Discovery of the signal pathways and major bioactive compounds responsible for the anti-hypoxia effect of Chinese cordyceps.

Ethnopharmacological Relevance: Hypoxia will cause an increase in the rate of fatigue and aging. Chinese cordyceps, a parasitic Thitarodes insect-Ophiocordyceps sinensis fungus complex in the Qinghai-Tibet Plateau, has long been used to ameliorate human conditions associated with aging and senescence, it is principally applied to treat fatigue, night sweating and other symptoms related to aging, and it may play the anti-aging and anti-fatigue effect by improving the body's hypoxia tolerance.

Aims Of The Study: The present study investigated the anti-hypoxia activity of Chinese cordyceps and explore the main corresponding signal pathways and bioactive compounds.

Materials And Methods: In this study, network pharmacology analysis, molecular docking, cell and whole pharmacodynamic experiments were hired to study the major signal pathways and the bioactive compounds of Chinese cordyceps for anti-hypoxia activity.

Results: 17 pathways which Chinese cordyceps acted on seemed to be related to the anti-hypoxia effect, and "VEGF signal pathway" was one of the most important pathway. Chinese cordyceps improved the survival rate and regulated the targets related VEGF signal pathway of H9C2 cells under hypoxia, and also had significant anti-hypoxia effects to mice. Chorioallantoic membrane model experiment showed that Chinese cordyceps and the main constituents of (9Z,12Z)-octadeca-9,12-dienoic acid and cerevisterol had significant angiogenic activity in hypoxia condition.

Conclusion: Based on the results of network pharmacology and molecular docking analysis, cell and whole pharmacodynamic experiments, promoting angiogenesis by regulating VEGF signal pathway might be one of the mechanisms of anti-hypoxia effect of Chinese cordyceps, (9Z, 12Z)-octadeca-9,12-dienoic acid and cerevisterol were considered as the major anti-hypoxia bioactive compounds in Chinese cordyceps.