Vindoline

Bioorg Med Chem Lett. 2017 Mar 1;27(5):1316-1318.

Synthesis and glucose-stimulate insulin secretion (GSIS) evaluation of vindoline derivatives.[Pubmed: 28162858 ]

It is demonstrated that natural product Vindoline can enhance the glucose-stimulated insulin secretion (GSIS) in MIN6 cells with the EC50 value of 50.2μM. In order to improve the activities, a series of Vindoline derivatives are synthesized and evaluated in MIN6 cells.
CONCLUSIONS:
Compounds 4, 8, 17 and 24 show about 4.5 times more effective stimulation insulin secretion ability (EC50: 10.4, 14.2, 11.0 and 12.7μM, respectively) than Vindoline.

Chinese Pharmacological Bulletin, 2012, 28(8):1096 -100.

Relaxant effect of vindoline in isolated rat renal arteries.[Reference: WebLink]

To explore the underlying relaxation mechanisms of Vindoline in isolated rat renal arteries.
METHODS AND RESULTS:
: Rings were quickly isolated and suspended in a Multi Myograph System and changes of isometric tension were recorded in the absence or presence of different receptor inhibitors or ion channel blockers. Vindoline produced a dose-dependent relaxation in rings with or without endothelia contracted by phenylephrine or KCl. Treatment with TEA + or Ro-34-0432 slightly blunt the relaxation induced by Vindoline, whereas gliclamide, BaCl 2 or Y-27632 failed to affect this relaxant effect. Vindoline reduced the contraction evoked by CaCl 2 in Ca-free 60 mmol·L -1 K + Kreb's solution, as well as in (-)-Bay K8644 in 15 mmol·L -1 K + solution. In addition, Vindoline caused the parallel relaxation in rings with or without endothelia.
CONCLUSIONS:
The current results suggest that Vindoline dilates renal arteries in vitro through one or more pathways including inhibition of calcium entry, TEA + sensitive potassium channel or protein kinase pathways in vascular smooth muscle cells.

Pharmacologia, 2013, 4(2013):243-8.

Vincamine and Vindoline from Catharanthus roseus linn. Protects the Gastric Mucosa of Gastric Ulcer in Rats[Reference: WebLink]

Currently, natural products have been shown to present interesting biological and pharmacological activities and are used as chemotherapeutic agents. Plants have historically been used in treating cancer and are recognized for their ability to produce secondary metabolites. The current study was designed to evaluate the antiulcer activity of total extract as well as several fractions from Cantharanthus roseous Linn. (Family; Apocyanaceae) leaves. The bioassay guided chloroform fraction of the ethanol extract yielded two major compounds which have shown a promising antiulcer activity.
METHODS AND RESULTS:
C. roseus leaves were evaluated against Cold Restraint Ulcer (CRU), Aspirin (AS), Alcohol (AL) and Pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity was observed. Potential anti-ulcer activity was observed against CRU (75.18%), AS (50.00%), AL (65.00%) and PL (50.00%) induced ulcer models. The standard drug omeprazole (10 mg kg-1, p.o.) showed 77.34% protection against CRU, 57.08% against AS and 69.42% against PL induced ulcer model. Sucralfate, another standard drug (500 mg kg-1, p.o.) showed 62.72% protection in AL induced ulcer model. Ethanol extract of C. roseus leaves significantly reduced free acidity (17.78%), total acidity (8.05%) and up regulated mucin secretion by 25.11%, respectively. Phytochemical investigations of chloroform fraction yielded vincamine and Vindoline . Further, Fr-CHCl3 and its compounds vincamine and Vindoline significantly showing protection against CRU 81.08 and 81.20%, respectively, confirming their anti-ulcer activity.
METHODS AND RESULTS:
The anti-ulcerogenic activity of the chloroform fraction might be due to its anti-secretory activity. This study is the first of its kind to show significant anti-ulcer effect of C. roseus. Therefore, it could act as a potent therapeutic agent against peptic ulcer disease.

J Ethnopharmacol. 2013 Oct 28;150(1):285-97.

Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models.[Pubmed: 24012527]

To systematically investigate the potential anti-diabetic effects and the underlying anti-diabetic mechanisms of Vindoline, one of the alkaloids in Catharanthus roseus.
METHODS AND RESULTS:
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. Vindoline enhanced GSIS in both glucose- and dose-dependent manners (EC50 = 50 μM). 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 β-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 β-cells from damage, decreasing fasting blood glucose and glycated hemoglobin (HbA1c), improving OGTT and reducing plasma triglyceride (TG).
CONCLUSIONS:
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 β-cell dysfunction and further the potential treatment of type 2 diabetes.