Components study on gastroprotective effect and holistic mechanism of the herbal pair Alpinia officinarum - Cyperus rotundus based on spectrum-effect relationship and integrated transcriptome and metabolome analyses.

Ethnopharmacological Relevance: The herbal pair Alpinia officinarum-Cyperus rotundus (HPAC) has an extended history of use in the treatment of gastric ulcers, and its curative effect is definite.

Aim Of The Study: To explore the material basis and holistic mechanism of HPAC on ethanol-induced gastric ulcers.

Materials And Methods: Three chemometrics, GRA, OPLS, and BCA, were used to construct the spectrum-effect relationship between the HPLC fingerprints of HPAC extracts and the bioactivity indices (cell viability; the levels of TNF-α, IL-6, COX-2, and PGE2; and wound healing rate) against GES-1 cell damage to screen the bioactive ingredients. The bioactive components were isolated and validated in vitro. Simultaneously, the effects of HPAC with concentrated bioactive ingredients was tested on ethanol-induced gastric ulcers in vivo, and the mechanism was investigated using transcriptomics and metabolomics. The mechanism was further validated by Western blotting. Finally, the contents of the main components of HPAC were determined before and after compatibility.

Results: Twelve bioactive components were screened, and the structures of nine compounds were confirmed. An in vitro verification test showed that DPHA and galangin could protect GES-1 cells from injury, and that their content increased after compatibility. The CHCl fraction of HPAC (HP-CHCl) can protect mice from ethanol-induced gastric mucosal injury by reducing hemorrhage and decreasing inflammatory cell infiltration. Western blot analysis indicated that this fraction may up-regulate TRPV1 protein and down-regulate PI3K and AKT proteins.

Conclusions: DPHA and galangin may be the bioactive components against ethanol-induced GES-1 cell injury. HP-CHCl may exert gastroprotective effects by regulating PI3K, AKT and TRPV1 proteins.