Red Clover (Trifolium pratense) Benefits in Dentistry: A Narrative Review

Jasim Ghazwan Hasan Jasim, Siti Noor Fazliah Mohd Noor, Ahmad Fakrurrozi Mohamad, Ihsan Abdullah Kumail

Abstract


The herbal plant red clover (Trifolium pratense) includes four phenolic compounds, categorised as phytoestrogens which are a set of isoflavones comprising daidzein, biochanin A, genistein, and formononetin. These compounds are plant-derived and practically equivalent to 17-estradiol. This study reviewed the scientific literature reporting the benefits of red clover as medicament and herbs in the field of dentistry. The PRISMA checklist was used to conduct the systematic review in Web of Science and PubMed which retrieved 197 records. The records related to the benefit of red clover in dentistry were screened, and after removal of duplicates, 46 records were identified, reviewed and incorporated in this study. The Trifolium pratense extracts provide several dental advantages, including increased calcium levels in bones and teeth and decreased bone porosity. It has a wide effect on the gingiva by improving blood flow and enhancing blood circulation. Besides, these compounds can regulate the level of glucose in the blood and lipid markers, assist in improving symptoms from menopause and its hormonal changes, while having acceptable effects as an anti-inflammatory and improving the skin texture. Further, it has tangible effect in increasing the secretion of salivary glands, broad effect in reducing caries and additional beneficial effects as an antioxidant and anticancer with significant effects on the development of most cells. The multiple benefits of Trifolium pratense promote essential and beneficial effects in preserving oral health providing significant effect in treating gingival diseases and dental problems.


Keywords


Dentistry, Herbal, Isoflavones, Osteoporosis, Trifolium Pratense

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References


Boyapati R, Pendyala R, Lanke RB, Anumala D. Herbal treatments used as an alternative in the treatment of periodontal diseases. Cumhuriyet Dent J. 2023;26(2):204–210.

Rani N, Singla RK, Narwal S, Tanushree, Kumar N, Rahman MM. Medicinal plants used as an alternative to treat gingivitis and periodontitis. Evid Based Complement Alternat Med. 2022;2327641.

Kumar G, Jalaluddin M, Rout P, Mohanty R, Dileep CL. Emerging trends of herbal care in dentistry. J Clin Diagn Res. 2013;7(8):1827–1829.

Havstad LT, Øverland JI, Aamlid TS, Gunnarstorp T, Knudsen GK, et al. Evaluation of pre-harvest desiccation strategies in red clover (Trifolium pratense L.) and white clover (Trifolium repens L.) seed crops. Acta Agric Scand B Soil Plant Sci. 2022;72(1):818–834.

Mohsen A, Fatemeh K, Leila N, Mona P, Mohammad Z, Mozafar K. Pharmacological and therapeutic properties of the Red Clover (Trifolium pratense L.): an overview of the new finding. J Tradit Chin Med. 2021;41(4):642-649.

Gligor O, Clichici S, Moldovan R, Muntean D, Vlase AM, Nadăș GC, et al. Red clover and the importance of extraction processes—ways in which extraction techniques and parameters affect Trifolium Pratense L. extracts’ phytochemical profile and biological activities. Processes. 2022;10(12):2581.

Horvat D, Tucak M, Viljevac Vuletić M, Čupić T, Krizmanić G, Kovačević Babić M. Phenolic content and antioxidant activity of the Croatian red clover germplasm collection. Poljoprivreda. 2020;26(2):3–10.

Boller B, Schubiger FX, Kölliker R. Red Clover. In: Boller, B., Posselt, U.K., Veronesi, F. (eds) Fodder Crops and Amenity Grasses. Handbook of Plant Breeding, vol 5:439-455. New York, NY. Springer 2010.

Brandli A, Simpson JS, Ventura S. Isoflavones isolated from red clover (Trifolium pratense) inhibit smooth muscle contraction of the isolated rat prostate gland. Phytomedicine. 2010 Sep;17(11):895–901.

Kole L, Giri B, Manna SK, Pal B, Ghosh S. Biochanin-A, an isoflavone, showed anti-proliferative and anti-inflammatory activities through the inhibition of iNOS expression, p38-MAPK and ATF-2 phosphorylation and blocking NFκB nuclear translocation. Eur J Pharmacol. 2011;653(1–3):8–15.

Sundaresan A, Radhiga T, Deivasigamani B. Biological activity of biochanin A: A review. Asian J Pharm Pharmacol. 2018;4(1):1-5.

