Ding Tang1, Renyi Yan2, Yuan Sun3, Guoyin Kai4, Keli Chen3, Juan Li5. 1. Key Laboratory of Ministry of Education on Traditional Chinese Medicine Resource and Compound Prescription, Hubei Province Key Laboratory of Traditional Chinese Medicine Resource and Chemistry, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China. 2. Tianjin Ubasio Biotechnology Group Co., Ltd., Tianjin 300457, China. 3. Key Laboratory of Ministry of Education on Traditional Chinese Medicine Resource and Compound Prescription, Hubei Province Key Laboratory of Traditional Chinese Medicine Resource and Chemistry, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China. 4. College of pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China. 5. Key Laboratory of Ministry of Education on Traditional Chinese Medicine Resource and Compound Prescription, Hubei Province Key Laboratory of Traditional Chinese Medicine Resource and Chemistry, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China. Electronic address: lz198207@126.com.
Abstract
BACKGROUND: The tuber of Pinellia ternata has been used for a thousand years in China. P. ternata possessed the activities of anti-emetic, sedative-hypnotic, anti-cancer, anti-asthmatic, anti-tussive, and anti-inflammatory. It is the representative of expectorant medicines in Traditional Chinese Medicine (TCM). Phlegm is the pathological product and a new pathogenic factor of the metabolite, which is analogous to the damage of oxidative stress. PURPOSE: The objectives of the study were to investigate the protective activity and mechanism of ethanol extract of P. ternata tubers (PTE) and its main constituents on oxidative stress-induced cell senescence. METHODS: H2O2 and AAPH were used to establish cellular senescence models. The anti-aging effects of PTE and its components were evaluated by SA-β-gal staining, flow cytometry, scanning electron microscope (SEM), and multiple microplate reader, the molecular mechanisms of them were investigated by qRT-PCR and Western Blot. RESULTS: We found PTE exhibited the apparent effect on cell senescence, evidenced by inhibiting senescence β-Galactosidase (SA-β-gal) expression, lipofuscin accumulation, cell cycle arrest at the G2/M phase, oxidative damage and apoptosis, and increasing telomerase activity. Their mechanisms were related to increase expressions of SIRT1, forkhead box 3a (Foxo3a), Bcl-2, active regulator of SIRT1, RPS19BP1 (AROS), and Hu antigen R (HuR), but decrease Bax, p53 and deleted in breast cancer 1 (DBC1) levels. Furthermore, adenosine, and succinic acid, as the critical substances in PTE, could also inhibit SA-β-gal expression and cell cycle arrest, down-regulate the expression of Bax, and up-regulate Bcl-2, SirT1, and Foxo3a. CONCLUSIONS: We have demonstrated that PTE slows down oxidative stress-induced cell senescence, and adenosine and succinic acid are the key active components.
BACKGROUND: The tuber of Pinellia ternata has been used for a thousand years in China. P. ternata possessed the activities of anti-emetic, sedative-hypnotic, anti-cancer, anti-asthmatic, anti-tussive, and anti-inflammatory. It is the representative of expectorant medicines in Traditional Chinese Medicine (TCM). Phlegm is the pathological product and a new pathogenic factor of the metabolite, which is analogous to the damage of oxidative stress. PURPOSE: The objectives of the study were to investigate the protective activity and mechanism of ethanol extract of P. ternata tubers (PTE) and its main constituents on oxidative stress-induced cell senescence. METHODS:H2O2 and AAPH were used to establish cellular senescence models. The anti-aging effects of PTE and its components were evaluated by SA-β-gal staining, flow cytometry, scanning electron microscope (SEM), and multiple microplate reader, the molecular mechanisms of them were investigated by qRT-PCR and Western Blot. RESULTS: We found PTE exhibited the apparent effect on cell senescence, evidenced by inhibiting senescence β-Galactosidase (SA-β-gal) expression, lipofuscin accumulation, cell cycle arrest at the G2/M phase, oxidative damage and apoptosis, and increasing telomerase activity. Their mechanisms were related to increase expressions of SIRT1, forkhead box 3a (Foxo3a), Bcl-2, active regulator of SIRT1, RPS19BP1 (AROS), and Hu antigen R (HuR), but decrease Bax, p53 and deleted in breast cancer 1 (DBC1) levels. Furthermore, adenosine, and succinic acid, as the critical substances in PTE, could also inhibit SA-β-gal expression and cell cycle arrest, down-regulate the expression of Bax, and up-regulate Bcl-2, SirT1, and Foxo3a. CONCLUSIONS: We have demonstrated that PTE slows down oxidative stress-induced cell senescence, and adenosine and succinic acid are the key active components.