Buyang Huanwu Decoction promotes neurogenesis via sirtuin 1/autophagy pathway in a cerebral ischemia model

Mol Med Rep. 2021 Nov;24(5):791. doi: 10.3892/mmr.2021.12431. Epub 2021 Sep 13.

Abstract

Stroke is one of the main causes of disease‑related mortality worldwide. Buyang Huanwu Decoction (BHD) has been used to protect against stroke and stroke‑induced disability for several years in China. Studies have shown that BHD can relieve neuronal damage in rats with cerebral ischemia/reperfusion (I/R) injury. However, the mechanism remains unclear. A middle cerebral artery occlusion and reperfusion (MCAO‑R) model was used in the present study. The animals were treated with BHD (5, 10 and 20 g/kg) or rapamycin. Infarct size and modified neurological severity score were calculated on day 5 following MCAO‑R surgery. Cellular changes around the ischemic penumbra were revealed by hematoxylin and eosin and Nissl staining. The protein expression levels of nestin, brain‑derived neurotrophic factor (BDNF), doublecortin on the X chromosome (DCX) and autophagy‑related proteins (beclin 1, LC3‑II and p62) in the peri‑ischemic area of the brain were detected. The results demonstrated that post‑surgical treatment with BHD reduced the brain infarct size and improved neurological deficits in MCAO‑R rats. BHD protected against MCAO‑R‑induced neuronal impairment and promoted neurogenesis, increased the protein expression of nestin, BDNF and DCX and markedly enhanced autophagy by increasing beclin 1 and LC3‑II and decreasing p62. Meanwhile, BHD promoted the expression of sirtuin 1 (SIRT1), an important regulator of autophagy. In conclusion, the present study suggested that post‑surgical treatment with BHD could protect rat brains from I/R injury, potentially through the SIRT1/autophagy pathway.

Keywords: Buyang Huanwu Decoction; autophagy; ischemia/reperfusion; neurogenesis; sirtuin 1.

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Autophagy / physiology
  • Brain / metabolism
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology
  • Brain-Derived Neurotrophic Factor / metabolism
  • China
  • Disease Models, Animal
  • Drugs, Chinese Herbal / metabolism
  • Drugs, Chinese Herbal / pharmacology*
  • Infarction, Middle Cerebral Artery / metabolism
  • Male
  • Neurogenesis / drug effects
  • Neurogenesis / physiology*
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism
  • Sirtuin 1 / metabolism
  • Stroke / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Drugs, Chinese Herbal
  • Neuroprotective Agents
  • buyang huanwu
  • Sirtuin 1

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant no. 81673717) and Guangdong Provincial Key Laboratory of Research on Emergency in TCM (grant no. 2017B030314176).