Diabetes, Metabolic Syndrome and Obesity (Sep 2022)
Guava Leaf Extract Suppresses Fructose Mediated Non-Alcoholic Fatty Liver Disease in Growing Rats
Abstract
Prateek Sharma,1 Jayachandran Nair,1 Anurag Sinh,1 Shivangi,1 Thirumurthy Velpandian,2 Ruchi Tripathi,1 Rajani Mathur1 1Department of Pharmacology, Delhi Institute of Pharmaceutical Science and Research, Delhi Pharmaceutical Sciences and Research University, New Delhi, 110017, India; 2Department of Ocular Pharmacology, Dr. R.P. Center for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, 110029, IndiaCorrespondence: Rajani Mathur, Department of Pharmacology, Delhi Institute of Pharmaceutical Science and Research, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, Sec III, New Delhi, 110017, India, Tel +91-011-29551490, Fax +91-011-29554503, Email [email protected]: Fructose is highly lipogenic, and its unhindered ingestion by children and adolescents is understood to induce hypertriglyceridemia and non-alcoholic fatty liver disease (ped-NAFLD) that is till date managed symptomatically or surgically. The aim of the present study was to investigate the potential of hydroethanolic extract of leaves of Guava (PG-HM) to suppress the alterations in the hepatic molecular signals due to unrestricted fructose (15%) drinking by growing rats.Methods: Weaned rats (4 weeks old) in control groups had ad libitum access to fructose drinking solution (15%) for four (4FDR) or eight (8FDR) weeks, ie, till puberty or early adulthood, respectively, while treatment groups (4PGR, 8PGR) additionally received PG-HM (500 mg/kg, po).Results: The PG-HM suppressed ped-NAFLD through hepatic signalling pathways of 1) leptin-insulin (Akt/FOX-O1/SREBP-1c), 2) hypoxia-inflammation (HIF-1ɑ/VEGF, TNF-ɑ), 3) mitochondrial function (complexes I–V), 4) oxidative stress (MDA, GSH, SOD) and 5) glycolysis/gluconeogenesis/de novo lipogenesis (hexokinase, phosphofructokinase, ketohexokinase, aldehyde dehydrogenase). Parri passu, the insulin sensitizing effect of PG-HM and its ethyl acetate fraction (PG-EA) was elucidated using HepG2 cells grown in media enhanced with fructose. Further, in murine hepatocytes cultured in fructose-rich media, PG-HM (35 μg mL-1) outperformed Pioglitazone (15 μM) and Metformin (5 mM), to suppress hepatic insulin resistance.Conclusion: This study established that hydroethanolic extract of leaves of Guava (PG-HM) has potential to suppress hepatic metabolic alteration for the management of the pediatric NAFLD.Graphical Abstract: Keywords: Psidium guajava, pediatric NAFLD, insulin sensitizer, mitochondrial function
