Inflammatory diseases such as rheumatoid arthritis (RA) can lead to chronic pain and joint deformity. First line treatment includes disease-modifying antirheumatic drugs (DMARDs) to slow disease progression, but RA patients are often left with debilitating symptoms. This article explores alternative topical and naturally based options to treat RA symptoms, with supporting evidence for their use. Considered options include Aloe vera , Perillyl Alcohol (POH), Aleurites moluccana , Calendula officinalis extract (quercetin), Achyranthes species, Guizhi Shaoyao Zhimu, Curcumin (turmeric), Wutou, Radix paeoniae extract (Paeoniflorin), Tripterygium wilfordii Hook F (TWHF), Capsaicin, Cannabinoids (CBD), and Berberine. Many of these products show promising data for supplemental treatment of RA through various mechanisms, with CBD and TWHF having the most robust evidence supporting their use.
Centers for Disease Control and Prevention (2020, July 27) Rheumatoid Arthritis (RA). https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html
McInnes, I.B. and Schett, G. (2011) The Pathogenesis of Rheumatoid Arthritis. New England Journal of Medicine, 365, 2205-2219. https://doi.org/10.1056/NEJMra1004965
Bustamante, M.F., Garcia-Carbonell, R., Whisenant, K.D., et al. (2017) Fibroblast-Like Synoviocyte Metabolism in the Pathogenesis of Rheumatoid Arthritis. Arthritis Research & Therapy, 19, 110.
Bartok, B. and Firestein, G.S. (2010) Fibroblast-Like Synoviocytes: Key Effector Cells in Rheumatoid Arthritis. Immunological Reviews, 233, 233-255. https://doi.org/10.1111/j.0105-2896.2009.00859.x
Mayo Clinic (2021) Rheumatoid Arthritis Diagnosis and Treatment. https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/diagnosis-treatment/drc-20353653
Mayo Clinic (2017) Managing Arthritis Pain. https://www.mayoclinic.org/diseases-conditions/arthritis/in-depth/arthritis/art-20046440
Le Loet, X., et al. (2012) Objectifs therapeutiques dans la polyarthrite rheumatoid [Goals of Therapy in Rheumatoid Arthritis]. La Revue du Practician, 62, 1094-1098.
Balan, B.J., Niemcewicz, M., Kocik, J., Jung, L., Skopińska-Rózewska, E. and Skopiński, P. (2014) Oral Administration of Aloe Vera Gel, Anti-Microbial and Anti-Inflammatory Herbal Remedy, Stimulates Cell-Mediated Immunity and Antibody Production in a Mouse Model. Central European Journal of Immunology, 39, 125-130. https://doi.org/10.5114/ceji.2014.43711
Paul, S., Modak, D., Chattaraj, S., et al. (2021) Aloe Vera Gel Homogenate Shows Anti-Inflammatory Activity through Lysosomal Membrane Stabilization and Downregulation of TNF-α and Cox-2 Gene Expressions in Inflammatory Arthritic Animals. Future Journal of Pharmaceutical Sciences, 7, Article No. 12.
Puppala, E.R., Jain, S., Saha, P., et al. (2022) Perillyl Alcohol Attenuates Rheumatoid Arthritis via Regulating TLR4/NF-κB and Keap1/Nrf2 Signaling Pathways: A Comprehensive Study on In-Vitro and In-Vivo Experimental Models. Phytomedicine, 97, Article ID: 153926. https://doi.org/10.1016/j.phymed.2022.153926
Quintao, N.L., Meyre-Silva, C., Silva, G.F., et al. (2011) Aleurites moluccana (L.) Willd. Leaves: Mechanical Antinociceptive Properties of a Standardized Dried Extract and Its Chemical Markers. Evidence-Based Complementary and Alternative Medicine, 2011, Article ID: 179890.
