Dataset Information

Metabolomic Assessment of Acute Cholestatic Injuries Induced by Thioacetamide and by Bile Duct Ligation, and the Protective Effects of Huang-Lian-Jie-Du-Decoction.

ABSTRACT: Huang-Lian-Jie-Du-Decoction, a traditional Chinese formula, has been reported to protect liver from various injuries. Two cholestasis models of rats induced by thioacetamide and by bile duct ligation were established and treated with Huang-Lian-Jie-Du-Decoction. Nuclear Magnetic Resonance-based urinary metabolic profiles were analyzed by orthogonal partial least squares discriminant analysis and univariate analysis to excavate differential metabolites associated with the injuries of the two models and the treatment effects of Huang-Lian-Jie-Du-Decoction. The two cholestatic models shared common metabolic features of excessive fatty acid oxidation, insufficient glutathione regeneration and disturbed gut flora, with specific characteristics of inhibited urea cycle and DNA damage in thioacetamide-intoxicated model, and perturbed Kreb's cycle and inhibited branched chain amino acid oxidation in bile duct ligation model. With good treatment effects, Huang-Lian-Jie-Du-Decoction could regain the balance of the disturbed metabolic status common in the two cholestasis injuries, e.g., unbalanced redox system and disturbed gut flora; and perturbed urea cycle in thioacetamide-intoxicated model and energy crisis (disturbed Kreb's cycle and oxidation of branched chain amino acid) in bile duct ligation model, respectively.

SUBMITTER: Wei DD

PROVIDER: S-EPMC5952270 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Metabolomic Assessment of Acute Cholestatic Injuries Induced by Thioacetamide and by Bile Duct Ligation, and the Protective Effects of Huang-Lian-Jie-Du-Decoction.

Wei Dan-Dan DD Wang Jun-Song JS Duan Jin-Ao JA Kong Ling-Yi LY

Frontiers in pharmacology 20180508

Huang-Lian-Jie-Du-Decoction, a traditional Chinese formula, has been reported to protect liver from various injuries. Two cholestasis models of rats induced by thioacetamide and by bile duct ligation were established and treated with Huang-Lian-Jie-Du-Decoction. Nuclear Magnetic Resonance-based urinary metabolic profiles were analyzed by orthogonal partial least squares discriminant analysis and univariate analysis to excavate differential metabolites associated with the injuries of the two mode ...[more]

PMID: 29867467

Similar Datasets

Project description:Huang-Lian-Jie-Du Decoction (HLJDD) is a "Fangji" made up of well-designed Chinese herb array and widely used to treat ischemic stroke. Here we aimed to investigate pharmacological mechanism by introducing an inter-module analysis to identify an overarching view of target profile and action mode of HLJDD. Stroke-related genes were obtained from OMIM (Online Mendelian Inheritance in Man). And the potential target proteins of HLJDD were identified according to TCMsp (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform). The two sets of molecules related to stroke and HLJDD were respectively imported into STRING database to construct the stroke network and HLJDD network, which were dissected into modules through MCODE, respectively. We analyzed the inter-module connectivity by quantify "coupling score" (CS) between HLJDD-modules (H-modules) and stroke-modules (S-module) to explore the pharmacological acting pattern of HLJDD on stroke. A total of 267 stroke-related proteins and 15 S-modules, 335 HLJDD putative targeting proteins, and 13 H-modules were identified, respectively. HLJDD directly targeted 28 proteins in stroke network, majority (16, 57.14%) of which were in S-modules 1 and 4. According to the modular map based on inter-module CS analysis, H-modules 1, 2, and 8 densely connected with S-modules 1, 3, and 4 to constitute a module-to-module bridgeness, and the enriched pathways of this bridgeness with top significance were TNF signaling pathway, HIF signaling pathway, and PI3K-Akt signaling pathway. Furthermore, through this bridgeness, H-modules 2 and 4 cooperatively work together to regulate mitochondrial apoptosis against the ischemia injury. Finally, the core protein in H-module 4 account for mitochondrial apoptosis was validated by an in vivo experiment. This study has developed an integrative approach by inter-modular analysis for elucidating the "shotgun-like" pharmacological mechanism of HLJDD for stroke.

Project description:Huang-Lian-Jie-Du Decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) formula with heat-dissipating and detoxifying effects. It is used to treat inflammation-associated diseases. However, no systematic pharmacokinetic (PK) and pharmacodynamic (PD) data concerning the activity of HLJDD under inflammatory conditions is available to date. In the present study, the concentration-time profiles and the hepatic clearance rates (HCR) of 41 major components in rat plasma in response to the oral administration of a clinical dose of HLJDD were investigated by LC-QqQ-MS using a dynamic multiple reaction monitoring (DMRM) method. Additionally, the levels of 7 cytokines (CKs) in the plasma and the body temperature of rats were analyzed. Furthermore, a PK-PD model was established to describe the time course of the hemodynamic and anti-inflammatory effects of HLJDD. As one of the three major active constituents in HLJDD, iridoids were absorbed and eliminated more easily and quickly than alkaloids and flavonoids. Compared with the normal controls, the flavonoids, alkaloids and iridoids in inflamed rats exhibited consistently changing trends of PK behaviors, such as higher bioavailability, slower elimination, delays in reaching the maximum concentration (Tmax) and longer substantivity. The HCR of iridoids was different from that of alkaloids and flavonoids in inflamed rats. Furthermore, excellent pharmacodynamic effects of HLJDD were observed in inflamed rats. The levels of tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6), IL-1?, IL-10, and macrophage inflammatory protein-2 (MIP-2) and body temperature significantly decreased after the administration of HLJDD. Based on PK-PD modeling with the three-phase synchronous characterization of time-concentration-effect, flavonoids exhibited one mechanism of action in the anti-inflammatory process, while iridoids and alkaloids showed another mechanism of action. Taken together, the results demonstrated that HLJDD may restrain inflammation synergistically via its major constituents (alkaloids, flavonoids and iridoids). A correlation between the exposure concentration of different types of compounds and their anti-inflammatory effects in the body was shown. This study provides a comprehensive understanding of the anti-inflammatory activity of HLJDD.

Dataset Information

Metabolomic Assessment of Acute Cholestatic Injuries Induced by Thioacetamide and by Bile Duct Ligation, and the Protective Effects of Huang-Lian-Jie-Du-Decoction.

Publications

Metabolomic Assessment of Acute Cholestatic Injuries Induced by Thioacetamide and by Bile Duct Ligation, and the Protective Effects of Huang-Lian-Jie-Du-Decoction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets