Therapeutic potential of bioconstituents in the prevention and treatment of rheumatoid arthritis

Srishti Morris; Yashashvi Srivastava; Kartikey Kumar; Vikash Jakhmola

doi:10.69857/joapr.v13i3.847

Authors

Srishti Morris Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Premnagar, Dehradun, Uttarakhand 248007, India
Yashashvi Srivastava Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Premnagar, Dehradun, Uttarakhand 248007, India
Kartikey Kumar Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Premnagar, Dehradun, Uttarakhand 248007, India
Vikash Jakhmola Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Premnagar, Dehradun, Uttarakhand 248007, India

DOI:

https://doi.org/10.69857/joapr.v13i3.847

Keywords:

Alkaloids, Autoimmune Diseases, Rheumatoid Arthritis, Herbal Medicine, Flavonoids, Quercetin, Tannins

Abstract

Background: Rheumatoid arthritis (RA), a joint disease characterized by inflammation and an autoimmune response, affects approximately 1% of the global population. The disruption of immunological tolerance causes the immune system to attack self-molecules, resulting in autoimmune disease. RA is characterized by synovial swelling, accompanied by morning stiffness and joint soreness. Methodology: Herbal pharmacotherapy is now a meaningful focus in the treatment of rheumatoid arthritis. Medicinal plants contain strong active components like flavonoids, alkaloids, stilbenoids, tannins, and sesquiterpene lactones. Their anti-inflammatory and antioxidant qualities make them a potential treatment option for RA. Results and Discussion: Standard medication aims to prevent further deterioration of the affected joint. This treatment includes several antirheumatic medications, such as methotrexate, biological agents, cytotoxic drugs, immunosuppressants, and NSAIDs. Urinary and respiratory tract infections have been reported in patients treated with certolizumab pegol. Several concerns regarding anti-rheumatoid medication arise during a woman's pregnancy. Therefore, rheumatoid arthritis is now being effectively treated with herbal pharmacotherapy. Conclusion: RA is a chronic autoimmune disorder that primarily affects joints through persistent inflammation. Conventional treatment regimens for RA can lead to the occurrence of adverse effects, such as urinary and respiratory tract infections. Given these challenges, herbal pharmacotherapy is emerging as a safer and more sustainable approach. This review highlights a variety of phytochemicals with anti-inflammatory and antiarthritic properties, including flavonoids, alkaloids, stilbenoids, tannins, and sesquiterpene lactones. It underscores the need for further research to elucidate their mechanisms of action, assess their long-term safety and clinical utility, and compare their efficacy.

Downloads

Download data is not yet available.

Author Biography

Yashashvi Srivastava, Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Premnagar, Dehradun, Uttarakhand 248007, India

Student

References

Smith DA, Germolec DR. Introduction to immunology and autoimmunity. Environ Health Perspect, 107(Suppl 5), 661–665 (1999) https://doi.org/10.1289/ehp.99107s5661

Jacobson DL, Gange SJ, Rose NR, Graham NM. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol, 84(3), 223–243 (1997) https://doi.org/10.1006/clin.1997.4412

Conforti A, Di Cola I, Pavlych V, Ruscitti P, Berardicurti O, Ursini F, Giacomelli R, Cipriani P. Beyond the joints, the extra-articular manifestations in rheumatoid arthritis. Autoimmun Rev, 20(2), 102735 (2021) https://doi.org/10.1016/j.autrev.2020.102735

Kaur C, Mishra Y, Kumar R, Singh G, Singh S, Mishra V, Tambuwala MM. Pathophysiology, diagnosis, and herbal medicine-based therapeutic implication of rheumatoid arthritis: an overview. Inflammopharmacology, 32(3), 1705–1720 (2024) https://doi.org/10.1007/s10787-024-01445-8

Chandrasekar R, Chandrasekar S. Natural herbal treatment for rheumatoid arthritis – a review. Int J Pharm Sci Res, 8(2), 368–384 (2017) http://dx.doi.org/10.13040/IJPSR.0975-8232.8(2).368-84