Mendes Hoepers, S., Tolentino de Souza, H.G.M., Meira Quintao, N.L., et al. (2015) Topical Anti-Inflammatory Activity of Semisolid Containing Standardized Aleurites moluccana L. Willd (Euphorbiaceae) Leaves Extract. Journal of Ethnopharmacology, 173, 251-255. https://doi.org/10.1016/j.jep.2015.07.024
Preethi, K.C., Kuttan, G. and Kuttan, R. (2009) Anti-Inflammatory Activity of Flower Extract of Calendula officinalis Linn. and Its Possible Mechanism of Action. Indian Journal of Experimental Biology, 47, 113-120.
Jurca, T., Józsa, L., Suciu, R., Pallag, A., Marian, E., Bácskay, I., Muresan, M., Stan, R.L., Cevei, M., Cioara, F., Vicas, L. and Fehér, P. (2021) Formulation of Topical Dosage Forms Containing Synthetic and Natural Anti-Inflammatory Agents for the Treatment of Rheumatoid Arthritis. Molecules, 26, 24. https://doi.org/10.3390/molecules26010024
He, X., Wang, X., Fang, J., et al. (2017) The Genus Achyranthes: A Review on Traditional Uses, Phytochemistry, and Pharmacological Activities. Journal of Ethnopharmacology, 203, 260-278. https://doi.org/10.1016/j.jep.2017.03.035
Zhao, X., Kim, D., Suminda, G.G.D., Min, Y., Yang, J., Kim, M., Zhao, Y., Ghosh, M. and Son, Y.-O. (2021) Inhibitory Effects of IL-6-Mediated Matrix Metalloproteinase-3 and -13 by Achyranthes japonica Nakai Root in Osteoarthritis and Rheumatoid Arthritis Mice Models. Pharmaceuticals, 14, 776. https://doi.org/10.3390/ph14080776
Zheng, W., Lu, X., Fu, Z., et al. (2016) Identification of Candidate Synovial Membrane Biomarkers after Achyranthes aspera Treatment for Rheumatoid Arthritis. Biochimica et Biophysica Acta (BBA)—Proteins and Proteomics, 1864, 308-316. https://doi.org/10.1016/j.bbapap.2015.12.010
Feng, C., Chen, R., Wang, K., Wen, C. and Xu, Z. (2021) Chinese Traditional Medicine (Guizhi-Shaoyao-Zhimu Decoction) as an Add-On Medication to Methotrexate for Rheumatoid Arthritis: A Meta-Analysis of Randomized Clinical Trials. Therapeutic Advances in Chronic Disease, 12. https://doi.org/10.1177/2040622321993438
Zhang, Q., Peng, W., Wei, S., et al. (2019) Guizhi-Shaoyao-Zhimu Decoction Possesses Anti-Arthritic Effects on Type II Collagen-Induced Arthritis in Rats via Suppression of Inflammatory Reactions, Inhibition of Invasion & Migration and Induction of Apoptosis in Synovial Fibroblasts. Biomedicine & Pharmacotherapy, 118, Article ID: 109367. https://doi.org/10.1016/j.biopha.2019.109367
Vaughn, A.R., Branum, A. and Sivamani, R.K. (2016) Effects of Turmeric (Curcuma longa) on Skin Health: A Systematic Review of the Clinical Evidence. Phytotherapy Research, 30, 1243-1264.
Ba, X., Huang, Y., Shen, P., et al. (2021) WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/AKT/mTOR/HIF-1α Pathway. Frontiers in Pharmacology, 12, Article ID: 696802.
Wu, D., Li, X., Liu, J., Hu, C. and Li, J. (2021) Wutou Decoction Attenuates Rheumatoid Arthritis by Modulating the Ahr/LOC101928120/SHC1 Pathway. Pharmaceutical Biology, 59, 809-820. https://doi.org/10.1080/13880209.2021.1941131
Tu, J., Guo, Y., Hong, W., et al. (2019) The Regulatory Effects of Paeoniflorin and Its Derivative Paeoniflorin-6’-O-Benzene Sulfonate CP-25 on Inflammation and Immune Diseases. Frontiers in Pharmacology, 10, Article No. 57.
Zhang, L. and Wei, W. (2020) Anti-Inflammatory and Immunoregulatory Effects of Paeoniflorin and Total Glucosides of Paeony. Pharmacology & Therapeutics, 207, Article ID: 107452. https://doi.org/10.1016/j.pharmthera.2019.107452
Bao, J. and Dai, S.M. (2011) A Chinese Herb Tripterygium wilfordii Hook F in the Treatment of Rheumatoid Arthritis: Mechanism, Efficacy, and Safety. Rheumatology International, 31, 1123-1129. https://doi.org/10.1007/s00296-011-1841-y
Cibere, J., Deng, Z., Lin, Y., et al. (2003) A Randomized Double Blind, Placebo Controlled Trial of Topical Tripterygium wilfordii in Rheumatoid Arthritis: Reanalysis Using Logistic Regression Analysis. The Journal of Rheumatology, 30, 465-467.
Jiao, J., Tang, X., Gong, X., Yin, H., Jiang, Q. and Wei, C. (2019) Effect of Cream, Prepared with Tripterygium wilfordii Hook F and Other Four Medicinals, on Joint Pain and Swelling in Patients with Rheumatoid Arthritis: A Double-Blinded, Randomized, Placebo Controlled Clinical Trial. Journal of Traditional Chinese Medicine, 39, 89-96.
Jiao, J., Tang, X.P., Yuan, J., Liu, X., Liu, H., Zhang, C.Y., Wang, L.Y. and Jiang, Q. (2016) Effect of External Applying Compound Tripterygium wilfordii Hook F. on Joint Pain of Rheumatoid Arthritis Patients. Chinese Journal of Integrated Traditional and Western Medicine, 36, 29-34.
Derry, S., Rice, A.S., Cole, P., Tan, T. and Moore, R.A. (2017) Topical Capsaicin (High Concentration) for Chronic Neuropathic Pain in Adults. Cochrane Database of Systematic Reviews, No. 1, CD007393.
Deal, C.L., Schnitzer, T.J., Lipstein, E., et al. (1991) Treatment of Arthritis with Topical Capsaicin: A Double-Blind Trial. Clinical Therapeutics, 13, 383-395.
Derry, S., Wiffen, P.J., Kalso, E.A., et al. (2017) Topical Analgesics for Acute and Chronic Pain in Adults—An Overview of Cochrane Reviews. Cochrane Database of Systematic Reviews, No. 5, CD008609.
Richards, B.L., Whittle, S.L. and Buchbinder, R. (2012) Neuromodulators for Pain Management in Rheumatoid Arthritis. Cochrane Database of Systematic Reviews, No. 1, CD008921.
Lowin, T., Tingting, R., Zurmahr, J., et al. (2020) Cannabidiol (CBD): A Killer for Inflammatory Rheumatoid Arthritis Synovial Fibroblasts. Cell Death & Disease, 11, 714.
Hammell, D.C., Zhang, L.P., Ma, F., et al. (2015) Transdermal Cannabidiol Reduces Inflammation and Pain-Related Behaviours in a Rat Model of Arthritis. European Journal of Pain, 20, 936-948. https://doi.org/10.1002/ejp.818
Mohammadzadeh, N., Mehri, S. and Hosseinzadeh, H. (2017) Berberis vulgaris and Its Constituent Berberine as Antidotes and Protective Agents against Natural or Chemical Toxicities. Iranian Journal of Basic Medical Sciences, 20, 538-551.
Shen, P., Jiao, Y., Miao, L., Chen, J. and Momtazi-Borojeni, A.A. (2020) Immunomodulatory Effects of Berberine on the Inflamed Joint Reveal New Therapeutic Targets for Rheumatoid Arthritis Management. Journal of Cellular and Molecular Medicine, 24, 12234-12245. https://doi.org/10.1111/jcmm.15803
Wang, X., Jiang, S. and Sun, Q. (2011) Effects of Berberine on Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes. Experimental Biology and Medicine, 236, 859-866. https://doi.org/10.1258/ebm.2011.010366
Elkomy, M.H., Alruwaili, N.K., Elmowafy, M., et al. (2022) Surface-Modified Bilosomes Nanogel Bearing a Natural Plant Alkaloid for Safe Management of Rheumatoid Arthritis Inflammation. Pharmaceutics, 14, 563. https://doi.org/10.3390/pharmaceutics14030563