Chinese Journal of Tissue Engineering Research ›› 2026, Vol. 30 ›› Issue (25): 6463-6471.doi: 10.12307/2026.433

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Grape seed proanthocyanidin oligomers alleviate demyelination in cuprizone-fed mice

Wang Qing1, Yang Zhichao1, Liu Jian1, Liang Yajie1, Tang Yibin1, Guo Yu1, Song Guobin2, Ma Cungen1, 2   

  1. 1Research Center of Neurobiology, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; 2Institute of Brain Science, Shanxi Datong University, Datong 037009, Shanxi Province, China
  • Received:2025-07-04 Revised:2026-01-26 Online:2026-09-08 Published:2026-04-17
  • Contact: Ma Cungen, PhD, Professor, Research Center of Neurobiology, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; Institute of Brain Science, Shanxi Datong University, Datong 037009, Shanxi Province, China
  • About author:Wang Qing, PhD, Research Center of Neurobiology, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China
  • Supported by:
    National Natural Science Foundation of China (Youth Fund), No. 81903596 (to WQ); Research Funding Project for Returned Overseas Chinese Scholars in Shanxi Province, No. 2022-165 (to WQ); Traditional Chinese Medicine Innovation Team of Shanxi Provincial Administration of Traditional Chinese Medicine, No. zyytd2024039 (to WQ); Basic Research Project of Shanxi Province, No. 202303021221162 (to WQ); Scientific Research Project of Shanxi Administration of Traditional Chinese Medicine, No. 2023ZYYB040 (to WQ); 2022 Traditional Chinese Medicine Scientific Research Project Plan of Shanxi Provincial Health Commission, No. 2022ZYYC090 (to MCG); 2022 Science and Technology Innovation Team of Shanxi University of Traditional Chinese Medicine, No. 2022TD2006 (to WQ); Basic Research on the Discipline of Integrated Traditional Chinese and Western Medicine for Neuritic Diseases at Shanxi University of Chinese Medicine, No. 2024XKJS-02 (to MCG)

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Abstract: BACKGROUND: Recent studies on the pathogenesis of multiple sclerosis suggest that intervening in glial cells may play a key role in reducing relapses and delaying disability progression. Grape seed proanthocyanidin oligomers significantly inhibit demyelination in cuprizone-treated mice.
OBJECTIVE: To explore the mechanism by which grape seed proanthocyanidin oligomers protect myelin sheaths through regulating astrocytes. 
METHODS: (1) Animal experiment: Thirty mice were randomly divided by body mass into a normal group, a cuprizone group, and a cuprizone+oligomeric proanthocyanidins group. The latter two groups were fed a diet containing 0.2% cuprizone daily for 6 weeks to induce a demyelination model. Starting from the 5th week, mice in the normal and cuprizone groups received oral administration of ddH₂O₂, while mice in the cuprizone+oligomeric proanthocyanidins group received oral administration of grape seed proanthocyanidin oligomers [50 mg/(kg·d)] once daily for 2 consecutive weeks. Behavioral changes in mice were observed, pathological changes of myelin sheaths using LFB and oil red O staining, inflammatory factor levels in the brain were measured using ELISA, and expression of relevant proteins in the brain was detected using immunofluorescence staining. (2) Cell experiment: Grape seed proanthocyanidin oligomers (30 μg/mL) were used to intervene in an astrocyte inflammation model in vitro induced by tumor necrosis factor-α, interleukin-1α, and C1q. Conditioned medium was collected and used to culture oligodendrocytes. Cells were then divided into normal, model, and model+oligomeric proanthocyanidin groups. Oligodendrocyte injury and cell viability were assessed using L-lactate dehydrogenase and cell counting kit-8 assays, while western blot assay was used to detect apoptosis-related protein expression.
RESULTS AND CONCLUSION: (1) Grape seed proanthocyanidin oligomers significantly ameliorated myelin loss in cuprizone-treated mice by suppressing pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, interleukin-1α, and interleukin-17) and promoting the secretion of anti-inflammatory transforming growth factor-β. This was accompanied by the proliferation of astrocytes, a significant reduction in C3d (a marker of proinflammatory astrocytes), and suppression of JNK (a signaling molecule associated with astrocyte polarization) phosphorylation in the corpus callosum. (2) Compared with the model group, conditioned medium treated with grape seed proanthocyanidin oligomers significantly reduced apoptosis in oligodendrocytes induced by inflammatory astrocytes, promoted Bcl-2 expression, and inhibited Bax and Caspase-3 expression in oligodendrocytes. To conclude, grape seed proanthocyanidin oligomers protect against cuprizone-induced demyelination by inhibiting JNK phosphorylation in astrocytes, thereby reducing pro-inflammatory A1 polarization and subsequently inhibiting apoptosis in oligodendrocytes induced by inflammatory astrocytes.

Key words: cuprizone, grape seed proanthocyanidin oligomers, astrocytes, inflammation, apoptosis, mouse

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