38] S. D. S. Banjarnahor and N. Artanti, “Antioxidant properties of flavonoids,” 2014. doi: 10.13181/mji.v23i4.1015.

[39] B. Fernández-Rojas and G. Gutiérrez-Venegas, “Flavonoids exert multiple periodontic benefits including anti-inflammatory, periodontal ligament-supporting, and alveolar bone-preserving effects,” Sep. 15, 2018, Elsevier Inc. doi: 10.1016/j.lfs.2018.08.029.

[40] H. Huang, Z. Cheng, H. Shi, W. Xin, T. T. Y. Wang, and L. Yu, “Isolation and characterization of two flavonoids, engeletin and astilbin, from the leaves of Engelhardia roxburghiana and their potential anti-inflammatory properties,” J. Agric. Food Chem., vol. 59, no. 9, 2011, doi: 10.1021/jf2002969.

[41] H. S. Youn et al., “Suppression of MyD88- and TRIF-dependent signaling pathways of toll-like receptor by (-)-epigallocatechin-3-gallate, a polyphenol component of green tea,” Biochem. Pharmacol., vol. 72, no. 7, 2006, doi: 10.1016/j.bcp.2006.06.021.

[42] F. J. Pérez-Cano, M. Massot-Cladera, M. J. Rodríguez-Lagunas, and M. Castell, “Flavonoids affect host-microbiota crosstalk through TLR modulation,” 2014. doi: 10.3390/antiox3040649.

[43] G. Gutiérrez-Venegas, O. A. Luna, J. A. Arreguín-Cano, and C. Hernández-Bermúdez, “Myricetin blocks lipoteichoic acid-induced COX-2 expression in human gingival fibroblasts,” Cell. Mol. Biol. Lett., vol. 19, no. 1, 2014, doi: 10.2478/s11658-014-0186-4.

[44] G. Gutiérrez-Venegas, O. A. Luna, J. A. Ventura-Arroyo, and C. Hernández-Bermúdez, “Myricetin suppresses lipoteichoic acid-induced interleukin-1β and cyclooxygenase-2 expression in human gingival fibroblasts,” Microbiol. Immunol., vol. 57, no. 12, pp. 849–856, Dec. 2013, doi: 10.1111/1348-0421.12103.

[45] H. Yoshida, W. Watanabe, H. Oomagari, E. Tsuruta, M. Shida, and M. Kurokawa, “Citrus flavonoid naringenin inhibits TLR2 expression in adipocytes,” Journal of Nutritional Biochemistry, vol. 24, no. 7, 2013, doi: 10.1016/j.jnutbio.2012.10.003.

[46] M. M. Hegazy, R. H. Mekky, A. E. Ibrahim, M. E. Abouelela, T. A. Kedra, and A. Al-Harrasi, “Essential Oils: The Science of Extraction and Its Implications for Composition and Biological Activity—A Review,” Food Anal. Methods, vol. 18, no. 7, pp. 1483–1513, 2025, doi: 10.1007/s12161-025-02808-9.

[47] D. P. de Sousa et al., “Essential Oils: Chemistry and Pharmacological Activities,” Jul. 01, 2023, Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/biom13071144.

[48] S. Bouhdid, J. Abrini, A. Zhiri, M. J. Espuny, and A. Manresa, “Investigation of functional and morphological changes in pseudomonas aeruginosa and staphylococcus aureus cells induced by origanum compactum essential oil,” J. Appl. Microbiol., vol. 106, no. 5, 2009, doi: 10.1111/j.1365-2672.2008.04124.x.

[49] K. Rhayour, T. Bouchikhi, A. Tantaoui-Elaraki, K. Sendide, and A. Remmal, “The mechanism of bactericidal action of oregano and clove essential oils and of their phenolic major components on escherichia coli and bacillus subtilis,” Journal of Essential Oil Research, vol. 15, no. 4, 2003, doi: 10.1080/10412905.2003.9712144.

[50] S. D. Cox et al., “Tea tree oil causes K+ leakage and inhibits respiration in Escherichia coli,” Lett. Appl. Microbiol., vol. 26, no. 5, 1998, doi: 10.1046/j.1472-765X.1998.00348.x.

[51] R. P. Allaker and C. W. I. Douglas, “Novel anti-microbial therapies for dental plaque-related diseases,” 2009. doi: 10.1016/j.ijantimicag.2008.07.014.

[52] A. L. A. Batista, R. Diógenes Alves UchÔa Lins, R. de Souza Coelho, D. do Nascimento Barbosa, N. Moura Belém, and F. J. Alves Celestino, “Clinical efficacy analysis of the mouth rinsing with pomegranate and chamomile plant extracts in the gingival bleeding reduction,” Complement. Ther. Clin. Pract., vol. 20, no. 1, pp. 93–98, Feb. 2014, doi: 10.1016/J.CTCP.2013.08.002.

[53] M. J. U. Ferreira, “Alkaloids in Future Drug Discovery,” 2022. doi: 10.3390/molecules27041347.

[54] S. Qiu et al., “Natural alkaloids: basic aspects, biological roles, and future perspectives,” Chin. J. Nat. Med., vol. 12, no. 6, pp. 401–406, Jun. 2014, doi: 10.1016/S1875-5364(14)60063-7.

[55] J. P. Hu, N. Takahashi, and T. Yamada, “Coptidis rhizoma inhibits growth and proteases of oral bacteria,” Oral Dis., vol. 6, no. 5, 2000, doi: 10.1111/j.1601-0825.2000.tb00142.x.

[56] S. Mohammadian Haftcheshmeh and A. A. Momtazi-Borojeni, “Berberine as a promising natural compound for the treatment of periodontal disease: A focus on anti-inflammatory properties,” J. Cell. Mol. Med., vol. 25, no. 24, 2021, doi: 10.1111/jcmm.17019.

[57] D. Y. Lu, C. H. Tang, Y. H. Chen, and I. H. Wei, “Berberine suppresses neuroinflammatory responses through AMP-activated protein kinase activation in BV-2 microglia,” J. Cell. Biochem., vol. 110, no. 3, 2010, doi: 10.1002/jcb.22580.

[58] L. G. Palchykovska et al., “Antiviral properties of herbal flavonoids - Inhibitors of the DNA and RNA synthesis,” Biopolym. Cell, vol. 29, no. 2, 2013, doi: 10.7124/bc.000813.

[59] M. Nagy, P. Mučaji, and D. Grančai, TEXTBOOK OF PHARMACOGNOSY AND PHYTOCHEMISTRY, 1st ed. Osveta: Martin, Slovakia, 2011.

[60] M. Irfan, S. Kumar, V. Amin, and C. E. Cuevas-Suárez, “Evaluation of the efficacy of triphala mouth rinse as coadjuvant in the treatment of chronic generalized periodontitis: a randomized clinical trial,” Mouth and Teeth, vol. 1, no. 1, 2017, doi: 10.15761/mtj.1000103.

[61] M. S. Kumar, S. Kirubanandan, R. Sripriya, and P. K. Sehgal, “Triphala Promotes Healing of Infected Full-Thickness Dermal Wound,” Journal of Surgical Research, vol. 144, no. 1, 2008, doi: 10.1016/j.jss.2007.02.049.

[62] A. I. Cuesta, V. M. Jewtuchowicz, M. I. Brusca, M. T. Mujica, and A. C. Rosa, “Antibiotic susceptibility of Staphylococcus aureus isolates in oral mucosa and pockets of patients with gingivitis-periodontitis.,” Acta Odontol. Latinoam., vol. 24, no. 1, 2011.

[63] D. Gupta, R. K. Gupta, D. J. Bhaskar, and V. Gupta, “Comparative evaluation of terminalia chebula extract mouthwash and chlorhexidine mouthwash on plaque and gingival inflammation - 4-week randomised control trial.,” Oral Health Prev. Dent., vol. 13, no. 1, 2015, doi: 10.3290/j.ohpd.a32994.

[64] A. Bag, S. K. Bhattacharyya, P. Bharati, and N. Kumar, “Evaluation of antibacterial properties of Chebulic myrobalan ( fruit of Terminalia chebula Retz .) extracts against methicillin resistant Staphylococcus aureus and trimethoprim-sulphamethoxazole resistant uropathogenic Escherichia coli,” African journal of plant science, vol. 3, no. 2, 2009.

