Abstract

The present study aimed to investigate the antioxidant and anti-inflammatory properties of defatted kenaf seed meal (DKSM) and its phenolic-saponin-rich extract (PSRE) in hypercholesterolemic rats. Hypercholesterolemia was induced using atherogenic diet feeding, and dietary interventions were conducted by incorporating DKSM (15% and 30%) or PSRE (at 2.3% and 4.6%, resp., equivalent to the total content of DKSM-phenolics and saponins in the DKSM groups) into the atherogenic diets. After ten weeks of intervention, serum total antioxidant capacities of hypercholesterolemic rats were significantly enhanced by DKSM and PSRE supplementation (p < 0.05). Similarly, DKSM and PSRE supplementation upregulated the hepatic mRNA expression of antioxidant genes (Nrf2, Sod1, Sod2, Gsr, and Gpx1) of hypercholesterolemic rats (p < 0.05), except for Gpx1 in the DKSM groups. The levels of circulating oxidized LDL and proinflammatory biomarkers were also markedly suppressed by DKSM and PSRE supplementation (p < 0.05). In aggregate, DKSM and PSRE attenuated the hypercholesterolemia-associated oxidative stress and systemic inflammation in rats, potentially by enhancement of hepatic endogenous antioxidant defense via activation of the Nrf2-ARE pathway, which may be contributed by the rich content of phenolics and saponins in DKSM and PSRE. Hence, DKSM and PSRE are prospective functional food ingredients for the potential mitigation of atherogenic risks in hypercholesterolemic individuals.

Highlights

  • Cardiovascular diseases (CVDs) remain as the leading cause of global mortality for the past 15 years

  • Our findings showed that phenolics and saponins are the two major bioactives in defatted kenaf seed meal (DKSM) that correspond to the aforementioned nutraceutical properties [18,19,20,21,22]

  • DKSM and its derived phenolic-saponin-rich extract (PSRE) supplementation improved in vivo antioxidant defense of hypercholesterolemic rats possibly via transcriptional activation of hepatic Nrf2-antioxidant response element (ARE) pathway and improvement of serum total antioxidant capacity (TAC)

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Summary

Introduction

Cardiovascular diseases (CVDs) remain as the leading cause of global mortality for the past 15 years. Hypercholesterolemia is related to excessively elevated levels of circulating total and Oxidative Medicine and Cellular Longevity non-high-density lipoprotein cholesterols in the blood, it is not solely a metabolic disorder of cholesterol homeostasis. Oxidative stress abrogates endothelial nitric oxide (NO) availability, uncouples endothelial nitric oxide synthase (eNOS), and enhances the oxidation of entrapped low-density lipoprotein (LDL) within the subendothelial space, thereby eliciting the vascular inflammation response by recruiting monocytes into the tunica intima. The unregulated uptake of oxidized LDL (oxLDL) by differentiated monocytes (macrophages) leads to the formation of foam cells, producing numerous proinflammatory and oxidative stress markers, cytokines, and growth factors, which further aggravate the atherogenic process [4,5,6,7]

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