Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Asiaticoside alleviates hypoxic pulmonary hypertension by regulating the voltage-gated potassium channel 1.5 through the protein tyrosine phosphatase non-receptor type 7 pathway.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Lu Guoqing, Sun Hongyan, Xu Meiyang, Fu Chengwen, Xu Mengwen, Tang Wenbo, Chen Ziyi, Tang Ying, Sun Zhengyu, Liu Leqiang, Chen Qing, Wang Hongju, Gao Qin, Ge Rongjing, Tan Xin, Fan Jili, Bo Xiaohong, Kang Pinfang, Tang Bi
Аннотация
BACKGROUND: Hypoxic pulmonary hypertension (HPH) is marked by abnormal contraction and hyperproliferation of pulmonary artery smooth muscle. This study aims to examine the diastolic effects of asiaticoside (AS) on pulmonary arteries and the mechanisms through which AS modulates HPH both in vitro and in vivo.
METHODS: The protective effects of AS on pulmonary circulation were evaluated in both acute and chronic hypoxia models. To assess AS on PASMCs proliferation and migration, channel wound healing, Transwell, and EdU staining assays were conducted. Transcriptomic analysis elucidated the mechanism by which AS suppresses the aberrant phenotype of hypoxic PASMCs, confirmed through immunofluorescence, qRT-PCR, and western blot analyses. The influence of AS on KV currents in PASMCs was investigated using whole-cell patch-clamp techniques, and the mechanism of AS action on KV channels was further examined using small-interference RNA targeting protein tyrosine phosphatase non-receptor type 7 (PTPN7).
RESULTS: AS mitigates pulmonary circulation injury in Sprague-Dawley rats subjected to acute hypoxia by reducing right ventricular pressure and counteracting hypoxia-induced inhibition of voltage-gated potassium channel KV currents. AS treatment decreases pulmonary vascular tone during acute hypoxia in a concentration-dependent manner, implicating the involvement of the KV1.5 channel in AS-mediated vasodilation of pulmonary arteries. AS was found to activate KV1.5 currents in PASMCs and reverse the acute hypoxia-induced inhibition of these currents, potentially through PTPN7 activation and ERK phosphorylation inhibition. Additionally, AS improved pulmonary vasoconstrictor-diastolic activity, increased KV current density, and inhibited abnormal PASMCs proliferation and migration under chronic hypoxic conditions, thereby enhancing electrophysiological and vascular remodeling in PASMCs.
CONCLUSION: Asiaticoside may partially restore KV1.5 channel function by modulating the PTPN7/ERK pathway, thereby alleviating HPH and offering a novel therapeutic strategy for HPH.
METHODS: The protective effects of AS on pulmonary circulation were evaluated in both acute and chronic hypoxia models. To assess AS on PASMCs proliferation and migration, channel wound healing, Transwell, and EdU staining assays were conducted. Transcriptomic analysis elucidated the mechanism by which AS suppresses the aberrant phenotype of hypoxic PASMCs, confirmed through immunofluorescence, qRT-PCR, and western blot analyses. The influence of AS on KV currents in PASMCs was investigated using whole-cell patch-clamp techniques, and the mechanism of AS action on KV channels was further examined using small-interference RNA targeting protein tyrosine phosphatase non-receptor type 7 (PTPN7).
RESULTS: AS mitigates pulmonary circulation injury in Sprague-Dawley rats subjected to acute hypoxia by reducing right ventricular pressure and counteracting hypoxia-induced inhibition of voltage-gated potassium channel KV currents. AS treatment decreases pulmonary vascular tone during acute hypoxia in a concentration-dependent manner, implicating the involvement of the KV1.5 channel in AS-mediated vasodilation of pulmonary arteries. AS was found to activate KV1.5 currents in PASMCs and reverse the acute hypoxia-induced inhibition of these currents, potentially through PTPN7 activation and ERK phosphorylation inhibition. Additionally, AS improved pulmonary vasoconstrictor-diastolic activity, increased KV current density, and inhibited abnormal PASMCs proliferation and migration under chronic hypoxic conditions, thereby enhancing electrophysiological and vascular remodeling in PASMCs.
CONCLUSION: Asiaticoside may partially restore KV1.5 channel function by modulating the PTPN7/ERK pathway, thereby alleviating HPH and offering a novel therapeutic strategy for HPH.