[65] A. K. Farha et al., “Tannins as an alternative to antibiotics,” 2020. doi: 10.1016/j.fbio.2020.100751.

[66] G. Hassan, S. Ghafoor, S. Atif, S. Chaudhry, and Z. Ahmed Khan, “Non-Surgical Periodontal Therapy Improves Clinical Outcomes in Patients with Chronic Periodontitis Independent of the Use of Nigella Sativa Oil or Normal Saline Mouthwash; Randomized Controlled Trial,” Journal of the Pakistan Dental Association, vol. 30, no. 02, pp. 81–86, Jun. 2021, doi: 10.25301/JPDA.302.81.

[67] S. Abullais, N. Dani, Hamiduddin, N. Priyanka, N. Kudyar, and A. Gore, “Efficacy of irrigation with different antimicrobial agents on periodontal health in patients treated for chronic periodontitis: A randomized controlled clinical trial,” AYU (An international quarterly journal of research in Ayurveda), vol. 36, no. 4, p. 380, 2015, doi: 10.4103/0974-8520.190702.

[68] S. Trivedi and J. Dixit, “Clinical effects of irrigation with Saussurea lappa extract in the treatment of chronic periodontitis: A pilot randomized trial,” J. Orofac. Sci., vol. 7, no. 2, pp. 80–85, Jul. 2015, doi: 10.4103/0975-8844.169752.

[69] G. Nimbulkar et al., “Microbiological and Clinical evaluation of Neem gel and Chlorhexidine gel on dental plaque and gingivitis in 20-30 years old adults: A Randomized Parallel-Armed, Double-blinded Controlled Trial,” J. Pharm. Bioallied Sci., vol. 12, no. 5, pp. S345–S351, Aug. 2020, doi: 10.4103/jpbs.JPBS_101_20.

[70] T. Kerdar, N. Rabienejad, Y. Alikhani, S. Moradkhani, and D. Dastan, “Clinical, in vitro and phytochemical, studies of Scrophularia striata mouthwash on chronic periodontitis disease,” J. Ethnopharmacol., vol. 239, Jul. 2019, doi: 10.1016/j.jep.2019.111872.

[71] V. Pedrazzi, M. F. Leite, R. C. Tavares, S. Sato, G. C. Do Nascimento, and J. P. M. Issa, “Herbal mouthwash containing extracts of baccharis dracunculifolia as agent for the control of biofilm: Clinical evaluation in humans,” Scientific World Journal, vol. 2015, 2015, doi: 10.1155/2015/712683.

[72] H. Sharma, G. Y. Yunus, A. K. Mohapatra, R. Kulshrestha, R. Agrawal, and M. Kalra, “Antimicrobial efficacy of three medicinal plants Glycyrrhiza glabra, Ficus religiosa, and Plantago major on inhibiting primary plaque colonizers and periodontal pathogens: An in vitro study,” Indian Journal of Dental Research, vol. 27, no. 2, pp. 200–204, Mar. 2016, doi: 10.4103/0970-9290.183135.

[73] B. Karasu and S. Eser, “The Application of Morinda citrifolia (noni) as An Alternative Herbal Product in Dentistry,” Essentials of Dentistry, vol. 4, no. 1, pp. 1–5, Feb. 2025, doi: 10.5152/EssentDent.2025.24014.

[74] K. Mirzaei, A. Fathi, S. M. Asadinejad, and N. C. Z. Moghadam, “Study the antimicrobial effects of Zataria multiflora-based mouthwash on the microbial community of dental plaques isolated from children: A candidate of novel plant-based mouthwash,” Academic Journal of Health Sciences, vol. 37, no. 3, 2022.

[75] F. Hussein Al-Bayaty, A. Hamad AI-Koubaisi, N. Abdul Wahid Ali, and M. Ameen Abdulla, “Effect of mouth wash extracted from Salvadora persica (Miswak) on dental plaque formation: A clinical trail,” Journal of Medicinal Plants Research, vol. 4, no. 14, 2010.

