Ameliorative effect of Eucommia ulmoides Oliv. leaves extract (ELE) on insulin resistance and abnormal perivascular innervation in fructose-drinking rats

Aim of the study: Eucommia ulmoides Oliv. leaf is a traditional Chinese medicine that exhibits an anti-diabetic action. This study was designed to investigate whether long-term administration of Eucommia ulmoides Oliv. leaves extract (ELE) ameliorates pre-diabetic state of insulin resistance and abnormal perivascular innervation in the hyperinsulinemic state. Materials and methods: ELE at doses of 500 and 1000. mg/kg was administered orally once daily for 4 weeks in fructose-drinking rats (FDRs). Plasma levels of insulin, blood glucose levels, and perivascular innervation were assessed using biochemical and immunohistochemical methods. Results: FDR showed significant increase in plasma levels of insulin, an index for insulin resistance (Homeostasis Model Assessment ratio-HOMA-IR) and systolic blood pressure (SBP), but not blood glucose levels, as compared with control rats. Immunohistochemical study showed significantly greater density of tyrosine hydroxylase (TH)-like immunoreactivity (LI)-containing nerves and significantly lower density of calcitonin gene-related peptide (CGRP)-LI-containing nerves in mesenteric arteries of FDR than those in control. A 4-week treatment with ELE (500 and 1000. mg/kg, p.o.) significantly decreased plasma levels of insulin and HOMA-IR without affecting blood glucose levels and significantly lowered SBP in FDR. ELE treatment in FDR resulted in significant increase in CGRP-LI never fiber density and significant decrease in TH-LI never fiber density in mesenteric arteries of FDR. Conclusions: These results suggest that long-term ELE treatment effectively prevents insulin resistance development and ameliorates abnormal perivascular innervation in FDR.