OBJECTIVE To investigate the vasorelaxant effect of pinocembrin(5,7-dihydroxyflavanone),one of the main flavonoids in propolis,on angiotensinⅡ(AngⅡ)induced vasoconstriction and the molecular mechanism of action.METH...OBJECTIVE To investigate the vasorelaxant effect of pinocembrin(5,7-dihydroxyflavanone),one of the main flavonoids in propolis,on angiotensinⅡ(AngⅡ)induced vasoconstriction and the molecular mechanism of action.METHODS The isometric vascular tone was measured in thoracic aortic rings from SD rat,and the effects of pinocembrin on the single dose and concentration cumulative response curves of AngⅡ were recorded.The binding of pinocembrin to the angiotensin type 1 receptor(AT1R)was studied by using molecule docking analysis.Intracellular[Ca2+]([Ca2+]i)was measured with Fura2/AM in VSMCs.The phosphorylation levels of myosin light chain 2(MLC2)and myosin phosphatase target unit 1(MYPT1),and protein level of Rho kinase 1(ROCK1)in the rat aortic rings were detected by Western blotting.RESULTS Pinocembrin was observed to inhibit AngⅡ-induced vasoconstriction in rat aortic rings with either intact or denuded endothelium.In endothelium-denuded tissues,pinocembrin(pD′2 4.28±0.15)counteracted the contractions evoked by cumulative concentrations of AngⅡ.In a docking model,pinocembrin showed effective binding at the active site of AT1R.Pinocembrin was shown to inhibit both AngⅡ-induced Ca2+ release from internal stores and Ca2+ influx.Moreover,the increase in the phosphorylation of MLC2 and MYPT1,and the increased protein level of ROCK1 induced by AngⅡ was blocked by pinocembrin.CONCLUSION Pinocembrin inhibits AngⅡ-induced rat aortic ring contraction in a Ca2+-dependent and Ca2+-independent manner via blocking AT1R.展开更多
Our recent study demonstrated that pinocembrin （PB）, the most abundant flavonoid in propolis, has neuroprotective effect against 1-methyl4-phenylpyridinium （ MPP^＋ ）-induced SH-SY5Y neurotoxicity. However, the me...Our recent study demonstrated that pinocembrin （PB）, the most abundant flavonoid in propolis, has neuroprotective effect against 1-methyl4-phenylpyridinium （ MPP^＋ ）-induced SH-SY5Y neurotoxicity. However, the mechanism as how PB can induce neuroprotection is not known. In the present study, we demonstrate here that PB increased heme oxygenase-1 （HO-1） expression, which conferred protection against MPP^＋ -induced cytotoxici- ty, because the inhibitor of HO-1 zinc protoporphyrin-IX attenuated the neuroprotection of PB. PB induced the phosphorylation of ERK1/2, and its cytoprotective effect was abolished by ERK1/2 inhibitors. Meanwhile, we have shown that MPP ＋ induce the expression in a concentration-dependent manner in SH-SY5Y cells, which was further enhanced by PB. Taken together, the results suggest that PB enhances HO-1 expression to suppress MPP^＋ -induced oxidative damage via ERK1/2 signaling pathways. These results revealed the mechanisms of PB enhances HO-1 ex- pression , and contribute to shed some light on the mechanisms whereby PB inhibit the MPP^＋ -induced neurotoxici- ty. These data indicated that PB might provide a valuable therapeutic strategy for the treatment of PD.展开更多
Aim To evaluate the vasorelaxant effects of the flavonone pinocembrin in isolated rat basilar artery rings and to investigate its possible mechanisms. Methods The isotonic contractions of the basilar artery rings from...Aim To evaluate the vasorelaxant effects of the flavonone pinocembrin in isolated rat basilar artery rings and to investigate its possible mechanisms. Methods The isotonic contractions of the basilar artery rings from SD rats were recorded. Results Pinocembrin exerted vasorelaxation in a close-dependent manner in KCL （60 mmol · L^-1 ） or 5-HT （ 1 μmol · L^- 1）-induced sustained contraction and partial loss of the vasorelaxation in endothelium- denuded rings. Pretreatment with pinocembrin （30 or 50 μmol · L^-1 ） attenuated contractile responses to KC1 （ 10 - 60 mmol · L^-1 ） and 5-HT （0. 