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

• Published in: International immunopharmacology 2024-12, Vol.142 (Pt A), p.112989, Article 112989
• Main Authors: Liu, Guanhong, Wang, Zhiqiang, Li, Xiaochun, Yu, Pengfei, Ji, Wanbo, Wu, Liming, Jiang, Hong, Xu, Suliang, Liu, Jintao
• Format: Article
• Language: English
• Subjects: Animals; Autophagy; Autophagy - drug effects; Bone and Bones - drug effects; Bone microcirculatory endothelial cell; Cell Movement - drug effects; Cell Survival - drug effects; Cells, Cultured; Drugs, Chinese Herbal - pharmacology; Endothelial Cells - drug effects; Glucocorticoids - pharmacology; Gumibao recipe; Humans; Hydrocortisone - pharmacology; Male; Microcirculation - drug effects; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - metabolism; Osteonecrosis of the femoral head; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt/mTOR; Plasminogen Activator Inhibitor 1 - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - metabolism; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112989

•Effects of glucocorticoids on viability and migration of BMECs.•Glucocorticoids may affect the endothelial function of BMECs.•Gumibao recipe can alleviate glucocorticoids induced endothelial dysfunction of BMECs.•Gumibao recipe may increase the autophagy of BMECs to alleviate glucocorticoids induced damage.•Gumibao recipe may increase the autophagy of BMECs through regulating PI3K/AKT/mTOR signaling pathway. To investigate the protective effects of Gumibao recipe on glucocorticoid-included bone microcirculatory endothelial cell (BMEC) injury, and elucidate the possible underlying mechanism. 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. 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. 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.