ABSTRACTS FOR INTERNATIONAL HEALTH AND MEDICAL SCIENCES CONFERENCE 2019 (IHMSC 2019). Accelerating Innovations in Translational and Precision Medicine. Held at Taylor’s University Lakeside Campus, Subang Jaya, Selangor, Malaysia. 8-9th March, 2019
Introduction: According to the National Health and Morbidity Survey (NHMS) 2015, 47.7% of the Malaysian population are either obese or overweight. The increased obesity prevalence has caused major health problems including cardiovascular diseases and diabetes. Although several anti-obesity drugs have been developed, they are limited due to adverse side effects. Previous studies demonstrated that xanthorrhizol (XNT) reduced the levels of serum free fatty acid and triglyceride in vivo, but the detailed anti-obesity activities and its related mechanisms are yet to be reported. Thus, this study aims to evaluate its abilities to inhibit adipocyte hyperplasia and hypertrophy employing 3T3-L1 adipocytes.
Methods: Statistical significance was established by one-way ANOVA, where p < 0.05 was considered statistically significant.
Results: In this study, the IC50 value of XNT (98.3% purity) from Curcuma xanthorrhiza Roxb. in 3T3-L1 adipocytes was 35 ± 0.24 μg/mL. The loss of cell viability was due to 20.01 ± 2.77% of early apoptosis and 24.13 ± 2.03% of late apoptosis. XNT elicited apoptosis via up-regulation of caspase-3 and cleaved PARP-1 protein expression for 4.09-fold and 3.12-fold, respectively. Moreover, XNT decreased adipocyte differentiation for 36.13 ± 3.64% and reduced GPDH activity to 52.26 ± 4.36%. The underlying mechanism was due to impaired expression of PPARγ to 0.36-fold and FAS to 0.38-fold, respectively. On the other hand, XNT increased glycerol release by 45.37 ± 6.08% compared to control. During lipolysis, XNT up-regulated the leptin protein for 2.08-fold but down-regulated the protein level of insulin to 0.36-fold. These results indicated that XNT reduced the volume of adipocytes through modulation of leptin and insulin.
Conclusion: To conclude, XNT exerted its anti-obesity mechanisms by suppression of adipocyte hyperplasia through induction of apoptosis and inhibition of adipogenesis whilst reduction of adipocyte hypertrophy through stimulation of lipolysis. Thus, XNT could be developed as a potential anti-obesity agent in the future.
Xanthorrhizol is a plant-derived pharmacologically active sesquiterpenoid compound isolated from Curcuma xanthorrhiza. Previously, we have reported that xanthorrhizol inhibited the proliferation of HepG2 human hepatoma cells by inducing apoptotic cell death via caspase activation. Here, we attempt to further elucidate the mode of action of xanthorrhizol. Apoptosis in xanthorrhizol-treated HepG2 cells as observed by scanning electron microscopy was accompanied by truncation of BID; reduction of both anti-apoptotic Bcl-2 and Bcl-X(L) expression; cleavage of PARP and DFF45/ICAD proteins and DNA fragmentation. Taken together, these results suggest xanthorrhizol as a potent antiproliferative agent on HepG2 cells by inducing apoptosis via Bcl-2 family members. Hence we proposed that xanthorrhizol could be used as an anti-liver cancer drug for future studies.