Rahman M, Beg S, Verma A, Al Abbasi FA, Anwar F, Saini S, Akhter S, Kumar V. Phytoconstituents as pharmacotherapeutics in rheumatoid arthritis: challenges and scope of nano/submicromedicine in its effective delivery. J Pharm Pharmacol, 69(1), 1–4 (2017) https://doi.org/10.1111/jphp.12661

Singh S, Singh TG, Mahajan K, Dhiman S. Medicinal plants used against various inflammatory biomarkers for the management of rheumatoid arthritis. J Pharm Pharmacol, 72(10), 1306–1327 (2020) https://doi.org/10.1111/jphp.13326

Marcucci E, Bartoloni E, Alunno A, Leone MC, Cafaro G, Luccioli F, Valentini V, Valentini E, La Paglia GM, Bonifacio AF, Gerli R. Extra-articular rheumatoid arthritis. Reumatismo, 70(4), 212–224 (2018) https://doi.org/10.4081/reumatismo.2018.1106

Rahman M, Beg S, Sharma G, Anwar F, Kumar V. Emergence of lipid-based vesicular carriers as nanoscale pharmacotherapy in rheumatoid arthritis. Recent Pat Nanomed, 5(2), 111–121 (2015) https://doi.org/10.2174/1877912305666150616215800

Gupta M. Natural products in treatment of rheumatoid arthritis. Int J Green Pharm, 11(3), (2017) https://doi.org/10.22377/ijgp.v11i03.1142

Batko B, Korkosz M, Juś A, Wiland P. Management of rheumatoid arthritis in Poland – where daily practice might not always meet evidence-based guidelines. Arch Med Sci, 17(5), 1286 (2019) https://doi.org/10.5114/aoms.2019.84092

Köhler BM, Günther J, Kaudewitz D, Lorenz HM. Current therapeutic options in the treatment of rheumatoid arthritis. J Clin Med, 8(7), 938 (2019) https://doi.org/10.3390/jcm8070938

Romão VC, Fonseca JE. Etiology and risk factors for rheumatoid arthritis: a state-of-the-art review. Front Med (Lausanne), 8, 689698 (2021) https://doi.org/10.3389/fmed.2021.689698

Radu AF, Bungau SG. Management of rheumatoid arthritis: an overview. Cells, 10, 2857 (2021) https://doi.org/10.3390/cells10112857

Firestein GS, McInnes IB. Immunopathogenesis of rheumatoid arthritis. Immunity, 46(2), 183–196 (2017) https://doi.org/10.1016/j.immuni.2017.02.006

Rahman M, Sharma G, Thakur K, Anwar F, Katare OP, Goni VG, Kumar V, Zamzami MA, Akhter S. Emerging advances in nanomedicine as a nanoscale pharmacotherapy in rheumatoid arthritis: state of the art. Curr Top Med Chem, 17(2), 162–173 (2017) https://doi.org/10.2174/1568026616666160530152354

Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P, Kvien TK, Navarro-Compán MV, Oliver S, Schoels M, Scholte-Voshaar M. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis, 75(1), 3–15 (2016) https://doi.org/10.1136/annrheumdis-2015-207524

Wang Y, Chen S, Du K, Liang C, Wang S, Boadi EO, Li J, Pang X, He J, Chang YX. Traditional herbal medicine: therapeutic potential in rheumatoid arthritis. J Ethnopharmacol, 279, 114368 (2021) https://doi.org/10.1016/j.jep.2021.114368

Smolen JS, van Vollenhoven R, Kavanaugh A, Strand V, Vencovsky J, Schiff M, Landewé R, Haraoui B, Arendt C, Mountian I, Carter D. Certolizumab pegol plus methotrexate: 5-year results from the rheumatoid arthritis prevention of structural damage (RAPID) 2 randomized controlled trial and long-term extension in rheumatoid arthritis patients. Arthritis Res Ther, 17, 1–5 (2015) https://doi.org/10.1186/s13075-015-0767-2

Ding Q, Hu W, Wang R, Yang Q, Zhu M, Li M, Cai J, Rose P, Mao J, Zhu YZ. Signaling pathways in rheumatoid arthritis: implications for targeted therapy. Signal Transduct Target Ther, 8(1), 68 (2023) https://doi.org/10.1038/s41392-023-01331-9

Choudhary M, Kumar V, Malhotra H, Singh S. Medicinal plants with potential anti-arthritic activity. J Intercult Ethnopharmacol, 4(2), 147 (2015) https://doi.org/10.5455/jice.20150313021918

Nimesh S. Herbal drug is better than allopathic drug in the treatment of rheumatoid arthritis. Int J Pharmacogn, 5(9), 539–545 (2018) http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.5(9).539-45

Zhao S, Otieno F, Akpan A, Moots RJ. Complementary and alternative medicine use in rheumatoid arthritis: considerations for the pharmacological management of elderly patients. Drugs Aging, 34, 255–264 (2017) https://doi.org/10.1007/s40266-017-0443-0

Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Sci World J, 2013(1), 162750 (2013) https://doi.org/10.1155/2013/162750

Mutha RE, Tatiya AU, Surana SJ. Flavonoids as natural phenolic compounds and their role in therapeutics: an overview. Future J Pharm Sci, 7, 1–3 (2021) https://doi.org/10.1186/s43094-020-00161-8

Rakha A, Umar N, Rabail R, Butt MS, Kieliszek M, Hassoun A, Aadil RM. Anti-inflammatory and anti-allergic potential of dietary flavonoids: a review. Biomed Pharmacother, 156, 113945 (2022) https://doi.org/10.1016/j.biopha.2022.113945

Khan J, Deb PK, Priya S, Medina KD, Devi R, Walode SG, Rudrapal M. Dietary flavonoids: cardioprotective potential with antioxidant effects and their pharmacokinetic, toxicological and therapeutic concerns. Molecules, 26(13), 4021 (2021) https://doi.org/10.3390/molecules26134021

Adeyemo-Salami OA, Choudhary MI. Cytotoxic, antibacterial, and leishmanicidal activities of Paullinia pinnata (Linn.) leaves. Avicenna J Med Biochem, 9(2), 88–92 (2021) https://doi.org/10.34172/ajmb.2021.08

Tseuguem PP, Nguelefack TB, Piégang BN, Mbankou Ngassam S. Aqueous and methanol extracts of Paullinia pinnata (Sapindaceae) improve monosodium urate‐induced gouty arthritis in rats: analgesic, anti‐inflammatory, and antioxidant effects. Evid Based Complement Alternat Med, 2019(1), 5946291 (2019) https://doi.org/10.1155/2019/5946291

Vyas S, Kothari SL, Kachhwaha S. Nootropic medicinal plants: therapeutic alternatives for Alzheimer’s disease. J Herb Med, 17, 100291 (2019) https://doi.org/10.1016/j.hermed.2019.100291

Rosas EC, Correa LB, de Almeida Pádua T, Costa TE, Mazzei JL, Heringer AP, Bizarro CA, Kaplan MA, Figueiredo MR, Henriques MG. Anti-inflammatory effect of Schinus terebinthifolius Raddi hydroalcoholic extract on neutrophil migration in zymosan-induced arthritis. J Ethnopharmacol, 175, 490–498 (2015) https://doi.org/10.1016/j.jep.2015.10.014

Deligiannidou GE, Gougoula V, Bezirtzoglou E, Kontogiorgis C, Constantinides TK. The role of natural products in rheumatoid arthritis: current knowledge of basic in vitro and in vivo research. Antioxidants, 10(4), 599 (2021) https://doi.org/10.3390/antiox10040599

Karati D, Varghese R, Mahadik KR, Sharma R, Kumar D. Plant bioactives in the treatment of inflammation of skeletal muscles: a molecular perspective. Evid Based Complement Alternat Med, 2022(1), 4295802 (2022) https://doi.org/10.1155/2022/4295802

