YiQiFuMai lyophilized injection attenuates cerebral ischemic injury with inhibition of neuronal autophagy through intervention in the NMMHC IIA-actin-ATG9A interaction.

Abstract

BACKGROUND:

YiQiFuMai lyophilized injection (YQFM) is derived from a traditional Chinese medicine prescription termed Shengmai San.YQFM is clinically applied to the treatment of cardiovascular and cerebrovascular diseases. It has been found that critical components of YQFM affect non-muscle myosin heavy chain IIA (NMMHC IIA), but its regulation in the excessive autophagy and the underlying mechanism has yet to be clarified.

PURPOSE:

To evaluate whether YQFM has neuroprotective effects on cerebral ischemia/reperfusion-induced injury by inhibiting NMMHC IIA-actin-ATG9A interaction for autophagosome formation.

METHODS:

The neuroprotective effects of YQFM were investigated in vivo in mice with middle cerebral artery occlusion/reperfusion (MCAO/R) (n = 6) by detecting neurological deficits, infarct volume, and histopathological changes. The NMMHC IIA-actin-ATG9A interaction was determined using immunofluorescence co-localization, co-immunoprecipitation, and proximity ligation assay. Rat pheochromocytoma (PC12) cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic neurons in in vitro experiments.

RESULTS:

In MCAO/R model mice, YQFM (1.342 g/kg) attenuated brain ischemia/reperfusion-induced injury by regulating NMMHC IIA-actin-mediated ATG9A trafficking. YQFM (400 μg/ml) also exerted similar effects on OGD/R-induced PC12 cells. Furthermore, RNAi of NMMHC IIA weakened the NMMHC IIA-F-actin-dependent ATG9A trafficking and, therefore, attenuated the neuroprotective activities of YQFM in vitro.

CONCLUSION:

These findings demonstrated that YQFM exerted neuroprotective effects by regulating the NMMHC IIA-actin-ATG9A interaction for autophagosome formation. This evidence sheds new light on the potential mechanism of YQFM in the treatment of cerebral ischemia/reperfusion.

• Authors: Linjie Su, Yining Liu, Huifen Ma, Fan Zheng, Yujie Daia, Tiezheng Wang, Guangyun Wang, Fang Li, Yuanyuan Zhang, Boyang Yu, Shuaishuai Gong, Junping Kou
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 95 Pg. 153882 (Jan 2022) ISSN: 1618-095X [Electronic] Germany
• PMID: 34968897 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier GmbH.

Chemical References

• ATG9A protein, rat
• Actins
• Atg9A protein, mouse
• Autophagy-Related Proteins
• Drugs, Chinese Herbal
• Membrane Proteins
• Neuroprotective Agents
• Vesicular Transport Proteins
• yi-qi-fu-mai

Topics

• Actins
• Animals
• Autophagy
• Autophagy-Related Proteins
• Brain Ischemia (drug therapy)
• Drugs, Chinese Herbal (pharmacology)
• Membrane Proteins
• Mice
• Neuroprotective Agents (pharmacology)
• Rats
• Reperfusion Injury (drug therapy)
• Vesicular Transport Proteins