Protection of Trigonelline on Experimental Diabetic Peripheral Neuropathy

Abstract

The mechanisms leading to diabetic peripheral neuropathy are complex and there is no effective drug to treat it. As an active component of several traditional Chinese medicines, trigonelline has beneficial effects on diabetes with hyperlipidemia. The protective effects and the mechanism of trigonelline on diabetic peripheral neuropathy were evaluated in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Rats were divided into four groups at the end of week 2: control, diabetes, diabetes + trigonelline (40 mg/kg), and diabetes + sitagliptin (4 mg/kg). After 48-week treatment, technologies of nerve conduction, cold and hot immersion test, transmission electron microscopy, real-time PCR, and Western blotting were applied. Serum glucose, serum insulin, insulin sensitivity index, lipid parameters, body weight, sciatic nerve conduction velocity, nociception, glucagon-like peptide-1 receptor mRNA and protein, total and phosphorylated p38 mitogen-activated protein kinases protein expression, malonaldehyde content, and superoxide dismutase activity were altered in diabetic rats, and were near control levels treated with trigonelline. Slight micropathological changes existed in sciatic nerve of trigonelline-treated diabetic rats. These findings suggest that trigonelline has beneficial effects for diabetic peripheral neuropathy through glucagon-like peptide-1 receptor/p38 mitogen-activated protein kinases signaling pathway, nerve conduction velocity, antioxidant enzyme activity, improving micropathological changes of sciatic nerve and decreasing lipid peroxidation.

Trigonelline and vildagliptin antidiabetic effect: improvement of insulin signalling pathway

“…Moreover, insulin, HOMA‐IR and altered lipid profile were corrected. These results match previous findings in diabetic and insulin‐resistant rats . The current work verified the involvement of the crucial insulin signalling pathway in the antihyperglycemic effect of TRG.…”

Drug combinations in diabetic neuropathic pain: an experimental validation

“…These results are consistent with a previous study that has reported increased pain sensitivity following sitagliptin administration for 35 days in STZ-nicotinamide-induced diabetic neuropathy in rats [42]. However, another study has reported that administration of sitagliptin for 48 weeks significantly reversed the decrease in tail-flick latencies in STZ-induced diabetic animals [43]. Therefore, further studies are required to comment on the presumptive role of sitagliptin in the prevention/delay of progression of diabetic neuropathy.…”

Ameliorative Potential of Morin in Streptozotocin-Induced Neuropathic Pain in Rats

“…In the current investigation, male rats was employed as an experimental model due to male rodents' lack of hormonal fluctuation, which makes developing metabolic disease less difficult than in female rats. Moreover, the STZ model of diabetic morin treated, compared with diabetic untreated group DN used in the current and several other experimental investigations, is standardized against numerous reference anti-diabetic drugs such as glibenclamide and sitagliptin [27,28] as well as antineuropathic pain medications such as pregabalin [29].…”