Natural Products for the Treatment of Autoimmune Arthritis: Their Mechanisms of Action, Targeted Delivery, and Interplay with the Host Microbiome

Abstract

Rheumatoid arthritis (RA) is a chronic, debilitating illness characterized by painful swelling of the joints, inflammation of the synovial lining of the joints, and damage to cartilage and bone. Several anti-inflammatory and disease-modifying drugs are available for RA therapy. However, the prolonged use of these drugs is associated with severe side effects. Furthermore, these drugs are effective only in a proportion of RA patients. Hence, there is a need to search for new therapeutic agents that are effective yet safe. Interestingly, a variety of herbs and other natural products offer a vast resource for such anti-arthritic agents. We discuss here the basic features of RA pathogenesis; the commonly used animal models of RA; the mainstream drugs used for RA; the use of well-characterized natural products possessing anti-arthritic activity; the application of nanoparticles for efficient delivery of such products; and the interplay between dietary products and the host microbiome for maintenance of health and disease induction. We believe that with several advances in the past decade in the characterization and functional studies of natural products, the stage is set for widespread clinical testing and/or use of these products for the treatment of RA and other diseases.

Keywords: EGCG; Tripterygium wilfordii; adjuvant-induced arthritis; arthritis; celastrol; curcumin; dietary supplements; green tea; inflammation; liposomes; microbiome; nanoparticles; natural products; resveratrol; rheumatoid arthritis; targeted delivery; traditional medicine; triptolide.

Figure 1

Immunopathogenesis of experimental autoimmune arthritis. Schematic representation of the key pathways is shown: The presentation of an autoantigen to autoreactive T cells and their differentiation into major T helper (Th) cell subsets under the influence of various cytokines; the activation and secretion of pro-inflammatory cytokines by myeloid cells; the T-B cell collaboration leading to autoantibody production by plasma cells; and the osteoimmune cross-talk leading to osteoclast differentiation. These intricate pathways regulate autoimmune inflammation of the synovial joint as shown by arrows (leading to activation/induction) and blunt ends (leading to suppression/inhibition).

Figure 2

Schematic representation of different types of nanoparticles for the delivery of natural products. (A) Polymer nanoparticles encapsulating triptolide; (B) Liposomes loaded with triptolide; (C) Nanoemulsions entrapping curcumin; (D) Micelles encapsulating curcumin; and (E) Lipid core nanocapsules co-encapsulating resveratrol and curcumin.