Xu Q, Li Y, Du W, Zheng N, Wang J, Zhao S. Effect of dietary biochanin A on lactation performance, antioxidant capacity, rumen fermentation and rumen microbiome of dairy goat. Front Microbiol. 2023;14:01–09.

Krenn L, Unterrieder I, Ruprechter R. Quantification of isoflavones in red clover by high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2002;777(1-2):123-128.

Ku-Cükboyaci N, Kadioğlu O, Adigüzel N, Tamer U, Güvenç A, Bani B. Determination of isoflavone content by HPLC-UV method and in vitro antioxidant activity of Red Clover (Trifolium Pratense L.). Turk J Pharm Sci. 2013;10(3):463-472.

Ong SKL, Shanmugam MK, Fan L, Fraser SE, Arfuso F, Ahn KS, Sethi G, Bishayee A. Focus on formononetin: anticancer potential and molecular targets. Cancers (Basel). 2019;11(5):611.

Almatroodi SA, Almatroudi A, Khan AA, Rahmani AH. Potential therapeutic targets of formononetin, a type of methoxylated isoflavone, and its role in cancer therapy through the modulation of signal transduction pathways. Int J Mol Sci. 2023;24(11):9719.

Oza MJ, Kulkarni YA. Trifolium pratense (Red Clover) Improve SIRT1 expression and glycogen content in high fat diet-streptozotocin induced Type 2 diabetes in rats. Chem Biodivers. 2020;17(4):e2000019.

Zanotto S, Ruttink T, Pégard M, Skøt L, Grieder C, Kölliker R, Ergon Å. A genome-wide association study of freezing tolerance in red clover (Trifolium pratense L.) germplasm of European origin. Front Plant Sci. 2023;14:1189662.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar;372:n71.

Gościniak A, Szulc P, Zielewicz W, Walkowiak J, Cielecka-Piontek J. Multidirectional effects of red clover (Trifolium pratense L.) in support of menopause therapy. Molecules. 2023 Jul 3;28(13):5178.

Petrović M, Sokolović D, Babić S, Vymyslický T, Marković J, Zornić V, et al. Isoflavones of the red and Hungarian clover and possible impact on animal diet. Czech J Food Sci. 2021;39(3):169-175.

Kazlauskaite JA, Ivanauskas L, Bernatoniene J. Novel extraction method using excipients to enhance yield of genistein and daidzein in Trifolium pratensis L. Pharmaceutics. 2021;13(6):777.

Bae SH, Ha MH, Choi EY, Choi JI, Choi IS, Kim SJ. Effects of daidzein on alveolar bone loss and internal microstructures of bone in a rat model of experimental periodontitis: A study using micro-computed tomography. J Periodontal Res. 2016;51(2):250–256.

Kwon DY, Jang JS, Lee JE, Kim YS, Shin DH, Park S. The isoflavonoid aglycone-rich fractions of Chungkookjang, fermented unsalted soybeans, enhance insulin signaling and peroxisome proliferator- activated receptor-γ activity in vitro. BioFactors. 2006;26(4):245–258.

Bhattarai G, Poudel SB, Kook SH, Lee JC. Anti-inflammatory, anti-osteoclastic, and antioxidant activities of genistein protect against alveolar bone loss and periodontal tissue degradation in a mouse model of periodontitis. J Biomed Mater Res A. 2017;105(9):2510–2521.

Carvalho VDC, Silveira VÁS, do Prado RF, Carvalho YR. Effect of oestrogen therapy, soy isoflavones, and the combination therapy on the submandibular gland of ovariectomized rats. Pathol Res Pract. 2011;207(5):300–305.

Šušaníková I, Puchl'ová M, Lachová V, Švajdlenka E, Mučaji P, Smetana K Jr, Gál P. Genistein and selected phytoestrogen-containing extracts differently modulate antioxidant properties and cell differentiation: an in vitro study in NIH-3T3, HaCaT and MCF-7 Cells. Folia Biol (Praha). 2019;65(1):24-35.

Liu S, Zhang Z, Hailemariam S, Zheng N, Wang M, Zhao S, Wang J. Biochanin A inhibits ruminal nitrogen-metabolising bacteria and alleviates the decomposition of amino acids and urea in vitro. Animals (Basel). 2020;10(3):368.

Medjakovic S, Jungbauer A. Red clover isoflavones biochanin A and formononetin are potent ligands of the human aryl hydrocarbon receptor. J Steroid Biochem Mol Biol. 2008;108(1-2):171-177.

