Puerarin attenuates high-glucose-and diabetes-induced vascular smooth muscle cell proliferation by blocking PKCbeta2/Rac1-dependent signaling.
ABSTRACT Oxidative stress has been implicated in several steps leading to the development of diabetic vascular complications. The purpose of this study was to determine the efficacy and the possible mechanism of puerarin on high-glucose (HG; 25 mM)-induced proliferation of cultured rat vascular smooth muscle cells (VSMCs) and neointimal formation in a carotid arterial balloon injury model of obese Zucker rats. Our data demonstrated that puerarin significantly inhibited rat VSMC proliferation as well as reactive oxygen species (ROS) generation and NADPH oxidase activity induced by HG treatment. Further studies revealed that HG treatment resulted in phosphorylation and membrane translocation of PKCbeta2 as well as Rac1, p47phox, and p67phox subunits, leading to NADPH oxidase activation. Puerarin treatment remarkably disrupted the phosphorylation and membrane translocation of PKCbeta2 as well as Rac1, p47phox, and p67phox subunits. Blocking PKCbeta2 by infection with AdDNPKCbeta2 also abolished HG-induced phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits as well as ROS production and NADPH oxidase activation in VSMCs. In vivo neointimal formation of obese Zucker rats evoked by balloon injury was evidently attenuated by the administration of puerarin. These results demonstrate that puerarin may exert inhibitory effects on HG-induced VSMC proliferation via interfering with PKCbeta2/Rac1-dependent ROS pathways, thus resulting in the attenuation of neointimal formation in the context of hyperglycemia in diabetes mellitus.
- SourceAvailable from: Chan-Min Liu[Show abstract] [Hide abstract]
ABSTRACT: Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against lead (Pb) induced injury in kidney have not been clarified. The aim of the present study was to investigate the effects of puerarin on renal oxidative stress and apoptosis in rats exposed to Pb. Wistar rats were exposed to lead acetate in the drinking water (500mg Pb/l) with or without puerarin co-administration (100, 200, 300 and 400mg PU/kg intragastrically once daily) for 75days. Our data showed that puerarin significantly prevented Pb-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of kidney damage (serum urea, uric acid and creatinine) and histopathological analysis. Moreover, Pb-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of intracellular reduced glutathione (GSH) level in kidney, were suppressed by treatment with puerarin. Furthermore, TUNEL assay showed that Pb-induced apoptosis in rat kidney was significantly inhibited by puerarin. In exploring the underlying mechanisms of puerarin action, we found that activities of caspase-3 were markedly inhibited by the treatment of puerarin in the kidney of Pb-treated rats. Puerarin increased phosphorylated Akt, phosphorylated eNOS and NO levels in kidney, which in turn inactivated pro-apoptotic signaling events including inhibition of mitochondria cytochrome c release and restoration of the balance between pro- and anti-apoptotic Bcl-2 proteins in kidney of Pb-treated rats. In conclusion, these results suggested that the inhibition of Pb-induced apoptosis by puerarin is due at least in part to its antioxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.Toxicology and Applied Pharmacology 12/2011; 258(3):330-42. DOI:10.1016/j.taap.2011.11.015 · 3.63 Impact Factor
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ABSTRACT: Puerarin accumulation during shoot cultures in static and liquid medium with or without aeration is described in Pueraria tuberosa (Roxb. ex Willd.) DC. Maximum shoot induction from nodal explants was achieved on Murashige and Skoog's medium supplemented with 1.13 μM TDZ and 0.25 μM IBA after 4 weeks of growth. Puerarin content was higher in shoot cultures grown in liquid medium as compared to static medium. When shoots were grown in growtek bioreactor with different aeration volume, maximum puerarin content (1484 μg/g DW) was recorded with 20 % v/v aeration which was ~2.3 fold higher than puerarin content recorded in control cultures (cultures grown in growtek without aeration). Aeration requirement for organized (shoot) cultures was different for growth and puerarin accumulation.Physiology and Molecular Biology of Plants 03/2011; 17(1):87-92. DOI:10.1007/s12298-011-0049-7
- European Journal of Integrative Medicine 12/2009; 1(4):246-246. DOI:10.1016/j.eujim.2009.08.045 · 0.65 Impact Factor