Objective  To explore the ameliorative effect of puerarin on diabetic peripheral neuropathy (DPN) in rats and its possible mechanism.

Methods  A total of 50 SD rats were randomly divided into control group, model group (DPN model was constructed), low-dose puerarin group (20 mg/kg puerarin was intraperitoneally injected after DPN model was constructed), high-dose puerarin group (40 mg/kg puerarin was intraperitoneally injected after DPN model was constructed), RAGE inhibitor group (0.5 mg/kg FPS- ZM1 was intraperitoneally injected after DPN model was constructed), with 10 rats in each group. After administration, the fasting blood glucose, blood lipid index and inflammatory index of rats in each group were measured, and mechanical pain threshold, thermal pain threshold, motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) were detected, the pathological changes of sciatic nerve in each group were observed through HE stain and transmission electron microscope. The content of AGEs and the expression of receptor for advanced glycation end products (RAGE) in sciatic nerve of rats in each group was detected by colorimetry and Western blot.

Results  Compared with the control group, fasting blood glucose, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) levels of rats in model group were significantly increased, high-density lipoprotein (HDL) levels were significantly decreased, the levels of inflammatory factors such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly increased, mechanical pain threshold, MNCV and SNCV were significantly decreased, heat pain threshold was significantly increased, the injury of sciatic nerve and pathological change of myelin sheath were obvious, AGEs content and RAGE protein relative expression level in sciatic nerve were significantly increased (P<0.05). Compared with model group, fasting blood glucose, TC, TG and LDL levels were significantly decreased, HDL levels were significantly increased, IL-1β, IL-6 and TNF-α contents were significantly decreased, mechanical pain threshold, MNCV and SNCV were significantly increased, and thermal pain threshold was significantly decreased, the injury of sciatic nerve and the pathological structure of myelin sheath of rats were improved to varying degrees, AGEs content and RAGE protein relative expression in sciatic nerve were decreased significantly (P<0.05) in low-dose puerarin group and high-dose puerarin group. Compared with the puerarin low dose group, the effect of puerarin high-dose group and RAGE inhibitor group was more obvious.

Conclusion  Puerarin can improve blood glucose and blood lipid levels in DPN rats, reduce serum inflammatory factors, neurological damage and histological damage, and this mechanism may be related to inhibiting the activation of AGEs/RAGE signaling pathway.

1.Yu MG, Gordin D, Fu J, et al. Protective factors and the pathogenesis of complications in diabetes[J]. Endocr Rev, 2024, 45(2): 227-252. DOI: 10.1210/endrev/bnad030.

2.Zhu J, Hu Z, Luo Y, et al. Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment[J]. Front Endocrinol (Lausanne), 2024, 14: 1265372. DOI: 10.3389/fendo.2023. 1265372.

3.申格格,周洁,付建芳,等. 高尿酸血症在糖尿病周围神经病变发病机制中的研究进展[J]. 医学新知, 2024, 34(4): 466-472. [Shen GG, Zhou J, Fu JF, et al. Research progress on the pathogenesis of hyperuricemia in diabetic peripheral neuropathy[J]. Yixue Xinzhi Zazhi, 2024, 34(4): 466-472.] DOI: 10.12173/j.issn.1004-5511.202309078.

4.Chauhan P, Wadhwa K, Mishra R, et al. Investigating the potential therapeutic mechanisms of puerarin in neurological diseases[J]. Mol Neurobiol, 2024, 61(12): 10747-10769. DOI: 10.1007/s12035-024-04222-4.

5.Wang D, Bu T, Li YQ, et al. Pharmacological activity, pharmacokinetics, and clinical research progress of puerarin[J]. Antioxidants (Basel), 2022, 11(11): 2121. DOI: 10.3390/antiox11112121.

6.Bai YL, Han LL, Qian JH, et al. Molecular mechanism of puerarin against diabetes and its complications[J]. Front Pharmacol, 2022, 12: 780419. DOI: 10.3389/fphar.2021.780419.

7.Wang C, Yao J, Ju L, et al. Puerarin ameliorates hyperglycemia in HFD diabetic mice by promoting β-cell neogenesis via GLP-1R signaling activation[J]. Phytomedicine, 2020, 70: 153222. DOI: 10.1016/j.phymed.2020.153222.

8.Hou BY, Zhao YR, Ma P, et al. Hypoglycemic activity of puerarin through modulation of oxidative stress and mitochondrial function via AMPK[J]. Chin J Nat Med, 2020, 18(11): 818-826. DOI: 10.1016/S1875-5364(20)60022-X.

