Gymnema montanum H. protects against alloxan-induced oxidative stress and apoptosis in pancreatic beta-cells.
The present study evaluated the molecular mechanism of antidiabetic property of G. montanum leaf extract (GLEt) against alloxan-induced apoptotic cell death in rat insulinoma cells (RINm5F). The pre-treatment of GLEt (5 microg and 10 microg/ml) resulted in significant decrease in intracellular Ca(2+) concentration, nitric oxide (NO) production along with increase in mitochondrial membrane potential in alloxan (7mM/ml) treated cells. Further GLEt reduced apoptosis by inhibiting the release of cytochrome c and subsequent cleavage of PARP and caspase-3. The immunochemical staining of 8-hydroxydeoxyguanosine (8-OHdG) also evidenced the suppression of oxidative stress by GLEt. The cell cycle analysis, annexin-V labelling assay and TUNEL assay showed the suppression of apoptosis by the treatment of GLEt. Moreover, GLEt significantly increased the cellular antioxidant levels and decreased the lipid peroxides in alloxan-treated RINm5F cells. Taken together, these findings suggest that G. montanum protects pancreatic beta-cells against reactive oxygen species (ROS) by counteracting with mitochondrial membrane permeability and inhibition of the apoptotic pathway.
Ramkumar
Kunga M
KM
Department of Internal Medicine, Research Institute of Clinical Medicine and Diabetes Research Center, Chonbuk National University Medical School, Jeonju, South Korea.
Lee
Ae Sin
AS
Krishnamurthi
Kannan
K
Devi
Sivanesan Saravana
SS
Chakrabarti
Tapan
T
Kang
Kyung Pyo
KP
Lee
Sik
S
Kim
Won
W
Park
Sung Kwang
SK
Lee
Nae Ho
NH
Rajaguru
Palanisamy
P
D000496:Alloxan / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D031103:Gymnema / Q000737:chemistry*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000496:Alloxan; D010088:Oxidoreductases; D053148:Caspase 3; D002118:Calcium