Objective:Recent investigations have demonstrated that Polygonum perfoliatum L.can protect against chemical liver injury,but the mechanism behind its efficacy is still unclear.Therefore,we studied the pharmacological ...Objective:Recent investigations have demonstrated that Polygonum perfoliatum L.can protect against chemical liver injury,but the mechanism behind its efficacy is still unclear.Therefore,we studied the pharmacological mechanism at work in P.perfoliatum protection against chemical liver injury.Methods:To evaluate the activity of P.perfoliatum against chemical liver injury,levels of alanine transaminase,lactic dehydrogenase,aspartate transaminase,superoxide dismutase,glutathione peroxidase and malondialdehyde were measured,alongside histological assessments of the liver,heart and kidney tissue.A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupoleorbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P.perfoliatum;these profiles were used to understand the possible mechanisms behind P.perfoliatum's protective activity.Results:Lipidomic studies indicated that P.perfoliatum protected against chemical liver injury,and the results were consistent between histological and physiological analyses.By comparing the profiles of liver lipids in model and control mice,we found that the levels of 89 lipids were significantly changed.In animals receiving P.perfoliatum treatment,the levels of 8 lipids were significantly improved,relative to the model animals.The results showed that P.perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury,especially glycerophospholipid metabolism.Conclusion:Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P.perfoliatum's protection against liver injury.展开更多
[Objectives]To study the effect of total flavonoids extracted from Polygonum perfoliatum L.(TFP)on immune-mediated liver injury induced by bacillus Calmette-Guerin plus lipopolysaccharide(BCG+LPS)in mice,and to explor...[Objectives]To study the effect of total flavonoids extracted from Polygonum perfoliatum L.(TFP)on immune-mediated liver injury induced by bacillus Calmette-Guerin plus lipopolysaccharide(BCG+LPS)in mice,and to explore its action mechanism.[Methods]60 Kunming mice were divided into normal group,model group,control group(bifendate)and TFP low,medium and high dose groups according to random number table method,with 10 mice in each group.On the first day of modeling,mice were injected with 0.2 mL of BCG solution(12.5 mg/mL)through the tail vein,and on the eleventh day,0.2 mL of LPS(37.5μg/mL)were injected into the tail vein to prepare a mouse model of immune-mediated liver injury;from the first day of modeling,the normal group and the model group were administered intragastrically with the corresponding volume of distilled water,and the bifendate group and the TFP high,medium,and low dose groups were administered intragastrically with the corresponding doses once a day for 11 d.After the last time administration,fasting but giving water for 16 h,took blood from eyes,then collected the liver tissue.The levels of alanine transaminase(ALT)and aspartate transaminase(AST)in serum were detected by biochemical method;transforming growth factor-β1(TGF-β1),intercellular adhesion molecule-1(ICAM-1),interleukin-6(IL-6)and interleukin-1β(IL-1β)expression levels in liver tissue were detected by enzyme-linked immunosorbent assay(ELISA);phosphorylated protein tyrosine kinase JAK-2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3)protein expression levels were detected by Western Blot method;the degree of liver tissue lesions was detected by HE staining.[Results]Compared with the model group,the levels of ALT and AST in the serum of mice in each dose group of TFP(high dose 600 mg/kg,medium dose 400 mg/kg,and low dose 200 mg/kg)were reduced,and the activities of T-SOD and GSH-Px were increased;the content or expression ofβ1,ICAM-1,IL-6,IL-1βdecreased,and the expression of p-JAK2 and p-STAT3 protein decreased;pathological sections showed that the degree of inflammatory necrosis and the degree of lesions in the liver tissues of each dose group of TFP were reduced by varying degrees.[Conclusions]TFP has a protective effect on BCG+LPS-induced immune-mediated liver injury in mice.The mechanism may be related to regulating the phosphorylation level of JAK2 and inhibiting the inflammatory reaction,thereby regulating the TGF-β1/STAT3 signaling pathway and improving the immune-mediated liver injury.展开更多
基金supported by the National Natural Science Foundation of China(No.81860738)Guizhou Province High-level Innovative Talents Training Project[Qiankehe Talents(2015)4033]Special Project for 2018 Academic New Seedling Cultivation and Innovation Exploration of Guizhou Normal University[Qiankehe Talents for talents(2018)5769-27].
