Therapeutic potential of wogonoside in hypertension-induced cardiac injury: Targeting apoptosis and MAPK signaling pathway

Hypertension caused cardiomyocyte Apoptosis and remodeling, leading to heart failure. Wogonoside (WOG), a flavonoid from Qingda granules, was evaluated for cardioprotective effects and mechanisms. Spontaneously hypertensive rats (SHRs) received WOG (0.075, 0.75, or 7.5 mg/kg/d) or valsartan (7.5 mg/kg/d) for 10 weeks. Blood pressure, cardiac function, histology, fibrosis, cardiomyocyte size, and Apoptosis were assessed using echocardiography, hematoxylin and eosin, Masson, TUNEL and wheat germ agglutinin staining. Network pharmacology and Kyoto Encyclopedia of Genes and Genomes analyses identified targets and pathways. In vitro, Annexin V/propidium iodide staining, JC-1 staining, and Western blotting were adopted for the assessment of Apoptosis and mitochondrial function in H9C2 cells stimulated by angiotensin II (Ang II). WOG treatment reduced elevated blood pressure and increased left ventricular ejection fraction and left ventricular fractional shortening in SHRs. Network pharmacology analysis revealed 74 overlapping targets enriched in Apoptosis and MAPK pathways. WOG reduced myocardial hypertrophy, fibrosis, and Apoptosis in SHRs, as evidenced by decreased expression of cleaved Caspase-3 and Bax, and increased expression of Bcl-2. WOG treatment reduced cell Apoptosis and mitochondrial depolarization, downregulated Bax and Cleaved Caspase 3, and upregulated Bcl-2. Mechanistically, WOG treatment suppressed the phosphorylation levels of ERK, p38MAPK, and JNK in Ang II-stimulated H9C2 cells, as evidenced by decreased ratios of p-ERK/ERK, p-p38MAPK/p38MAPK, and p-JNK/JNK, in Ang II-stimulated H9c2 cells. WOG relieves cardiac injury and cardiomyocyte Apoptosis induced by hypertension, likely by suppressing multiple signaling pathways including the MAPK signaling pathway.