The increase in autophagy induced by naringin alleviates Schwann cell apoptosis mediated by the AMPK/mTOR signalling pathway

Abstract Background Peripheral nerve injury (PNI) is currently an intractable disease for clinical therapeutics. Schwann cells (SCs) play pivotal roles in peripheral nerve regeneration. Naringin, a natural flavonoid, has potent beneficial effects on peripheral neuropathy. Researchers have rarely rep...

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Main Authors: Jianwei Lv, Duo Shan, Haobo Jia, Zengliang Wang
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-025-05969-9
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author Jianwei Lv
Duo Shan
Haobo Jia
Zengliang Wang
author_facet Jianwei Lv
Duo Shan
Haobo Jia
Zengliang Wang
author_sort Jianwei Lv
collection DOAJ
description Abstract Background Peripheral nerve injury (PNI) is currently an intractable disease for clinical therapeutics. Schwann cells (SCs) play pivotal roles in peripheral nerve regeneration. Naringin, a natural flavonoid, has potent beneficial effects on peripheral neuropathy. Researchers have rarely reported whether naringin attenuates SC apoptosis and the relevant mechanisms. Therefore, this study aimed to evaluate the antiapoptotic effects of naringin on SCs and probe the potential molecular mechanisms involved. Methods An in vitro SC apoptotic model was established by culturing RSC96 cells in foetal bovine serum (FBS)-free medium, namely, serum starvation. SC apoptosis was assessed by TUNEL staining and flow cytometry. The activities of the mitochondrial apoptotic pathway and autophagy in SCs were detected by western blotting and immunofluorescence staining. The autophagy inhibitor 3-methyladenine (3-MA) and the AMPK inhibitor Compound C were used to investigate whether autophagy mediated by AMPK/mTOR signalling is involved in the regulation of SC apoptosis by naringin. Results The results showed that starvation induced SC apoptosis and blocked autophagic flux. Naringin ameliorated SC apoptosis under starvation conditions by increasing the autophagy activity mediated by the AMPK/mTOR cascade, as Compound C inhibited its autophagy-activating effect, and 3-MA reversed its antiapoptotic efficacy. Conclusions Naringin mitigated starvation-induced SC apoptosis by increasing autophagy, which was attributed to the regulation of the AMPK/mTOR pathway. This study provides evidence that naringin could be an effective alternative drug for promoting peripheral nerve regeneration.
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spelling doaj-art-7ee9dc440cef435da918f589301bafb82025-08-20T03:10:34ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2025-06-0120111310.1186/s13018-025-05969-9The increase in autophagy induced by naringin alleviates Schwann cell apoptosis mediated by the AMPK/mTOR signalling pathwayJianwei Lv0Duo Shan1Haobo Jia2Zengliang Wang3Department of Orthopaedics, Tianjin HospitalDepartment of Orthopaedics, Tianjin HospitalDepartment of Orthopaedics, Tianjin HospitalDepartment of Orthopaedics, Tianjin HospitalAbstract Background Peripheral nerve injury (PNI) is currently an intractable disease for clinical therapeutics. Schwann cells (SCs) play pivotal roles in peripheral nerve regeneration. Naringin, a natural flavonoid, has potent beneficial effects on peripheral neuropathy. Researchers have rarely reported whether naringin attenuates SC apoptosis and the relevant mechanisms. Therefore, this study aimed to evaluate the antiapoptotic effects of naringin on SCs and probe the potential molecular mechanisms involved. Methods An in vitro SC apoptotic model was established by culturing RSC96 cells in foetal bovine serum (FBS)-free medium, namely, serum starvation. SC apoptosis was assessed by TUNEL staining and flow cytometry. The activities of the mitochondrial apoptotic pathway and autophagy in SCs were detected by western blotting and immunofluorescence staining. The autophagy inhibitor 3-methyladenine (3-MA) and the AMPK inhibitor Compound C were used to investigate whether autophagy mediated by AMPK/mTOR signalling is involved in the regulation of SC apoptosis by naringin. Results The results showed that starvation induced SC apoptosis and blocked autophagic flux. Naringin ameliorated SC apoptosis under starvation conditions by increasing the autophagy activity mediated by the AMPK/mTOR cascade, as Compound C inhibited its autophagy-activating effect, and 3-MA reversed its antiapoptotic efficacy. Conclusions Naringin mitigated starvation-induced SC apoptosis by increasing autophagy, which was attributed to the regulation of the AMPK/mTOR pathway. This study provides evidence that naringin could be an effective alternative drug for promoting peripheral nerve regeneration.https://doi.org/10.1186/s13018-025-05969-9Schwann cellNaringinAutophagyApoptosisAMPKPeripheral nerve regeneration
spellingShingle Jianwei Lv
Duo Shan
Haobo Jia
Zengliang Wang
The increase in autophagy induced by naringin alleviates Schwann cell apoptosis mediated by the AMPK/mTOR signalling pathway
Journal of Orthopaedic Surgery and Research
Schwann cell
Naringin
Autophagy
Apoptosis
AMPK
Peripheral nerve regeneration
title The increase in autophagy induced by naringin alleviates Schwann cell apoptosis mediated by the AMPK/mTOR signalling pathway
title_full The increase in autophagy induced by naringin alleviates Schwann cell apoptosis mediated by the AMPK/mTOR signalling pathway
title_fullStr The increase in autophagy induced by naringin alleviates Schwann cell apoptosis mediated by the AMPK/mTOR signalling pathway
title_full_unstemmed The increase in autophagy induced by naringin alleviates Schwann cell apoptosis mediated by the AMPK/mTOR signalling pathway
title_short The increase in autophagy induced by naringin alleviates Schwann cell apoptosis mediated by the AMPK/mTOR signalling pathway
title_sort increase in autophagy induced by naringin alleviates schwann cell apoptosis mediated by the ampk mtor signalling pathway
topic Schwann cell
Naringin
Autophagy
Apoptosis
AMPK
Peripheral nerve regeneration
url https://doi.org/10.1186/s13018-025-05969-9
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