The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B- induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase （ALT/AST） levels. Ferulic acid also decreases lipid peroxide （LPO） levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase （CuZn-SOD） and catalase （CAT） are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity.
This study observes the therapeutic detoxification of quercetin, a well-known flavonoid, against carbon tetrachlodde （CCI4） induced acute liver injury in vivo and explores its mechanism. QuerceUn decreased CCI4-increased serum activities of alanine and aspartate aminotransferases （ALT/AST） when orally taken 30 min after CCI4 intoxica- tion. The results of a histological evaluation further evidenced the ability of quercetin to protect against CCI4-induced liver injury. Quercetin decreased the CCI4-increased malondialdehyde （MDA） and reduced the glutathione （GSH） amounts in the liver. It also reduced the enhanced immunohistochemical staining of the 4-hydroxynonenal （4-HNE） in the liver induced by CCI4. Peroxiredoxin （Prx） 1, 2, 3, 5, 6, thioredoxin reductase 1 and 2 （TrxRl/2）, thioredoxin 1 and 2 （Trxl/2）, nuclear factor erythroid 2-related factor 2 （Nrf2）, and heme oxygenase-1 （HO-1） all play critical roles in maintaining cellular redox homeostasis. Real-time polymerase chain reaction （PCR） results demonstrated that quercetin reversed the decreased mRNA expression of all those genes induced by CCI4. In conclusion, our results demonstrate that quercetin ameliorates CCI4-induced acute liver injury in vivo via alleviating oxidative stress injuries when orally taken after CCI4 intoxication. This protection may be caused by the elevation of the antioxidant capacity induced by quercetin.
Jia-qi ZHANGLiang SHIXi-ning XUSi-chong HUANGBin LULi-li JIZheng-tao WANG
Chlorogenic acid（CGA）, a polyphenolic compound, is abundant in fruits, dietary vegetables, and some medicinal herbs. This study investigated the prevention of CGA against acetaminophen（AP）-induced hepatotoxicity and its engaged mechanisms. CGA reversed the decreased cell viability induced by AP in L-02 cells in vitro. In addition, CGA reduced the AP-induced increased serum levels of alanine/aspartate aminotransferase（ALT/AST） in vivo. The effect of CGA on cytochrome P450（CYP） enzymatic（CYP2E1, CYP1A2, and CYP3A4） activities showed that CGA caused very little inhibition on CYP2E1 and CYP1A2 enzymatic activities, but not CYP3A4. The measurement of liver malondialdehyde（MDA）, reactive oxygen species（ROS）, and glutathione（GSH） levels showed that CGA prevented AP-induced liver oxidative stress injury. Further, CGA increased the AP-induced decreased m RNA expression of peroxiredoxin（Prx） 1, 2, 3, 5, 6, epoxide hydrolase（Ephx） 2, and polymerase（RNA） II（DNA directed） polypeptide K（Polr2k）, and nuclear factor erythroid-2-related factor 2（Nrf2）. In summary, CGA ameliorates the AP-induced liver injury probably by slightly inhibiting CYP2E1 and CYP1A2 enzymatic properties. In addition, cellular important antioxidant signals such as Prx1, 2, 3, 5, 6, Ephx2, Polr2 k, and Nrf2 also contributed to the protection of CGA against AP-induced oxidative stress injury.
