Electroacupuncture Inhibits Neuronal Autophagy and Apoptosis the PI3K/AKT Pathway Following Ischemic Stroke

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2020 Jun 2

PMID 32477073

Citations 40

Authors

Man-Man Wang

Min Zhang

Ya-Shuo Feng

Ying Xing

Zi-Xuan Tan

Wen-Bin Li

Fang Dong

Feng Zhang

Affiliations

Soon will be listed here.

Abstract

Electroacupuncture (EA) is a safe and effective therapy for ischemic stroke in both clinical and laboratory settings. However, the underlying mechanism behind EA treatment for stroke remains unclear. Here, we aimed to evaluate whether EA treatment at the acupoints of Zusanli (ST36) and Quchi (LI11) exerted a neuroprotective effect on ischemic stroke rats by modulating autophagy and apoptosis the PI3K/AKT/mTOR signaling pathway. EA was performed at 24 h following brain ischemia/reperfusion (I/R) for 30 min per day for 3 days. Our results indicated that EA treatment significantly decreased neurological deficits and cerebral infarct volume in ischemic stroke rats. Also, EA intervention markedly reduced neuronal apoptosis by suppressing the activation of cleaved caspase-3 (CCAS3) at 72 h following I/R, as shown by a Western blot analysis. Furthermore, EA treatment after ischemic stroke suppressed the ischemia activated expression level of LC3II/I and Atg7 and increased the ischemia inhibited expression level of PI3K, phosphorylation of mTOR, phosphorylation of AKT, P62 and LAMP1, hence mediating the autophagy level of the neurocyte, which was reversed by the PI3K inhibitor Dactolisib. In summary, our results indicate that the protective effects of EA treatment at points of Quchi (LI11) and Zusanli (ST36) in rats following cerebral I/R injury was associated with the inhibition of neuronal apoptosis and autophagy activating the PI3K/AKT/mTOR signaling pathway.

Citing Articles

The Mechanism of Acupuncture Regulating Autophagy: Progress and Prospect.

He J, He M, Sun M, Chen H, Dou Z, Nie R Biomolecules. 2025; 15(2).

PMID: 40001566 PMC: 11852493. DOI: 10.3390/biom15020263.

Experimental evidence-based construction of electroacupuncture for ischemic stroke: a meta-analysis and systematic review.

Guo Y, Hu S, Luo S, Tu L, Tang Y, Zeng F Front Neurol. 2025; 16:1491132.

PMID: 39974363 PMC: 11835673. DOI: 10.3389/fneur.2025.1491132.

Molecular Targeting of Ischemic Stroke: The Promise of Naïve and Engineered Extracellular Vesicles.

Lee J, Geum D, Park D, Kim J Pharmaceutics. 2025; 16(12.

PMID: 39771472 PMC: 11678501. DOI: 10.3390/pharmaceutics16121492.

Electroacupuncture attenuates ferroptosis by promoting Nrf2 nuclear translocation and activating Nrf2/SLC7A11/GPX4 pathway in ischemic stroke.

Yang X, Jin Y, Ning R, Mao Q, Zhang P, Zhou L Chin Med. 2025; 20(1):4.

PMID: 39755657 PMC: 11699709. DOI: 10.1186/s13020-024-01047-0.

Electroacupuncture alleviated post-stroke cognitive impairment via the mTOR/NLRP3-mediated autophagy-inflammatory pathway.

Lang J, Luo J, Lang J, Wang L, Xu W, Jia J Eur J Med Res. 2024; 29(1):532.

PMID: 39497200 PMC: 11536957. DOI: 10.1186/s40001-024-02131-9.

References

Wu Z, Zou Z, Zou R, Zhou X, Cui S . Electroacupuncture pretreatment induces tolerance against cerebral ischemia/reperfusion injury through inhibition of the autophagy pathway. Mol Med Rep. 2015; 11(6):4438-46. DOI: 10.3892/mmr.2015.3253. View

. Interaction between rifampicin and trimethoprim. J Antimicrob Chemother. 1979; 5(1):113-5. DOI: 10.1093/jac/5.1.113. View

Zhao Y, Feng X, Li B, Sha J, Wang C, Yang T . Dexmedetomidine Protects Against Lipopolysaccharide-Induced Acute Kidney Injury by Enhancing Autophagy Through Inhibition of the PI3K/AKT/mTOR Pathway. Front Pharmacol. 2020; 11:128. PMC: 7052304. DOI: 10.3389/fphar.2020.00128. View

Xue X, You Y, Tao J, Ye X, Huang J, Yang S . Electro-acupuncture at points of Zusanli and Quchi exerts anti-apoptotic effect through the modulation of PI3K/Akt signaling pathway. Neurosci Lett. 2013; 558:14-9. DOI: 10.1016/j.neulet.2013.10.029. View

