Ameliorative Effects of Moringa oleifera Leaf Extract on Mitochondrial Dysfunction, Oxidative Stress, and Insulin Resistance in High-Fat Diet-Induced Metabolic Syndrome in Rats

Abstract

Background: Metabolic syndrome includes a combination of conditions, which are dyslipidemia, frequent hyperglycemia, obesity, elevated HOMA-IR, oxidative stress, inflammation, and dysregulation of mitochondrial function. Many bioactive components in Moringa oleifera can promote the balance of metabolism; however, the impact of Moringa oleifera on the pathways of mitochondrial biogenesis is uncertain.
Aim: This study aims to investigate the effects of Moringa oleifera ethanolic leaf extract on mitochondrial biogenesis, inflammation, oxidative stress, mitochondrial dysfunction, and insulin resistance, as well as the expression of genes related to mitochondrial biogenesis, in rats with metabolic syndrome.
Methods: Forty male Wistar rats were randomly assigned to four groups of 10. One group was the negative control; one group was the metabolically disrupted control; one group was treated with metformin; and one group was treated with Moringa oleifera extract. Induction of disruption of metabolism by diet (high fat) was for 8 weeks. Treatments for the remaining 8 weeks by gavage were 200 mg/kg/day metformin and 300 mg/kg/day of Moringa oleifera leaf extract. The following were measured and compared: weight, glucose levels, insulin levels, HOMA, fasting levels, lipids, inflammatory response, oxidative stress, liver and kidney function, ATP levels, mitochondrial potential, and ROS levels. Expression levels of SIRT1, PPARGC1A, NRF1, and TFAM were also measured.
Results: Compared to the negative control group, the metabolically disrupted group that did not receive treatment (control for metabolic disruption) showed a statistically significant elevated weight, levels of fasting glucose, total and HOMA insulin, lipids and levels of biomarkers for hepatic and renal function, inflammatory cytokines, MDA and mitochondrial reactive oxygen species, and a decrease in the activity of antioxidant enzymes, ATP levels, mitochondrial potential and significantly decreased the expression of SIRT1 and PPARGC1A, NRF1 and TFAM. Compared to the untreated metabolic syndrome group, Moringa oleifera treatment improved various metabolic and inflammatory conditions (p < 0.001). However, the contrasting effects of Metformin and Moringa oleifera include improvements in HOMA-IR and in various antioxidant enzymes. HOMA-IR showed a positive correlation with malondialdehyde and mitochondrial ROS, and a negative correlation with ATP, mitochondrial membrane potential, and mitochondrial gene expression.
Conclusion: Methanolic extract of Moringa oleifera leaves has the potential to serve as a therapeutic agent for treating Metabolic Syndrome, as demonstrated by its effects on several components of metabolic syndrome, including the oxidative and inflammatory challenges associated with mitochondrial bioenergetics and biogenesis. However, more clinical and mechanistic studies are necessary to validate these therapeutic effects of Moringa oleifera.