Natural Products and their Role in the Management of Rheumatoid arthritis: A Review of Current Evidence
DOI:
https://doi.org/10.22270/ajprd.v13i2.1546Abstract
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent joint inflammation, pain, and progressive cartilage and bone damage. Conventional pharmacological treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs), provide symptomatic relief but are associated with adverse effects and long-term management challenges. Consequently, natural products have gained attention as alternative or complementary therapeutic agents due to their anti-inflammatory and immunomodulatory properties.
Aim: This review examines the potential of natural products in managing RA by targeting key inflammatory pathways and oxidative stress, with a focus on bioactive compounds such as flavonoids, terpenoids, alkaloids, and polyphenols.
Methods: A comprehensive literature review was conducted to evaluate preclinical and clinical studies on the efficacy of natural products in RA treatment. The mechanisms of action, bioavailability concerns, and potential combination therapies were analyzed.
Results: Compounds such as curcumin, resveratrol, Boswelliaserrata, and ginger have demonstrated significant anti-inflammatory and immunomodulatory effects in RA models. These natural products regulate cytokine production (TNF-α, IL-6), inhibit cyclooxygenase (COX), and mitigate oxidative stress, offering multi-targeted therapeutic potential. However, challenges such as poor bioavailability and variability in composition necessitate advanced formulations and standardization.
Conclusion: Natural products provide a promising adjunct in RA management. While clinical evidence supports their efficacy, further research, large-scale clinical trials, and standardized formulations are crucial for their integration into clinical practice.
Downloads
References
Bax M, Huizinga TW, Toes RE. The pathogenic potential of autoreactive antibodies in rheumatoid arthritis. Semin Immunopathol (2014);36:313–25.
Van Delft MAM, Huizinga TWJ. An overview of autoantibodies in rheumatoid arthritis. J Autoimmun (2020);110:102392.
Bartok, B.; Firestein, G.S. Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis. Immunol. Rev., 2010; 233(1):233-255.
Perlman, H.; Pope, R.M. The synovial lining micromass system: Toward rheumatoid arthritis in a dish? Arthritis Rheum., 2010;62(3):643-646.
Müller-Ladner, U.; Ospelt, C.; Gay, S.; Distler, O.; Pap, T. Cells of the synovium in rheumatoid arthritis. Synovial fibroblasts. Arthritis Res.Ther., 2007;9(6):223.
England BR, Thiele GM, Anderson DR, Mikuls TR. Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications. BMJ (2018);361:1036.
De Cock D, Hyrich K. Malignancy and rheumatoid arthritis: Epidemiology, risk factors and management. Best Pract Res Clin Rheumatol (2018);32:869–86.
Chang K, Yang SM, Kim SH, Han KH, Park SJ, Shin JI. Smoking and rheumatoid arthritis. Int J Mol Sci (2014) 15:22279–95.
Alpizar-Rodriguez D, Finckh A. Environmental factors and hormones in the development of rheumatoid arthritis. Semin Immunopathol (2017);39:461–8. doi: 10.1007/s00281-017-0624-2
Barnes, P.M.; Bloom, B.; Nahin, R.L. Complementary and Alternative Medicine Use Among Adults and Children: United States, 2007; National Health Statistics Reports; U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics: Hyattsville, MD, USA, 2008; pp. 1–23
Ben-Arye, E.; Frenkel, M.; Klein, A.; Scharf, M. Attitudes toward integration of complementary and alternative medicine in primary care: Perspectives of patients, physicians and complementary practitioners. Patient Educ. Couns. 2008, 70, 395–402.
Ekor, M. The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front. Pharmacol. 2014; 4:177.
Cassotta, M.; Forbes-Hernandez, T.Y.; Cianciosi, D.; Elexpuru Zabaleta, M.; Sumalla Cano, S.; Dominguez, I.; Bullon, B.; Regolo, L.; Alvarez-Suarez, J.M.; Giampieri, F.; et al. Nutrition and Rheumatoid Arthritis in the ‘Omics’ Era. Nutrients 2021;13, 763.
Turesson, C.; Bergström, U.; Pikwer, M.; Nilsson, J.A.; Jacobsson, L.T.H. High serum cholesterol predicts rheumatoid arthritis in women, but not in men: A prospective study. Arthritis Res. Ther. 2015;17:284.
