4-Hydroxyboesenbergin B of Alpinia japonica protected gastrointestinal tract by inhibiting vancomycin-resistant enterococcus and balancing intestinal microbiota

Abstract

Ethnopharmacological relevance

Alpinia japonica, a traditional herb utilized in Miao medicine in southwestern China, has been employed to alleviate symptoms such as stomachache, diarrhea, and abdominal pain, some of these symptoms may be associated with bacterial infections of the gastrointestinal tract.

Aim of the study

To explore antimicrobial compounds related to traditional uses of A. japonica and its potential pathway in vitro and in vivo.

Materials and methods

Bioactive components of A. japonica were isolated by bioguide separation method. The antibacterial bioactivity of 4-hydroxyboesenbergin B (4-HB) was evaluated by time-kill curve and drug resistance induction. The pathway of 4-HB against VRE was investigated through network pharmacological analysis and validated by in vitro experiments and RT-qPCR assays. Moreover, a mouse gastrointestinal tract model was established to validate the antibacterial bioactivity of 4-HB in vivo.

Results

4-HB from A. japonica inhibited VRE (MIC = 16 μg/mL), rapidly killed the bacteria within 4 h at the 4 MIC concentration and exhibited low susceptibility to drug resistance. 4-HB specifically targeted VRE biofilms by down-regulating the expression of AtlA, SgrA, GelE, and Ace. As a result, 4-HB diminished the adhesion and aggregation ability of VRE, reduced the extracellular matrix content, disrupted biofilm structure and morphology, thereby reducing VRE resistance and virulence. Additionally, 4-HB significantly reduced VRE colonization, enhanced intestinal microbiota diversity, and promoted the restoration of intestinal microbiota balance in vivo. Notably, 4-HB enhanced the abundance of beneficial bacteria genera, such as Lactobacillus and Limosilactobacillus.

Conclusions

4-HB has a significant ability to destroy VRE biofilms and balance intestinal microbiota, which might be responsible for the traditional use of A. japonica partly.