Intravenous administration of walnut leaf extract attenuates oxidative stress and improves insulin sensitivity and adipose tissue metabolism in feed-restricted fat-tailed ewes.

Plants produce secondary metabolites such as polyphenolic compounds, particularly flavonoids, which exhibit antioxidant, anti-inflammatory, and immunomodulatory properties that can improve livestock health and productivity. In ruminants, however, the bioavailability and efficacy of these compounds are often limited by ruminal microbial degradation. This study evaluated the effects of intravenous administration of walnut leaf extract (WLE) on oxidative status, metabolic parameters, and insulin signaling in feed-restricted Makui ewes. Twelve healthy, non-pregnant, non-lactating ewes were assigned to a Latin square design and received either saline (control) or WLE at 50, 75, or 100 mg/kg body weight during four 10-day treatment periods with washouts periods, under feed restriction to induce negative energy balance. Plasma concentrations of glucose, insulin, non-esterified fatty acids (NEFA), and malondialdehyde (MDA) were measured, and the expression of metabolic and inflammatory genes (INSR, GLUT4, PPARγ, TNF-α) was analyzed. WLE, particularly at 100 mg/kg, significantly decreased MDA and NEFA levels, improved insulin sensitivity, and upregulated INSR and GLUT4 expression. Histological analysis showed reduced adipocyte numbers and increased cell size in treated groups. These findings suggest that intravenous WLE mitigates oxidative stress and improves metabolic function during negative energy balance, supporting its potential as a phytogenic intervention to enhance ruminant metabolic health.