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Panax ginseng alleviates diabetic peripheral neuropathy by suppressing mitochondrial dysfunction and oxidative stress via modulation of the RAGE, NF-κB, and Nrf2 pathways

Year: 2025
Type: article
Abstract: Background: Diabetic peripheral neuropathy (DPN) represents a prevalent complication associated with diabetes mellitus, characterized by progressive nerve degeneration that leads to chronic pain and sensory dysfunction. Existing treatment options are inadequate in addressing the multifaceted underlying mechanisms of DPN, underscoring the necessity for the development of novel multitarget therapeutic strategies. Methods: 's (GS) therapeutic efficacy using a multidisciplinary approach, administering the extract to diabetic rats for nerve assessments and conducting in vitro tests on Schwann cells and ND7/23 neuron cells under high glucose. Network pharmacology and molecular docking identified key targets and pathways, validated through experiments on mitochondrial function, oxidative stress, inflammation, and apoptosis. Results: Administration of GS significantly improved motor nerve conduction velocity, increased pain thresholds, and restored myelination in DPN rats. In vitro, GS enhanced RSC96 and ND7/23 cell viability and migration. Network pharmacology indicated GS modulates RAGE/NF-κB and Nrf2/PPARγ pathways, reducing oxidative stress, enhancing mitochondrial function, and lowering inflammatory cytokines. It also normalizes the Bcl2/Bax ratio to mitigate apoptosis. Conclusion: The findings of this study illustrate that GS mitigates DPN through a synergistic modulation of mitochondrial function, oxidative stress, neuroinflammation, and apoptosis pathways, with particularly significant effects on maintaining Schwann cell and Neuron cell functionality. Our results provide mechanistic insights that advocate for the repurposing of whole GS extract as a multitarget therapeutic agent for managing diabetic complications.
Authors: Pengcheng Liu, Teng Yang, Jie Zhang, Bang Su, Qidong Shi, Yao Song, Xin Yu
Language: English
Open Access status: diamond
OpenAlex ID: W4416573266
FWCI: 1.776
Cites: 42
Cited by: 7
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