001 - 10 μmol · L^-1 ）. The pinocembrin -induced vasorelaxation was significant- ly reduced by the nitric oxide synthase inhibitor Nco-nitro-L-arginine methyl ester （L-NAME, 100 μmol · L^-1） , the guanylate cyclase inhibitor ODQ （5 μmol · L^-1） and the cyclooxygenase inhibitor indomethacin （5 μmol · L^-l）. The voltage-dependent K＋ channel blocker 4-aminopyridine （100 μmol · L^-1）, the ATP-sensitive K ＋ channel blocker glibenclamide （10μmol · L^-1） and Ca2＋-activated K ＋ channel blocker tetraethylammonium （1 retool· L^-1） remarkably attenuated pinocembrin-induced relaxations. Pinocembrin also inhibited contraction in- duced by increasing external calcium in Ca2＋-free medium plus 60 mmol · L^-1 KC1. Conclusion These results demonstrate that pinocembrin has a vasorelaxant effect on isolated rat basilar artery rings and may exert its action through an endothelium-dependent pathway, involving NO-cGMP, and also through an endothelium-independent 2＋ pathway, opening K ＋ channels and blockade of Ca channels.展开更多
The exacerbation of progressive multiple sclerosis(MS)is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells(OPCs).To discover novel therapeutic compounds for enhancing remye...The exacerbation of progressive multiple sclerosis(MS)is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells(OPCs).To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs,we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds.One of the most effective drugs was pinocembrin,which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival.Based on these in vitro effects,we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases.We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis(EAE)and enhanced the repair of demyelination in lysolectin-induced lesions.Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin(mTOR).Taken together,our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway,and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.展开更多
Four minor impurities in pinocembrin （1）--a new drug to treat ischemic stroke, were analysed and identified by means of HPLC-UV-MS analysis, spectroscopic evidences and chemical synthetic methods. Their chemical str...Four minor impurities in pinocembrin （1）--a new drug to treat ischemic stroke, were analysed and identified by means of HPLC-UV-MS analysis, spectroscopic evidences and chemical synthetic methods. Their chemical struc- tures were identified as 5,7-dihydroxy-2-phenyl-4H-l-benzopyran-4-one （2）, 3-phenyl-l-（2,4,6-trihydroxyphenyl）- 1-propanone （3）, 5,%dihydroxy-2-cyclohexyl-4H-l-benzopyran-4-one （4）, and 2,3-dihydro-5,7-dihydroxy-2- cyclohexyl-4H-l-benzopyran-4-one （5）, respectively. All of the impurities were side products of excessive hydro- genation of the target product I or the starting material 2 in the course of synthesis, and 5 was a new compound.展开更多
基金The project supported by National Natural Science Foundation of China(81102444)the Major Scientific and Technological Special Project for"Significant New Drugs Creation"(2009ZX09302-003,2013ZX09508104)the Central Public Scientific Research Institution Fundamental Project(2014CX05)
文摘OBJECTIVE To investigate the vasorelaxant effect of pinocembrin(5,7-dihydroxyflavanone),one of the main flavonoids in propolis,on angiotensinⅡ(AngⅡ)induced vasoconstriction and the molecular mechanism of action.METHODS The isometric vascular tone was measured in thoracic aortic rings from SD rat,and the effects of pinocembrin on the single dose and concentration cumulative response curves of AngⅡ were recorded.The binding of pinocembrin to the angiotensin type 1 receptor(AT1R)was studied by using molecule docking analysis.Intracellular[Ca2+]([Ca2+]i)was measured with Fura2/AM in VSMCs.The phosphorylation levels of myosin light chain 2(MLC2)and myosin phosphatase target unit 1(MYPT1),and protein level of Rho kinase 1(ROCK1)in the rat aortic rings were detected by Western blotting.RESULTS Pinocembrin was observed to inhibit AngⅡ-induced vasoconstriction in rat aortic rings with either intact or denuded endothelium.In endothelium-denuded tissues,pinocembrin(pD′2 4.28±0.15)counteracted the contractions evoked by cumulative concentrations of AngⅡ.In a docking model,pinocembrin showed effective binding at the active site of AT1R.Pinocembrin was shown to inhibit both AngⅡ-induced Ca2+ release from internal stores and Ca2+ influx.Moreover,the increase in the phosphorylation of MLC2 and MYPT1,and the increased protein level of ROCK1 induced by AngⅡ was blocked by pinocembrin.CONCLUSION Pinocembrin inhibits AngⅡ-induced rat aortic ring contraction in a Ca2+-dependent and Ca2+-independent manner via blocking AT1R.
