The antidiabetic activity of Momordica charantia (L.), Cucurbitaceae, a widely-used treatment for diabetes in a number of traditional medicine systems, was investigated in vitro. Antidiabetic activity has been reported for certain saponins isolated from M. charantia. In this study insulin secretion was measured in MIN6 β-cells incubated with an ethanol extract, saponin-rich fraction, and five purified saponins and cucurbitane triterpenoids from M. charantia, 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (1), momordicine I (2), momordicine II (3), 3-hydroxycucurbita-5,24-dien-19-al-7,23-di-O-β-glucopyranoside (4), and kuguaglycoside G (5). Treatments were compared to incubation with high glucose (27 mM) and the insulin secretagogue, glipizide (50 μM). At 125 μg/ml, an LC-ToF-MS characterized saponin-rich fraction stimulated insulin secretion significantly more than the DMSO vehicle, p=0.02. At concentrations 10 and 25 μg/ml, compounds 3 and 5 also significantly stimulated insulin secretion as compared to the vehicle, p≤0.007, and p= 0.002, respectively. This is the first report of a saponin-rich fraction, and isolated compounds from M. charantia, stimulating insulin secretion in an in vitro, static incubation assay.

Miller MW, Knaub LA, Olivera-Fragoso LF, Keller AC, Balasubramaniam V, Watson PA, Reusch JE. Nitric oxide regulates vascular adaptive mitochondrial dynamics. Am J Physiol Heart Circ Physiol 304: H1624 -H1633, 2013. First published April 12, 2013 doi:10.1152/ajpheart.00987.2012.-Cardiovascular disease risk factors, such as diabetes, hypertension, dyslipidemia, obesity, and physical inactivity, are all correlated with impaired endothelial nitric oxide synthase (eNOS) function and decreased nitric oxide (NO) production. NO-mediated regulation of mitochondrial biogenesis has been established in many tissues, yet the role of eNOS in vascular mitochondrial biogenesis and dynamics is unclear. We hypothesized that genetic eNOS deletion and 3-day nitric oxide synthase (NOS) inhibition in rodents would result in impaired mitochondrial biogenesis and defunct fission/fusion and autophagy profiles within the aorta. We observed a significant, eNOS expression-dependent decrease in mitochondrial electron transport chain (ETC) protein subunits from complexes I, II, III, and V in eNOS heterozygotes and eNOS null mice compared with age-matched controls. In response to NOS inhibition with N G -nitro-L-arginine methyl ester (L-NAME) treatment in Sprague Dawley rats, significant decreases were observed in ETC protein subunits from complexes I, III, and IV as well as voltagedependent anion channel 1. Decreased protein content of upstream regulators of mitochondrial biogenesis, cAMP response elementbinding protein and peroxisome proliferator-activated receptor-␥ coactivator-1␣, were observed in response to 3-day L-NAME treatment. Both genetic eNOS deletion and NOS inhibition resulted in decreased manganese superoxide dismutase protein. L-NAME treatment resulted in significant changes to mitochondrial dynamic protein profiles with decreased fusion, increased fission, and minimally perturbed autophagy. In addition, L-NAME treatment blocked mitochondrial adaptation to an exercise intervention in the aorta. These results suggest that eNOS/NO play a role in basal and adaptive mitochondrial biogenesis in the vasculature and regulation of mitochondrial turnover.endothelial nitric oxide synthase; vascular mitochondria THE VASCULATURE IS A COMPLEX tissue with a cellular architecture that permits specific contractile profiles for optimal tissue perfusion and adaptation to physiological demands. One of the primary regulators of physiological vasomotion is nitric oxide (NO), generated enzymatically by a family of nitric oxide synthases (NOS): endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS. In addition to the regulation of blood flow, NO modulates vascular structure and function through direct signaling to vascular endothelium, vascular smooth muscle cells, and inflammatory and adventitial cells (reviewed in Ref. 11). Endothelium-derived NO is a physiologically significant vasodilator and inhibitor of platelet aggregation and adhesion. Vascular NO also prevents leukocyte adhesion to the endothelium and inhibits proliferation of vas...