Jinmaitong, a Traditional Chinese Compound Prescription, Ameliorates the Streptozocin-Induced Diabetic Peripheral Neuropathy Rats by Increasing Sciatic Nerve IGF-1 and IGF-1R Expression.

Wei Song,Wen Jiang,Wei Liu,Ling Qu,Liyun Gong,Xiaochun Liang,Chao Wang,Jun Xie,Ying Sun

doi:10.3389/fphar.2019.00255

Abstract

Jinmaitong (JMT) is a Traditional Chinese Compound Prescription for the treatment of diabetic peripheral neuropathy (DPN). This study aims to investigate the effect of JMT on the insulin-like growth factor 1 (IGF-1) and the insulin like growth factor 1 receptor (IGF-1R) expression in sciatic nerves of diabetic rats. Firstly, the chemical profile of JMT was characterized by UPLC/Q-TOF-MS analysis. A total of 72 compounds were putatively identified. Secondly, streptozotocin (STZ)-induced diabetic rats were treated with neurotropin (NTP, 2.67 NU/kg/day) or JMT at low-dosage (0.4375 g/kg/day), medium-dosage (0.875 g/kg/day), and high-dosage (1.75 g/kg/day) for continuous 16 weeks. Blood glucose and body weight were detected every 4 weeks during the experiment. The mechanical pain and morphological change on sciatic nerves were detected by pain measurement instrument and microscopy. The IGF-1 level in serum and tissues were measured though ELISA and immunohistochemistry. The mRNA and protein expressions of IGF-1, IGF-1R, peripheral myelin protein zero (P0), and peripheral myelin protein 22 (PMP22) in the tissues were measured by qRT-PCR and western blot. As a result, JMT had no significant effect on body weight, but reduced the fasting blood glucose levels of diabetic rats. Besides, the pathological morphology, mechanical pain thresholds, serum level and tissue expression of IGF-1, mRNA, and protein levels of IGF-1R, P0, and PMP22 were significantly improved in JMT group at middle dosage. In conclusion, JMT could ameliorate the behavioristics and morphology changes in DPN rats by promoting IGF-1 and IGF-1R gene and protein expressions in sciatic nerves, as well as regulating the peripheral nerve remyelination genes P0 and PMP22 expressions, which provides scientific evidence for the clinical application of JMT in DPN patients.

Highlights

Diabetic peripheral neuropathy (DPN), the main type of diabetic neuropathy, is one of the most common chronic complications of diabetes
The present study aims to identify the main constituents in JMT and investigate the effect of JMT on specific markers of myelin sheath P0 and peripheral myelin protein 22 (PMP22), as well as insulin growth factors involved in demyelination and remyelination, such as insulin-like growth factor 1 (IGF-1) and insulin like growth factor 1 receptor (IGF-1R) in the sciatic nerve of a diabetic rat model
On the molecular biology level, the serum IGF-1 concentration of diabetic model (DM) rats was significantly reduced, and the expression of IGF-1, pIGF-1R, P0, and PMP22 protein and corresponding mRNA in the sciatic nerve of the DM rats was inhibited, suggesting that the peripheral nerve tissue myelin regeneration disorder in DM rats was associated with the inhibition of IGF-1 and its receptor IGF-1R

Summary

Introduction

Diabetic peripheral neuropathy (DPN), the main type of diabetic neuropathy, is one of the most common chronic complications of diabetes. Typical pathological manifestations of DPN include aregeneratory and demyelination of myelinated nerve fibers, axonal dislocation, neuronal degeneration, and regeneration delay (Zenker et al, 2013). Because of the existence of myelin sheath, the axon between the node of Ranvier is isolated from the outside world, the foundation for the fast jumping conduction of nerve impulse. The conduction speed of myelinated nerve fibers is faster than the unmyelinated. Once they are injured, it will take a long time for remyelination and repair, which is the main difficulty for nerve regeneration in DPN

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