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

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.

A Metabolic Insight Into the Neuroprotective Effect of Jin-Mai-Tong (JMT) Decoction on Diabetic Rats With Peripheral Neuropathy Using Untargeted Metabolomics Strategy

“…Presl. ], Rhizoma Corydalis (the rhizoma of Corydalis yanhusuo W. T. Wang), Semen Persicae (the seeds of Prunus persica L.), Senmen Cassiae [the seeds of Senna obtusifolia (L.) H. S. Irwin & Barneby], Radix et Rhizoma Asari (the radix and rhizoma of Asarum heterotropiodes F. Schmidt), and Hirudo (Hirudo nipponica W.), with a fixed ratio of 10: 10: 10: 10: 30: 3: 10: 10: 10: 30: 3: 3 as our previously report (Song et al, 2019). All the crude drugs were purchased from Tong Ren Tang Lit.…”

“…The electrospray ion source temperature and spray voltage were 450 • C and 4500 V, respectively. Following this approach, a total of 55 compounds were putatively identified by comparing their high-resolution MS data with reported data, all of which had been identified from a 1:1-combined methanol extract and water extract of JMT decoction in our previous study (Song et al, 2019). The base peak chromatography and detailed information of the 55 compounds were given in Supplementary Tables S1, S2 and Supplementary Figure S2.…”

“…After 12 weeks of treatment, mechanical sensitivity to noxious stimuli was assessed using an aesthesiometer of the Von Frey Pain Measurement Instrument (IITC Life Science Inc., Woodland Hills, CA, United States) (Choi et al, 2014;Yerra et al, 2018). As described earlier, after the rats adapted the surrounding environment, the hind paw was stimulated by a probe of the Von Frey instrument (Song et al, 2019). Mechanical pain threshold was measured as the force at which paw withdrawal was observed and recorded in grams.…”

“…We found that JMT decoction played the therapeutic role in reducing oxidative stress (Yin et al, 2015), increasing neurotrophic factors (Shi et al, 2013), inhibiting high glucose induced apoptosis of Schwann cells (Wang et al, 2013) and regulating autophagy in vivo and in vitro (Qu et al, 2016). Besides, our recent research found that JMT decoction could increase gene and protein expression of insulin-like growth factor 1 (IGF-1) and the insulin like growth factor 1 receptor (IGF-1R), as well as regulate the expression of nerve remyelination genes P0 and PMP22 in sciatic nerves of diabetic rats (Song et al, 2019). However, TCM has been characterized as a multi-target therapy and JMT decoction could be the same.…”

<p>Jinmaitong Ameliorates Diabetic Peripheral Neuropathy Through Suppressing TXNIP/NLRP3 Inflammasome Activation In The Streptozotocin-Induced Diabetic Rat Model</p>

“…The chemical profile of JMT was characterized by UPLC/Q-TOF-MS analysis and a total of 72 compounds were putatively identified. We recently published a representative chromatogram summarizing this characterization 10. According to our previous studies, JMT improved the clinical symptoms of numbness, cold, and pain experience in DPN patients, decreased blood glucose levels and lipid metabolism, and accelerated nerve conduction velocity, evidenced by clinical double-blind randomized controlled studies 11,12.…”