* Equally contributing authors
Currently, the Republic of Palau faces a prevalence of overweight and obese adults of around 80 % according to WHO data. A reverse pharmacology approach [1] was implemented to study the traditional herbal medicines used in Palau in relation to obesity management. The decoction of the leaves of Phaleria nisidai Kaneh (Thymelaeaceae) (DAK [2] ) was selected by a retrospective treatment outcome method [3] . Afterward, a pilot clinical study evaluated DAK as an adjuvant therapy for patients with insufficient diabetes control [2] .
Based on these encouraging findings, we examined the biological activity of DAK in a murine obesity model and its chemical composition. Mice fed a high-fat diet supplemented with DAK revealed greater sensitivity to insulin, improved glucose tolerance and higher insulin secretion. Furthermore, in vitro administration of DAK promoted insulin-stimulated glucose uptake into adipocytes and increased their capacity to metabolize glucose as measured by extracellular flux analysis.
Metabolites profiling of DAK obtained by UHPLC-PDA-ELSD-HRMS confirmed the high amount of the C-glycoside xanthone mangiferin and other minor related xanthones.
We next aimed at evaluating whether mangiferin was the sole bioactive substance. Therefore, DAK was fractionated by MPLC into four fractions, which were tested in vivo. Interestingly, although the mangiferin-rich fraction was bioactive, another fraction showed overall higher bioactivity, including increased insulin sensitivity, ameliorated glucose tolerance and reduced random-fed blood glucose levels. Dereplication of this fraction revealed the presence of mangiferin-related xanthones and flavones. Further research is on-going to elucidate the mode of action in vitro.
These investigations highlighted the potential of the reverse pharmacology method for the identification of traditional herbs with high therapeutic value.
1. Willcox M, et al. Malar J 2011; 10: Suppl 1: p. S8.
2. Kitalong C, et al. J Ethnopharmacol 2017; 205: p. 116-122.
3. Graz B, et al. J Ethnopharmacol 2015; 161: p. 233-7.