Tang Bi formula alleviates diabetic sciatic neuropathy via AMPK/PGC-1α/MFN2 pathway activation
Abstract Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus, which affects various regions of the nervous system. Tang Bi formula (TBF) has been proven effective for DPN, while the underlying mechanism remains unclarified. This study aimed to cl...
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Nature Portfolio
2025-07-01
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| author | Cunqing Yang Honghai Yu Linfeng Zhou Hang Su Xiangyan Li Wenxiu Qi Fengmei Lian |
| author_facet | Cunqing Yang Honghai Yu Linfeng Zhou Hang Su Xiangyan Li Wenxiu Qi Fengmei Lian |
| author_sort | Cunqing Yang |
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| description | Abstract Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus, which affects various regions of the nervous system. Tang Bi formula (TBF) has been proven effective for DPN, while the underlying mechanism remains unclarified. This study aimed to clarifiy the neurprotective mechanism of TBF intervention in DPN through animal and cell models. UHPLC/QTOF-MS and network pharmacology analysis were utilized to identify the bioactive components and potential targets of TBF. DPN models were established in rats and Schwann cells to evaluate the therapeutic effects of TBF. In the DPN rats, body weight, fasting blood glucose, mechanical withdrawal threshold (MWT), paw withdrawal latency (PWL), sciatic motor nerve conduction velocity (MNCV), and sciatic nerve blood flow were measured. Pathological sections of the sciatic nerve (SN) were also examined. In vitro experiments, the Schwann cells (SCs) were cultured in a medium containing 30 mM glucose and treated with TBF for 48 h. Cell viability was assessed using the CCK-8 assay. The degree of apoptosis was evaluated by flow cytometry. The mitochondrial membrane potential was determined using JC—1 staining, and the generation of ROS was measured using DCFH—DA staining. Moreover, the expression levels of proteins related to the AMPK-PGC-1α-MFN2 pathway in the SN and SCs were detected. A total of 11 bioactive components of TBF were identified through UHPLC/QTOF-MS and network pharmacology analysis. In vivo experiments, MWT and PWL were decreased in DPN rats, which were restored after TBF administered daily for 12 weeks, TBF significantly attenuated thermal hyperalgesia and mechanical allodynia, and improved nerve conduction velocities. Further histopathological observations indicated that treatment with TBF promoted the regeneration of the myelin sheath of the SN, increased the density of intraepidermal nerve fibers, effectively improved distal microcirculation disorders, and alleviated demyelination and axonal degeneration. In vitro experiments were conducted to evaluate the protective effect of TBF on high-glucose-induced dysfunction of SCs. The data showed that treatment with TBF significantly inhibited the apoptosis of SCs. Meanwhile, TBF exhibited apparent antioxidant capacity, reducing the accumulation of intracellular ROS, and ameliorating mitochondrial dysfunction. Western blot analysis revealed that TBF activated the AMPK-PGC -1α-MFN2 pathway and upregulated the protein expressions of p-AMPK (Thr172), PGC-1α, and MFN2, suggesting that the neuroprotective effect of TBF was associated with the activation of this pathway. TBF ameliorated DPN by rectifying mitochondrial dynamic imbalance and modulating the activation of the AMPK-PGC-1α-MFN2 pathway. This, in turn, promoted neurogenesis and alleviated peripheral nerve lesions. Thus, this study demonstrated the therapeutic potential of TBF for DPN. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-3bd4b4142c3a4d139ebadb3a5c25a3962025-08-20T03:46:03ZengNature PortfolioScientific Reports2045-23222025-07-0115111810.1038/s41598-025-10513-0Tang Bi formula alleviates diabetic sciatic neuropathy via AMPK/PGC-1α/MFN2 pathway activationCunqing Yang0Honghai Yu1Linfeng Zhou2Hang Su3Xiangyan Li4Wenxiu Qi5Fengmei Lian6Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical SciencesDepartment of Traditional Chinese Medicine, Hunan University of Medicine General HospitalNortheast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese MedicineNortheast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese MedicineNortheast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese