Total Flavonoids of Rhizoma Drynariae Treat Osteoarthritis by Inhibiting Arachidonic Acid Metabolites Through AMPK/NFκB Pathway

Abstract

Previous clinical studies have found that total flavonoids of Rhizoma Drynariae (TFRD) have a good therapeutic effect on osteoarthritis (OA), but its therapeutic mechanism needs further research. Methods: OA rat model was established by Hulth method and was intervened by TFRD. Pathological assessments were conducted to assess the protective effect of TFRD on cartilage. Serum metabolomics and network pharmacology were detected to predict the mechanism of TFRD treating OA. In further experiments, molecular biology experiment was carried out to confirm the predicted mechanisms in vivo and in vitro. Results: TFRD can effectively reduce chondrocyte apoptosis and cartilage degeneration in OA model rats. Serum metabolomics revealed that the intervention effect may be closely related to arachidonic acid metabolism pathway. Network pharmacologic prediction showed that COX-2 was the key target of TFRD in treating OA, and its mechanism might be related with NFκB, apoptosis, AMPK and arachidonic acid metabolism pathway. In vivo experiments indicated that TFRD can inhibit the abnormal expression of COX-2 mRNA in OA model rats. In the in vitro studies, the expression of COX-2 mRNA and protein increased, AMPK phosphorylation was inhibited, and NFκB signaling pathway was activated in IL-1β-induced chondrocytes, and these changes can be reversed by TFRD. After the activation of AMPK signaling pathway or the block-down of NFκB signaling pathway, the effect of TFRD on COX-2 mRNA expression was significantly weakened. Conclusion: TFRD can inhibit COX-2-mediated arachidonic acid metabolites, and its mechanism is closely related to AMPK/NFκB pathway, which may be a key mechanism in the treatment of OA.

The Role of Natural Extracts in the Management of Infantile Hemangiomas and Vascular Tumors

“…There are studies in the literature that demonstrate the favorable effect of proanthocyanidins in the treatment of hemangiomas, although the beneficial role of these substances in conditions involving the proliferation of vascular endothelial cells and uncontrolled angiogenesis has already been demonstrated. 37 , 38 , 42 Proanthocyanidins bind to VEGF and inhibit HIF-1α translation; the decrease of VEGF expression through mediating the PI3K/Akt and mTOR/p70S6K signaling pathways arrests the proliferation, invasion, and metastasis of tumor cell. This may be the process of proanthocyanidin controlling hemangioma growth.…”