1, 2 di-substituted idopyranose from Vitex negundo L. protects against streptozotocin-induced diabetes by inhibiting nuclear factor-kappa B and inducible nitric oxide synthase expression.

The aim of this study is to investigate the mechanism of an action of compound isolated from Vitex negundo in streptozotocin-induced diabetic mice. Light microscopic examination of liver, kidney and pancreatic sections of streptozotocin-induced diabetic mice showed changes like coarsening of acinar cells of endoplasmic reticulum, destruction of ß-cells, and alteration in their secretory function were observed in the pancreas. Changes like dilation of vein, unusual concentric arrangement of hepatocytes, and liver fibrosis were observed in the liver. Thickening of tubules and expansion of glomerulus were observed in kidneys. All these altered parameters were reversed close to normal condition upon treatment using idopyranose. The results show the antidiabetic potential of idopyranose. Interestingly, liver, kidney, and pancreatic sections of diabetic mice fed with the isolated 1, 2 di-substituted idopyranose showed regeneration of hepatocytes, nephrocytes, as well as ß-cells and acinar region appeared normal with increased numbers of ß-cells. To understand the probable mechanism of action of 1, 2 di-substituted idopyranose, we analyzed proinflammatory inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) expression by immunohistochemistry and the results showed an increased iNOS and NF-κB levels in streptozotocin-induced diabetic liver, kidney and pancreas. Such high iNOS and NF-κB levels were inhibited in 1, 2 di-substituted idopyranose treated mice. The results suggest that 1, 2 di-substituted idopyranose helps in the protection of hepatocytes, nephrocytes and pancreatic ß-cells probably by its action against NF-κB and iNOS mediated inflammation in streptozotocin-induced diabetes.

Curcumin prevents free radical-mediated cataractogenesis through modulations in lens calcium.

The generation of free radicals has been implicated in the causation of cataract, and compounds that can scavenge free radicals ameliorate the disease process. This study investigated the possible free radical scavenging potential of curcumin at a dose of 75 mg/kg body wt on selenium-induced cataract in rat pups. Intraperitoneal injection of sodium selenite (15 micromol/kg body wt) into 8- to 10-day-old rat pups led to severe oxidative stress in the eye lens as evidenced by increased nitric oxide, superoxide anion, and hydroxyl radical generation and inducible nitric oxide synthase expression that probably led to cataract formation. Selenium exposure also caused an increase in total calcium in the eye lens and significantly inhibited the activity of Ca(2+) ATPase but not Na(+)/K(+) ATPase or Mg(2+) ATPase. On the other hand, pretreatment with curcumin, but not simultaneous or posttreatment, led to a decrease in oxidative stress and also rescued the selenium-mediated increase in lens Ca(2+) and inhibition of Ca(2+) ATPase activity in the eye lens. The results of this study demonstrate that an increase in free radical generation triggered by selenium could cause inactivation of lens Ca(2+) ATPase leading to Ca(2+) accumulation. This enhanced Ca(2+) can cause activation of calpain-mediated proteolysis in the lens, resulting in lens opacification. Curcumin in this study was able to prevent selenium-induced oxidative stress leading to activation of Ca(2+) ATPase and inhibition of lens opacification. Thus, curcumin has the potential to function as an anticataractogenic agent, possibly by preventing free radical-mediated accumulation of Ca(2+) in the eye lens.

Curcumin protects against hepatic and renal injuries mediated by inducible nitric oxide synthase during selenium-induced toxicity in Wistar rats.

The aim of this study is to evaluate the effect of curcumin in protecting against selenium-induced toxicity in liver and kidney of Wistar rats. Light microscopy evaluation of selenium alone administered rats showed liver to be infiltrated with mononuclear cells, vacuolation, necrosis, and pronounced degeneration. Control liver sections showed a regular morphology of parenchymal cells with intact hepatocytes and sinusoids. Kidney from selenium alone administered rats showed vacuolar degeneration changes in the epithelial cells, cellular proliferation with fibrosis, thickening of capillary walls, and glomerular tuft atrophy. Such changes were also observed in rats administered with selenium and curcumin simultaneously and rats administered first with selenium and then curcumin 24 h later. Interestingly, such degenerative changes observed in liver and kidney induced by selenium were not seen in rats that were administered with curcumin first and selenium 24 h later. This clearly suggests the protective nature of curcumin against selenium toxicity. To understand the probable mechanism of action of curcumin, we analyzed inducible nitric oxide synthase (iNOS) expression by immunohistochemistry, and the results showed an increased iNOS expression in selenium-alone induced liver and kidney. Such high iNOS levels were inhibited in liver and kidney of rats pretreated with curcumin and then with selenium 24 h later. Based on the histological results, it can be concluded that curcumin functions as a protective agent against selenium-induced toxicity in liver as well as kidney, and this action is probably by the regulatory role of curcumin on iNOS expression.