Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from...Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from sera df normal lipidemic donors was separated bysequential ultracentrifugation. The separated human IDL 1 mg·mL^(-1) in phosphate buffer saline, pH7.4, was incubated with cupric sulfate (10 μmol·L^(-1) ) at 37℃ for 10 h in the presence orabsence of various concentrations of Iso. Malondialdehyde (MDA) formation, vitamin E consumption,electrophoretic mobility of LDL, mitochondria] membrane potential of mouse peritoneal macrophages,phagocytosis of neutral red, and release of nitric oxide (NO) from macrophages were determined byvarious methods. Results Iso 1 - 100 μmol·L^(-1) significantly inhibited the increase of MDAformation, vitamin E consumption and electrophoretic mobility of LDL induced by Cu^(2+) in aconcentration-dependent manner. The injury of the mitochondrial membrane potential of mouseperitoneal macrophages due to incubation with ox-LDL (0.1 mg·mL^(-1)) at 37℃ for 12 h was markedlyprotected by 10 μmol·L^(-1) Iso. After pretreat-ment of the macrophages with 10 μmol · L^(-1)of Iso and then exposure to ox-LDL for 4 h, the reduction of phagocytosis of neutral red and releaseof NO in response to lipopolysaccharide (IPS) stimulation were significantly prevented. ConclusionIso has protective action against Cu^(2+) - mediated LDL peroxidation and ox-LDL induced toxicity tomacrophages in vitro.展开更多
Gnetuhainin P, a new isorhapontigenin dimer, was isolated from the Lianas of Gnetum hainanense C. Y. Cheng. Its structure was established on the basis of spectroscopic evidence, especially 2D NMR techniques.
We have developed an alternative route to synthesize the natural product. isorhapotogenin. The synthetic product was characterized by IR and H-1-NMR in comparison with the corresponding natural product.
OBJECTIVE To investigate the machenism that isorhapontigenin(ISO)induced autophagy and cell growth inhibition in human bladder cancer cells on the basis of the existing research results,for providing a new mechanistic...OBJECTIVE To investigate the machenism that isorhapontigenin(ISO)induced autophagy and cell growth inhibition in human bladder cancer cells on the basis of the existing research results,for providing a new mechanistic insight into understanding the anti-cancer properties of ISO.METHODS Western blotting analysis was used to detect the expression of autophagypasswayproteins.Poly Jet transfection technology was used to establish transfected cell lines,and indirect immunofluorescence staining was applied to observe the punctuate dots of GFP-LC3.Anchorage-independent growth assaywas used to detect cell colony formation.RT-PCR was used to detect the m RNA levelof SESN2 after ISO treatment.The chromatin immunoprecipitation(CHIP)was used to detect the binding of transcription factor c-Jun and specificity SESN2 promoter sequence.RESULTS Our studies revealed that ISO-mediated autophagy induction occurred in a Sestrin2(SESN2)-dependent and Beclin 1(BECN1)-independent manner.Furthermore,we identified that ISO treatment induced SESN2 expression via a c-Jun N-terminal kinase(JNK)/c-Jun-dependent mechanism,in which ISO triggered JNK1-dependent c-Jun activation and facilitated the binding of c-Jun to consensus AP-1 binding site in the SESN2 promoter region,thereby led to a significant transcriptional induction of SESN2.Importantly,we found that SESN2 expression was dramatically down-regulated or even lost in human bladder cancer tissues as compared to their paired adjacent normal tissues,while ISO treatment was capable of elevating SESN2 expression effectively and inhibiting bladder cancer formation in BBN-induced mouse bladder tumors in vivo.CONCLUSION ISO treatment is able to induce autophagy and inhibit bladder cancer growth through JNK1/c-Jun dependent transcriptional induction of SESN2,which provides a novel mechanistic insight into understanding the inhibitory effect of ISO on bladder cancers and suggests that ISO might act as a promising preventive and/or therapeutic drug against human bladder cancer.展开更多
As an effective anticancer drug, the clinical limitation of doxorubicin(Dox) is the time-and dose-dependent cardiotoxicity. Yes-associated protein 1(YAP1) interacts with transcription factor TEA domain 1(TEAD1) and pl...As an effective anticancer drug, the clinical limitation of doxorubicin(Dox) is the time-and dose-dependent cardiotoxicity. Yes-associated protein 1(YAP1) interacts with transcription factor TEA domain 1(TEAD1) and plays an important role in cell proliferation and survival. However, the role of YAP1 in Dox-induced cardiomyopathy has not been reported. In this study, the expression of YAP1 was reduced in clinical human failing hearts with dilated cardiomyopathy and Dox-induced in vivo and in vitro cardiotoxic model. Ectopic expression of Yap1 significantly blocked Dox-induced cardiomyocytes apoptosis in TEAD1 dependent manner. Isorhapontigenin(Isor) is a new derivative of stilbene and responsible for a wide range of biological processes. Here, we found that Isor effectively relieved Doxinduced cardiomyocytes apoptosis in a dose-dependent manner in vitro. Administration with Isor(30 mg/kg/day, intraperitoneally, 3 weeks) significantly protected against Dox-induced cardiotoxicity in mice. Interestingly, Isor increased Dox-caused repression in YAP1 and the expression of its target genes in vivo and in vitro. Knockout or inhibition of Yap1 blocked the protective effects of Isor on Dox-induced cardiotoxicity. In conclusion, YAP1 may be a novel target for Dox-induced cardiotoxicity and Isor might be a new compound to fight against Dox-induced cardiotoxicity by increasing YAP1 expression.展开更多
篢he oxidative coupling reaction of isorhapontigenin using sliver oxide as oxidant afforded a major product, named shegansu B（2）， which was isolated from the roots of Belamcanda chinensis (L．)DC. Both the natural ...篢he oxidative coupling reaction of isorhapontigenin using sliver oxide as oxidant afforded a major product, named shegansu B（2）， which was isolated from the roots of Belamcanda chinensis (L．)DC. Both the natural and synthetic Shegansu B have the same potent antagonism activities of leukotriene B4，D4 receptor．展开更多
文摘Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from sera df normal lipidemic donors was separated bysequential ultracentrifugation. The separated human IDL 1 mg·mL^(-1) in phosphate buffer saline, pH7.4, was incubated with cupric sulfate (10 μmol·L^(-1) ) at 37℃ for 10 h in the presence orabsence of various concentrations of Iso. Malondialdehyde (MDA) formation, vitamin E consumption,electrophoretic mobility of LDL, mitochondria] membrane potential of mouse peritoneal macrophages,phagocytosis of neutral red, and release of nitric oxide (NO) from macrophages were determined byvarious methods. Results Iso 1 - 100 μmol·L^(-1) significantly inhibited the increase of MDAformation, vitamin E consumption and electrophoretic mobility of LDL induced by Cu^(2+) in aconcentration-dependent manner. The injury of the mitochondrial membrane potential of mouseperitoneal macrophages due to incubation with ox-LDL (0.1 mg·mL^(-1)) at 37℃ for 12 h was markedlyprotected by 10 μmol·L^(-1) Iso. After pretreat-ment of the macrophages with 10 μmol · L^(-1)of Iso and then exposure to ox-LDL for 4 h, the reduction of phagocytosis of neutral red and releaseof NO in response to lipopolysaccharide (IPS) stimulation were significantly prevented. ConclusionIso has protective action against Cu^(2+) - mediated LDL peroxidation and ox-LDL induced toxicity tomacrophages in vitro.
文摘Gnetuhainin P, a new isorhapontigenin dimer, was isolated from the Lianas of Gnetum hainanense C. Y. Cheng. Its structure was established on the basis of spectroscopic evidence, especially 2D NMR techniques.
基金Prot'essor M. I.in. \'ho kindly pro\ ided the natural product.
文摘We have developed an alternative route to synthesize the natural product. isorhapotogenin. The synthetic product was characterized by IR and H-1-NMR in comparison with the corresponding natural product.