AL-Ghaban N, Jasem G. Histomorphometric evaluation of the effects of local application of red clover oil (trifolium pratense) on bone healing in rats. J Baghdad College Dent. 2020;32(2):26–31.

Fernández-Rojas B, Gutiérrez-Venegas G. Flavonoids exert multiple periodontic benefits including anti-inflammatory, periodontal ligament-supporting, and alveolar bone-preserving effects. Life Sci.

;209:435-454.

Healy WB, Cutress TW, Michie C. Wear of sheep’s teeth. New Zealand J Agric Res. 1967;10(2):201–209.

Ramdarshan A, Blondel C, Brunetière N, Francisco A, Gautier D, Surault J, et al. Seeds, browse, and tooth wear: a sheep perspective. Ecol Evol. 2016;6(16):5559–5569.

Suparwitri S, Pudyani PS, Haryana SM, Agustina D. Effects of soy isoflavone genistein on orthodontic tooth movement in guinea pigs. Dental Journal (Majalah Kedokteran Gigi). 2016;49(3):168.

Zhang S, Zhang X, Xiong Z, Li K, Gao Y, Bu Y, et al. Effect of red clover isoflavones on hormone, immune, inflammatory, and plasma biochemistry in lactating dairy cows. Animal Nutrition. 2023;16:306–312.

Reynolds MA, Aberdeen GW, Pepe GJ, Sauk JJ, Albrecht ED. Estrogen suppression induces papillary gingival overgrowth in pregnant baboons. J Periodontol. 2004;75(5):693-701.

Gürsoy M, Gürsoy UK, Sorsa T, Pajukanta R, Könönen E. High salivary estrogen and risk of developing pregnancy gingivitis. J Periodontol. 2013;84(9):1281–1289.

Jensen J, Liljemark W, Bloomquist C. The effect of female sex hormones on subgingival plaque. J Periodontol. 1981;52(10):599–602.

Farooq I, Bugshan A. The role of salivary contents and modern technologies in the remineralization of dental enamel: a narrative review. F1000Res. 2020;9:171.

Katz J, Blake E, Medrano TA, Sun Y, Shiverick KT. Isoflavones and gamma irradiation inhibit cell growth in human salivary gland cells. Cancer Lett. 2008;270(1):87–94.

Ryo K, Takahashi A, Tamaki Y, Ohnishiikameyama M, Inoue H, Saito I. Therapeutic effects of isoflavones on impaired salivary secretion. J Clin Biochem Nutr. 2014;55(3):168–73.

Elsherbini AM, Mohammed MAR, Ibrahim FM. Effect of biochanin a versus 17β estradiol in rat submandibular salivary gland. J Oral Sci. 2017;59(4):579–88.

Mu H, Bai YH, Wang ST, Zhu ZM, Zhang YW. Research on antioxidant effects and estrogenic effects of formononetin from Trifolium pratense (red clover). Phytomedicine. 2009;16(4):314–319.

Rüfer CE, Kulling SE. Antioxidant activity of isoflavones and their major metabolites using different in vitro assays. J Agric Food Chem. 2006 Apr 19;54(8):2926–2931.

Lam ANC, Demasi M, James MJ, Husband AJ, Walker C. Effect of

red clover isoflavones on Cox-2 activity in murine and human monocyte/macrophage cells. Nutr Cancer. 2004;49(1):89–93.

Simoncini T, Fornari L, Mannella P, Caruso A, Garibaldi S, Baldacci C, Genazzani AR. Activation of nitric oxide synthesis in human endothelial cells by red clover extracts. Menopause. 2005;12(1):69-77.

Occhiuto F, Pasquale RD, Guglielmo G, Palumbo DR, Zangla G, Samperi S, Renzo A, Circosta C. Effects of phytoestrogenic isoflavones from red clover (Trifolium pratense L.) on experimental osteoporosis. Phytother Res. 2007;21(2):130-134.

Circosta C, De Pasquale R, Palumbo DR, Samperi S, Occhiuto F. Effects of isoflavones from red clover (Trifolium pratense) on skin changes induced by ovariectomy in rats. Phytother Res. 2006;20(12):1096-1099.

Huang CC, Hsu BY, Wu NL, Tsui WH, Lin TJ, Su CC, et al. Anti-photoaging effects of soy isoflavone extract (aglycone and acetylglucoside form) from soybean cake. Int J Mol Sci. 2010;11(12):4782–4795




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