Leptadenia hastata and caffeic acid attenuate hepatic glycogen depletion in Type 2 diabetic rats

Type 2 diabetes mellitus (T2DM) is an increasing global health concern currently affecting about 590 million adults, with projections reaching 853 million by 2050. It involves disrupted hepatic glycogen metabolism, oxidative stress, and nuclear factor-kappa B (NF-κB)-driven inflammation. Existing therapies are limited by side effects and cost. Leptadenia hastata and its major phenolic constituent, caffeic acid (CAFA), possess antioxidant and anti-inflammatory properties, but their mechanistic effects on diabetic liver injury remain unclear. This study investigated the modulatory effects of aqueous leaf extract of L. hastata (AELH) and CAFA on these hepatic disturbances in diabetic rats. Thirty-six male Wistar rats were randomly assigned to six groups (n=6). T2DM was induced by 10% fructose solution administration for six weeks, followed by an intraperitoneal injection of streptozotocin (35 mg/kg). Diabetic status was confirmed, after which the rats received daily oral treatments of AELH (500 mg/kg), CAFA (50 mg/kg), or metformin (100 mg/kg) for eight weeks. Diabetic rats showed significant depletion of hepatic glycogen, elevation of malondialdehyde (MDA), alanine transaminase, alkaline phosphatase, NF-κB, and interleukin-6, and reduction in superoxide dismutase (SOD) activity. AELH significantly increased hepatic glycogen synthase activity, glycogen content, and SOD activity while reducing MDA and inflammatory mediators. CAFA and metformin elicited similar but less complete effects. Histological/immunohistochemical analyses confirmed hepatocyte preservation and NF-κB suppression by AELH. The AELH and CAFA ameliorate hepatic oxidative-inflammatory response and restore glycogen metabolism in T2DM, demonstrating L. hastata’s polyphenol-mediated hepatoprotective potential as a phytotherapeutic adjunct in diabetic liver dysfunction.