Role of Natural Products in Combatting Rheumatoid Arthritis: Phytochemical Strategies and Antioxidant Defences
Authors
-
Department of Pharmacognosy, Sarojini Naidu Vanita Pharmacy Maha Vidyalaya, Secunderabad – 500017, Telangana ,IN
Leemol Varghese -
Department of Pharmacognosy, Dayananda Sagar University, Bangalore – 560068, Karnataka ,INShanaz Banu
DOI:
https://doi.org/10.18311/jnr/2024/44250Keywords:
Anti-inflammatory, Antioxidant, NF-κB, Phytocompounds, Rheumatoid ArthritisAbstract
Rheumatoid Arthritis (RA) is a persistent inflammatory autoimmune illness that damages bones by causing joint discomfort, edema, and stiffness. In RA, inflammatory cell infiltration and synovial hyperplasia lead to the generation of proinflammatory cytokines like TNF-α and IL-1. To find phytochemical substances utilised in RA treatment, SciELO, Virtual Health Library, and PubMed databases were searched for rheumatoid arthritis, herbal remedies, and medicinal plants. One of the predominant transcription factors is NF-κB, in regulating inflammatory response. Translocation of active NF-κB into the nucleus leads to gene transcription that produces proinflammatory cytokines. Oxidative stress changes transcription factors, which affects inflammatory gene expression. Phytochemicals have treated various diseases, blocking NF-κB translocation mitigates proinflammatory cascade activation (Withanolides, Gugglosterone, Epigallocatechin-3-gallate, O-glucosylcimifugin, Andrographolide, Curcuminoids, and Resveratrol), Flavonoids (Quercetin, Hesperidin, Kaempferol, Liquirin). Their therapeutic potential aids in creating safe and effective medicines for NF-κB-driven immune-inflammatory disorders like RA. This study emphasises the involvement of NF-κB in a series of events of inflammation, highlighting the role of phytochemicals in regulating its activity. It also discusses the effectiveness of polyphenols in relieving RA by blocking the signalling pathways and suggests a further study to support their usage.
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Copyright (c) 2024 Leemol Varghese, Shanaz Banu (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Accepted 2024-08-12
Published 2024-10-07
References
Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016; 388:2023-38. https://doi.org/10.1016/S01406736(16)30173-8 PMid:27156434
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011; 365(23):2205-19. https://doi.org/10.1056/NEJMra1004965 PMid:22150039
Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci. 2019; 20(23):6008. PMid:31795299 PMCid:PMC6929211
Zhao X, Kim YR, Min Y, Zhao Y, Do K, Son YO. Natural plant extracts and compounds for rheumatoid arthritis therapy. Medicina (Kaunas). 2021; 57(3):266. https://doi.org/0.3390/ medicina57030266 PMid:33803959 PMCid:PMC8001474
Behl T, Upadhyay T, Singh S, Chigurupati S, Alsubayiel AM, Mani V, et al. Polyphenols targeting MAPK mediated oxidative stress and inflammation in Rheumatoid Arthritis. Molecules. 2021; 26(21):6570. https://doi.org/10.3390/ molecules26216570 PMid:34770980 PMCid:PMC8588006
Arulselvan P, Fard MT, Tan WS, Gothai S, Fakurazi S, Norhaizan ME, et al. Role of antioxidants and natural products in inflammation. Oxid Med Cell Longev. 2016; 2016:5276130. https://doi.org/10.1155/2016/5276130 PMid:27803762 PMCid:PMC5075620
Roman-Blas JA, Jimenez SA. NF-κB as a potential therapeutic target in osteoarthritis and Rheumatoid Arthritis. Osteoarthr Cartil. 2006; 14:839-48. https://doi.org/10.1016/j.joca.2006.04.008 PMid:16730463
Makarov SS. NF-κB in Rheumatoid Arthritis: A pivotal regulator of inflammation, hyperplasia, and tissue destruction. Arthritis Res. 2001; 3:200-6. https://doi.org/10.1186/ar300 PMid:11438035 PMCid:PMC128895
Aravilli RK, Vikram SL, Kohila V. Phytochemicals as potential antidotes for targeting NF-κB in rheumatoid arthritis. 3 Biotech. 2017; 7(4):253. https://doi.org/10.1007/ s13205-017-0888-1 PMid:28721679 PMCid:PMC5515733
Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): A review. Altern Med Rev. 2000; 5:334-46.
