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Papers of the Week


2022 Aug


Zhongguo Zhong Yao Za Zhi


47


15

[Anti-osteoarthritis components and mechanism of Fufang Duzhong Jiangu Granules].

Authors

Chen Z-J, Huo X-Q, Ren YE, Shu Z, Zhang Y-L
Zhongguo Zhong Yao Za Zhi. 2022 Aug; 47(15):4156-4163.
PMID: 36046906.

Abstract

Osteoarthritis is a common disease characterized by degenerative lesions of articular cartilage in the elderly.Fufang Duzhong Jiangu Granulues(FDJG), a classical prescription for the treatment of osteoarthritis, has the effects of nourishing liver and kidney, nourishing blood and sinew, and dredging collaterals and relieving pain.In this study, molecular simulation technology was combined with molecular biology methods to explore and verify the potential pharmacodynamic substances and molecular mechanism of FDJG in the treatment of osteoarthritis.Arachidonic acid(AA) metabolic pathway is a typical anti-inflammatory pathway, and secretory phospholipase A2 group ⅡA(sPLA2-ⅡA), 5-lipoxygenase(5-LOX), cyclooxygenase-2(COX-2), and leukotriene A4 hydrolase(LTA4 H) are the key targets of the pathway.Therefore, in this study, based on the pharmacophores and molecular docking models of the four key targets in AA pathway, a total of 1 522 chemical components in 12 medicinals of FDJG were virtually screened, followed by weighted analysis of the screening results in combination with the proportions of the medicinals in the prescription.The results showed that mainly 73 components in the preparation could act on the above four targets, suggesting they might be the potential anti-osteoarthritis components of FDJG.Considering the predicted effectiveness, availability, and compatibility of the medicinals, coniferyl ferulate, olivil, and baicalin were selected for further verification.Specifically, lipopolysaccharide(LPS)-induced RAW264.7 inflammatory cell model was used to verify the anti-inflammatory activity of the three components.The results showed that the three can effectively inhibit the release of NO, supporting the above selection.In addition, targets 5-LOX, COX-2, and LTA4 H had high activity, which suggested that they may be the key anti-osteoarthritis targets of FDJG.The comprehensive activity values of Eucommiae Cortex, Achyranthis Bidentatae Radix, Ginseng Radix et Rhizoma, Lycii Fructus, and Astragali Radix were much higher than that of other medicinals in the prescription, indicating that they may be the main effective medicinals in FDJG acting on the AA pathway.In this study, the potential anti-osteoarthritis components of FDJG were obtained.Moreover, it was clarified that the anti-osteoarthritis mechanism of FDJG was to act on LOX and COX pathway in AA metabolic pathway, which provided a reference for the study of pharmacodynamic substances and molecular mechanism of FDJG.