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


METHODS
ELE at doses of 500 and 1000mg/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 1000mg/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.
Jin
Xin
X
Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
Amitani
Keisuke
K
Zamami
Yoshito
Y
Takatori
Shingo
S
Hobara
Narumi
N
Kawamura
Naomi
N
Hirata
Tetsuya
T
Wada
Atsunori
A
Kitamura
Yoshihisa
Y
Kawasaki
Hiromu
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D004326:Drinking; D031283:Eucommiaceae / Q000737:chemistry*; D005632:Fructose / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation*; D018515:Plant Leaves / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D005632:Fructose; D015740:Calcitonin Gene-Related Peptide