Deane, K.D.; Demoruelle, M.K.; Kelmenson, L.B.; Kuhn, K.A.; Norris, J.M.; Holers, V.M. Genetic and environmental risk factors for rheumatoid arthritis. Best Prac. Res. Clin. Rheumatol. 2017;31:3–18.
Alpízar-Rodríguez, D.; Pluchino, N.; Canny, G.; Gabay, C.; Finckh, A. The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology 2017, 56, 1254–1263.
Yu, X.H.; Bo, L.; Cao, R.R.; Yang, Y.Q.; He, P.; Lei, S.F.; Deng, F.Y. Systematic Evaluation of Rheumatoid Arthritis Risk by Integrating Lifestyle Factors and Genetic Risk Scores. Front. Immunol. 2022, 13, 901223.
Oliveira ALB, Monteiro VVS, Navegantes-Lima KC, Reis JF, Gomes RS, Rodrigues DVS, et al. Resveratrol role in autoimmune disease-a mini-review. Nutrients (2017) 9(12):1306.. doi: 10.3390/nu9121306
Khojah HM, Ahmed S, Abdel-Rahman MS, Elhakeim EH. Resveratrol as an effective adjuvant therapy in the management of rheumatoid arthritis: a clinical study. Clin Rheumatol (2018) 37:2035–42. doi: 10.1007/s10067-018-4080-8.
Jia X, Wei F, Sun X, Chang Y, Xu S, Yang X, et al. CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co-cultured with BAFFactivated CD4(+) T cells. J Ethnopharmacol (2016) 189:194–201. doi: 10.1016/ j.jep.2016.05.034
Shu JL, Zhang XZ, Han L, Zhang F, Wu YJ, Tang XY, et al. Paeoniflorin-6'O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-kappaB signaling: comparison with biological agents. Acta Pharmacol Sin (2019) 40:801–13. doi: 10.1038/s41401-018-0169-5
Cheng H, Huang H, Guo Z, Chang Y, Li Z. Role of prostaglandin E2 in tissue repair and regeneration. Theranostics (2021) 11:8836–54. doi: 10.7150/ thno.63396.
Huang Z, Luo R, Yang L, Chen H, Zhang X, Han J, et al. CPT1A-mediated fatty acid oxidation promotes precursor osteoclast fusion in rheumatoid arthritis. Front Immunol (2022) 13:838664. doi: 10.3389/fimmu.2022.838664
Tu, Y. (2019). Glycine tabacina Ethanol Extract Ameliorates Collagen-Induced Arthritis in Rats via Inhibiting Pro-Inflammatory Cytokines and Oxidation. Journal of Ethnopharmacology, 239, 111919.
Tan, L., Wang, Y., Zhang, Y., & Li, Y. (2020). Exploring Protective Effect of Glycine tabacina Aqueous Extract AgainstNephrotic Syndrome by Network Pharmacology and Experimental Verification. Chinese Medicine, 15(1), 1–14.
Bingham, R., & Bellow, B. A. (1975). Yucca Plant Saponin in the Management of Arthritis. Journal of Applied Nutrition, 27(1), 45–51.
Oleszek, W., Sitek, M., Stochmal, A., &Cheeke, P. (2001). Antioxidant Properties of Yucca schidigera Products. In W. Pfannhauser, G. R. Fenwick, & S. Khokhar (Eds.), Biologically-Active Phytochemicals in Food Analysis, Metabolism, Bioavailability and Function (pp. 303–306). Royal Society of Chemistry.
Bingham, R. New and Effective Approaches to the Prevention and Treatment of Arthritis. Journal of Applied Nutrition, 1976;28(1):38–47.
Bingham, R., Harris, D. H., &Laga, T. Yucca Plant Saponin in the Treatment of Hypertension and Hypercholesterolemia. Journal of Applied Nutrition, 1978;30(3):127–136.
Wyburn-Mason, R. Naegleria in Rheumatoid and Malignant Disease. South African Medical Journal, 1983;63(1):31.
Parke, A. L., Parke, D. V., & Jones, F. A. Diet and Nutrition in Rheumatoid Arthritis and Other Chronic Inflammatory Diseases. Journal of Clinical Biochemistry and Nutrition, 1996; 20(1):1–26.
Martin, R. H. The Role of Nutrition and Diet in Rheumatoid Arthritis. Proceedings of the Nutrition Society, 1998;57(2):231–234.
Southon, S., Wright, A. J. A., Price, K. R., Fairweather-Tait, S. J., & Fenwick, G. R. (1988). The Effect of Three Types of Saponin on Iron and Zinc Absorption from a Single Meal in the Rat. British Journal of Nutrition, 59(3), 389–396.
Cordain, L., Toohey, L., Smith, M. J., & Hickey, M. S. (2000). Modulation of Immune Function by Dietary Lectins in Rheumatoid Arthritis. British Journal of Nutrition, 83(3), 207–217.
Katsunuma, Y., Nakamura, Y., Toyoda, A., & Minato, H. (2000). Effect of Yucca schidigera Extract and Saponins on Growth of Bacteria Isolated from Animal Intestinal Tract. Animal Science Journal, 71(2), 64–170.
Wang, Y., McAllister, T. A., Yanke, L.-J., &Cheeke, P. R. (2000). Effect of Steroidal Saponin from Yucca schidigera Extract on Ruminal Microbes. Journal of Applied Microbiology, 88(6), 887–896.
Ali, B. H., & Blunden, G. (2003). Pharmacological and Toxicological Properties of Nigella sativa. Phytotherapy Research, 17(4), 299–305.
Fahmy, N. M., Al-Sayed, E., Abdel-Daim, M. M., &Aleya, L. (2019). Promising Antirheumatic Activity of Black Cumin (Nigella sativa) and its Nano-Formulation. Environmental Science and Pollution Research, 26(8), 7665–7675.
Gautam, R., Jachak, S. M., &Saklani, A. (2011). Anti-Inflammatory Effect of Ajugabracteosa Wall Ex Benth. Mediated through Cyclooxygenase (COX) Inhibition. Journal of Ethnopharmacology, 133(2), 928–930.
Sharma, P., &Samant, S. S. (2014). Antioxidant Activities of Some Medicinal Plants of the Western Himalaya. Journal of Traditional and Folk Practices, 2(1), 19–24.
Kumar, V., Van Staden, J., &Jäger, A. K. (2002). Screening of Zulu Medicinal Plants for Angiotensin Converting Enzyme (ACE) Inhibitors. Journal of Ethnopharmacology, 79(3), 337–343.
Krishnaswamy, M., &Purushotham, K. K. (1980). Plumbagin: A study of its anticancer, antibacterial and antifungal properties. Indian Journal of Experimental Biology, 18, 876-877
Wang, R., Ding, Y., Liu, R., Xiang, L., & Du, L. (2010). Pomegranate: Constituents, bioactivities and pharmacokinetics. Fruit, Vegetable and Cereal Science and Biotechnology, 4(2):77-87
Kumar, S., &Kumari, R. (2023). Study of Chemical Characterization of Medicinal Plants Used for Traditional Medicine: A Review. Biomedical and Pharmacology Journal, 18(1).
Baseer, A. Phytochemical Analysis of Selected Medicinal Plants of India. International Journal of Pharmaceutical Sciences and Research, 2023;14(2):123-130.
Gopalakrishnan, L., Doriya, K., & Kumar, D. S. Moringaoleifera: A review on nutritive importance and its medicinal application. Food Science and Human Wellness, 2016;5(2):49–56.
Kumar, A., &Kalita, J. Phytopharmacology of Ficusreligiosa.Pharmacognosy Reviews, 2017;11(21):149–153.
Kumar, N., Singh, A. K., & Singh, R. Ricinuscommunis: A review on pharmacological activities and phytochemistry. International Journal of Pharmacy and Pharmaceutical Sciences, 2012;4(4):25–29.
Dhankhar, S., Ruhil, S., Balhara, M., Dhankhar, S., &Chhillar, A. K. A review on Justiciaadhatoda: A potential source of natural medicine. African Journal of Plant Science, (2011);5(11):620–627.
McKay, D. L., & Blumberg, J. B. A review of the bioactivity and potential health benefits of peppermint tea (Menthapiperita L.).Phytotherapy Research, 2006;20(8):619–633.
Monsef, H. R., Ghobadi, A., Iranshahi, M., & Abdollahi, M. Antinociceptive effects of Peganumharmala L. alkaloid extract on mouse formalin test. Journal of Pharmacy & Pharmaceutical Sciences, 2004;7(1):65–69.
Koumanov, F., Bozadjieva, E., Andreeva, M., &Platonva, E. Clinical trial of Tribestan. Experimental Medicine and Surgery, 1998;26(3):253–256.
