Qizhi Kebitong Formula Ameliorates Sciatic Nerve Injury in Streptozocin-induced Diabetic Mice through PERK/ATF4/CHOP Endoplasmic Reticulum Stress Signaling Pathway.

Background: The Qizhi Kebitong formula (QKF) has been utilized as a traditional Chinese medicine (TCM) remedy for over two decades in treating diabetic peripheral neuropathy (DPN) with notable clinical efficacy. However, its precise mechanism and bioactive constituents remain elusive.

Methods: Through ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) analysis was used to identify the primary components of QKF. Nerve conduction function in mice was assessed by measuring sensory thresholds and nerve conduction velocities. Laser speckle contrast imaging (LSCI) was used to examine the effect of QKF on foot pads and perineural blood flow in mice. Additionally, Transmission electron microscopy (TEM) and various pathologic stains were utilized to observe QKF's therapeutic effect on sciatic nerve (SN) damage in DPN mice. The impact of QKF on the pathological mechanism of the DPN model was explored through qRT-PCR, Western blot, and immunohistochemistry.

Results: Our results demonstrated that QKF improved phenotypic features in a mouse model of DPN, increased blood flow around the foot pad and SN, and somewhat repaired the pathological structure and function of SN. Furthermore, the study revealed that QKF slowed down the progression of DPN by inhibiting the endoplasmic reticulum (ER) stress apoptosis signaling pathway mediated by PERK/ATF4/CHOP pathway.

Conclusion: The significant neuroprotective effects of QKF in experimental DPN mice were confirmed by our findings, which offer important scientific evidence supporting its potential utilization in DPN treatment.