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 ... -  《-》

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 《-》

Hepatoprotective properties of sesamin against CCl4 induced oxidative stress-mediated apoptosis in mice via JNK pathway.

Sesamin (Ses), one of the major lignan derived from sesame seeds, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl4) induced injury in liver have not been clarified. The aim of the present study was to investigate the hepatoprotective effects of sesamin on oxidative stress and apoptosis in mice exposed to CCl4. Our data showed that sesamin significantly prevented CCl4-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, CCl4-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of the total antioxidant capacity (TAC) in liver, were suppressed by treatment with sesamin. Furthermore, TUNEL assay showed that CCl4-induced apoptosis in mouse liver was significantly inhibited by sesamin. In exploring the underlying mechanisms of sesamin action, we found that activities of caspase-3 were markedly inhibited by the treatment of sesamin in the liver of CCl4 treated mice. Sesamin increased expression levels of phosphorylated Jun N-terminal kinases (JNK) in liver, which in turn inactivated pro-apoptotic signaling events restoring the balance between mitochondrial pro- and anti-apoptotic Bcl-2 proteins and decreasing the release of mitochondrial cytochrome c in liver of CCl4 treated mice. JNK was also involved in the mitochondrial extrinsic apoptotic pathways of sesamin effects against CCl4 induced liver injury by regulating the expression levels of phosphorylated c-Jun proteins, necrosis factor-alpha (TNF-α) and Bak. In conclusion, these results suggested that the inhibition of CCl4-induced apoptosis by sesamin is due at least in part to its anti-oxidant activity and its ability to modulate the JNK signaling pathway.

Ma JQ ，Ding J ，Zhang L ，Liu CM ... -  《-》

Ursolic acid protects mouse liver against CCl4-induced oxidative stress and inflammation by the MAPK/NF-κB pathway.

Ursolic acid (UA), a natural pentacyclic triterpenoid, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl(4)) induced hepatotoxicity have not been clarified. The aim of the present study was to investigate the effects of UA on oxidative stress and inflammation in liver of CCl(4) treated mice. Male ICR mice were injected with CCl(4) with or without UA co-administration (25 and 50 mg/kg intragastrically once daily) for one week. Our data showed that UA significantly prevented CCl(4)-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, CCl(4)-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of the total antioxidant capacity (TAC) level in liver, were suppressed by treatment with UA. Furthermore, western blot analysis showed that UA significantly decreased CYP2E1 expression levels and production of pro-inflammatory markers including TNF-α, IL-1β and COX-2 in CCl(4)-treated mouse liver. In exploring the underlying mechanisms of UA action, we found that UA decreased the activation of mitogen-activated protein kinases (JNK, p38 MAPK, ERK), which in turn inactivated the immunoregulatory transcription factor nuclear factor kappa B (NF-κB) in liver of CCl(4) treated mice. In conclusion, these results suggested that the inhibition of CCl(4)-induced inflammation by UA is due at least in part to its anti-oxidant activity and its ability to modulate the MAPK and NF-κB signaling pathway.

Ma JQ ，Ding J ，Zhang L ，Liu CM ... -  《-》

Puerarin ameliorates carbon tetrachloride-induced oxidative DNA damage and inflammation in mouse kidney through ERK/Nrf2/ARE pathway.

Puerarin (PU), a natural flavonoid, has been shown to possess many benefits and medicinal properties. In this study, we evaluated the effect of puerarin on oxidative stress and inflammation in kidney induced by carbon tetrachloride (CCl4) and explored the potential mechanisms underlying this effect. Our results showed that puerarin administration significantly inhibited CCl4-induced kidney injury, which indicated by both diagnostic indicators and histopathological analysis. One of the potential mechanisms of puerarin action was decreased the oxidative stress, as evidenced by decreasing of lipid peroxidation level, increasing of SOD, CAT and GPx activities and GSH level. Puerarin also decreased 8-hydroxy-2-deoxyguanosine (one product of oxidative DNA damage) level and increased the expression levels of NQO1, GST and HO-1 in kidneys of CCl4-treated mice. Moreover, western blot analysis showed that puerarin decreased production of pro-inflammatory markers including iNOS and COX-2 in CCl4-treated mouse kidney. We found that puerarin significantly inhibited the ERK phosphorylation and increased the translocation of Nrf2 from the cytosol to the nuclear fraction, which in turn inactivated NF-κB and the inflammatory cytokines in kidneys of the CCl4-treated mice. Altogether, these results suggest that puerarin could protect the CCl4-induced oxidative stress and inflammation by ERK/Nrf2/ARE pathway.

Ma JQ ，Ding J ，Xiao ZH ，Liu CM ... -  《-》