4.7 Article

Tetrahydrocurcumin mitigates acute hypobaric hypoxia-induced cerebral oedema and inflammation through theNF-κB/VEGF/MMP-9 pathway

期刊

PHYTOTHERAPY RESEARCH
卷 34, 期 11, 页码 2963-2977

出版社

WILEY
DOI: 10.1002/ptr.6724

关键词

HACE; inflammation; MMP-9; oedema; tetrahydrocurcumin; VEGF

资金

  1. Major new drug creation of major science and technology projects of China [2018ZX09201018-029]
  2. Research and promotion of quality testing of traditional Chinese medicine and certification of authentic Chinese medicine and certification of authentic Chinese medicine [18ZDYF0821]

向作者/读者索取更多资源

High-altitude cerebral oedema (HACE) is a potentially fatal manifestation of high-altitude sickness and is caused partly by inflammation and the blood-brain barrier disruption. Tetrahydrocurcumin (THC) has been reported to exert effective antioxidative and anti-inflammatory effects; This study sought to elucidate the underlying mechanism of THC in mitigating HACE using a mouse model. Our results revealed that prophylactic administration of THC (40 mg/kg) for 3 days significantly alleviated the increase in brain water content (BWC), interleukin-1 beta (IL-1 beta) and TNF-alpha levels caused by acute hypobaric hypoxia (AHH). Additionally, superoxide dismutase (SOD) activity was increased by THC to enhance the ability to resist hypoxia. Histological and ultrastructural analysis of the cerebrum revealed that THC administration mitigated AHH-induced pericellular oedema and reduced the perivascular space, resulting in the simultaneous remission of oedema and protection of mitochondria in the cerebrum. In vitro, astrocytes exposed to hypoxia (4% O-2) for 24 hr exhibited and increase in IL-1 beta expression followed by an increase in vascular endothelial growth factor (VEGF) levels.Furthermore, THC administration remarkably downregulated VEGF, matrix metallopeptidase-9 (MMP-9), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) expression, both in vivo and in vitro. Our data highlight the potential prophylactic activity of THC in HACE, it effectively mitigates AHH-induced cerebral oedema and inflammation is associated with the inhibition of the NF-kappa B/ VEGF/MMP-9 pathways.

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