FIGURE 1. Structural modifications to glabridin improvein vivo weight-reduction effect and chemical stability. (A) Schematic of development of HSG4112 from glabridin (B-C) HFD-mice (n = 4 for non-vehicle groups, n = 2 for vehicle group) were orally administered with vehicle or glabridin-derivatives (150 mg·kg-1·day-1) for 4-6 weeks for screening purpose in (B) hydrogenation, (C) etherification and (D) chain elongation steps. Data represent mean only, without statistical analysis. For (E) enantiomerization, n = 5 per group with 50mg·kg-1·day-1 dosage. Data represent mean ± SEM. ***P < 0.001; two-way ANOVA with Tukey’s multiple comparison test. (F, G) Degradation of glabridin and HSG4112 was measured by HPLC in (F) acidic solution – 1% hydrochloride methanol solution (v/v%) and in (G) basic solution – 1% sodium hydroxide methanol solution (w/v%). Three replicates were performed. Data represent mean ± SD; error bar is not visible because of negligible deviance. ***P < 0.001; two-way ANOVA with Sidak’s multiple comparison test.