Sun F, Wang X, Mao X, Xie L, Jin K . Ablation of neurogenesis attenuates recovery of motor function after focal cerebral ischemia in middle-aged mice. PLoS One. 2012; 7(10):e46326. PMC: 3482223. DOI: 10.1371/journal.pone.0046326. View

Huang H, Zhong R, Xia Z, Song J, Feng L . Neuroprotective effects of rhynchophylline against ischemic brain injury via regulation of the Akt/mTOR and TLRs signaling pathways. Molecules. 2014; 19(8):11196-210. PMC: 6270871. DOI: 10.3390/molecules190811196. View

Parzych K, Klionsky D . An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal. 2013; 20(3):460-73. PMC: 3894687. DOI: 10.1089/ars.2013.5371. View

Xing Y, Zhang M, Li W, Dong F, Zhang F . Mechanisms Involved in the Neuroprotection of Electroacupuncture Therapy for Ischemic Stroke. Front Neurosci. 2019; 12:929. PMC: 6297779. DOI: 10.3389/fnins.2018.00929. View

Liu L, Wang N, Zhang Q, Li S, Gu W, Wu Y . [Micro-ribonucleic acids participate in electroacupuncture intervention-induced improvement of ischemic stroke]. Zhen Ci Yan Jiu. 2019; 44(9):686-92. DOI: 10.13702/j.1000-0607.180643. View

10.

Liu W, Shang G, Yang S, Huang J, Xue X, Lin Y . Electroacupuncture protects against ischemic stroke by reducing autophagosome formation and inhibiting autophagy through the mTORC1-ULK1 complex-Beclin1 pathway. Int J Mol Med. 2015; 37(2):309-18. PMC: 4716798. DOI: 10.3892/ijmm.2015.2425. View

11.

Luo H, Zeng Z, Yu X, He J, Cao J, Xu B . [Effect of electroacupuncture with different frequencies on hindlimb locomotor function and expression of LC3, Beclin 1 and cleaved Caspase-3 proteins in spinal cord injury rats]. Zhen Ci Yan Jiu. 2019; 44(9):625-31. DOI: 10.13702/j.1000-0607.190068. View

12.

Graham S, Liu H . Life and death in the trash heap: The ubiquitin proteasome pathway and UCHL1 in brain aging, neurodegenerative disease and cerebral Ischemia. Ageing Res Rev. 2016; 34:30-38. PMC: 5250550. DOI: 10.1016/j.arr.2016.09.011. View

13.

Sekerdag E, Solaroglu I, Gursoy-Ozdemir Y . Cell Death Mechanisms in Stroke and Novel Molecular and Cellular Treatment Options. Curr Neuropharmacol. 2018; 16(9):1396-1415. PMC: 6251049. DOI: 10.2174/1570159X16666180302115544. View

14.

Wu Z, Cui S, Zhu L, Zou Z . Study on the Mechanism of mTOR-Mediated Autophagy during Electroacupuncture Pretreatment against Cerebral Ischemic Injury. Evid Based Complement Alternat Med. 2016; 2016:9121597. PMC: 4980529. DOI: 10.1155/2016/9121597. View

15.

Samakova A, Gazova A, Sabova N, Valaskova S, Jurikova M, Kyselovic J . The PI3k/Akt pathway is associated with angiogenesis, oxidative stress and survival of mesenchymal stem cells in pathophysiologic condition in ischemia. Physiol Res. 2019; 68(Suppl 2):S131-S138. DOI: 10.33549/physiolres.934345. View

16.

He H, Zeng Q, Huang G, Lin Y, Lin H, Liu W . Bone marrow mesenchymal stem cell transplantation exerts neuroprotective effects following cerebral ischemia/reperfusion injury by inhibiting autophagy via the PI3K/Akt pathway. Brain Res. 2018; 1707:124-132. DOI: 10.1016/j.brainres.2018.11.018. View

17.

Currarino G, WILLIS K, Johnson Jr A, Miller W . Pulmonary telangiectasia. AJR Am J Roentgenol. 1976; 127(5):775-9. DOI: 10.2214/ajr.127.5.775. View

18.

Hou Y, Wang K, Wan W, Cheng Y, Pu X, Ye X . Resveratrol provides neuroprotection by regulating the JAK2/STAT3/PI3K/AKT/mTOR pathway after stroke in rats. Genes Dis. 2018; 5(3):245-255. PMC: 6176158. DOI: 10.1016/j.gendis.2018.06.001. View

19.

Wang B, Zheng W, Feng N, Wang T, Zou H, Gu J . The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone. Toxins (Basel). 2018; 10(10). PMC: 6215106. DOI: 10.3390/toxins10100398. View

20.

Xing Y, Wang M, Feng Y, Dong F, Zhang F . Possible Involvement of PTEN Signaling Pathway in the Anti-apoptotic Effect of Electroacupuncture Following Ischemic Stroke in Rats. Cell Mol Neurobiol. 2018; 38(8):1453-1463. PMC: 11469873. DOI: 10.1007/s10571-018-0615-4. View