Phytomedicine: Yiqi Fumai for injection (freeze-dried) reduces cerebral ischemic damage by inhibiting neuronal autophagy

Background: Yiqi Fumai freeze-dried injection (YQFM) is derived from the classic ancient prescription Shengmai San , composed of red ginseng, Ophiopogon japonicus and Schisandra chinensis , and is clinically used in the treatment of cardiovascular and cerebrovascular diseases
.

ATG9A is the only transmembrane protein responsible for transporting membrane components to autophagosomes.

Yiqi Fumai Freeze-dried Injection (YQFM) Yiqi Fumai Freeze-dried Injection (YQFM) Red Ginseng, Ophiopogon and Schisandra 3 Chinese Medicine Red Ginseng, Ophiopogon and Schisandra 3 Chinese Medicine Cardiovascular and Cerebrovascular Diseases Cardiovascular and Cerebrovascular Diseases ATG9A ATG9A NMMHC IIA NMMHC IIA oxygen-glucose deprivation and reoxidation (OGD/R) oxygen-glucose deprivation and reoxidation (OGD/R)

Objective: To evaluate whether YQFM can form autophagosomes by inhibiting the interaction of NMMHC IIA-actin-ATG9A, which has a neuroprotective effect on cerebral ischemia-reperfusion injury
.

Methods: The neurological deficit, infarct volume and histopathological changes of middle cerebral artery occlusion/reperfusion (MCAO/R) mice were detected to observe the protective effect of YQFM on brain nerves .
NMMHC IIA-actin-ATG9A by interaction colocalization immunofluorescence , immunoprecipitation determined .
In vitro experiments used rat pheochromocytoma (PC12) cells to simulate neurons after oxygen-glucose deprivation/reoxidation (OGD/R) .

Middle cerebral artery occlusion/reperfusion (MCAO/R) mouse Middle cerebral artery occlusion/reperfusion (MCAO/R) mouse neurological deficit, infarct volume and histopathology Neurological deficit, infarct volume and histopathology immunofluorescence colocalization immunofluorescence colocalization immunoprecipitation immunoprecipitation analog neuron analog neuron

Results: The neuroprotection of different doses of YQFM (0.

336, 0.
671, 1.
342 g/kg) and positive control drug nimodipine (5 mg/kg) on ​​MCAO mice was evaluated by the area of ​​infarct area and the score of neurological deficit 24h after reperfusion.

Histopathology, morphology, and neurological deficit scores indicate that YQFM has neuroprotective effects on MCAO/R mice, which may be related to autophagy
.

Western blotting results of autophagy-specific marker proteins p62 and LC3B showed that MCAO/R damage was reduced after YQFM treatment

The results of immunofluorescence staining showed that YQFM can significantly inhibit the translocation of ATG9A induced by MCAO/R and play a protective role
.

Fluorescence colocalization results show that YQFM regulates the interaction of NMMHC IIA-F-actin-ATG9A, inhibits ATG9A translocation in MCAO/R mice, and reduces cerebral ischemia/reperfusion injury

Immunofluorescence staining immunofluorescence staining

Using PC12 cells to simulate neurons in vitro, the results show that YQFM (400 μg/ml) can significantly inhibit OGD/R-induced excessive autophagy in PC12 cells by interfering with the translocation of ATG9A
.

In addition, the RNAi of NMMHC IIA attenuates the NMMHC IIA-F-actin-mediated ATG9A transport, thereby weakening the in vitro neuroprotective activity of YQFM

Conclusion: YQFM inhibits excessive autophagy and exerts neuroprotective effects by interfering with NMMHC IIA-actin-mediated ATG9A translocation .
It is a promising drug for the treatment of brain I/R injury
.

The results of this study provide experimental evidence for YQFM to prevent and treat brain I/R, but the importance of various components in YQFM is still unclear, and further research is needed

Inhibition of excessive autophagy Inhibition of excessive autophagy

Literature source:

Literature source:

Su, L.

Su, L.
, Liu, Y.
, Ma, H.
, et al.
(2021).
YiQiFuMai lyophilized injection attenuates cerebral ischemic injury with inhibition of neuronal autophagy through intervention in the NMMHC IIA-actin-ATG9A interaction.
Phytomedicine: international journal of phytotherapy and phytopharmacology, 95, 153882.
Advance online publication.
https://doi.
org/10.
1016/j.
phymed.
2021.
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