Molecular regulatory mechanisms of hypoxia-inducible factor and interventional effect of Chinese herbal medicine

LIU Bu-hui1,2 WANG Mei-zi2 SUN Wei1 WAN Yi-gang3 WU Wei3 FANG Qi-jun2 WANG Wen-wen2 YEE Hong-yun2 YUAN Can-can2 LIU Ying-lu3 TU Yue4 CHONG Fee-lan5

(1.Nephrology Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China 210029)
(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;


【Funds】 General Programs of National Natural Science Foundation of China (81774245 and 81573903) Youth Program of National Natural Science Foundation of China (81603675) Natural Science Foundation of Jiangsu Province (BK20161046) Traditional Chinese Medicine Science and Technology Development Project of Jiangsu Province (YB201937) Project for Medical Science and Technology Development in Nanjing (QRX17042)

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This Article


CN: 11-2272/R

Vol 45, No. 20, Pages 4805-4811

October 2020


Article Outline


  • 1 Structures, functions, and degradation of HIFs
  • 2 Molecular regulation mechanism of HIF-1α
  • 3 HIF-1α and inflammatory response as well as intervention with Chinese herbal medicines
  • 4 HIF-1α and autophagy as well as intervention with Chinese herbal medicine
  • 5 HIF-1α and epigenetic modification as well as intervention with Chinese herbal medicine
  • 6 HIF-1α and pyroptosis as well as intervention with Chinese herbal medicine
  • References