9.曾小红. 葛根素注射液治疗2型糖尿病并发周围神经病变的疗效[J]. 深圳中西医结合杂志, 2020, 30(3): 28-29. [Zeng  XH. Efficacy of puerarin injection in the treatment of type 2 diabetes mellitus complicated with peripheral neuropathy[J]. Shenzhen Journal of Integrated Traditional Chinese and Western Medicine, 2020, 30(3): 28-29.] DOI: 10.16458/j.cnki.1007-0893.2020.03.014.

10.Khalid M, Adem A. The dynamic roles of advanced glycation end products[J]. Vitam Horm, 2024, 125: 1-29. DOI: 10.1016/bs.vh.2024.02.008.

11.赵静,张建,胡爱民. 补阳还五汤对糖尿病周围神经病变大鼠的止痛作用及机制研究[J]. 广州中医药大学学报, 2024, 41(4): 1002-1010. [Zhao J, Zhang J, Hu AM. Study on the analgesic effect and mechanism of Buyang Huanwu Decoction on diabetic peripheral neuropathy rats[J]. Journal of Guangzhou University of Traditional Chinese Medicine, 2024, 41(4): 1002-1010.] DOI: 10.13359/j.cnki.gzxbtcm.2024.04.028.

12.孔令娟,计小清,刘岩,等. 葛根素通过调控AMPK/GSK-3β/β-catenin信号通路缓解糖尿病大鼠心肌损伤[J]. 中药材, 2023, 46(2): 474-478. [Kong LJ, Ji XQ, Liu Y, et al. Puerarin alleviates myocardial damage in diabetic rats by regulating AMPK/GSK-3β/β-catenin signaling pathway[J]. Journal of Chinese Medicinal Materials, 2023, 46(2): 474-478.] DOI: 10.13863/j.issn1001-4454.2023.02.035.

13.Sun H, Saeedi P, Karuranga S, et al. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045[J]. Diabetes Res Clin Pract, 2022, 183: 109119. DOI: 10.1016/j.diabres.2021.109119.

14.Elafros MA, Andersen H, Bennett DL, et al. Towards prevention of diabetic peripheral neuropathy: clinical presentation, pathogenesis, and new treatments[J]. Lancet Neurol, 2022, 21(10): 922-936. DOI: 10.1016/S1474-4422(22)00188-0.

15.Khalid M, Petroianu G, Adem A. Advanced glycation end products and diabetes mellitus: mechanisms and perspectives[J]. Biomolecules, 2022, 12(4): 542. DOI: 10.3390/biom12040542.

16.Vitorakis N, Piperi C. Pivotal role of AGE-RAGE axis in brain aging with current interventions[J]. Ageing Res Rev, 2024, 100: 102429. DOI: 10.1016/j.arr.2024.102429.

17.Wang X, Li Q, Han X, et al. Electroacupuncture alleviates diabetic peripheral neuropathy by regulating glycolipid-related GLO/AGEs/RAGE axis[J]. Front Endocrinol (Lausanne), 2021, 12: 655591. DOI: 10.3389/fendo.2021.655591.

18.Cheng Y, Chen Y, Li K, et al. How inflammation dictates diabetic peripheral neuropathy: an enlightening review[J]. CNS Neurosci Ther, 2024, 30(4): e14477. DOI: 10.1111/cns.14477.

19.Sun J, Wei N, Yu C, et al. Natural polysaccharides: the potential biomacromolecules for treating diabetes and its complications via AGEs-RAGE-oxidative stress axis[J]. Int Immunopharmacol, 2024, 143(2): 113426. DOI: 10.1016/j.intimp.2024.113426.

20.Liang T, Xu X, Ye D, et al. Caspase/AIF/apoptosis pathway: a new target of puerarin for diabetes mellitus therapy[J]. Mol Biol Rep, 2019, 46(5): 4787-4797. DOI: 10.1007/s11033-021-07112-3.

21.Kaur M, Misra S, Swarnkar P, et al. Understanding the role of hyperglycemia and the molecular mechanism associated with diabetic neuropathy and possible therapeutic strategies[J]. Biochem Pharmacol, 2023, 215: 115723. DOI: 10.1016/j.bcp. 2023.115723.

22.Xie B, Wang Q, Zhou C, et al. Efficacy and safety of the injection of the traditional Chinese medicine puerarin for the treatment of diabetic peripheral neuropathy: a systematic review and Meta-analysis of 53 randomized controlled trials[J]. Evid Based Complement Alternat Med, 2018, 2018: 2834650. DOI: 10.1155/2018/2834650.