Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
Weill Cornell Medicine Qatar, Doha, Qatar.
Pharmacol Res. 2018 Nov;137:159-169. doi: 10.1016/j.phrs.2018.10.009. Epub 2018 Oct 10.
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that consists of two subunits, the HIF-1α and HIF-1β (ARNT). Under hypoxic conditions, HIF-1 is an adaptive system that regulates the transcription of multiple genes associated with growth, angiogenesis, proliferation, glucose transport, metabolism, pH regulation and cell death. However, aberrant HIF-1 activation contributes to the pathophysiology of several human diseases such as cancer, ischemic cardiovascular disorders, and pulmonary and kidney diseases. A growing body of evidence indicates that curcumin, a natural bioactive compound of turmeric root, significantly targets both HIF-1 subunits, but is more potent against HIF-1α. In this review, we have summarized the knowledge about the pharmacological effects of curcumin on HIF-1 and the related molecular mechanisms that may be effective candidates for the development of multi-targeted therapy for several human diseases.
缺氧诱导因子-1（HIF-1）是一种转录因子，由两个亚基组成，即 HIF-1α 和 HIF-1β（ARNT）。在缺氧条件下，HIF-1 是一种适应性系统，可调节与生长、血管生成、增殖、葡萄糖转运、代谢、pH 调节和细胞死亡相关的多种基因的转录。然而，异常的 HIF-1 激活导致了多种人类疾病的病理生理学，如癌症、缺血性心血管疾病以及肺部和肾脏疾病。越来越多的证据表明，姜黄素，一种来自姜黄根的天然生物活性化合物，显著靶向 HIF-1 的两个亚基，但对 HIF-1α 的作用更强。在这篇综述中，我们总结了姜黄素对 HIF-1 的药理作用及其相关分子机制的认识，这些分子机制可能是针对多种人类疾病开发多靶点治疗的有效候选药物。
