Pharmacological Effect of Caulophyllum robustum on Collagen-Induced Arthritis and Regulation of Nitric Oxide, NF-κB, and Proinflammatory Cytokines In Vivo and In Vitro

Received Mar 9, 2017; Revised Aug 8, 2017; Accepted Sep 10, 2017

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1. Introduction

As an autoimmune disease, human rheumatoid arthritis (RA) is a major cause of disability characterized by chronic inflammation and joint damage. The pathogenesis of RA is a complex process involving synovial cell proliferation and fibrosis, pannus formation, and cartilage and bone erosion [1, 2]. To date, it has been found that the joint destruction is caused by several mechanisms including the overexpression of inflammatory response cytokines and transcription factors relevant to RA inflammation during the occurrence of RA [3]. In RA, the transcription factor nuclear factor-kappa B (NF-κB) is overexpressed in the inflamed synovium [4, 5]. It participates in the transactivation of various genes and inducible nitric oxide (iNOS) [6], which mediate immune and inflammatory responses [7]. It can activate and be activated by proinflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin- (IL-) 1, Prostaglandin E (PGE), and IL-6, resulting in a positive regulatory circle that causes amplification of local inflammatory responses [8]. TNF-α stimulates synovial fibroblasts to express intercellular adhesion molecules, which increases the migration of leukocytes into the RA joints. It is a central factor in the pathogenesis of RA as it amplifies inflammation and causes joint damage. IL-6 is also known as another proinflammatory cytokine that closely contributes to vascular endothelial growth and that stimulates the growth of blood vessels, including those in hypertrophy of joints. IL-1 is another key mediator involved in bone resorption and cartilage destruction that can modulate the production of nitric oxide and PGE2. PGE2 can act to mediate hyperalgesia-induced sensitizing pain receptors and induce fever [9]. Relieving inflammation and reducing proinflammatory cytokine overexpression are therefore regarded as one...