Dantongding Formulation Alleviates Nerve Damage in Diabetic Peripheral Neuropathy Rats by Reducing Oxidative Stress Through Nrf2/Ho-1 Signaling Pathway

Rui Qian, Yun Zhang, Zhangjin Wei, Di Ma, Jie Yan, Yueqi Chen, Yao Liu and Hongyi Liu

Background and Objective: Diabetic peripheral neuropathy (DPN), affecting over 50% of diabetic patients, is a major cause of ulcers and amputation, severely impacting quality of life. Despite extensive research, DPN's mechanisms remain elusive. This study aims to explore the Traditional Chinese Medicine of Dantongding, particularly through the Nrf2/HO-1-mediated oxidative stress pathway, to advance DPN treatment strategies. Materials and Methods: A rat model of DPN was induced using a high-fat diet and streptozotocin (STZ) comprised of six groups. Histopathological changes in the sciatic nerves of rats were observed by Hematoxylin & Eosin (H&E) and Weil staining. The changes in sciatic nerve conduction velocity were measured. Serum malondialdehyde (MDA), superoxide dismutase (SOD), Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6) levels were measured. The mRNA and protein expression of Nrf2, HO-1 and p65 in the sciatic nerve was assessed using qRT-PCR and western blotting. Results: Compared to the control group, DPN rats exhibited characteristic changes in sciatic nerve tissue, including nerve fiber loss, vacuolar defects, axonal atrophy and myelin dissolution. Pathological damage to the sciatic nerve in the low-, medium- and high-dose dantongding formulation groups, as well as in the capsaicin group, showed varying degrees of improvement. Compared to the DPN group, the high-dose dantongding and capsaicin groups showed significant increases in sciatic nerve conduction velocity, serum SOD levels, Nrf2, HO-1 mRNA and protein levels, along with significant decreases in serum TNF-α, IL-6 and p65 mRNA and protein levels. Conclusion: The therapeutic effects of the Dantongding formulation on DPN in rats may be associated with the inhibition of oxidative stress, activation of the Nrf-2/HO-1 pathway and suppression of the Nuclear Factor kappa-B (NF-κB) pathway.

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