Work

Protective effects of Gumibao recipe on glucocorticoid-included bone microcirculatory endothelial cell injury and the underlying mechanism

Year: 2024

Type: article

Abstract: OBJECTIVE: To investigate the protective effects of Gumibao recipe on glucocorticoid-included bone microcirculatory endothelial cell (BMEC) injury, and elucidate the possible underlying mechanism. METHODS: BMECs were treated with different concentrations of hydrocortisone at different time points, and the viability as well as migration of BMECs were evaluated; furthermore, the release of LDH, levels of VEGF, PAI-1, t-PA, and the content of NO by BMECs have been evaluated by commercially available kits; moreover, the expressions of eNOS, p-PI3K, p-Akt and p-mTOR in BMECs were examined by WB methods. Next, hydrocortisone treated BMECs were co-treated with Gumibao recipe, and the viability, migration and autophagy of BMECs were evaluated. RESULTS: 0.2 mg/ml and 0.3 mg/ml hydrocortisone significantly decreased viability and migration ability of BMECs, and also impeded the endothelial function of BMECs by decreasing the levels of VEGF, t-PA, the content of NO, and increasing the level of PAI-1. Gumibao medicated serum markedly increased the viability and migration of BMECs, and also increased the levels of VEGF, t-PA, the content of NO, meanwhile decreased the level of PAI-1 in 0.3 mg/ml hydrocortisone treated BMECs; moreover, glucocorticoids inhibited the autophagy of BMECs, and Gumibao recipe significantly increased the autophagy of BMECs; meanwhile, autophagy inhibitor 3-MA partially blocked the protective effects of Gumibao recipe. Finally, gumibao recipe partially abrogated the inhibitory effects of hydrocortisone on the activation of PI3K/Akt/mTOR singling, and these effects were further counteracted by PI3K and mTOR inhibitor NVP-BEZ235. CONCLUSIONS: We reported for the first time the protective effects of Gumibao recipe on glucocorticoid-included BMECs injury, and the possible underlying mechanism may be regulating the autophagy of BMECs via PI3K/AKT/mTOR signaling pathway.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2024.112989