[76] H. P. Singh, Muzammil, G. Sathish, K. Nagendra Babu, K. S. Vinod, and H. P. Rao, “Comparative Study to Evaluate the Effectiveness of Aloe vera and Metronidazole in Adjunct to Scaling and Root Planing in Periodontitis Patients,” Journal of International Oral Health, vol. 8, no. 3, pp. 374–377, 2016, doi: 10.2047/jioh-08-03-14.

[77] Dr. P. Patel, A. Patel, S. Gujjari, and J. Holmes, “Effect of subgingival application of topical ozonated olive oil in the treatment of chronic periodontitis: a randomized, controlled, double blind, clinical and microbiological study,” Minerva Stomatol., vol. 61, pp. 381–398, Sep. 2012. PMID: 22976566.

[78] Jorge MP et al., “Clinical Safety Evaluation of an Herbal Gel Containing 2.5% Arrabidaea chica Verlot Standardized Extract,” Clinical Case Reports International, vol. 4, p. 1104, 2020, [Online]. Available: http://clinicalcasereportsint.com/

[79] F. Taleghani, G. Rezvani, M. Birjandi, and M. Valizadeh, “Impact of green tea intake on clinical improvement in chronic periodontitis: A randomized clinical trial,” J. Stomatol. Oral Maxillofac. Surg., vol. 119, no. 5, 2018, doi: 10.1016/j.jormas.2018.04.010.

[80] G. D. Deore, A. N. Gurav, R. Patil, A. R. Shete, R. S. Naiktari, and S. P. Inamdar, “Herbal anti-inflammatory immunomodulators as host modulators in chronic periodontitis patients: A randomised, double-blind, placebo-controlled, clinical trial,” J. Periodontal Implant Sci., vol. 44, no. 2, 2014, doi: 10.5051/jpis.2014.44.2.71.

[81] Patki, sunita amruthesh, Tandur, tandur, and Malini, “Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial,” J. Exp. Pharmacol., 2010, doi: 10.2147/jep.s10957.

[82] U.S. Food and Drug Administration, “Patient Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims,” Silver Spring, MD, USA, 2009.

[83] N. K. Jokar, S. A. Noorhosseini, M. S. Allahyari, and C. A. Damalas, “Consumers’ acceptance of medicinal herbs: An application of the technology acceptance model (TAM),” J. Ethnopharmacol., vol. 207, 2017, doi: 10.1016/j.jep.2017.06.017.

[84] R. Mathur, “Investigating the prevalence and effectiveness of herbal and natural remedies used by patients to manage periodontal health, including their sources of information and satisfaction with these alternatives,” International Journal of Preventive and Clinical Dental Research, vol. 11, no. 2, 2024, DOI: 10.4103/ijpcdr.ijpcdr_16_24.

[85] S. Cabrera-Jaime et al., “Efficacy of Plantago major, chlorhexidine 0.12% and sodium bicarbonate 5% solution in the treatment of oral mucositis in cancer patients with solid tumour: A feasibility randomised triple-blind phase III clinical trial,” European Journal of Oncology Nursing, vol. 32, 2018, doi: 10.1016/j.ejon.2017.11.006.

[86] H. Wang, Y. Chen, L. Wang, Q. Liu, S. Yang, and C. Wang, “Advancing herbal medicine: enhancing product quality and safety through robust quality control practices,” 2023. doi: 10.3389/fphar.2023.1265178.

[87] P. Mirmiran, Z. Bahadoran, and Z. Gaeini, “Common limitations and challenges of dietary clinical trials for translation into clinical practices,” 2021. doi: 10.5812/IJEM.108170.

[88] G. S. Chatzopoulos, P. Karakostas, S. Kavakloglou, A. Assimopoulou, P. Barmpalexis, and L. Tsalikis, “Clinical Effectiveness of Herbal Oral Care Products in Periodontitis Patients: A Systematic Review,” Aug. 01, 2022, MDPI. doi: 10.3390/ijerph191610061.

[89] B. Mohamad et al., “) Short Title: The role of herbal medicine in periodontal treatment: A systematic review The role of herbal medicine in periodontal treatment: A systematic review”, doi: 10.5281/zenodo.15300437.

[90] L. Tsalikis, “Oral Health Case Reports A Metaanalysis of the Clinical Effectiveness of Herbal Oral Care Products in Periodontitis Patients,” 2022, doi: 10.37421/2471-8726.2022.8.67.