SoRelle JA, Itoh T, Peng H, Kanak MA, Sugimoto K, Matsumoto S, Levy MF, Lawrence MC, Naziruddin B. Withaferin A inhibits pro-inflammatory cytokine-induced damage to islets in culture and following transplantation. Diabetologia. 2013; 56:814-24. https://doi.org/10.1007/ s00125-012-2813-9 PMid:23318585
Grover A, Shandilya A, Punetha A, Bisaria VS, Sundar D. Inhibition of the NEMO/IKKβ association complex formation, a novel mechanism associated with the NFκB activation suppression by Withania somnifera’s key metabolite withaferin A. BMC Genom. 2010; 11:1-11. https://doi.org/10.1186/1471-2164-11-1 PMid:21143809 PMCid:PMC3005936
Bao J, Dai SM. A Chinese herb Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis: Mechanism, efficacy, and safety. Rheumatol Int. 2011; 31:1123-9. https:// doi.org/10.1007/s00296-011-1841-y PMid:21365177
Matta R, Wang X, Ge H, Ray W, Nelin LD, Liu Y. Triptolide induces anti-inflammatory cellular responses. Am J Transl Res. 2009; 1:267-82.
Xiao D, Singh SV. z-Guggulsterone, a constituent of ayurvedic medicinal plant Commiphora mukul, inhibits angiogenesis in vitro and in vivo. Mol Cancer Ther. 2008; 7:171-80. https://doi.org/10.1158/1535-7163.MCT-07-0491 PMid:18202020
Patel SS, Shah PV. Evaluation of anti-inflammatory potential of the multidrug herbomineral formulation in male Wistar rats against rheumatoid arthritis. J Ayurveda Integr Med. 2013; 4:86-93. https://doi.org/10.4103/0975-9476.113869 PMid:23930040 PMCid:PMC3737452
Shishodia S, Aggarwal BB. Guggulsterone inhibits NF-κB and IκB Kinase activation, suppresses expression of antiapoptotic gene products, and enhances apoptosis. J Biol Chem. 2004; 279:47148-58. https://doi.org/10.1074/jbc.M408093200 PMid:15322087
Wu PH, Lin SK, Lee BS, Kok SH, Wang JH, Hou KL, et al. Epigallocatechin-3-gallate diminishes cytokine-stimulated Cyr61 expression in human osteoblastic cells: A therapeutic potential for arthritis. Rheumatol. 2012; 51:1953-65. https:// doi.org/10.1093/rheumatology/kes174 PMid:22843790
Bork PM, Schmitz ML, Kuhnt M, Escher C, Heinrich M. Sesquiterpene lactone containing Mexican Indian medicinal plants and pure sesquiterpene lactones as potent inhibitors of transcription factor NF-κB. FEBS Lett. 1997; 402:85-90. https://doi.org/10.1016/S0014-5793(96)01502-5 PMid:9013864
Hehner SP, Heinrich M, Bork PM, Vogt M, Ratter F, Lehmann V, et al. Sesquiterpene lactones specifically inhibit activation of NF-κB by preventing the degradation of IκB-α and IκB-β. J Biol Chem. 1998; 273:1288-97. https://doi.org/10.1074/jbc.273.3.1288 PMid:9430659
Burgos RA, Hancke JL, Bertoglio JC, Aguirre V, Arriagada S, Calvo M, et al. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: A prospective randomised placebo-controlled trial. Clin Rheumatol. 2009; 28:931-46. https://doi.org/10.1007/ s10067-009-1180-5 PMid:19408036
Basnet P, Skalko-Basnet N. Curcumin: An anti-inflammatory molecule from a curry spice on the path to cancer treatment. Molecules. 2011; 16:4567-98. https://doi.org/10.3390/ molecules16064567 PMid:21642934 PMCid:PMC6264403
Sharma RA, Gescher AJ, Steward WP. Curcumin: The story so far. Eur J Cancer. 2005; 41:1955-68. https://doi.org/10.1016/j.ejca.2005.05.009 PMid:16081279
Funk JL, Oyarzo JN, Frye JB, Chen G, Clark R, Jolad SD, et al. Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis. J Nat Prod. 2008; 69:3515. https://doi.org/10.1021/np050327j PMid:16562833 PMCid:PMC2533857
Shakibaei M, Csaki C, Nebrich S, Mobasheri A. Resveratrol suppresses interleukin-1β-induced inflammatory signaling and apoptosis in human articular chondrocytes: Potential for use as a novel nutraceutical for the treatment of osteoarthritis. Biochem Pharmacol. 2008; 76:1426-39. https://doi.org/10.1016/j.bcp.2008.05.029 PMid:18606398
Csaki C, Keshishzadeh N, Fischer K, Shakibei M. Regulation of inflammation signaling by resveratrol in human chondrocytes in vitro. Biochem Pharmacol. 2008; 75:677-87. https://doi.org/10.1016/j.bcp.2007.09.014 PMid:17959154
