A low-molecular-mass protein fraction from Moringa oleifera leaves improves glucose tolerance and insulin responsiveness in mice

Moringa oleifera leaves have a long history of nutritional and ethnomedicinal use, including traditional applications related to glycemic disorders, but the specific bioactive constituents that may contribute to these effects remain poorly defined. We isolated Mo – D3 , an anion-exchange protein fraction from M. oleifera leaves selected by reactivity with an anti-insulin antibody, and evaluated its metabolic effects in male C57BL/6 mice ( n = 6/group). In glucose-challenged mice, Mo –D3 reduced glycemia at 30 and 60 min and decreased the 0–180-min area under the glucose curve at doses of 5–500 mg/kg; 5 mg/kg was the lowest effective dose and was used thereafter. Mo –D3 increased hepatic and skeletal-muscle glycogen and acutely reduced total cholesterol while increasing high-density lipoprotein cholesterol. In dexamethasone-treated mice, Mo –D3 partially restored the glucose disappearance rate constant and reversed the increases in intestinal maltase and sucrase activities. Five-day Mo –D3 treatment also approximately doubled skeletal-muscle Akt messenger RNA and increased pancreatic Ins1 messenger RNA by more than tenfold. Collectively, these findings support a multimodal metabolic effect involving improved glucose disposal, tissue glycogen storage, recovery of insulin responsiveness, and coordinated intestinal and transcriptional responses. Mo–D3 is a low-molecular-mass, anti-insulin-immunoreactive protein-enriched fraction obtained from Moringa oleifera leaves. In mice, intraperitoneal administration of Mo–D3 (5 mg/kg; n = 6/group) improved glucose tolerance, reduced glucose AUC₀–₁₈₀, and increased hepatic and skeletal-muscle glycogen. In the five-day model of glucocorticoid-induced insulin resistance, once-daily dexamethasone administration (0.1 mg/kg s.c.) reduced the glucose disappearance rate constant during the insulin-tolerance test (Kiₜₜ), indicating impaired insulin responsiveness. Coadministration of Mo–D3 (5 mg/kg i.p.) increased Kiₜₜ relative to dexamethasone alone, indicating partial recovery toward control values, and normalized dexamethasone-associated elevations in intestinal maltase and sucrase activities. Mo–D3 treatment was also associated with an approximately twofold increase in skeletal-muscle A kt mRNA and a greater than tenfold increase in pancreatic Ins 1 mRNA. The acute reductions in total cholesterol and increases in HDL cholesterol are considered exploratory findings. Dashed connectors represent observed associations and do not establish direct molecular activation or a specific mechanism of action