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.