The Potential Prophylactic Effect of Moringa oleifera Lam. Leaf Extracts Against Fructose-Induced Metabolic Dysfunction in Early-Weaned Female Rats

Abstract

Early weaning has become increasingly common worldwide due to urbanisation, socioeconomic demands, and health reasons. It is estimated that 88% of infants are early-weaned (less than 6 months old) globally. Consequently, early-weaned infants, especially when weaned onto high fructose diets, are at risk of developing disorders like metabolic dysfunction associated with fatty liver disease and kidney disease early in childhood. These metabolic disorders then progress into adulthood, affecting their lifespan and functionality, and are a financial burden to the healthcare system. This study investigated the long-term potential prophylactic effects of Moringa oleifera leaf extracts when administered for the first two weeks post-weaning, in female Sprague-Dawley rats early-weaned onto high fructose diets. The rats were weaned early (18 days old), and fed either standard rat feed, a fructose-rich diet, a normal diet with Moringa extracts, or a combination of high fructose with Moringa extracts for 18 days. The normal control group was weaned at 21 days old. Post weaning, the rats were fed a high-fructose diet or a normal diet for 111 days. The rats were terminated on postnatal day 112. Early weaning with fructose-induced elevated serum concentrations of leptin, low-density lipoproteins (LDL), triglyceride, total cholesterol, and alanine transaminase (p<0.05, ANOVA). It also resulted in increased hepatic micro- and macrosteatosis, hypertrophy, inflammation, area fraction of the collagen, peroxisome proliferator-activated receptor alpha (PPARα), and sterol regulatory element-binding protein 1c (SREBP-1c) gene expression (p<0.05). Early weaning with fructose decreased serum concentrations of insulin, adiponectin, high-density lipoprotein (HDL), and hepatic carnitine palmitoyltransferase I (CPT-1) gene expression (p<0.05). However, early weaning treatment with Moringa for only two weeks, demonstrated a broad scope of protection against the fructose-induced metabolic dysfunction, specifically hepatic steatosis, and modulated gene expression related to lipogenesis and fatty acid oxidation by decreasing hepatic SREBP-1c, Acetyl-CoA Carboxylase 1 (ACC-1), and fatty acid synthase (FAS) gene expression and increasing CPT-1 and PPARα gene expression (p<0.05), with dose- dependent effects observed. Early weaning alone did not significantly affect kidney mass, relative mass, serum renal function markers (kidney injury molecule-1 (KIM-1), creatinine, or blood urea nitrogen (BUN) levels, but led to increased serum neutrophil gelatinase-associated lipocalin (NGAL) serum concentrations) and kidney glomerular/Bowman’s capsule area (BCA) (p<0.0001). Fructose caused significant v functional (↑KIM-1, BUN, NGAL; ↓creatinine) and structural kidney damage (enlarged and deformed glomeruli), which Moringa reversed. Dose differences were minimal but indicated slightly better biochemical function with higher doses, but greater histopathological protection with lower doses. In conclusion, early weaning combined with high fructose consumption resulted in significant metabolic dysfunction, hepatic steatosis, and renal damage in female Sprague-Dawley rats. The short-term supplementation of Moringa oleifera leaf extract immediately after early weaning offered long term sustained, multi-organ protection. Given its low cost, accessibility, and translational potential, Moringa represents a promising early-life nutritional strategy to protect against long-term metabolic, hepatic, and renal dysfuncti