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

Noruddin NAA, Hamzah MF, Rosman Z, Salin NH, Shu-Chien AC, Muhammad TST

Molecules, 2021 May 03;26(9).
PMID: 34063700 DOI: 10.3390/molecules26092682

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.
Fulltext Phytol and bilimbi phytocompounds induce thermogenic adipocyte differentiation: An in vitro study on potential anti-obesity effects

Md Fauzi F, Hamzah MF, Mahmud MZ, Amanah A, Mohd Noor MH, Zainuddin Z, et al.

Heliyon, 2024 Dec 15;10(23):e40518.
PMID: 39698098 DOI: 10.1016/j.heliyon.2024.e40518

Obesity is a major health concern associated to diabetes, cardiovascular disease, and cancer. Brown adipocytes, which specialise in thermogenesis, offer a potential therapeutic target for obesity prevention and related conditions. This study builds on previous findings of the browning activity of Averrhoa bilimbi hexane fractions and aims to elucidate the underlying mechanisms in vitro. Squalene and phytol, key phytocompounds from bilimbi leaf extract and fractions, were assessed for their ability to induce thermogenic adipocyte using 3T3-L1 preadipocytes and C2C12 myoblasts in vitro models. The result shows that bilimbi fractions F7, F8, and F9, along with squalene and phytol, effectively induced thermogenic adipocyte differentiation. This was evidenced by the upregulation of key markers, including Ucp1, Prdm16, and Pgc1α, and increased expression of the brown adipocyte-specific protein CIDEA in treated 3T3-L1 preadipocytes. Notably, all treatments promoted thermogenic adipocytes differentiation in C2C12 myoblasts via the upregulation of Pgc1α, Ucp1 genes, and UCP1 protein. These findings suggest that bilimbi fractions and its phytocompounds may hold potential as nutraceutical interventions for obesity management.
Fulltext Novel discovery of Averrhoa bilimbi ethanolic leaf extract in the stimulation of brown fat differentiation program in combating diet-induced obesity

Lau WK, Noruddin NAA, Ariffin AH, Mahmud MZ, Noor MHM, Amanah A, et al.

BMC Complement Altern Med, 2019 Sep 05;19(1):243.
PMID: 31488120 DOI: 10.1186/s12906-019-2640-3

BACKGROUND: Brown adipocytes are known to promote energy expenditure and limit weight gain to combat obesity. Averrhoa bilimbi, locally called belimbing buluh (DBB), is mainly used as an ethnomedicine in the treatment of metabolic disorders including diabetes mellitus, hypertension and obesity. The present study aims to investigate the browning activity on white adipocytes by A. bilimbi leaf extract and to evaluate the potential mechanisms.
METHODS: Ethanolic leaf extract of A. bilimbi was exposed to Myf5 lineage precursor cells to stimulate adipocyte differentiation. Protein expressions of brown adipocyte markers were determined through high content screening analysis and validated through western blotting. Mito Stress Test assay was conducted to evaluate the cellular oxygen consumption rate upon A. bilimbi treatment.
RESULTS: A. bilimbi ethanolic leaf extract exhibited an adipogenesis effect similar to a PPARgamma agonist. It also demonstrated brown adipocyte differentiation in myoblastic Myf5-positive precursor cells. Expression of UCP1 and PRDM16 were induced. The basal metabolic rate and respiratory capacity of mitochondria were increased upon A. bilimbi treatment.
CONCLUSIONS: The findings suggest that Averrhoa bilimbi ethanolic leaf extract induces adipocyte browning through PRDM16 activation and enhances mitochondria activity due to UCP1 up-regulation.

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