文摘OBJECTIVE To investigate the machenism that isorhapontigenin(ISO)induced autophagy and cell growth inhibition in human bladder cancer cells on the basis of the existing research results,for providing a new mechanistic insight into understanding the anti-cancer properties of ISO.METHODS Western blotting analysis was used to detect the expression of autophagypasswayproteins.Poly Jet transfection technology was used to establish transfected cell lines,and indirect immunofluorescence staining was applied to observe the punctuate dots of GFP-LC3.Anchorage-independent growth assaywas used to detect cell colony formation.RT-PCR was used to detect the m RNA levelof SESN2 after ISO treatment.The chromatin immunoprecipitation(CHIP)was used to detect the binding of transcription factor c-Jun and specificity SESN2 promoter sequence.RESULTS Our studies revealed that ISO-mediated autophagy induction occurred in a Sestrin2(SESN2)-dependent and Beclin 1(BECN1)-independent manner.Furthermore,we identified that ISO treatment induced SESN2 expression via a c-Jun N-terminal kinase(JNK)/c-Jun-dependent mechanism,in which ISO triggered JNK1-dependent c-Jun activation and facilitated the binding of c-Jun to consensus AP-1 binding site in the SESN2 promoter region,thereby led to a significant transcriptional induction of SESN2.Importantly,we found that SESN2 expression was dramatically down-regulated or even lost in human bladder cancer tissues as compared to their paired adjacent normal tissues,while ISO treatment was capable of elevating SESN2 expression effectively and inhibiting bladder cancer formation in BBN-induced mouse bladder tumors in vivo.CONCLUSION ISO treatment is able to induce autophagy and inhibit bladder cancer growth through JNK1/c-Jun dependent transcriptional induction of SESN2,which provides a novel mechanistic insight into understanding the inhibitory effect of ISO on bladder cancers and suggests that ISO might act as a promising preventive and/or therapeutic drug against human bladder cancer.
基金supported by grants from the National Natural Science Foundation of China (81872860, 81803521, 81673433)National Major Special Projects for the Creation and Manufacture of New Drugs (2019ZX09301104, China)+5 种基金Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01Y093, China)National Engineering and Technology Research Center for New drug Druggability Evaluation(Seed Program of Guangdong Province, 2017B090903004,China)Natural Science Foundation of Guangdong Province(2019A1515010273, China)Foundation from Guangdong Traditional Medicine Bureau (20191060, China)Fundamental Research Funds for the Central Universities (19ykpy131, China)Research and Industrialization team of Taxus chinensis var.mairel (2014YT02S044, China)。
文摘As an effective anticancer drug, the clinical limitation of doxorubicin(Dox) is the time-and dose-dependent cardiotoxicity. Yes-associated protein 1(YAP1) interacts with transcription factor TEA domain 1(TEAD1) and plays an important role in cell proliferation and survival. However, the role of YAP1 in Dox-induced cardiomyopathy has not been reported. In this study, the expression of YAP1 was reduced in clinical human failing hearts with dilated cardiomyopathy and Dox-induced in vivo and in vitro cardiotoxic model. Ectopic expression of Yap1 significantly blocked Dox-induced cardiomyocytes apoptosis in TEAD1 dependent manner. Isorhapontigenin(Isor) is a new derivative of stilbene and responsible for a wide range of biological processes. Here, we found that Isor effectively relieved Doxinduced cardiomyocytes apoptosis in a dose-dependent manner in vitro. Administration with Isor(30 mg/kg/day, intraperitoneally, 3 weeks) significantly protected against Dox-induced cardiotoxicity in mice. Interestingly, Isor increased Dox-caused repression in YAP1 and the expression of its target genes in vivo and in vitro. Knockout or inhibition of Yap1 blocked the protective effects of Isor on Dox-induced cardiotoxicity. In conclusion, YAP1 may be a novel target for Dox-induced cardiotoxicity and Isor might be a new compound to fight against Dox-induced cardiotoxicity by increasing YAP1 expression.
文摘篢he oxidative coupling reaction of isorhapontigenin using sliver oxide as oxidant afforded a major product, named shegansu B（2）， which was isolated from the roots of Belamcanda chinensis (L．)DC. Both the natural and synthetic Shegansu B have the same potent antagonism activities of leukotriene B4，D4 receptor．