MedicineNortheast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese MedicineCollege of Traditional Chinese Medicine, Changchun University of Chinese MedicineAbstract Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus, which affects various regions of the nervous system. Tang Bi formula (TBF) has been proven effective for DPN, while the underlying mechanism remains unclarified. This study aimed to clarifiy the neurprotective mechanism of TBF intervention in DPN through animal and cell models. UHPLC/QTOF-MS and network pharmacology analysis were utilized to identify the bioactive components and potential targets of TBF. DPN models were established in rats and Schwann cells to evaluate the therapeutic effects of TBF. In the DPN rats, body weight, fasting blood glucose, mechanical withdrawal threshold (MWT), paw withdrawal latency (PWL), sciatic motor nerve conduction velocity (MNCV), and sciatic nerve blood flow were measured. Pathological sections of the sciatic nerve (SN) were also examined. In vitro experiments, the Schwann cells (SCs) were cultured in a medium containing 30 mM glucose and treated with TBF for 48 h. Cell viability was assessed using the CCK-8 assay. The degree of apoptosis was evaluated by flow cytometry. The mitochondrial membrane potential was determined using JC—1 staining, and the generation of ROS was measured using DCFH—DA staining. Moreover, the expression levels of proteins related to the AMPK-PGC-1α-MFN2 pathway in the SN and SCs were detected. A total of 11 bioactive components of TBF were identified through UHPLC/QTOF-MS and network pharmacology analysis. In vivo experiments, MWT and PWL were decreased in DPN rats, which were restored after TBF administered daily for 12 weeks, TBF significantly attenuated thermal hyperalgesia and mechanical allodynia, and improved nerve conduction velocities. Further histopathological observations indicated that treatment with TBF promoted the regeneration of the myelin sheath of the SN, increased the density of intraepidermal nerve fibers, effectively improved distal microcirculation disorders, and alleviated demyelination and axonal degeneration. In vitro experiments were conducted to evaluate the protective effect of TBF on high-glucose-induced dysfunction of SCs. The data showed that treatment with TBF significantly inhibited the apoptosis of SCs. Meanwhile, TBF exhibited apparent antioxidant capacity, reducing the accumulation of intracellular ROS, and ameliorating mitochondrial dysfunction. Western blot analysis revealed that TBF activated the AMPK-PGC -1α-MFN2 pathway and upregulated the protein expressions of p-AMPK (Thr172), PGC-1α, and MFN2, suggesting that the neuroprotective effect of TBF was associated with the activation of this pathway. TBF ameliorated DPN by rectifying mitochondrial dynamic imbalance and modulating the activation of the AMPK-PGC-1α-MFN2 pathway. This, in turn, promoted neurogenesis and alleviated peripheral nerve lesions. Thus, this study demonstrated the therapeutic potential of TBF for DPN.https://doi.org/10.1038/s41598-025-10513-0Diabetic peripheral neuropathy, UHPLC/QTOFMS, AMPKPGC1αMFN2 pathway, Mitochondrial dynamics, Schwann cell |
| spellingShingle | Cunqing Yang Honghai Yu Linfeng Zhou Hang Su Xiangyan Li Wenxiu Qi Fengmei Lian Tang Bi formula alleviates diabetic sciatic neuropathy via AMPK/PGC-1α/MFN2 pathway activation Scientific Reports Diabetic peripheral neuropathy, UHPLC/QTOF MS, AMPK PGC 1α MFN2 pathway, Mitochondrial dynamics, Schwann cell |
| title | Tang Bi formula alleviates diabetic sciatic neuropathy via AMPK/PGC-1α/MFN2 pathway activation |
| title_full | Tang Bi formula alleviates diabetic sciatic neuropathy via AMPK/PGC-1α/MFN2 pathway activation |
| title_fullStr | Tang Bi formula alleviates diabetic sciatic neuropathy via AMPK/PGC-1α/MFN2 pathway activation |
| title_full_unstemmed | Tang Bi formula alleviates diabetic sciatic neuropathy via AMPK/PGC-1α/MFN2 pathway activation |
| title_short | Tang Bi formula alleviates diabetic sciatic neuropathy via AMPK/PGC-1α/MFN2 pathway activation |
| title_sort | tang bi formula alleviates diabetic sciatic neuropathy via ampk pgc 1α mfn2 pathway activation |
| topic | Diabetic peripheral neuropathy, UHPLC/QTOF MS, AMPK PGC 1α MFN2 pathway, Mitochondrial dynamics, Schwann cell |
| url | https://doi.org/10.1038/s41598-025-10513-0 |
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