Evaluating the Anti-Inflammatory and Chondroprotective Effects of Adenocaulon himalaicum Extract Through Network Pharmacology and Experimental Validation.

Conventional osteoarthritis treatments have several side effects and poor efficacy. This study explored the anti-inflammatory and cartilage-protective effects of Adenocaulon himalaicum, with a focus on its potential application in osteoarthritis treatment. The anti-inflammatory effects of A. himalaicum extract (AHLE) were investigated in lipopolysaccharide-induced RAW264.7 macrophages, interleukin (IL)-1β-stimulated chondrocytes, and rats with carrageenan-induced hind paw oedema. We also evaluated AHLE's analgesic activity in mice with acetic acid-induced writhing. The components of AHLE were subjected to network pharmacological analysis to elucidate their mechanisms of action and validate potential pathways and targets in vitro. AHLE markedly reduced nitric oxide, IL-1β, IL-6, tumour necrosis factor-alpha, and prostaglandin E2 production in both RAW264.7 macrophages and chondrocytes. In animal models, AHLE reduced carrageenan-induced hind paw swelling and provided analgesic effects in writhing tests. The main components were chlorogenic acid; 1,3-dicaffeoylquinic acid; 3,4-dicaffeoylquinic acid; 3,5-dicaffeoylquinic acid; and 4,5-dicaffeoylquinic acid. According to network pharmacological analysis, AHLE's main therapeutic targets are the mitogen-activated protein kinase (MAPK) signalling pathway and extracellular matrix (ECM) degradation. These targets were verified through the MAPK pathway and expression of matrix metalloproteinase, an enzyme involved in ECM degradation. In conclusion, AHLE has considerable anti-inflammatory and cartilage-protective properties, making it a promising candidate for osteoarthritis therapy.