文摘Our recent study demonstrated that pinocembrin （PB）, the most abundant flavonoid in propolis, has neuroprotective effect against 1-methyl4-phenylpyridinium （ MPP^＋ ）-induced SH-SY5Y neurotoxicity. However, the mechanism as how PB can induce neuroprotection is not known. In the present study, we demonstrate here that PB increased heme oxygenase-1 （HO-1） expression, which conferred protection against MPP^＋ -induced cytotoxici- ty, because the inhibitor of HO-1 zinc protoporphyrin-IX attenuated the neuroprotection of PB. PB induced the phosphorylation of ERK1/2, and its cytoprotective effect was abolished by ERK1/2 inhibitors. Meanwhile, we have shown that MPP ＋ induce the expression in a concentration-dependent manner in SH-SY5Y cells, which was further enhanced by PB. Taken together, the results suggest that PB enhances HO-1 expression to suppress MPP^＋ -induced oxidative damage via ERK1/2 signaling pathways. These results revealed the mechanisms of PB enhances HO-1 ex- pression , and contribute to shed some light on the mechanisms whereby PB inhibit the MPP^＋ -induced neurotoxici- ty. These data indicated that PB might provide a valuable therapeutic strategy for the treatment of PD.
文摘Aim To evaluate the vasorelaxant effects of the flavonone pinocembrin in isolated rat basilar artery rings and to investigate its possible mechanisms. Methods The isotonic contractions of the basilar artery rings from SD rats were recorded. Results Pinocembrin exerted vasorelaxation in a close-dependent manner in KCL （60 mmol · L^-1 ） or 5-HT （ 1 μmol · L^- 1）-induced sustained contraction and partial loss of the vasorelaxation in endothelium- denuded rings. Pretreatment with pinocembrin （30 or 50 μmol · L^-1 ） attenuated contractile responses to KC1 （ 10 - 60 mmol · L^-1 ） and 5-HT （0. 001 - 10 μmol · L^-1 ）. The pinocembrin -induced vasorelaxation was significant- ly reduced by the nitric oxide synthase inhibitor Nco-nitro-L-arginine methyl ester （L-NAME, 100 μmol · L^-1） , the guanylate cyclase inhibitor ODQ （5 μmol · L^-1） and the cyclooxygenase inhibitor indomethacin （5 μmol · L^-l）. The voltage-dependent K＋ channel blocker 4-aminopyridine （100 μmol · L^-1）, the ATP-sensitive K ＋ channel blocker glibenclamide （10μmol · L^-1） and Ca2＋-activated K ＋ channel blocker tetraethylammonium （1 retool· L^-1） remarkably attenuated pinocembrin-induced relaxations. Pinocembrin also inhibited contraction in- duced by increasing external calcium in Ca2＋-free medium plus 60 mmol · L^-1 KC1. Conclusion These results demonstrate that pinocembrin has a vasorelaxant effect on isolated rat basilar artery rings and may exert its action through an endothelium-dependent pathway, involving NO-cGMP, and also through an endothelium-independent 2＋ pathway, opening K ＋ channels and blockade of Ca channels.
基金This work was supported by the National Natural Science Foundation of China(31771129).
文摘The exacerbation of progressive multiple sclerosis(MS)is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells(OPCs).To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs,we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds.One of the most effective drugs was pinocembrin,which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival.Based on these in vitro effects,we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases.We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis(EAE)and enhanced the repair of demyelination in lysolectin-induced lesions.Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin(mTOR).Taken together,our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway,and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.
文摘Four minor impurities in pinocembrin （1）--a new drug to treat ischemic stroke, were analysed and identified by means of HPLC-UV-MS analysis, spectroscopic evidences and chemical synthetic methods. Their chemical struc- tures were identified as 5,7-dihydroxy-2-phenyl-4H-l-benzopyran-4-one （2）, 3-phenyl-l-（2,4,6-trihydroxyphenyl）- 1-propanone （3）, 5,%dihydroxy-2-cyclohexyl-4H-l-benzopyran-4-one （4）, and 2,3-dihydro-5,7-dihydroxy-2- cyclohexyl-4H-l-benzopyran-4-one （5）, respectively. All of the impurities were side products of excessive hydro- genation of the target product I or the starting material 2 in the course of synthesis, and 5 was a new compound.
