Tangbikang Granules Improve Diabetic Peripheral Neuropathy by Inhibiting Ferroptosis via AMPK/Nrf2 Signaling Pathway
10.13422/j.cnki.syfjx.20252328
- VernacularTitle:糖痹康颗粒通过调控AMPK/Nrf2信号通路抑制铁死亡改善糖尿病周围神经病变
- Author:
Zehong YANG
1
;
Tonghua LIU
2
;
Xiaohong MU
3
;
Yaqi ZHANG
4
;
Huizhong BAI
3
;
Lingling QIN
5
;
Xiaolei JIA
1
Author Information
1. The Third Affiliated Hospital， Beijing University of Chinese Medicine，Beijing 100029，China
2. International Joint Research Center for Traditional Chinese Medicine in Diabetes Prevention and Treatment， Ministry of Science and Technology，Beijing 100029，China
3. Dongzhimen Hospital， Beijing University of Chinese Medicine，Beijing 100700，China
4. Henan Luoyang Orthopedic Hospital Zhengzhou Campus，Zhengzhou 450000，China
5. Beijing University of Chinese Medicine，Beijing 100029，China
- Publication Type:Journal Article
- Keywords:
Tangbikang granules;
ferroptosis;
diabetic peripheral neuropathy;
adenosine monophosphate-activated protein kinase （AMPK）;
nuclear factor erythroid 2-related factor 2 （Nrf2）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(9):52-60
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 （AMPK/Nrf2） signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty （ZDF） rats. After successful modeling， the rats were divided into a normal group， a model group， high-， medium-， and low-dose Tangbikang granules groups， and a metformin hydrochloride group. The high-， medium-， and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5， 1.25， 0.625 g·kg-1， respectively. The metformin hydrochloride group received 0.135 g·kg-1 by gavage， while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration， and at 4， 8， 12 weeks. Following the 12-week intervention， the thermal pain threshold and the sciatic nerve conduction velocity （SNCV） were measured. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and adenosine triphosphate （ATP） in the sciatic nerve were measured using enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the sciatic nerve were observed using hematoxylin and eosin （HE） staining， and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 （GPx4） were detected using immunofluorescence （IF） assay. The protein expression levels of p-AMPK， Nrf2， GPx4， and acyl-CoA synthetase long-chain family member 4 （ACSL4） were detected using Western blot. ResultsCompared with the normal group， the model group had significantly higher blood glucose levels after administration and at weeks 4， 8 and 12 （P<0.01）. The thermal pain threshold was significantly prolonged （P<0.01）， and the SNCV was significantly slowed down （P<0.01）. The SOD and ATP levels significantly decreased （P<0.01）， while the MDA levels significantly increased （P<0.01）. Pathologically， the sciatic nerve fibers in the model group showed a dispersed structure， disordered and sparse arrangement， axonal atrophy， irregular myelin sheath halo， increased and swollen Schwann cell nuclei， obvious endoneurial fibrosis， and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 （P<0.01）. Western blot analysis showed significantly decreased protein expression levels of p-AMPK， Nrf2， and GPx4 （P<0.01）， and significantly increased expression of ACSL4 （P<0.01） in the model group. Compared with the model group， fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 （P<0.05）. The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SOD levels were significantly elevated in the high-dose Tangbikang granules group （P<0.01）. The MDA levels significantly decreased in all Tangbikang granules groups （P<0.01）. Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups （P<0.01）. The protein expression levels of p-AMPK， Nrf2， and GPx4 were significantly increased （P<0.01）， while ACSL4 protein expression significantly decreased （P<0.01）. ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.
