title: Tinospora cordifolia inhibits autoimmune arthritis by regulating key immune mediators of inflammation and bone damage.
abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints leading to tissue damage. Despite the availability of potent drugs including the biologics, many patients fail to respond to them, whereas others suffer adverse effects following long-term use of these drugs. Accordingly, the use of natural herbal products by RA patients has been increasing over the years. However, limited information about the mechanism of action of these natural products is a major shortcoming that prevents the widespread acceptance of herbal therapy by professionals and patients alike. In this study, we demonstrated the anti-arthritic activity of Tinospora cordifolia extract (TCE) using the rat adjuvant-induced arthritis model of human RA and elaborated the immune mechanisms underlying this effect. TCE treatment suppressed arthritic inflammation and bone and cartilage damage. The anti-inflammatory effect of TCE was mediated via reduction of the pro-inflammatory cytokines such as: IL-1β, TNF-α, IL-6, and IL-17; the frequency of IL-17-producing T cells; and the production of chemokines such as RANTES. Furthermore, TCE treatment limited bone damage by shifting the balance of mediators of bone remodeling (e.g., receptor activator of nuclear factor-kB ligand [RANKL] and MMP-9) in favor of anti-osteoclastic activity. Our results suggest that TCE and its bioactive components should be evaluated for their utility as therapeutic adjuncts to conventional drugs against RA.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA Department of Biochemistry, Government College for Women, Mandya, Karnataka, India.
authors.forename: K M
authors.initials: KM
authors.lastname: Sannegowda
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Venkatesha
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA Division of Rheumatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA kmoudgil@som.umaryland.edu.
authors.forename: K D
authors.initials: KD
authors.lastname: Moudgil
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D016723:Bone Remodeling / Q000187:drug effects*; D018836:Inflammation Mediators / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D031610:Tinospora
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D020381:Interleukin-17; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D007371:Interferon-gamma
keywords: Tinospora cordifolia; adjuvant arthritis; autoimmunity; bone remodeling; chemokines; cytokines; natural products; rheumatoid arthritis