Protective role of puerarin on lead-induced alterations of the hepatic glutathione antioxidant system and hyperlipidemia in rats.

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. The aim of the present study was to investigate the effects of puerarin on hepatic oxidative stress and hyperlipidemia in rats exposed to lead. Our data showed that puerarin significantly prevented lead-induced hepatotoxicity, indicated by both diagnostic indicators of liver damage (serum aminotransferase levels) and histopathological analysis. Moreover, lead-induced profound elevation of ROS production and oxidative stress, as evidenced by increasing of lipid peroxidation level, reducing of GPx, GST, GR and GCL activities and depleting of intracellular reduced GSH level in liver, were suppressed by treatment with puerarin. Furthermore, the increase of serum cholesterol, triglycerides and LDL induced by lead was effectively suppressed by puerarin. The HDL level in the lead treatment rats was also increased by puerarin. Western blot analysis showed that puerarin remarkably inhibited hyperlipidemia by regulating the expression of cholesterol 7a-hydroxylase (CYP7A1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and low-density lipoprotein receptor (LDL-R) in liver of lead treated rats. Altogether, these results suggest that puerarin could protect the lead-induced liver injury and hyperlipidemia by reducing ROS production, renewing the activities of antioxidant enzymes and influencing expression of hepatic lipid biosynthesis and metabolism genes.

Liu CM ，Ma JQ ，Sun YZ 《-》

Puerarin attenuates carbon tetrachloride-induced liver oxidative stress and hyperlipidaemia in mouse by JNK/c-Jun/CYP7A1 pathway.

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. The aim of this study was to investigate the effects of puerarin on hepatic oxidative stress and hyperlipidaemia in mice exposed to carbon tetrachloride (CCl4). Male ICR mice were injected with CCl4 with or without puerarin co-administration (200 and 400 mg/kg intragastrically once-daily) for 8 weeks. Our data showed that puerarin significantly prevented CCl4-induced hepatotoxicity, indicated by both diagnostic indicators of the liver damage (serum aminotransferase levels) and histopathological analysis. Puerarin decreased the thiobarbituric acid reactive substances (TBARS) and the protein carbonyl content (PCO) in the liver of CCl4-treated mice. Puerarin also restored the levels of reduced glutathione (GSH) and total antioxidant capacity (TAC) in the liver. Furthermore, the increase in serum cholesterol, triglycerides and low-density lipoproteins (LDL) induced by CCl4 was effectively suppressed by puerarin. The high-density lipoprotein (HDL) level in the CCl4 treatment mice was also increased by puerarin. Western blot analysis showed that puerarin remarkably inhibited hyperlipidaemia by regulating the expression of phosphorylated Jun N-terminal kinases (JNK), phosphorylated c-Jun protein and cholesterol 7a-hydroxylase (CYP7A1) in the liver of CCl4-treated mice. Altogether, these results suggest that puerarin could protect the CCl4-induced liver injury and hyperlipidaemia by reducing reactive oxygen species S production, renewing the total antioxidant capacity and influencing expression of hepatic lipid biosynthesis and metabolism genes.

Ma JQ ，Ding J ，Zhao H ，Liu CM ... -  《-》

Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway.

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.

Liu CM ，Ma JQ ，Sun YZ 《-》

Puerarin protects the rat liver against oxidative stress-mediated DNA damage and apoptosis induced by lead.

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. In this study, we valuated the protective effect of puerarin against lead-induced oxidative DNA damage and apoptosis in rat liver. A total of forty male Wistar rats (8-week-old) was divided into 4 groups: control group; lead-treated group (500 mg Pb/l as the only drinking fluid); lead+puerarin treated group (500 mg Pb/l as the only drinking fluid plus 400 mg PU/kg bwt intra-gastrically once daily); and puerarin-treated group (400 mg PU/kg bwt intra-gastrically once daily). The experimental period was lasted for 75 successive days. Our data showed that puerarin significantly effectively improved the lead-induced histology changes in rat liver and decreased the serum ALT and AST activities in lead-treated rats. Puerarin markedly restored Cu/Zn-SOD, CAT and GPx activities and the GSH/GSSG ratio in the liver of lead-treated rat. Furthermore, the increase of 8-hydroxydeoxyguanosine induced by lead was effectively suppressed by puerarin. The enhanced caspase-3 activity in the rat liver induced by lead was also inhibited by puerarin. TUNEL assay showed that lead-induced apoptosis in rat liver was significantly inhibited by puerarin, which might be attributed to its antioxidant property. In conclusion, these results suggested that puerarin could protect the rat liver against lead-induced injury by reducing ROS production, renewing the activities of antioxidant enzymes and decreasing DNA oxidative damage.

Liu CM ，Ma JQ ，Sun YZ 《-》

Hepatoprotective activity of puerarin against carbon tetrachloride-induced injuries in rats: a randomized controlled trial.

The protective effects of puerarin on liver damage were evaluated by carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. Male rats were orally treated with puerarin daily, and received CCl₄ intraperitoneally twice a week for 4 weeks. Our results showed that puerarin at doses of 50, 100, and 200 mg/kg b. w. significantly reduced the elevated activities of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase at least 15%, 17%, 14% and 18%, respectively. In addition, puerarin at different doses significantly decreased (p<0.05) the level of hepatic thiobarbituric acid reactive substances compared to the CCl₄-treated group. Furthermore, the treatment of puerarin was also found to significantly increase the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and glutathione content at least 40%, 12%, 25%, 52%, 17% and 44% in the liver of CCl₄-treated rats, respectively. Liver histopathology also showed that puerarin reduced the incidence of liver lesions induced by CCl₄. The results suggest that puerarin exhibits potent hepatoprotective effects on CCl₄-induced liver damages in rats, and that the hepatoprotective effects of puerarin may be due to both the inhibition of lipid peroxidation and to increase of antioxidant enzymes activity.

Xia DZ ，Zhang PH ，Fu Y ，Yu WF ，Ju MT ... -  《-》