Navarro M, Arnaez E, Moreira I, Hurtado A, Monge D, Monagas M. Polyphenolic composition and antioxidant activity of Uncaria tomentosa commercial bark products. Antioxidants, 8(9), 339 (2019) https://doi.org/10.3390/antiox8090339

Sordi R, Castro SN, Lera AT, Irene MN, Farinazzo MD, Sette C, Cubero DD, Baccarin AD, Del Giglio A. Randomized, double-blind, placebo-controlled phase II clinical trial on the use of Uncaria tomentosa (Cat's claw) for aromatase inhibitor-induced arthralgia: a pilot study. J Nat Remedies, 19(1), 24–31 (2019) https://doi.org/10.18311/jnr/2019/22867

Dvorakova M, Landa P. Anti-inflammatory activity of natural stilbenoids: a review. Pharmacol Res, 124, 126–145 (2017) https://doi.org/10.1016/j.phrs.2017.08.002

Hasan MK, Zanzabil KZ, Ara I, Rahman T, Kieu A, Östlundh L, Junaidi S, Khan MA. Herbal therapies for pain management: a scoping review of the current evidence. Phytochem Rev, (2024), 1–52 https://doi.org/10.1007/s11101-024-09916-0

Matos MS, Anastácio JD, Nunes dos Santos C. Sesquiterpene lactones: promising natural compounds to fight inflammation. Pharmaceutics, 13(7), 991 (2021) https://doi.org/10.3390/pharmaceutics13070991

Paço A, Brás T, Santos JO, Sampaio P, Gomes AC, Duarte MF. Anti-inflammatory and immunoregulatory action of sesquiterpene lactones. Molecules, 27(3), 1142 (2022) https://doi.org/10.3390/molecules27031142

Gao S, Wang Q, Tian XH, Li HL, Shen YH, Xu XK, Wu GZ, Hu ZL, Zhang WD. Total sesquiterpene lactones prepared from Inula helenium L. has potentials in prevention and therapy of rheumatoid arthritis. J Ethnopharmacol, 196, 39–46 (2017) https://doi.org/10.1016/j.jep.2016.12.020

Pillai MK, Thebe P, Matamane RE. Antioxidant activity of extracts from Xanthium strumarium–a medicinal plant from the Kingdom of Lesotho. Int J Plant Based Pharm, 3(1), 114–122 (2023) https://doi.org/10.29228/ijpbp.23

Och A, Podgórski R, Nowak R. Biological activity of berberine—A summary update. Toxins (Basel), 12(11), 713 (2020) https://doi.org/10.3390/toxins12110713

Uttra AM, Shahzad M, Shabbir A, Jahan S, Bukhari IA, Assiri AM. Ribes orientale: a novel therapeutic approach targeting rheumatoid arthritis with reference to pro-inflammatory cytokines, inflammatory enzymes and anti-inflammatory cytokines. J Ethnopharmacol, 237, 92–107 (2019) https://doi.org/10.1016/j.jep.2019.03.019

Talib WH, Mahasneh AM. Antimicrobial, cytotoxicity and phytochemical screening of Jordanian plants used in traditional medicine. Molecules, 15(3), 1811–1824 (2010) https://doi.org/10.3390/molecules15031811

Sharma D, Chaubey P, Suvarna V. Role of natural products in alleviation of rheumatoid arthritis—A review. J Food Biochem, 45(4), e13673 (2021) https://doi.org/10.1111/jfbc.13673

Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, Liu H, Yin Y. Quercetin, inflammation and immunity. Nutrients, 8(3), 167 (2016) https://doi.org/10.3390/nu8030167

Majid M, Nasir B, Zahra SS, Khan MR, Mirza B, Haq IU. Ipomoea batatas L. Lam. ameliorates acute and chronic inflammations by suppressing inflammatory mediators, a comprehensive exploration using in vitro and in vivo models. BMC Complement Altern Med, 18, 1–20 (2018) https://doi.org/10.1186/s12906-018-2279-5

Malek Mahdavi A, Seyedsadjadi N, Javadivala Z. Potential effects of pomegranate (Punicagranatum) on rheumatoid arthritis: A systematic review. Int J Clin Pract, 00, e13999 (2021) https://doi.org/10.1111/ijcp.13999

Malik EM, Müller CE. Anthraquinones as pharmacological tools and drugs. Med Res Rev, 36(4), 705–748 (2016) https://doi.org/10.1002/med.21391

Jalindar JV, Ashok NS, Prafulla JT, Shendge DS. Review on Aloe vera plant and its medicinal applications. World J Pharm Res, 11(4), 815–831 (2022) https://doi.org/10.20959/wjpr20224-23632

Baheti AM, Pawar AT, Upaganlawar A. Herbal formulations useful in the treatment of rheumatoid arthritis. Nat Prod Manag Arthritic Disord, 5, 164 (2022) https://doi.org/10.2174/97898150507761220101

Budai MM, Varga A, Milesz S, Tőzsér J, Benkő S. Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages. Mol Immunol, 56(4), 471–479 (2013) https://doi.org/10.1016/j.molimm.2013.05.005

Kshirsagar AD, Panchal PV, Harle UN, Nanda RK, Shaikh HM. Anti‐inflammatory and antiarthritic activity of anthraquinone derivatives in rodents. Int J Inflamm, 2014(1), 690596 (2014) https://doi.org/10.1155/2014/690596

Yagi A, Yu BP. Prophylactic aloe components on autoimmune diseases: barbaloin, aloe emodin, emodin, and fermented butyrate. J Gastroenterol Hepatol Res, 7(2), 2535–2541 (2018) https://doi.org/10.17554/j.issn.2224-3992.2018.07.762

Wang SC, Chou IW, Hung MC. Natural tannins as anti-SARS-CoV-2 compounds. Int J Biol Sci, 18(12), 4669–4678 (2022) https://doi.org/10.7150/ijbs.74676

Fraga Corral M, Otero P, Cassani L, Echave J, Garcia Oliveira P, Carpena M, et al. Traditional applications of tannin rich extracts supported by scientific data: Chemical composition, bioavailability and bioaccessibility. Foods, 10(2), 251 (2021) https://doi.org/10.3390/foods10020251

Zhao K, Huang Z, Lu H, Zhou J, Wei T. Induction of inducible nitric oxide synthase increases the production of reactive oxygen species in RAW264.7 macrophages. Biosci Rep, 30(4), 233–241 (2010) https://doi.org/10.1042/BSR20090048

Yeo J, Lee J, Yoon S, Kim WJ. Tannic acid-based nanogel as an efficient anti-inflammatory agent. Biomater Sci, 8(4), 1148–1159 (2020) https://doi.org/10.1039/c9bm01384a

Sultan MT, Anwar MJ, Imran M, Khalil I, Saeed F, Neelum S, et al. Phytochemical profile and pro-healthy properties of Terminalia chebula: A comprehensive review. Int J Food Prop, 26(1), 526–551 (2023) https://doi.org/10.1080/10942912.2023.2166951

Dhikale R, Gulecha V, Zalte A. Protective effects of Lantana camara (aculeata) in rheumatoid arthritis using in vitro and in vivo Complete Freund’s Adjuvant induced arthritis in rats. J Health Sci, 9(4), 123–125 (2022) https://doi.org/10.21276/apjhs.2022.9.4.25

Bergman ME, Davis B, Phillips MA. Medically useful plant terpenoids: biosynthesis, occurrence, and mechanism of action. Molecules, 24(21), 3961–3983 (2019) https://doi.org/10.3390/molecules24213961

Tan SC, Bhattamisra SK, Chellappan DK, Candasamy M. Actions and therapeutic potential of madecassoside and other major constituents of Centella asiatica: a review. Appl Sci, 11(18), 8475 (2021) https://doi.org/10.3390/app11188475