Surjushe, A., Vasani, R., &Saple, D. G. Aloe vera: A short review. Indian Journal of Dermatology, 2008;53(4):163–166.
Zhong, C., Hu, D., Hou, L.-B., Song, L.-Y., Zhang, Y.-J., Xie, Y., &Tian, L.-W. Phenolic Compounds from the Rhizomes of Smilax china L. and Their Anti-Inflammatory Activity. Molecules, 2017; 22(4):515.
Hussain, F., Unab, S., &Shahid, M. Exploring the Pharmacological Potential of Smilax china. Pakistan Journal of Scientific and Industrial Research Series B: Biological Sciences, 2022; 65(2):135–144.
Di Pierro, F., Bellone, I., Rapacioli, G., &Putignano, P. Clinical role of a fixed combination of standardized Berberisaristata and Silybummarianum extracts in diabetic and hypercholesterolemic patients intolerant to statins. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2015; 8:89–96.
Derosa, G., Romano, D., D'Angelo, A., & Maffioli, P. Berberisaristata/Silybummarianum fixed combination (Berberol®) effects on lipid profile in dyslipidemic patients intolerant to statins at high dosages: a randomized, placebo-controlled, clinical trial. Phytomedicine, 2015; 22(2):231–237.
Hasheminia, S. M., Sendi, J. J., Talebi, K., &Moharramipour, S. (2011). The effects of Artemisia annua L. and Achilleamillefolium L. crude leaf extracts on the toxicity, development, feeding efficiency and chemical activities of small cabbage Pierisrapae L. (Lepidoptera: Pieridae). Pesticide Biochemistry and Physiology, 99(3), 244–249.
Kumar, S., Gupta, P., & Sharma, A. (2015). Justiciagendarussa: A Review on Its Phytochemical and Pharmacological Profile. International Journal of Pharmacy and Pharmaceutical Sciences, 7(4), 1-7.
Saha, S., &Saha, K. (2018). Pharmacological and Medicinal Properties of Leucasaspera – A Review. Asian Journal of Pharmaceutical and Clinical Research, 2018; 11(2):45-50.
Patel, J. R., Tripathi, P., Sharma, V., Chauhan, N. S., & Dixit, V. K. (2011). Phyllanthusamarus: Ethnomedicinal Uses, Phytochemistry, and Pharmacology: A Review. Journal of Ethnopharmacology, 138(2), 286-313.
Rahmatullah, M., Ferdausi, D., Ahmed, M., & Jahan, R. A Survey of Medicinal Plants Used by Folk Medicinal Practitioners in Bangladesh. American-Eurasian Journal of Sustainable Agriculture, 2010;4(2):176-180.
Nayak, S., & Suresh, D. (2012). Ecliptaprostrata: Phytochemistry, Traditional Uses, and Pharmacological Properties – A Review. International Journal of Research in Ayurveda and Pharmacy,2012; 3(6):803-808.
Sharma, R., Thakur, G. S., &Sanodiya, B. S. Traditional and Medicinal Uses of Abutilon indicum: An Overview. Pharmacognosy Journal, 2012;4(31):6-9.
Roy, S., & De, S. Clerodendrumserratum: An Overview of Its Ethnomedicinal Uses, Phytochemistry, and Pharmacology. Journal of Ayurveda and Integrative Medicine, 2017;8(3):165-171.
Sharma, P., & Singh, R. Vitexnegundo and its medicinal value. Asian Journal of Pharmaceutical and Clinical Research, 20185;11(10):25-29.
Kumar, S., & Kumar, V. Phytochemistry and pharmacology of Plumbagozeylanica: A review. International Journal of Pharmaceutical Sciences and Research,2015; 6(6):2304-2312.
Dey, P., & De, J. N. (2012). Costusspeciosus (Koen ex. Retz.) Sm.: A review on its ethnomedicinal uses and pharmacological activities. Journal of Ethnopharmacology, 2012;40(2):299-313.
Published
How to Cite
Issue
Section
Copyright (c) 2025 M.Mohammed Lukman, P.Gowthaman, S.Anbazhagan, S.Karthika, K.Yuvarani, B.Sathya, S.A.Vadivel
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
AUTHORS WHO PUBLISH WITH THIS JOURNAL AGREE TO THE FOLLOWING TERMS:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
. 