Lycium Barbarum Polysaccharides Upregulate Trx2 in Schwann Cells through ESR1 to Repair Sciatic Nerve Injury in Rats
Guoxu Ma, Yonglu Huang, Fan Gong, Jianke Wu, Yi Ding, Ziyang Zhang, Xiaoliang Li, Jian Gao, Tingting Dang, Bowen Zhang*
Department of Hand and Foot Microsurgery, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
* Corresponding Author: Bowen Zhang. Email: 
(This article belongs to the Special Issue: Bioactive Natural Components as Regulators of Cellular Pathways and Disease Progression)
BIOCELL https://doi.org/10.32604/biocell.2026.078402
Received 30 December 2025; Accepted 24 February 2026; Published online 09 March 2026
Abstract
Objectives: Sciatic nerve injury (SNI) impairs quality of life, and
Lycium barbarum polysaccharides (LBP) may exert therapeutic effects via regulating Schwann cell (SC) mitochondrial stability, though the mechanism remains unclear. The study aimed to elucidate the therapeutic mechanisms of LBP in mitigating sciatic nerve injury by protecting Schwann cells via the estrogen receptor 1 (ESR1)/thioredoxin 2 (Trx2) pathway.
Methods: An
in vitro SNI model was established by inducing RSC96 cells with H
2O
2. Cell counting kit-8 (CCK8) assay, enzyme-linked immunosorbent assay (ELISA), Western blot, reactive oxygen species (ROS) and adenosine triphosphate (ATP) quantification, and mitochondrial membrane potential (MMP) detection were used to evaluate cellular functions and molecular changes. Network pharmacology and molecular docking were employed to predict potential targets of LBP. Chromatin immunoprecipitation (ChIP) assays verified the interaction between ESR1 and Trx2, and ESR1 was knocked down in SCs to confirm the regulatory pathway. Additionally,
in vivo validation was performed using a rat SNI model.
Results: LBP intervention significantly reduced H
2O
2-induced mitochondrial dysfunction, inflammation, and oxidative stress in RSC96 cells (
p < 0.05). It also regulated the expression of apoptosis-related proteins, Trx2, and mitochondrial apoptosis-inducing factor (AIF;
p < 0.001). Network pharmacology and molecular docking identified ESR1 as a key target of LBP, and ChIP assays confirmed that ESR1 promoted Trx2 transcription. Moreover, LBP enhanced SC proliferation (OD
450 at day 5 = 1.25-fold; colony formation = 1.85-fold), increased MMP and ATP levels (MMP = 2.25-fold; ATP = 1.75-fold), inhibited inflammation, and reduced apoptosis (
p < 0.001), while ESR1 knockdown abrogated these effects (
p < 0.05). In rat SNI models, LBP effectively alleviated nerve injury (
p < 0.001).
Conclusion: LBP may modulate Trx2 via ESR1 for the purpose of restoring the dysfunction of SCs induced by H
2O
2. This potentially offers a new strategy for the therapy of SNI.
Keywords
Lycium barbarum polysaccharide (LBP); sciatic nerve injury (SNI); Schwann cells (SCs); estrogen receptor 1 (ESR1); thioredoxin 2 (Trx2); mitochondrial membrane potential (MMP)
Open Access
Login
Register
Submit a Paper
Propose a Special lssue
Download PDF
Supplementary Material File
Downloads
Citation Tools
