Phytomedicine : international journal of phytotherapy and phytopharmacology · 2022
Tabersonine attenuates Angiotensin II-induced cardiac remodeling and dysfunction through targeting TAK1 and inhibiting TAK1-mediated cardiac inflammation.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Dai Chengyi, Luo Wu, Chen Yanghao, Shen Siyuan, Wang Zhe, Chen Ruijie, Wang Jun, Chattipakorn Nipon, Huang Weijian, Liang Guang
Аннотация
BACKGROUND: Angiotensin II (Ang II)-induced cardiac inflammation contribute to pathological cardiac remodeling and hypertensive heart failure (HF). Tabersonine (Tab) is an indole alkaloid mainly isolated from Catharanthus roseus and exhibits anti-inflammatory activity in various systems. However, the role of Tab in hypertensive HF and its molecular targets remains unknown.
HYPOTHESIS/PURPOSE: We aimed to investigate potential cardioprotective effects and mechanism of Tab against Ang II-induced cardiac injuries.
METHODS: C57BL/6 mice were administered Ang II (at 1000 ng/kg/min) by micro-osmotic pump infusion for 30 days to develop hypertensive HF. Tab at 20 and 40 mg/kg/day was administered during the last 2 weeks to elucidate the cardioprotective properties. Cultured cardiomyocyte-like H9c2 cells and rat primary cardiomyocytes were used for mechanistic studies of Tab.
RESULTS: We demonstrate for the first time that Tab provides protection against Ang II-induced cardiac dysfunction in mice, associated with reduced cardiac inflammation and fibrosis. Mechanistically, we show that Tab may interacts with TAK1 to inhibit Ang II-induced TAK1 ubiquitination and phosphorylation. Disruption of TAK1 activation by Tab blocked downstream NF-κB and JNK/P38 MAPK signaling activation and decreased cardiac inflammation and fibrosis both in vitro and in vivo. TAK1 knockdown also blocked Ang II-induced cardiomyocytes injuries and prevented the innately pharmacological effects of Tab.
CONCLUSION: Our results indicate that Tab protects hearts against Ang II-mediated injuries through targeting TAK1 and inhibiting TAK1-mediated inflammatory cascade and response. Thus, Tab may be a potential therapeutic candidate for hypertensive HF.
HYPOTHESIS/PURPOSE: We aimed to investigate potential cardioprotective effects and mechanism of Tab against Ang II-induced cardiac injuries.
METHODS: C57BL/6 mice were administered Ang II (at 1000 ng/kg/min) by micro-osmotic pump infusion for 30 days to develop hypertensive HF. Tab at 20 and 40 mg/kg/day was administered during the last 2 weeks to elucidate the cardioprotective properties. Cultured cardiomyocyte-like H9c2 cells and rat primary cardiomyocytes were used for mechanistic studies of Tab.
RESULTS: We demonstrate for the first time that Tab provides protection against Ang II-induced cardiac dysfunction in mice, associated with reduced cardiac inflammation and fibrosis. Mechanistically, we show that Tab may interacts with TAK1 to inhibit Ang II-induced TAK1 ubiquitination and phosphorylation. Disruption of TAK1 activation by Tab blocked downstream NF-κB and JNK/P38 MAPK signaling activation and decreased cardiac inflammation and fibrosis both in vitro and in vivo. TAK1 knockdown also blocked Ang II-induced cardiomyocytes injuries and prevented the innately pharmacological effects of Tab.
CONCLUSION: Our results indicate that Tab protects hearts against Ang II-mediated injuries through targeting TAK1 and inhibiting TAK1-mediated inflammatory cascade and response. Thus, Tab may be a potential therapeutic candidate for hypertensive HF.