Yuan-Chuan Lin1, Chih-Hsueh Lin2, Hsien-Tsung Yao3, Wei-Wen Kuo4, Chia-Yao Shen5, Yu-Lan Yeh6, Tsung-Jung Ho7, V Vijaya Padma8, Yu-Chen Lin1, Chih-Yang Huang10, Chih-Yang Huang10. 1. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan. 2. Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. 3. Department of Nutrition, China Medical University, Taichung, Taiwan. 4. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan. 5. Department of Nursing, Mei Ho University, Pingguang Road, Pingtung, Taiwan. 6. Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan; Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan. 7. Chinese Medicine Department, China Medical University Beigang Hospital, Taichung, Taiwan. 8. Department of Biotechnology, Bharathiar University, Coimbatore 641046, India. 9. Translation Research Core, China Medical University Hospital, China Medical University, Taichung, Taiwan. 10. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan; Department of Biological Science, Asia University, Taichung, Taiwan; Faculty of Applied Sciences, Ton Duc Thang University, Tan Phong Ward, District 7, 700000 Ho Chi Minh City, Vietnam. Electronic address: cyhuang@mail.cmu.edu.tw.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Platycodon grandiflorum (PG) is a Chinese medical plant used for decades as a traditional prescription to eliminate phlegm, relieve cough, reduce inflammation and lower blood pressure. PG also has a significant effect on the cardiovascular systems. MATERIALS AND METHODS: The aqueous extract of Platycodon grandiflorum (JACQ.) A. DC. root was screened for inhibiting Ang II-induced IGF-IIR activation and apoptosis pathway in H9c2 cardiomyocytes. The effects were also studied in spontaneously hypertensive rats (five groups, n=5) using low and high doses of PG for 50 days. The Ang II-induced IGF-IIR activation was analyzed by luciferase reporter, RT-PCR, western blot and surface IGF-IIR expression assay. Furthermore, the major active constituent of PG was carried out by high performance liquid chromatography-mass spectrometry (HPLC-MS). RESULTS: Our results indicate that a crude extract of PG significantly suppresses the Ang II-induced IGF-IIR signaling pathway to prevent cardiomyocyte apoptosis. PG extract inhibits Ang II-mediated JNK activation and SIRT1 degradation to reduce IGF-IIR activity. Moreover, PG maintains SIRT1 stability to enhance HSF1-mediated IGF-IIR suppression, which prevents cardiomyocyte apoptosis. In animal models, the administration of PG markedly reduced this apoptotic pathway in the heart of SHRs. CONCLUSION: Taken together, PG may be considered as an effective treatment for cardiac diseases in hypertensive patients.
ETHNOPHARMACOLOGICAL RELEVANCE: Platycodon grandiflorum (PG) is a Chinese medical plant used for decades as a traditional prescription to eliminate phlegm, relieve cough, reduce inflammation and lower blood pressure. PG also has a significant effect on the cardiovascular systems. MATERIALS AND METHODS: The aqueous extract of Platycodon grandiflorum (JACQ.) A. DC. root was screened for inhibiting Ang II-induced IGF-IIR activation and apoptosis pathway in H9c2 cardiomyocytes. The effects were also studied in spontaneously hypertensiverats (five groups, n=5) using low and high doses of PG for 50 days. The Ang II-induced IGF-IIR activation was analyzed by luciferase reporter, RT-PCR, western blot and surface IGF-IIR expression assay. Furthermore, the major active constituent of PG was carried out by high performance liquid chromatography-mass spectrometry (HPLC-MS). RESULTS: Our results indicate that a crude extract of PG significantly suppresses the Ang II-induced IGF-IIR signaling pathway to prevent cardiomyocyte apoptosis. PG extract inhibits Ang II-mediated JNK activation and SIRT1 degradation to reduce IGF-IIR activity. Moreover, PG maintains SIRT1 stability to enhance HSF1-mediated IGF-IIR suppression, which prevents cardiomyocyte apoptosis. In animal models, the administration of PG markedly reduced this apoptotic pathway in the heart of SHRs. CONCLUSION: Taken together, PG may be considered as an effective treatment for cardiac diseases in hypertensivepatients.