Natural Compound 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al from Momordica charantia Acts as PPARγ Ligand.

Nur Adelina Ahmad Noruddin,Zulfadli Rosman,Nurul Hanim Salin,Mohamad Faiz Hamzah,Alexander Chong Shu-Chien,Tengku Sifzizul Tengku Muhammad

doi:10.3390/molecules26092682

Abstract

Momordica charantia is a popular vegetable associated with effective complementary and alternative diabetes management in some parts of the world. However, the molecular mechanism is less commonly investigated. In this study, we investigated the association between a major cucurbitane triterpenoid isolated from M. charantia, 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (THCB) and peroxisome proliferator activated receptor gamma (PPARγ) activation and its related activities using cell culture and molecular biology techniques. In this study, we report on both M. charantia fruit crude extract and THCB in driving the luciferase activity of Peroxisome Proliferator Response Element, associated with PPARγ activation. Other than that, THCB also induced adipocyte differentiation at far less intensity as compared to the full agonist rosiglitazone. In conjunction, THCB treatment on adipocytes also resulted in upregulation of PPAR gamma target genes expression; AP2, adiponectin, LPL and CD34 at a lower magnitude compared to rosiglitazone’s induction. THCB also induced glucose uptake into muscle cells and the mechanism is via Glut4 translocation to the cell membrane. In conclusion, THCB acts as one of the many components in M. charantia to induce hypoglycaemic effect by acting as PPARγ ligand and inducing glucose uptake activity in the muscles by means of Glut4 translocation.

Highlights

Diabetes mellitus is a type of metabolic disease that is characterised by a high glucose level in blood or hyperglycaemia
In 2019, World Health Organisation published an update on the classification of diabetes mellitus which comprises of type 1 diabetes, type 2 diabetes (T2DM), hybrid forms of diabetes, other specific types, unclassified diabetes and hyperglycaemia first detected during pregnancy [5]
peroxisome proliferator responsive element (PPRE) originated from Acyl-Coenzyme A Oxidase (ACOX) gene, cells that were transfected in T75 flasks and subsequently transferred to 96-well plate for treatment together in the presence of expression plasmids of PPARγ2 and RXRα produced the most optimised and sensitive high throughput based screening platform

Summary

Introduction

Diabetes mellitus is a type of metabolic disease that is characterised by a high glucose level in blood or hyperglycaemia This pathophysiological condition occurs when the pancreas does not secrete sufficient insulin or/and the body cannot effectively use insulin leading to hyperglycaemia. In 2019, World Health Organisation published an update on the classification of diabetes mellitus which comprises of type 1 diabetes, type 2 diabetes (T2DM), hybrid forms of diabetes, other specific types, unclassified diabetes and hyperglycaemia first detected during pregnancy [5]. Of all these types, T2DM is the highest prevalence form affecting

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