Centratherum Anthelminticum (L.) Kuntze Seed Oil Restoring Hepatic Balance in Type 2 Diabetic Rats through Nrf2/Keap1/HO-1 and NF-κB Pathway Modulation

Introduction Diabetes Mellitus (DM) contributes to global morbidity and mortality. The liver also takes the brunt in the form of diabetic hepatopathy (DH). The spectrum of liver involvement varies from glycogen-hepatopathy, non-alcoholic fatty liver disease (NAFLD), fibrosis and cirrhosis to hepatocellular carcinoma. The insufficient choices for managing DH necessitates the exploration of other novel treatment options. Therefore, fixed oil (FO) extracted from the seeds of Centratherum anthelminticum (CA) and its hexane (HF), chloroform (CF) and ethanol (EF) fractions were explored for their anti-inflammatory, antioxidant, antidiabetic and anti-apoptotic properties in mitigating liver damage in diabetic rats. Methods The STZ-induced diabetic model was developed with challenging the rats first with high-fat and fructose diet followed by STZ (60mg/Kg). Following the development of DM rats were subjected to four-weeks of treatment with CA seed’s FO and their HF, CF and EF soluble fractions alongside with gliclazide (Glic) as a treatment-control. The efficacy of oil’s anti-inflammatory, antioxidant and anti-apoptotic pathways were evaluated through a comprehensive array of biochemical, histological and molecular parameters. Results Mitigation of inflammation (TNF-α, IL-1β, COX-1, and NF- κ B) was observed. However, the antioxidant effects (expression of HO-1 and Keap1/Nrf2) were opposite to what has been observed in the kidney (previous-work). The seed’s oil and its all soluble-fraction dampen and reverse the deleterious perturbation of hyperglycemia (FBS, Insulin, and HbA1c) induced inflammation and oxidation (SOD, CAT, GPx, LPO, GSH and HMG CoA/Mevalonate ratio) in the liver to near-normal constitutive-levels. The liver-function-tests, lipid-profile also improved along with mitigation of apoptosis (Bcl2 and Bax) Conclusions Our study holds the promise of identifying a putative natural adjuvant-remedy with a potential to slow or reverse the progression of liver insult in diabetes. It also identifies the gap and gives confident for further exploration of DM models developed chronically; as a means for appropriate representation of the pathophysiology of diabetes and DH.