Zhu X, Liu Q, Wang M, Liang M, Yang X, Xu X, et al. Activation of Sirt1 by resveratrol inhibits TNF-α induced inflammation in fibroblasts. PLoS One. 2011; 6:11. https:// doi.org/10.1371/annotation/60addd69-bd2d-4ecf-83696a5a1bf2cd04 PMid:22069489 PMCid:PMC3206084
Oliviero F, Scanu A, Zamudio-Cuevas Y, Punzi L. Antiinflammatory effects of polyphenols in arthritis. J Sci Food Agric. 2018; 98(5):1653-9. https://doi.org/10.1002/jsfa.8664 PMid:28886220
Ansari MY, Ahmad N, Haqqi TM. Butein activates autophagy through AMPK/TSC2/ULK1/mTOR pathway to inhibit IL-6 expression in IL-1β stimulated human chondrocytes. Cell Physiol Biochem. 2018; 49:932-46. https://doi.org/10.1159/000493225 PMid:30184535
Ansari MY, Khan NM, Haqqi TM. A standardized extract of Butea monosperma (Lam.) flowers suppresses the IL-1βinduced expression of IL-6 and matrix-metalloproteases by activating autophagy in human osteoarthritis chondrocytes. Biomed Pharmacother. 2017; 96:198-207. https://doi.org/10.1016/j.biopha.2017.09.140 PMid:28987943
De Villiers A, Venter P, Pasch H. Recent advances and trends in the liquid-chromatography-mass spectrometry analysis of flavonoids. J Chromatogr A. 2015; 1430:16-78. https://doi.org/10.1016/j.chroma.2015.11.077 PMid:26718188
Jackson JK, Higo T, Hunter WL, Burt HM. The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis. Inflamm Res. 2006; 55(4):168–75. https://doi.org/10.1007/s00011-006-0067-z PMid:16807698
Burda S, Oleszek W. Antioxidant and antiradical activities of flavonoids. J Agric Food Chem. 2001; 49(6):2774-9. https://doi.org/10.1021/jf001413m PMid:11409965
Cao G, Sofic E, Prior RL. Antioxidant and prooxidant behavior of flavonoids: Structure-activity relationships. Free Radic Biol Med. 1997; 22(5):749-60. https://doi.org/10.1016/S0891-5849(96)00351-6 PMid:9119242
Yang Y, Zhang X, Xu M, Wu X, Zhao F, Zhao C. Quercetin attenuates collagen-induced arthritis by restoration of Th17/ Treg balance and activation of Heme Oxygenase 1-mediated anti-inflammatory effect. Int Immunopharmacol. 2018; 54:153-62. https://doi.org/10.1016/j.intimp.2017.11.013 PMid:29149703
Ahmad S, Alam K, Hossain MM, Fatima M, Firdaus F, Zafeer MF, et al. Anti-arthritogenic and cardioprotective action of hesperidin and daidzein in collagen-induced Rheumatoid Arthritis. Mol Cell Biochem. 2016; 423(1-2):115-27. https://doi.org/10.1007/s11010-016-2830-y PMid:27704466
Dinda B, Dinda S, DasSharma S, Banik R, Chakraborty A, Dinda M. Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. Eur J Med Chem. 2017; 131:68-80.https://doi.org/10.1016/j.ejmech.2017.03.004 PMid:28288320
Jiang CP, He X, Yang XL, Zhang SL, Li H, Song ZJ, et al. Anti-rheumatoid arthritic activity of flavonoids from Daphne genkwa. Phytomedicine. 2014; 21(6):830-7. https://doi.org/10.1016/j.phymed.2014.01.009 PMid:24561028
Zhai KF, Duan H, Cui CY, Cao YY, Si JL, Yang HJ, et al. Liquiritin from Glycyrrhiza uralensis attenuating rheumatoid arthritis via reducing inflammation, suppressing angiogenesis, and inhibiting MAPK signaling pathway. J Agric Food Chem. 2019; 67(10):2856-64. https://doi.org/10.1021/acs.jafc.9b00185 PMid:30785275
Wang Y, Gao J, Xing LZ. Therapeutic potential of Oroxylin A in rheumatoid arthritis. Int Immuno Pharmacol. 2016; 40:294-9. https://doi.org/10.1016/j.intimp.2016.09.006 PMid:27643663
Lee CJ, Moon SJ, Jeong JH, Lee S, Lee MH, Yoo SM, et al. Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis. Cell Death Dis. 2018; 9(3). https://doi.org/10.1038/s41419-018-0433-0 PMid:29540697 PMCid:PMC5851988
Pan D, Li N, Liu Y, Xu Q, Liu Q, You Y, et al. Kaempferol inhibits the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes by blocking activation of the MAPK pathway. Int Immuno Pharmacol. 2018; 55:174-82. https://doi.org/10.1016/j.intimp.2017.12.011 PMid:29268189
Zhang Y, Wang G, Wang T Cao W, Zhang L, Chen X. Nrf2–Keap1 pathway–mediated effects of resveratrol on oxidative stress and apoptosis in hydrogen peroxide–treated rheumatoid arthritis fibroblast-like synoviocytes. Ann N Y Acad Sci. 2019; 1457:166-78. https://doi.org/10.1111/nyas.14196 PMid:31475364
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