文摘Objective:Recent investigations have demonstrated that Polygonum perfoliatum L.can protect against chemical liver injury,but the mechanism behind its efficacy is still unclear.Therefore,we studied the pharmacological mechanism at work in P.perfoliatum protection against chemical liver injury.Methods:To evaluate the activity of P.perfoliatum against chemical liver injury,levels of alanine transaminase,lactic dehydrogenase,aspartate transaminase,superoxide dismutase,glutathione peroxidase and malondialdehyde were measured,alongside histological assessments of the liver,heart and kidney tissue.A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupoleorbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P.perfoliatum;these profiles were used to understand the possible mechanisms behind P.perfoliatum's protective activity.Results:Lipidomic studies indicated that P.perfoliatum protected against chemical liver injury,and the results were consistent between histological and physiological analyses.By comparing the profiles of liver lipids in model and control mice,we found that the levels of 89 lipids were significantly changed.In animals receiving P.perfoliatum treatment,the levels of 8 lipids were significantly improved,relative to the model animals.The results showed that P.perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury,especially glycerophospholipid metabolism.Conclusion:Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P.perfoliatum's protection against liver injury.
基金Natural Science Foundation Project of Guangxi(2017GXNSFAA 198326)。
文摘[Objectives]To study the effect of total flavonoids extracted from Polygonum perfoliatum L.(TFP)on immune-mediated liver injury induced by bacillus Calmette-Guerin plus lipopolysaccharide(BCG+LPS)in mice,and to explore its action mechanism.[Methods]60 Kunming mice were divided into normal group,model group,control group(bifendate)and TFP low,medium and high dose groups according to random number table method,with 10 mice in each group.On the first day of modeling,mice were injected with 0.2 mL of BCG solution(12.5 mg/mL)through the tail vein,and on the eleventh day,0.2 mL of LPS(37.5μg/mL)were injected into the tail vein to prepare a mouse model of immune-mediated liver injury;from the first day of modeling,the normal group and the model group were administered intragastrically with the corresponding volume of distilled water,and the bifendate group and the TFP high,medium,and low dose groups were administered intragastrically with the corresponding doses once a day for 11 d.After the last time administration,fasting but giving water for 16 h,took blood from eyes,then collected the liver tissue.The levels of alanine transaminase(ALT)and aspartate transaminase(AST)in serum were detected by biochemical method;transforming growth factor-β1(TGF-β1),intercellular adhesion molecule-1(ICAM-1),interleukin-6(IL-6)and interleukin-1β(IL-1β)expression levels in liver tissue were detected by enzyme-linked immunosorbent assay(ELISA);phosphorylated protein tyrosine kinase JAK-2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3)protein expression levels were detected by Western Blot method;the degree of liver tissue lesions was detected by HE staining.[Results]Compared with the model group,the levels of ALT and AST in the serum of mice in each dose group of TFP(high dose 600 mg/kg,medium dose 400 mg/kg,and low dose 200 mg/kg)were reduced,and the activities of T-SOD and GSH-Px were increased;the content or expression ofβ1,ICAM-1,IL-6,IL-1βdecreased,and the expression of p-JAK2 and p-STAT3 protein decreased;pathological sections showed that the degree of inflammatory necrosis and the degree of lesions in the liver tissues of each dose group of TFP were reduced by varying degrees.[Conclusions]TFP has a protective effect on BCG+LPS-induced immune-mediated liver injury in mice.The mechanism may be related to regulating the phosphorylation level of JAK2 and inhibiting the inflammatory reaction,thereby regulating the TGF-β1/STAT3 signaling pathway and improving the immune-mediated liver injury.
