Tsaokoflavanols A1-J1: Flavanol-fatty alcohol hybrids with HPL inhibitory activity from Amomum tsao-ko

Abstract

Ten previously undescribed compounds were isolated from the fruits of Amomum tsao-ko (Zingiberaceae), including nine undescribed flavanol-fatty alcohol hybrids (1-6, 10-11, 13), and a flavanol-monoterpenoid hybrid (14), along with seven known flavanol hybrids (7-9, 12, 15-17). The structures of these compounds were determined using various analyses, such as HRESIMS, 1D/2D NMR, and ECD calculations. In terms of biological activity, compounds 1, 2, 5, and 6 exhibited inhibitions of human pancreatic lipase (HPL), with IC₅₀ values ranging from 0.017 to 0.193 mM. Some of these values were found to be stronger than that of the positive control, orlistat (IC₅₀, 0.067 mM). Molecular docking studies were also conducted to investigate the interactions between these compounds and HPL. The docking simulations revealed the importance of the orientation of the 3,4-dihydroxyphenyl in binding with HPL. Additionally, compound 9 demonstrated cytotoxicity against HepG2, with a CC₅₀ value of 14.96 ± 0.62 μM as determined by the MTT assay. Flow cytometry analysis indicated that compound 9 induced apoptosis in HepG2 cells. Western blot results showed an up-regulation of apoptosis-related proteins, such as p53 protein, Bax and Caspase-3 proteins, while the expression of Bcl-2 protein was down-regulated.

Keywords: Amomum tsao-ko (Zingiberaceae); Cell apoptosis; Flavanol−fatty alcohol hybrid; Flavanol−monoterpenoid hybrid; Human pancreatic lipase inhibitors; Molecular docking.