This study aims to elucidate the antiproliferative mechanism of hydroxychavicol(HC).Its effects on cell cycle,apoptosis,and the expression of c-Jun N-terminal kinase(JNK)and P38 mitogen-activated protein kinase(MAPK)i...This study aims to elucidate the antiproliferative mechanism of hydroxychavicol(HC).Its effects on cell cycle,apoptosis,and the expression of c-Jun N-terminal kinase(JNK)and P38 mitogen-activated protein kinase(MAPK)in HT-29 colon cancer cells were investigated.HC was isolated from Piper betle leaf(PBL)and verified by high-performance liquid chromatography(HPLC),nuclear magnetic resonance(NMR),and gas chromatography-mass spectrometry(GC-MS).The cytotoxic effects of the standard drug 5-fluorouracil(5-FU),PBL water extract,and HC on HT-29 cells were measured after 24,48,and 72 h of treatment.Cell cycle and apoptosis modulation by 5-FU and HC treatments were investigated up to 30 h.Changes in phosphorylated JNK(pJNK)and P38(pP38)MAPK expression were observed up to 18 h.The half maximal inhibitory concentration(IC_(50))values of HC(30μg/mL)and PBL water extract(380μg/mL)were achieved at 24 h,whereas the IC_(50)of 5-FU(50μmol/L)was obtained at 72 h.Cell cycle arrest at the G0/G1 phase in HC-treated cells was observed from12 h onwards.Higher apoptotic cell death in HC-treated cells compared to 5-FU-treated cells(P<0.05)was observed.High expression of pJNK and pP38 MAPK was observed at 12 h in HC-treated cells,but not in 5-FU-treated HT-29 cells(P<0.05).It is concluded that HC induces cell cycle arrest and apoptosis of HT-29 cells,with these actions possibly mediated by JNK and P38 MAPK.展开更多
Objectives： To investigate the protective effects of Sapindus saponins in spontaneously hypertensive rats, and the possible cellular and molecular mechanisms. Methods： Thirty-two 16-week-old spontaneously hypertensi...Objectives： To investigate the protective effects of Sapindus saponins in spontaneously hypertensive rats, and the possible cellular and molecular mechanisms. Methods： Thirty-two 16-week-old spontaneously hypertensive rats were randomly divided into four groups （8 in each group）： model group （placebo）, positive control group （27 mg/kg of Captopril Tablets）, Sapindus saponins groups （27 mg/kg and 108 mg/kg, respectively）. Another 8 healthy Wistar-Kyoto strain （WKY） rats were used as the normal group. The animals were treated for 8 weeks. Blood pressure of rats was determined by non-invasive blood pressure meter （BP-6）. Furthermore, the contents of angiotensin Ⅱ （Ang Ⅱ） in plasma and myocardial tissue were determined by enzyme-linked immunosorbent assay （ELISA）, the gene expression of receptor angiotensin type 1 （AT1R） in aorta was determined by quantitative real- time polymerase chain reaction （qRT-PCR）. The protein expression of transforming growth factor- β1 （TGF- 1β1） and AT1R in heart was determined by immunohistochemical staining. The protein expression of p-phosphorylation of p38 mitogen-activated protein kinase （p-p38MAPK） was determined by Western blotting. The contents of interleukin （IL）-1, IL-6 and tumor necrosis factor （TNF） in serum were determined by radioimmunoassay. And the histopathological and morphological changes of aorta and heart tissue samples were assessed semi-quantitatively by hematoxylin-eosin （HE） or Masson staining. Results： Thirty minutes after single or continuous treatment, systolic blood pressure （SBP） was reduced significantly in Sapindus saponins groups. And the contents of Ang 11, IL-1, IL-6 and TNF-α in serum, the expression of AT1R mRNA, p-p38MAPK and TGF- β1 were significantly suppressed dose-dependently （P〈0.05 or 1=〈0.01）. With the Sapindus saponins treatment, compared with those of the model group, the cardiac and aortic pathological changes were ameliorated significantly. Conclusions： Our findings suggest that Sapindus saponins might have protective effects in spontaneously hypertensive rats, the cellular and molecular mechanisms of which might be relevant to the regulation of inflammatory responses mediated by p-p38MAPK signal pathway based on activated Ang Ⅱ and AT1R.展开更多
基金supported by the Taylor’s Research Grant Scheme(No.TRGS/MFS/2/2013/SBS/003),Malaysia。
文摘This study aims to elucidate the antiproliferative mechanism of hydroxychavicol(HC).Its effects on cell cycle,apoptosis,and the expression of c-Jun N-terminal kinase(JNK)and P38 mitogen-activated protein kinase(MAPK)in HT-29 colon cancer cells were investigated.HC was isolated from Piper betle leaf(PBL)and verified by high-performance liquid chromatography(HPLC),nuclear magnetic resonance(NMR),and gas chromatography-mass spectrometry(GC-MS).The cytotoxic effects of the standard drug 5-fluorouracil(5-FU),PBL water extract,and HC on HT-29 cells were measured after 24,48,and 72 h of treatment.Cell cycle and apoptosis modulation by 5-FU and HC treatments were investigated up to 30 h.Changes in phosphorylated JNK(pJNK)and P38(pP38)MAPK expression were observed up to 18 h.The half maximal inhibitory concentration(IC_(50))values of HC(30μg/mL)and PBL water extract(380μg/mL)were achieved at 24 h,whereas the IC_(50)of 5-FU(50μmol/L)was obtained at 72 h.Cell cycle arrest at the G0/G1 phase in HC-treated cells was observed from12 h onwards.Higher apoptotic cell death in HC-treated cells compared to 5-FU-treated cells(P<0.05)was observed.High expression of pJNK and pP38 MAPK was observed at 12 h in HC-treated cells,but not in 5-FU-treated HT-29 cells(P<0.05).It is concluded that HC induces cell cycle arrest and apoptosis of HT-29 cells,with these actions possibly mediated by JNK and P38 MAPK.
基金Supported by the Foundation for Young Talents in College of Anhui Province under Grant(No.2009SQRZ114)Youth Scientific Research Foundation of Anhui University of Traditional Chinese Medicine(No.2012QN005)
文摘Objectives： To investigate the protective effects of Sapindus saponins in spontaneously hypertensive rats, and the possible cellular and molecular mechanisms. Methods： Thirty-two 16-week-old spontaneously hypertensive rats were randomly divided into four groups （8 in each group）： model group （placebo）, positive control group （27 mg/kg of Captopril Tablets）, Sapindus saponins groups （27 mg/kg and 108 mg/kg, respectively）. Another 8 healthy Wistar-Kyoto strain （WKY） rats were used as the normal group. The animals were treated for 8 weeks. Blood pressure of rats was determined by non-invasive blood pressure meter （BP-6）. Furthermore, the contents of angiotensin Ⅱ （Ang Ⅱ） in plasma and myocardial tissue were determined by enzyme-linked immunosorbent assay （ELISA）, the gene expression of receptor angiotensin type 1 （AT1R） in aorta was determined by quantitative real- time polymerase chain reaction （qRT-PCR）. The protein expression of transforming growth factor- β1 （TGF- 1β1） and AT1R in heart was determined by immunohistochemical staining. The protein expression of p-phosphorylation of p38 mitogen-activated protein kinase （p-p38MAPK） was determined by Western blotting. The contents of interleukin （IL）-1, IL-6 and tumor necrosis factor （TNF） in serum were determined by radioimmunoassay. And the histopathological and morphological changes of aorta and heart tissue samples were assessed semi-quantitatively by hematoxylin-eosin （HE） or Masson staining. Results： Thirty minutes after single or continuous treatment, systolic blood pressure （SBP） was reduced significantly in Sapindus saponins groups. And the contents of Ang 11, IL-1, IL-6 and TNF-α in serum, the expression of AT1R mRNA, p-p38MAPK and TGF- β1 were significantly suppressed dose-dependently （P〈0.05 or 1=〈0.01）. With the Sapindus saponins treatment, compared with those of the model group, the cardiac and aortic pathological changes were ameliorated significantly. Conclusions： Our findings suggest that Sapindus saponins might have protective effects in spontaneously hypertensive rats, the cellular and molecular mechanisms of which might be relevant to the regulation of inflammatory responses mediated by p-p38MAPK signal pathway based on activated Ang Ⅱ and AT1R.
