Cardioprotective effects of Bassia indica via NF-κB and BCL-2/BAX modulation in isoproterenol-induced myocardial injury

Fayyaz Anjum¹Saad Touqeer²QurratulAin Jamil¹Ayesha Rida¹Esraa M Haji³Sulaiman Mohammed Abdullah Alnasser⁴Ali F Almutairy⁴Hajar Alghamdi³Ashfaq Ahmad³Shahid Muhammad Iqbal^5*

• ¹The Islamia University of Bahawalpur, Bahawalpur, Pakistan
• ²Al Ain University, Abu Dhabi, United Arab Emirates
• ³University of Hafr Al Batin, Hafr Al Batin, Saudi Arabia
• ⁴Qassim University, Buraydah, Saudi Arabia
• ⁵Michael Sars Center, University of Bergen, Bergen, Norway

Background: Myocardial infarction (MI) is a fatal coronary heart disease that develops due to prolonged hypoxia. During MI progression, uncontrolled inflammation and apoptosis mediated by NF-κB, BAX/BCL-2 signaling pathways, potentiate the cardiac injury. Phenolic and flavonoid-rich medicinal plants have shown efficacy in suppressing the inflammatory pathways, thus reducing the adverse cardiac remodeling. This study evaluated the cardioprotective and anti-inflammatory potential of Bassia indica (Wight) A.J. Scott, a locally used plant for cardiac disorders. Methods: B. indica extract (BiE) was prepared and characterized by UHPLC-MS/MS. Its anti-inflammatory activity was determined by in vitro inhibition of COX-2 and 5-LOX enzymes, followed by in vivo suppression of acute inflammation induced by carrageenan, histamine, and serotonin. The role of anti-inflammatory activity in the amelioration of myocardial injury was assessed by isoproterenol (ISO) induced MI, and qPCR studies were performed to explore underlying mechanisms. Results: UHPLC/MS/MS analysis of BiE tentatively identified several plant metabolites, including kaempferol 3-glucoside-7-sophoroside, kaempferol 3-rutinoside-7-sophoroside, kaempferol 3-(2G-glucosylrutinoside), and phenolic derivatives. It inhibited COX-2 (IC50 = 0.6 µg/mL) and 5-LOX (IC50 = 8.3 µg/mL) enzymes. BiE-treated animals exhibited reduced inflammation in response to carrageenan, histamine, and serotonin. Pre-treatment with BiE significantly reduced infarct size, preserved cardiac tissue architecture, and lowered cardiac biomarkers (cTnI, CK-MB, LDH, and AST), downregulated NF-κB, COX-2, TNF-α, and IL-1β, and upregulated IL-10 and BCL-2. Conclusions: These findings suggest that BiE has cardioprotective effects, mediated by suppression of inflammation and apoptosis.