Molecular regulatory mechanisms of hypoxia-inducible factor and interventional effect of Chinese herbal medicine
(2.Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China 210008)
(3.Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China 210008)
(4.Teaching and Research Section of Health Preservation with Traditional Chinese Medicine, Acupuncture and Moxibustion and Massage College·Health Preservation and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China 210023)
(5.The School of Pharmacy, Management and Science University, Shah Alam 40100, Malaysia)
【Abstract】Hypoxia-inducible factors (HIFs) are the key transcription factors that sense and regulate cellular oxygen concentration in vivo. HIF-1 is composed of 2 subunits, α and β. The molecular regulatory mechanism of HIF-1α involves degradation and activation. The degradation of HIF-1α is regulated by oxygen-dependent pathways, including “von hippel-lindau protein (pVHL)-dependent pathway” and “pVHL-independent pathway.” The activation of HIF-1α is regulated by oxygen-independent pathways, including mammalian target of rapamycin (mTOR)/eukaryotic initiation factor 4 E-binding protein 1 (4EBP1)/HIF-1α pathway, phosphatidylinositol 3-kinase (PI3K)/proteirrserinc-threonine kinases (Akt)/HIF-1α pathway, and silent information regulator 1 (Sirt1)/HIF-1α pathway. In recent years, based on the molecular regulatory mechanism of HIFs, roxadustat, a new drug for the treatment of renal anemia, has been developed. Besides, some macromolecular substances with similar pharmacological effects to those of HIFs have been found in the extracts from Chinese herbal medicines, such as emodin, notoginsenoside, honokiol, and clematichinenoside. These natural macromolecular substances play the regulatory roles in inflammatory response, autophagy, epigenetic modification, and pyroptosis. It is worth noting that, for common hypoxia-related diseases including diabetic kidney disease (DKD), HIFs-mediated “pyroptosis” may be a new target of heat-clearing and diuresis-inducing Chinese herbal medicines and its representative classical prescriptions (e.g., Ermiao Pills) in treating inflammatory injury in cells and tissues.
【Keywords】 hypoxia-inducible factors; Chinese herbal medicine; molecular mechanism; signaling pathway; pyroptosis;
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