Effect of Sonneratia alba Fruit Extract on LOX-1 and Nrf2 Expression in the Aortic Arches of High Fat Diet Induced Rats

Abstract

Atherosclerosis, the primary cause of ischemic heart disease, is a major contributor to global mortality. This highlights the urgent need for therapeutic strategies that are not only beneficial and safe but also economically sustainable, such as those derived from natural bioactive compounds. This study investigated the anti-atherogenic effect of mangrove Sonneratia alba, a source of bioactive compounds with known antioxidant and anti-inflammatory properties. The objective was to determine the extract’s effect on the pro-atherogenic receptor LOX-1 and its subsequent effect on foam cell formation and the endogenous antioxidant axis Nrf2-MnSOD in the aortic arch of male Wistar rats exposed to a 10-week high-fat diet. A total of twenty-four rats were randomly divided into six groups; normal control, HFD control, atorvastatin control (10 mg/day) and HFD groups treated with S. alba extract at 200, 400 and 800 mg/kg/day. The expression of LOX-1, Nrf2, and MnSOD was assessed using immunohistochemistry, while foam cells were identified through H&E staining. The results showed S. alba fruit extract at the dose of 800 mg/kg/day significantly reduced circulating LDL-C levels. Within the aortic arch, the S. alba extract at the same dose significantly suppressed LOX-1 expression, significantly reduced approximately 82% of foam cell formation and significantly elevated Nrf2 expression. The expression of MnSOD was enhanced however this change did not reach statistical significance. These data collectively suggest that S. alba fruit extract ameliorates early atherogenic features, associated with the modulation of key regulatory proteins LOX-1 and Nrf2, and subsequent reduction in foam cell formation. Thus, the extract seems promising as a natural agent for vascular protection, but further functional investigations are needed to definitively confirm the underlying mechanism.

HIGHLIGHTS

• Sonneratia alba fruit possesses diverse secondary metabolites and exhibits strong antioxidant activity.
• The extract was administered to male Wistar rats to counteract high-fat diet-induced atherogenesis.
• Treatment significantly reduced circulating LDL, suppressed LOX-1 expression and inhibited foam cell formation in the aortic arch of hyperlipidemic rats.
• The therapeutic protection is likely mediated through the upregulation of Nrf2 expression.
• Sonneratia alba extract exhibits potential as a novel Nrf2 activator for mitigating vascular oxidative stress.

GRAPHICAL ABSTRACT