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A discovery of clinically approved Panlongqi Tablet for repositioning to treat osteoarthritis by inhibiting PI3K/AKT activation

作者:Lu Wang, Panyu Xu, Ying Xu, Ruiqin Cui, Yibo Yang, Zhao Zou, Hanqian Du, Chunyan Zhu, Guoxin Zhang, Tengfei Han, Na Lin · 发表于:Phytomedicine · 年份:2022 · DOI:10.1016/j.phymed.2022.154360 · 被引用次数:17 · 研究领域:Osteoarthritis Treatment and Mechanisms、Bone Metabolism and Diseases、Traditional Chinese Medicine Analysis

Panlongqi Tablet (PLQT) is a Chinese patent drug composed of 29 kinds of traditional Chinese medicines. Clinical practice has shown that PLQT can relieve osteoarthritis-caused joint pain, but its effects and mechanisms in other pathological links of osteoarthritis have not been characterized. The purpose of this study is to reposition the pharmacodynamic effects of PLQT through network pharmacology analysis combined with experimental validation, and also to preliminarily explore its possible mechanism. On the basis of integrating the relevant targets of PLQT in multiple drug databases and osteoarthritis-related targets in the disease database, an interaction network of related genes was constructed. The hub candidate targets of PLQT in the treatment of osteoarthritis were determined by calculating the main network topological characteristics, The specific functions and pathways of these targets acting on osteoarthritis were modularly analyzed. In addition, the modified Hulth-induced rat model of osteoarthritis and IL-1β-induced in vitro model of osteoarthritis were established to further validate the potential efficacy and possible mechanism of PLQT. A total of 138 key targets related to osteoarthritis were selected based on topological parameters, and their biological functions were mainly enriched in four over-expressed modules of cartilage degeneration, inflammatory response, immune response, and subchondral bone metabolism. The hub candidate targets had the highest enrich...