Phytochemical add-on therapy to DMARDs therapy in rheumatoid arthritis: In vitro and in vivo bases, clinical evidence and future trends. (July 2021)

• Record Type: Journal Article
• Authors: Kour, Gurleen; Haq, Syed Assim; Bajaj, Bijender Kumar; Gupta, Prem N.; Ahmed, Zabeer
• Is Part Of: Pharmacological research. Volume 169(2021)
• Publication Date: 2021-07
• Subjects: ADH Andrographolide -- ACR American College of Rheumatology -- AIA Adjuvant induced arthritis -- ALP Alkaline phosphatase -- ALT Alanine aminotransferase -- AST Aspartate aminotransferase -- AUC Area under the curve -- BCRP breast cancer resistance protein -- CAT Catalase -- CCl4 Carbon tetrachloride -- CGA Chlorogenic acid -- CIA Collagen induced arthritis -- CoQ10 Coenzyme Q10 -- COX-2 Cyclooxygenase-2 -- CRP C-reactive proteins -- DAS Disease activity score -- DMARDs Disease modifying anti-rheumatic drugs -- ECGC Epigallocatechin gallate -- ESR Erythrocyte sedimentation rate -- EULAR European League Against Rheumatism -- FA Ferulic acid -- FLS Fibroblast-like-synoviocytes -- FS N-Feruloylserotonin -- GPx Glutathione peroxidase -- GSH Reduced glutathione -- I3C Indole-3-carbinol -- IFN Interferon -- IL Interleukin -- iNOS inducible nitric oxide synthase -- LDL Low-density lipoprotein -- LEF Leflunomide -- LFTs Liver function tests -- LOX Lipoxygenase -- MCP Monocyte chemoattractant protein -- MDA Malondialdehyde -- MgIG Magnesium glycyrrhizinate -- MMPs Matrix metalloproteinases -- MPO myeloperoxidase -- MTX Methotrexate -- OPG Osteoprotegerin -- OPN Osteopontin -- PGE2 Prostaglandin E2 -- RA Rheumatoid arthritis -- RANK Ligand-receptor activator of nuclear factor kappa-B -- RF Rheumatoid factor -- RSV Resveratrol -- SGOT serum glutamic oxaloacetic transaminase -- SGPT serum glutamic pyruvic transaminase -- SIN Sinomenine -- SJC-28 swollen joint count-28 -- SOD Superoxide dismutase -- TGP Total glucosides of paeony -- TJC-28 tender joint count-28 -- TNF tumor necrosis factor -- TwHF Tripterygium wilfordii Hook F -- ULN Upper limit of normal; Phytochemicals -- Rheumatoid arthritis -- Methotrexate -- Hepatotoxicity -- Nephrotoxicity; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105618
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: The use of biologically active compounds derived from plants i.e. phytochemicals, have been known for ages for their pharmacological activities in the treatment of autoimmune disorders like rheumatoid arthritis (RA). Besides enormous scientific evidence, the therapeutic potential of phytochemicals is often undervalued. The treatment in RA involves the use of synthetic and biological disease modifying anti-rheumatic drugs (DMARDs). However, the long-term treatment in RA is associated with the risk of gastrointestinal, liver, pulmonary and renal toxicities and serious infections including latent tuberculosis, pneumococcus influenza, herpes zoster and hepatitis. These adverse effects sometimes lead to discontinuation of the therapy. A relatively new vision based on the combination of DMARDs with phytochemicals exhibiting anti-inflammatory, anti-arthritic, anti-oxidant, hepatoprotective and nephroprotective properties for the treatment of RA has achieved substantial importance in the last decade. From this perspective, the present review focuses on the combination of DMARDs (primarily MTX) with phytochemicals that have shown synergistic therapeutic effects while decreasing the toxic repercussions of current RA therapy. The review covers recent evidences of such combination studies that have shown promising results both in experimental arthritic models and clinical arthritis. Few of the combinations including resveratrol, sinomenine, coenzyme Q10 exhibited considerable interest because of their efficacy as an adjuvant to the MTX/standard DMARDs therapy in clinical trials. Besides giving an overview of such combination studies the review also critically discusses the limitations with the use of phytochemicals (e.g. solubility, permeability and bioavailability) compromising their clinical application. Additionally, it stresses upon the need of novel delivery systems and pharmaceutical technologies to increase the therapeutic efficacy of the combination therapy. Overall, the review unveils the potential of phytochemicals in combination with DMARDs with increased tolerability and superior efficacy in further refining the future of the RA therapy. Graphical Abstract: ga1 Highlights: Combination of phytochemicals with DMARDs showed potential in pre-clinical setting. Combination therapy could improve the efficacy, safety and tolerability of the current RA therapy. Rational drug delivery strategies are needed for combination therapy. Few phytochemicals exhibited clinical success with DMARDs for RA therapy.