Ginseng and aconite are well‐known couplet medicinals. Ginsenoside Rg1 is the main active ingredient in ginseng, and aconitine (AC), benzoylaconine (BAC) and aconine (ACN) are three representative alkaloids in aconite, which belong to the diester alkaloids, monoester alkaloids and alkanolamine alkaloids respectively. The aim of this study was to investigate the pharmacokinetic effects of ginsenoside Rg1 on the three types of alkaloids and to provide evidences for their compatibility mechanism. In this study, the ginsenoside Rg1 was simultaneously intragastrically administered to rats with AC, BAC and ACN, respectively, and the rat plasma was collected at different time points. The plasma drug concentrations of the three types of alkaloids were determined by UHPLC–MS/MS, and the pharmacokinetic parameters were calculated. The results indicated that the peak concentration and area under the concentration–time curve of BAC were significantly increased (P < 0.05), those for AC were decreased (P < 0.05), and the values for ACN did not change after pretreatment with ginsenoside Rg1. It was inferred that ginsenoside Rg1 may affect the absorption and metabolism of AC and BAC and then change their pharmacokinetic parameters. Subsequently, their absorption and metabolism were further investigated using the Caco‐2 cell monolayer and rat liver microsomes in vitro. The Caco‐2 cell monolayer absorption assay indicated that ginsenoside Rg1 could promote the absorption of AC and BAC, and the rat liver microsomes metabolism assay indicated that ginsenoside Rg1 accelerated the metabolism of AC and did not affect the other two alkaloids. All of the results indicated that ginsenoside Rg1 may reduce the toxicity of aconite and improve its efficacy by promoting the absorption of BAC and accelerating the metabolism of AC. These results could provide evidence for the compatibility mechanism of the traditional Chinese herbal formula Shenfu Decoction.
Background: Gegen Qinlian Decoction(GQD) has been used to treat acute colitis (AC) for several years in China and it has shown good efficacy. However, the active components and target proteins of its anti-AC effects remains to be deciphered. Methods: In this study, serum pharmacochemistry and network pharmacology strategy were integrated to identify the constituents in blood and the mechanism of GQD for the treatment of AC. Ultra-performance liquid chromatography and LTQ-Orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS) was used to identify the absorbed components of GQD in rat serum; molecular docking and compound-target network analysis were used to predict candidate targets and critical components in GQD responsible for efficacy; In addition, the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis and Gene Ontology(GO) enrichment analysis were used to predict the related pathways and biological process respectively; Finally, the model rats with acute colitis were induced by DSS(Dextran Sulfact Sodium) in order to verify the effects and potential mechanism of baicalein, which is an important component of GQD. Results: Based on our comprehensive systematic approach, 23 components were successfully identified in rat serum after oral administration of GQD. The predicted results of molecular docking indicated that these 23 active components closely interacted with 41 protein targets associated with inflammation, immunity and enteric mucos. Among the 23 compounds identified, baicalin, baicalein, wogonoside , liquiritin and daidzin may be the most important components of GQD. Futhermore, according to GO enrichment analysis, the 41 candidate targets identified were mainly involved in two biological process, immune system process and inflammatory response. The KEGG pathway analysis revealed that 41 candidate targets were associated with 62 biological pathways, including HIF-1 signaling pathway and PI3K/Akt signaling pathway. Animal experiments found that baicalein could inhibit the activation of PI3K/Akt/HIF-1 signaling pathway and significantly reduce pro-inflammatory cytokines, such as IL-1β, IL-6, IL-8 and TNF-α to alleviate intestinal mucosal damage and achieve a therapeutic effect on AC. Conclusion: This research not only provides a novel and scientific strategy to better understand the complex mechanism of GQD, but also offers a new perspective to identify and/or discover novel active ingredients of TCM drugs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.