Screening Of Anti-hypoxia Compounds Of Medicinal Edible Tibetan Medicine And Research On Its Activity And Mechanism

Acute mountain sickness（AMS）usually refers to people in low-altitude areas who enter high-altitude（>2400 m）areas in a short period of time.Because they have not yet adapted to the high-altitude,low-pressure,and low-oxygen environment,they manifest as headache,sleep disturbance,and fatigue,dizziness,poor appetite and other symptoms of the disease.Severe cases will further develop into high altitude cerebral edema（HACE）and high-altitude pulmonary edema（HAPE）,which seriously threaten people’s lives and health.At present,Western medicine,decoction,Chinese patent medicine or health care products are mainly used in china to prevent or treat acute altitude sickness,and there are few anti-hypoxia health care medicines composed of Tibetan medicines.Because the medicinal and edible homologous medicinal materials have the characteristics of mild medicinal properties,no toxic side effects,and health care,and Tibet is rich in anti-hypoxia medicinal and edible homologous Tibetan medicines,it is yet to be developed into an anti-hypoxia medicinal and food homologous compound of health care medicines.By constructing the hypoxia model of CoCl₂-induced H9C2 cells and PC12 cells in vitro,it was investigated whether the compound could improve the cell survival rate of CoCl₂-induced hypoxia of H9C2 cells and PC12 cells.Compound screening optimization results:Compound 18 can significantly improve the cell survival rate of CoCl₂-induced hypoxia in H9C2 cells and PC12 cells.The kits and Western Blot technology were used to detect related biochemical indicators and the expression of HIF-1α,Cleaved-Caspase3and PI3K/Akt/m TOR signaling pathway proteins in cells,and further study the active mechanism of compound 18 anti-CoCl2-induced hypoxia in H9C2 cells and PC12 cells.Experimental results:Compound 18 can significantly reduce the contents of LDH and intracellular MDA in the culture supernatant of H9C2cells and PC12 cells,and significantly increase the contents of antioxidant enzymes such as SOD,GSH-PX and T-AOC in cells.Compound 18 can significantly reduce HIF-1αprotein expression in H9C2 cells and PC12cells,significantly reduce Cleaved-Caspase3 protein expression in H9C2cells,activate PI3K/Akt signaling pathway in H9C2 cells and PC12 cells,and reduce CoCl₂-induced hypoxia injury.