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题名:Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models.
作者:YAO XG; CHEN F; LI P; QUAN L; CHEN J; YU L; DING H; LI C; CHEN L; GAO Z; WAN P; HU L; JIANG H; SHEN X;
来源:J Ethnopharmacol. 2013 Sep 5. pii: S0378-8741(13)00597-7. doi: [ IF= 0.00 ] ]
URL :10.1016/j.jep.2013.08.043
日期:20131002
摘要:ETHNOPHARMACOLOGICAL RELEVANCE: Catharanthus roseus (L). Don (Catharanthus
roseus) is a traditional anti-diabetic herb widely used in many countries, and
the alkaloids of Catharanthus roseus are considered to possess hypoglycemic
ability. AIM OF THE STUDY: To systematically investigate the potential
anti-diabetic effects and the underlying anti-diabetic mechanisms of vindoline,
one of the alkaloids in Catharanthus roseus. MATERIALS AND METHODS: The
regulation of vindoline against the glucose-stimulated insulin secretion (GSIS)
was examined in insulinoma MIN6 cells and primary pancreatic islets. Insulin
concentration was detected by Elisa assay. Diabetic models of db/db mice and type
2 diabetic rats induced by high-fat diet combining with streptozotocin
(STZ/HFD-induced type 2 diabetic rats) were used to evaluate the anti-diabetic
effect of vindoline in vivo. Daily oral treatment with vindoline (20mg/kg) to
diabetic mice/rats for 4 weeks, body weight and blood glucose were determined
every week, oral glucose tolerance test (OGTT) was performed after 4 weeks.
RESULTS: Vindoline enhanced GSIS in both glucose- and dose-dependent manners
(EC50=50muM). It was determined that vindoline acted as a Kv2.1 inhibitor able to
reduce the voltage-dependent outward potassium currents finally enhancing insulin
secretion. It protected beta-cells from the cytokines-induced apoptosis following
its inhibitory role in Kv2.1. Moreover, vindoline (20mg/kg) treatment
significantly improved glucose homeostasis in db/db mice and STZ/HFD-induced type
2 diabetic rats, as reflected by its functions in increasing plasma insulin
concentration, protecting the pancreatic beta-cells from damage, decreasing
fasting blood glucose and glycated hemoglobin (HbA1c), improving OGTT and
reducing plasma triglyceride (TG). CONCLUSION: Our findings suggested that
vindoline might contribute to the anti-diabetic effects of Catharanthus roseus,
and this natural product may find its more applications in the improvement of
beta-cell dysfunction and further the potential treatment of type 2 diabetes.

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