# Ficus carica leaf extract ameliorates cardiac injury through Nrf2/Keap1 pathway activation and dual oxidase inhibition

## TL;DR

Ficus carica leaf extract reduces heart damage in rats by reducing oxidative stress and apoptosis through specific molecular pathways.

## Contribution

This study demonstrates FCLE's novel therapeutic potential via Nrf2/Keap1 pathway activation and dual oxidase inhibition in a cardiac injury model.

## Key findings

- FCLE significantly reduced markers of cardiac injury and oxidative stress in rats.
- Quercetin and chlorogenic acid in FCLE showed high affinity for Duox1 and Keap1.
- FCLE modulated gene expressions related to oxidative stress and apoptosis pathways.

## Abstract

To investigate the therapeutic potential of Ficus carica leaf extract (FCLE) against high-fat diet (HFD) coupled with isoproterenol-induced cardiac injury in a rat model that mimics myocardial infarction.

HPLC was performed to check the phytochemical composition of FCLE. Analysis of the drug-likeness of phytochemicals and molecular docking was conducted. Four groups of rats were allocated as negative control (NC), positive control (PC), standard (STD), and FCLE treatment groups. After the experiment, serum samples were collected to carry out biochemical analyses. Histopathological assessments of the heart and aorta tissues were performed. The heart tissue gene expression analysis was conducted.

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Four active compounds were identified in HPLC. Drug-likeness analysis of bioactive phytochemical compounds from FCLE indicated no violations of Lipinski’s and Veber’s rules, except for one compound. Quercetin and chlorogenic acid exhibited high affinity for Duox1 and Keap1 (<-8 kcal/mol). FCLE demonstrated a significant reduction in Troponin I (P<0.01), CK-MB (P<0.001), triglycerides (P<0.001), total cholesterol (P<0.001), LDL-C (P<0.001), MDA (P<0.001), and NO (P<0.0001) alongside significant increases in HDL-C (P<0.01), SOD (P<0.001), and CAT (P<0.0001) when compared to PC. FCLE treatment significantly (P<0.0001) down-regulated gene expressions of Duox1, Duoxa1, Duoxa2, Bax, and Bad, whereas the expressions of Nfe2l2, Nrf1, and Bcl2 were significantly (P<0.0001) up-regulated when compared with PC.

Our results suggest that FCLE mitigates cardiac injury by modulating oxidative stress and apoptosis through dual oxidases, the Nrf2/Keap1 pathway, and related apoptotic signaling cascades.