Network pharmacology-based screening and pharmacokinetic evaluation of key active compounds in Jinhong tablets against chronic superficial gastritis

Abstract

Ethnopharmacological relevance: Jinhong tablet (JHT), a traditional Chinese patent medicine prepared from four Chinese medicinal materials, is highly effective in soothing the liver and relieving depression, regulating qi and promoting blood circulation, and regulating the stomach and relieving pain. It is clinically used to treat chronic superficial gastritis (CSG) with liver-stomach disharmony. However, research on its pharmacokinetics remains limited.

Aim of the study: This study aims to investigate the pharmacokinetic characteristics of JHT in normal rats and examine its pharmacokinetic differences across normal, CSG, and intestinal microbial disorder rats.

Materials and methods: The chemical composition of JHT was identified using Orbitrap, and the main components were quantitatively analyzed. A network pharmacology screening framework was established to screen the key active ingredients of JHT in treating CSG. A quantitative method was developed to measure these ingredients in rat plasma. After oral administration of JHT at different doses, the pharmacokinetics of seven ingredients was evaluated in normal rats. Pharmacokinetic differences of four major compounds were further compared among normal, CSG, and fecal microbiota transplantation (FMT) rats. Gut microbiota changes in the three groups were analyzed using high-throughput sequencing, and Spearman correlation analysis was conducted to explore the relationship between the in vivo exposure and microbial alterations.

Results: Leveraging network pharmacology analysis, we screened seven key active compounds of JHT in the treatment of CSG and conducted pharmacokinetic studies on them. In normal rats, all seven ingredients were rapidly absorbed. Tetrahydropalmatine, corydaline, costunolide, and rhamnosylvitexin showed good exposure, whereas dehydrocorydaline, allocryptopine, and palmatine hydrochloride had low exposure. Additionally, tetrahydropalmatine, corydaline, and costunolide exhibited linear pharmacokinetics between 0.7-5.6 g/kg, whereas rhamnosylvitexin and dehydrocorydaline were linear within 0.7 and 2.8 g/kg. In CSG and FMT rats, pharmacokinetic profiles changed. CSG increased the exposure and C_max of costunolide and rhamnosylvitexin, whereas FMT enhanced the exposure of corydaline and C_max of rhamnosylvitexin, which correlated with 20 altered gut bacterial genera.

Conclusions: JHT exhibited linear pharmacokinetic characteristics within the appropriate dose ranges, and both the CSG pathological state and intestinal microbial disorder obviously affected its absorption and metabolism. These findings provide valuable insights for the mechanism research and clinical application of JHT.

Keywords

chronic superficial gastritis / fecal microbiota transplantation / Jinhong tablet / network pharmacology / pharmacokinetics / UPLC-TQ-MS/MS

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