ORIGINAL RESEARCH article
Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Inflammatory and Neurotoxic Risk of Atorvastatin in Diabetic Peripheral Neuropathy: TNF-Centered Evidence Integrating Network Toxicology, scRNA-Seq, and Cell Validation
Jing Chen
Meng Yuan
Siyu Mao
Yujun He
Xin Wang
Jingni Wang
Xingchun Wang
XINGXIA WANG
Southwest Medical University, Luzhou, China
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Abstract
Objective: To clarify atorvastatin's role in diabetic peripheral neuropathy (DPN) amid its controversial neuroprotective and neurotoxic effects. Methods: Integrated network toxicology, single-cell RNA sequencing (scRNA-seq), molecular docking, molecular dynamics simulations, and in vitro assays (CCK-8, ELISA) on high-glucose-induced RSC 96 Schwann cells. Results: Network toxicology identified TNF, CTNNB1, CASP3 as core targets (TNF as key hub), enriched in DPN-related pathways (oxidative stress, inflammation). scRNA-seq suggested that these targets are expressed in sensory neuron populations. Molecular docking and molecular dynamics simulations suggested that atorvastatin can interact with the selected targets, with relatively favorable predicted affinity for TNFα. In vitro, atorvastatin reduced cell viability in a time-and dose-dependent manner and was associated with increased TNFα levels under high-glucose conditions. Conclusion: Our findings are consistent with a potential involvement of TNF/TNFα-associated inflammatory responses in atorvastatin-related cellular injury under the tested in vitro conditions. Further TNFα blocking/knockdown experiments will be needed to determine causality.
Summary
Keywords
atorvastatin, DPN, molecular docking, Network toxicology, single-cell RNA sequencing, TNFα
Received
04 November 2025
Accepted
22 January 2026
Copyright
© 2026 Chen, Yuan, Mao, He, Wang, Wang, Wang and WANG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: XINGXIA WANG
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