The Bidens pilosa extract Jacein alleviates hypertension by restoring mitochondrial dynamic balance through modulating the FAM210A/OPA1 signaling pathway.

This study aimed to investigate the mechanism by which Jacein, an extract from Bidens pilosa, alleviates hypertension through regulating mitochondrial dynamics via the FAM210A/OPA1 signaling pathway. Methods For in vitro experiments, rat aortic vascular smooth muscle cells (VSMCs) were divided into 6 groups. Control group was cultured under normal conditions. Model group was treated with 1 µM angiotensin II (Ang II) for 24 h. Positive control group received 0.1 µM valsartan on the basis of the model group for 24 h. Jacein low/medium/high dose groups were treated with 10/20/40 µM Jacein respectively on the basis of the model group for 24 h. Cell viability, ATP levels, reactive oxygen species (ROS) levels, and mitochondrial membrane potential were assessed. Mitochondrial morphology was evaluated using transmission electron microscopy. mRNA and protein expression levels were analyzed using qPCR, WB, and co-immunoprecipitation. For in vivo experiments, ten Wistar-Kyoto rats served as controls and fifty spontaneously hypertensive rats (SHRs) were randomly divided into 5 groups. Model group received intragastric administration of normal saline. Positive control group received 100 mg/kg/d valsartan. Jacein low/medium/high dose groups received 50/100/150 mg/kg/d Jacein respectively for 28 d. Blood pressure was measured before euthanasia, followed by tissue collection for analysis of mitochondrial ultrastructure, cell apoptosis, ATP levels, and ROS levels. An additional ten SHRs were used in antagonist experiments with weekly intravenous injections of 5 nmol/kg OPA1 inhibitor MYLS22. In vitro, Ang II treatment significantly reduced cell viability, mitochondrial membrane potential, and ATP content, while significantly increasing ROS levels and mitochondrial fragmentation (P < 0.001). Jacein treatment dose-dependently reversed these effects (P < 0.001). Jacein also upregulated FAM210A, L-OPA1, and MFN2 expression, downregulated DRP1, S-OPA1, and FIS1 expression, and enhanced the interaction between FAM210A and OPA1 (P < 0.05). In vivo, Jacein exhibited dose-dependent blood pressure-lowering effects in SHR rats, while improving mitochondrial ultrastructure, reducing cell apoptosis, increasing ATP content, and lowering ROS levels (P < 0.01). The antagonist experiment showed that OPA1 inhibition significantly weakened Jacein’s beneficial effects on blood pressure, mitochondrial ultrastructure, cell apoptosis, and the interaction between FAM210A/OPA1 (P < 0.01). This study elucidates the mechanism by which Jacein alleviates hypertension by improving mitochondrial dynamics, which is partially associated with the regulation of the FAM210A/OPA1 signaling pathway.