Effect of Hibiscus anthocyanins-rich extract induces apoptosis of proliferating smooth muscle cell via activation of P38 MAPK and p53 pathway.
Hibiscus sabdariffa L. (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in Sudan and in eastern Taiwan. It has been reported to contain a number of protocatechuic acid and anthocyanins. In vitro experimental studies have shown that anthocyanins administration of the extract produces anti-inflammation and chemoprevention effects. In spite of the wide use of Hibiscus sabdariffa L. in folk medicine for treating various diseases, our previous study indicated a potency of Hibiscus sabdariffa extract (HSE) in anti-atherosclerosis. The mechanisms of anthocyanins administration of the extract produce from Hibiscus sabdariffa L. to attenuate atherosclerosis were not clarified. In this study, we found that Hibiscus anthocyanins (HAs) could inhibit the serum-stimulated proliferation of smooth muscle cell (SMC) and result in cell apoptosis. The HAs inducing cell apoptosis was dose dependent. We further used SB203580 (p38 inhibitor) to block cellular apoptosis and evaluate its effect on the HAs-inducing SMC death via some apoptosis criteria including DNA fragmentation and flow cytometry. We suggested that the mechanisms of the inhibitory effect of HAs on atherosclerosis could be via inhibiting the proliferation of SMC. HAs induces apoptosis via (i) activating p38 MAP kinase that subsequently phosphorylates target protein c-Jun and transduces the signal to further activate the apoptotic protein cascades that contain Fas-mediated signaling (Fas/caspase-8 signaling module) and (ii) activating p53 and inducing bax expression. As an outcome of the events, cytochrome c releases from the mitochondria, leading to cell apoptosis. In these experiments, HAs showed strong potential to induce SMC cell apoptosis via p38 and p53 pathway. In consequence, the rate of atherosclerotic formation is slowed down, and the progress is suppressed.
Lo
Chia-Wen
CW
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No. 110 Section 1 Chien-Kuo N. Road, Taichung, Taiwan.
Huang
Hui-Pei
HP
Lin
Hui-Mei
HM
Chien
Cheng-Ting
CT
Wang
Chau-Jong
CJ
D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D001011:Aorta; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D005434:Flow Cytometry; D035264:Flowers / Q000737:chemistry; D031584:Hibiscus / Q000737:chemistry*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000872:Anthocyanins; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53; D045304:Cytochromes c; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases