Scutellarein alleviates the dysfunction of inner blood-retinal-barrier initiated by hyperglycemia-stimulated microglia cells

AIM:To investigate the alleviation of scutellarein(SN)against inner blood-retinal-barrier(iBRB)dysfunction in microglia cells stimulated by hyperglycemia and to elucidate the engaged mechanism.METHODS:Microglia BV2 cells were stimulated by using 25 mmol/L D-glucose.The same concentration of mannitol(25 mmol/L)was applied as an isotonic contrast.Real-time PCR,Western-blot assay and immunofluorescence staining assay was performed.The dysfunction of iBRB in vitro was detected by using transendothelial electrical resistance(TEER)assay.Additionally,the leakage of fluorescein isothiocyanate(FITC)-conjugated dextran(70 kDa)was detected.RESULTS:SN abrogated microglia BV2 cells activation and reduced the phosphorylated activation of extracellular signal-regulated protein kinase(ERK)1/2.SN also decreased the transcriptional activation of nuclear factorκB(NFκB)and the elevated expression of tumor necrosis factorα(TNFα),interleukin(IL)-6 and IL-1βin BV2 cells treated with D-glucose(25 mmol/L).SN attenuated iBRB dysfunction in human retinal endothelial cells(HRECs)or choroid-retinal endothelial RF/6 A cells when those cells were treated with TNFα,IL-1βor IL-6,or co-cultured with microglia cells stimulated by D-glucose.Moreover,SN restored the decreased protein expression of tight junctions(TJs)in TNFα-treated HRECs and RF/6 A cells.CONCLUSION:SN not only alleviate iBRB dysfunction via directly inhibiting retinal endothelial injury caused by TNFα,IL-1βor IL-6,but also reduce the release of TNFα,IL-1βand IL-6 from microglia cells by abrogating hyperglycemia-mediated the activation of microglia cells.

Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo

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.

Chlorogenic acid prevents acetaminophen-induced liver injury: the involvement of CYP450 metabolic enzymes and some antioxidant signals

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.