Dual therapeutic potential of ethanolic plant extracts in diabetes and liver cancer: Comparative study with liraglutide and doxorubicin

Abstract

Diabetes mellitus (DM) is a chronic disease that can lead to severe complications, including progressive liver damage and liver cancer if left untreated. Although Liraglutide, a glucagon-like peptide-1 receptor agonist, is effective in managing type 2 DM, its high cost and associated side effects limit its widespread use. This is the first study to systematically compare the therapeutic potential of the five plant ethanolic extracts: Cinnamomum zeylanicum , Nigella sativa , Saussurea lappa , Moringa oleifera , and Curcuma longa with Liraglutide and Doxorubicin for dual antidiabetic and anticancer activities, respectively. In vitro cytotoxicity was assessed in HepG2 cells, and in vivo efficacy was tested in alloxan-induced diabetic rats. Effects on glucose regulation, oxidative stress, inflammation, and liver histopathology were evaluated. Molecular pathway analysis focused on the Nrf2/HO-1/NQO1 and NF-κB/IKK-β signaling mechanisms in the pancreas. Among the tested ethanolic extracts, S . lappa , N . sativa , and M . oleifera showed the most potent cytotoxic effects on HepG2 cells. In diabetic rats, all extracts demonstrated improvements in glycemic control, reduced oxidative stress and inflammation, and enhanced liver tissue structure. M. oleifera and C. longa reduced HbA1c levels by >60 % and restored insulin and GLP-1 close to normal levels, showing comparable results to Liraglutide. These findings suggest M. oleifera and C. longa as affordable, accessible, and dual-acting natural alternatives for diabetes and liver cancer management, potentially through modulation of oxidative stress and inflammatory pathways. Further clinical studies are necessary to confirm their therapeutic efficacy in human populations.