The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has created the need for better therapeutic options. In this study, five natural xanthones were extracted and purified from the fruit hull of Garcinia mangostana and their antimicrobial properties were investigated. α-Mangostin was identified as the most potent among them against Gram-positive pathogens (MIC=0.78-1.56 μg/mL) which included two MRSA isolates. α-Mangostin also exhibited rapid in vitro bactericidal activity (3-log reduction within 5 min). In a multistep (20 passage) resistance selection study using a MRSA isolated from the eye, no resistance against α-mangostin in the strains tested was observed. Biophysical studies using fluorescence probes for membrane potential and permeability, calcein encapsulated large unilamellar vesicles and scanning electron microscopy showed that α-mangostin rapidly disrupted the integrity of the cytoplasmic membrane leading to loss of intracellular components in a concentration-dependent manner. Molecular dynamic simulations revealed that isoprenyl groups were important to reduce the free energy for the burial of the hydrophobic phenyl ring of α-mangostin into the lipid bilayer of the membrane resulting in membrane breakdown and increased permeability. Thus, we suggest that direct interactions of α-mangostin with the bacterial membrane are responsible for the rapid concentration-dependent membrane disruption and bactericidal action.

Destruction in intestinal barrier is concomitant with the intestinal diseases. There is growing evidence that tryptophan-derived intestinal bacterial metabolites play a critical role in maintaining the balance of intestinal mucosa. In this study, the Caco-2/HT29 coculture model was used to evaluate the effect of indole-3-propionic acid (IPA) on the intestinal barrier and explore its underlying mechanism. We found that IPA increased transepithelial electrical resistance and decreased paracellular permeability which was consistent with the increase in tight junction proteins (claudin-1, occludin, and ZO-1). Furthermore, IPA strengthened the mucus barrier by increasing mucins (MUC2 and MUC4) and goblet cell secretion products (TFF3 and RELMβ). Additionally, IPA weakened the expression of LPS-induced inflammatory factors. These discoveries provide new views for understanding the improvement of intestinal barrier by gut microbial metabolites of aromatic amino acids.

A new prenylated isoflavonoid, flemiphilippinin G (1), and a new flavonol glycoside, flemiphilippininside (2), along with eleven known isoflavonoids were obtained from the roots of Flemingia philippinensis (Merr. et Rolfe) Li. Their structures were elucidated on the basis of spectroscopic data. The in vitro cytotoxicities of compounds 1–13 against MCF‐7, A549, and Hep‐G2 cell lines were determined by using the MTT (=3‐(4,5‐dimethylthazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) colorimetric assay, and their antioxidant activities were evaluated by ferric‐reducing antioxidant power (FRAP) method. Compound 1 exhibited significant cytotoxicity against all the tested cell lines with IC50 values of 4.8–7.3 μM, and compound 2 was found to be inactive. Both compounds 1 and 2 showed weak antioxidant activities with FRAP values of 110±15 and 124±16 μmol/g, respectively.