Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Andrographolide ameliorates vascular injury in hypertension by suppressing EndMT via Sp1-Notch1 signaling.
СтатьяНазвание и аннотация: Перевод в очереди
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.
Tu Qiang, Li Wenling, Qiu Yanxia, Qiu Yumin, Liu Zhefu, Zhang Meixin, Liu Zhangchi, Xia Wenhao, Zhang Bin, Cao Zheng, Tao Jun
Аннотация
BACKGROUND: Endothelial-to-mesenchymal transition (EndMT) is a potential therapeutic target for hypertension-induced vascular injury. Andrographolide (AGP) is a bioactive labdane diterpenoid that confers cardiovascular protective effects. However, the role of AGP in regulating EndMT during hypertension-related vascular injury is not clear.
PURPOSE: In this study, we investigated the effect of AGP on EndMT in vascular injury and elucidated its underlying mechanism in hypertension.
METHODS: Angiotensin II (Ang II)-induced hypertensive mice were used to evaluate the vascular protective effects of AGP. Mechanistic experiments were performed in Ang II-stimulated endothelial cells. We detected EndMT markers both in vitro and in vivo. We also conducted a small-scale clinical trial to assess the effects of AGP on vascular damage in patients with hypertension.
RESULTS: In Ang II-induced hypertensive mice, AGP improved endothelial function, alleviated arterial stiffness, and decreased aortic remodeling while also lowering blood pressure. It also suppressed EndMT in hypertensive mice and Ang II-treated endothelial cells. Quantitative co-immunofluorescence staining of aortic sections revealed that the percentage of CD31/vimentin double-positive cells was significantly higher in Ang II-induced hypertensive mice, whereas AGP treatment considerably decreased this proportion. Endothelial Notch1 expression was upregulated during EndMT, whereas genetic or pharmacological inhibition of Notch1 blocked Ang II-induced EndMT. Ang II downregulated the expression of Sp1, whereas the overexpression of Sp1 mitigated Ang II-induced EndMT; moreover, knocking down Sp1 abrogated the protective effects of AGP. In mice, the overexpression of Sp1 via adeno-associated virus 9 or Notch1 inhibition attenuated vascular injury by suppressing EndMT. Moreover, AGP improved flow-mediated dilation and reduced brachial-ankle pulse wave velocity in hypertensive patients (ChiCTR2300071970).
CONCLUSIONS: We found that AGP ameliorates hypertension-induced vascular injury by inhibiting EndMT through the Sp1-Notch1 pathway. These findings suggest that AGP may serve as a promising therapeutic candidate for restoring vascular homeostasis in patients suffering from hypertension.
PURPOSE: In this study, we investigated the effect of AGP on EndMT in vascular injury and elucidated its underlying mechanism in hypertension.
METHODS: Angiotensin II (Ang II)-induced hypertensive mice were used to evaluate the vascular protective effects of AGP. Mechanistic experiments were performed in Ang II-stimulated endothelial cells. We detected EndMT markers both in vitro and in vivo. We also conducted a small-scale clinical trial to assess the effects of AGP on vascular damage in patients with hypertension.
RESULTS: In Ang II-induced hypertensive mice, AGP improved endothelial function, alleviated arterial stiffness, and decreased aortic remodeling while also lowering blood pressure. It also suppressed EndMT in hypertensive mice and Ang II-treated endothelial cells. Quantitative co-immunofluorescence staining of aortic sections revealed that the percentage of CD31/vimentin double-positive cells was significantly higher in Ang II-induced hypertensive mice, whereas AGP treatment considerably decreased this proportion. Endothelial Notch1 expression was upregulated during EndMT, whereas genetic or pharmacological inhibition of Notch1 blocked Ang II-induced EndMT. Ang II downregulated the expression of Sp1, whereas the overexpression of Sp1 mitigated Ang II-induced EndMT; moreover, knocking down Sp1 abrogated the protective effects of AGP. In mice, the overexpression of Sp1 via adeno-associated virus 9 or Notch1 inhibition attenuated vascular injury by suppressing EndMT. Moreover, AGP improved flow-mediated dilation and reduced brachial-ankle pulse wave velocity in hypertensive patients (ChiCTR2300071970).
CONCLUSIONS: We found that AGP ameliorates hypertension-induced vascular injury by inhibiting EndMT through the Sp1-Notch1 pathway. These findings suggest that AGP may serve as a promising therapeutic candidate for restoring vascular homeostasis in patients suffering from hypertension.