Abstract
We isolated isobavachalcone (IBC) from Angelica keiskei (AK) as an anti-obesity component. IBC dose-dependently inhibited 3T3-L1 adipocyte differentiation by down-regulating adipogenic factors. At the mitotic clonal expansion stage (MCE), IBC caused cell cycle arrest in G0/G1 with decreased expression of cell cycle-regulating proteins. IBC also inhibited autophagic flux by inducing intracellular accumulation of LC3B and SQSTM1/p62 proteins while decreasing expression levels of regulating factors for autophagy initiation. In parallel with the inhibition of adipocyte differentiation, IBC decreased intrahepatic fat deposits and rescued the liver steatosis in high fat cholesterol diet-fed zebrafish. In this study, we found that IBC isolated from AK suppresses mitotic clonal expansion and autophagy flux of adipocytes and also shows anti-obesity activity in a high cholesterol-diet zebrafish model by decreasing intrahepatic fat deposits. These results suggest that IBC could be a leading pharmacological compound for the development of anti-obesity drugs.
Highlights
Obesity is caused by excessive nutrition, a sedentary lifestyle, and genetic factors, resulting in energy imbalance
IBC was isolated from the ethyl acetate soluble fraction of A. keiskei (AK) extracts and its structure was identified by spectroscopic analysis (Figure 1A) [6]
We found that 48 h treatment of IBC showed no effect on cell viability of 3T3-L1 preadipocytes
Summary
Obesity is caused by excessive nutrition, a sedentary lifestyle, and genetic factors, resulting in energy imbalance. Obesity is associated with metabolic disorders such as diabetic mellitus, hypertension, cardiovascular disease, dyslipidemia, gallbladder disease, and cancer. Treatment for obesity consists of bariatric surgery and non-pharmacological treatment such as exercise, change in lifestyle, caloric intake limitation, and pharmacological treatment. When non-pharmacological treatment and bariatric surgery have unsatisfactory results, more promising and safe pharmacological treatments are needed to treat obesity. Anti-obesity drugs including orlistat, lorcaserin, phentermine, and topiramate are currently available for weight loss, they might have side effects. We have focused on discovering anti-obesity agents from natural products that can be less toxic and can be combined with conventional treatments [2]
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