Protective Effect of a Polyherbal Formulation (Cardojith) Against Angiotensin II-induced Hypertension and Cardiomyocyte Hypertrophy Via Modulation of Oxidative Stress and MAPK Signalling.

Hypertension remains a critical contributor to cardiovascular morbidity, driven largely by angiotensin II (Ang II)-mediated oxidative stress, inflammation, and hypertrophic remodelling. Although polyherbal formulations are valued for their multitargeted actions, systematic evidence at the cellular level is important. Thus, the present study explored the protective effects of a polyherbal formulation (Cardojith (CJ)) against Ang II-induced hypertensive injury in H9c2 cardiomyocytes. H9c2 cells were exposed to Ang II with or without CJ treatment. Cell viability was assessed by MTT assay, while oxidative stress parameters (ROS, TBARS, SOD, CAT) and hypertrophic/inflammatory mediators (ANP, BNP, IL-6, TNF-α) were quantified. Gene expression of AT1R, NF-κB, and COX-2 was evaluated by RT-PCR, and p38 MAPK activation was analysed by Western blotting. Apoptosis was evaluated using AO/EtBr fluorescence staining. Ang II triggered a pathological phenotype characterized by reduced cell viability, increased ROS and lipid peroxidation, and diminished antioxidant enzyme activity. These biochemical changes coincided with elevated ANP, BNP, IL-6, and TNF-α levels and increased apoptotic cell death. At the molecular level, Ang II significantly upregulated AT1R, NF-κB, and COX-2 expression and enhanced p38 MAPK phosphorylation, confirming activation of pro-hypertrophic and inflammatory pathways. In contrast, CJ treatment attenuated these alterations by restoring antioxidant enzyme activities, reducing ROS, TBARS and apoptotic cell death, while normalizing ANP and BNP levels. Importantly, CJ downregulated AT1R, NF-κB, and COX-2 and inhibited p38 MAPK phosphorylation, underscoring its capacity to modulate key signalling pathways. Therefore, Cardojith exerts its potent cardioprotective and antihypertensive effects by simultaneously attenuating oxidative stress, inflammation, apoptosis and hypertrophic signalling. These findings highlight its therapeutic potential as a multitargeted phytomedicine for managing hypertension-associated cardiac complications.