Da-Huang-Xiao-Shi decoction protects against3, 5-diethoxycarbonyl-1,4-dihydroxychollidine-induced chronic cholestasis by upregulating bile acid metabolic enzymes and efflux transporters

Xue, Haoyu; Fang, Su; Zheng, Min; Wu, Jiasheng; Li, Hongyu; Zhang, Mengdie; Li, Yuanyuan; Wang, Tianming; Shi, Rong

doi:10.1016/j.jep.2020.113706

Cited by 11 publications

(5 citation statements)

References 41 publications

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“…According to previous statistic, the pathways of AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and insulin resistance were also enriched in non-alcoholic fatty liver and involved in the regulation of liver function [ 53 ]. Xue et al [ 54 ] found that Da-Huang-Xiao-Shi decoction could upregulate the expression of the metabolic enzyme cytochrome P450 in chronic cholestasis. Our previous study suggested that TNF signaling pathway may be the important mechanism for SHCZF against cholestasis [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology analysis and molecular docking to unveil the potential mechanisms of San-Huang-Chai-Zhu formula treating cholestasis

et al. 2022

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Objective Chinese medicine formulae possess the potential for cholestasis treatment. This study aimed to explore the underlying mechanisms of San-Huang-Chai-Zhu formula (SHCZF) against cholestasis. Methods The major chemical compounds of SHCZF were identified by high-performance liquid chromatography. The bioactive compounds and targets of SHCZF, and cholestasis-related targets were obtained from public databases. Intersected targets of SHCZF and cholestasis were visualized by Venn diagram. The protein-protein interaction and compound-target networks were established by Cytoscape according to the STRING database. The biological functions and pathways of potential targets were characterized by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The biological process-target-pathway network was constructed by Cytoscape. Finally, the interactions between biological compounds and hub target proteins were validated via molecular docking. Results There 7 major chemical compounds in SHCZF. A total of 141 bioactive compounds and 83 potential targets were screened for SHCZF against cholestasis. The process of SHCZF against cholestasis was mainly involved in AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and drug metabolism-cytochrome P450. ALB, IL6, AKT1, TP53, TNF, MAPK3, APOE, IL1B, PPARG, and PPARA were the top 10 hub targets. Molecular docking showed that bioactive compounds of SHCZF had a good binding affinity with hub targets. Conclusions This study predicted that the mechanisms of SHCZF against cholestasis mainly involved in AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and drug metabolism-cytochrome P450. Moreover, APOE, AKT1, and TP53 were the critical hub targets for bioactive compounds of SHCZF.

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Section: Discussionmentioning

confidence: 99%

Network pharmacology analysis and molecular docking to unveil the potential mechanisms of San-Huang-Chai-Zhu formula treating cholestasis

et al. 2022

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“…DHXSD was prepared as previously described (Xue et al, 2021). Briefly, DH (12 g), ZZ (15 grains, 13 g) and HB (12 g) were immersed in water (1:10, w/v) for 0.5 h at room temperature and then decocted by boiling for 0.5 h. After filtration, the residue was re‐extracted.…”

Section: Methodsmentioning

confidence: 99%

“…Clinical studies have confirmed that DHXSD has a good therapeutic effect against cholestatic liver injury (Kong et al, 2014). Moreover, modern pharmacological studies have shown that DHXSD exhibits favorable pharmacological effects on α ‐naphthylisothiocyanate‐induced acute cholestasis and 3, 5‐diethoxycarbonyl‐1, 4‐dihydroxychollidine‐induced chronic cholestasis by regulating the disordered homeostasis of bile acids (Xue et al, 2021; Zhu & Feng, 2019). Owing to the correlation between pharmacological effects and chemical constituents, it is essential to quantify the multiple bioactive components comprising DHXSD.…”

Section: Introductionmentioning

confidence: 99%

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Determination of multiple active constituents in Da‐Huang‐Xiao‐Shi decoction using HPLC–LTQ–Orbitrap mass spectrometry: Application in comparing the differences in the formula and its constituent herbs

Jin

Xue

et al. 2022

Biomedical Chromatography

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Da-Huang-Xiao-Shi decoction (DHXSD) is a traditional Chinese medicine formula and is used to treat cholestasis. In this study, we developed a reliable and comprehensive HPLC coupled with a linear ion trap-Orbitrap mass spectrometry method for the separation and determination of 21 components including six alkaloids, five anthraquinones, three tannins, three terpenes, two iridoid glycosides, one organic acid and one flavonoid in DHXSD. A C18 column was eluted using a gradient mobile phase at a flow rate of 1 ml/min. Detection was operated with an electrospray ionization source in positive and negative ion modes using selective ion monitoring. The calibration curves for all analytes showed good linearity (r > 0.9901), and the interand intra-day precision did not exceed 4.98%. The recovery, repeatability and stability were also within the acceptable limits. The method was successfully applied to determine multiple active constituents in DHXSD and its constituent herbs. Compared with Da Huang, the total contents of the five anthraquinones were significantly higher in DHXSD. However, the changes in the components from Zhi Zi/Huang Bo were complicated in DHXSD. The study could serve as a fundamental reference for establishing comprehensive DHXSD quality control measures and be helpful to understand some compatibility laws of DHXSD.

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“…(Zhi Zi). Studies have shown that DHXSD effectively improves cholestasis in mice and rats ( Zhu and Feng, 2019 ; Xue et al, 2021 ). We removed Mirabilitum (Mang xiao) in the clinical application instead of adding Atractylodes macrocephala Koidz.…”

Section: Introductionmentioning

confidence: 99%

The IDI1/SREBP2 axis drives intrahepatic cholestasis and is a treatment target of San-Huang-Cai-Zhu formula identified by sequencing and experiments

et al. 2023

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San-Huang-Chai-Zhu formula (SHCZF), originates from Da-Huang-Xiao-Shi decoction (DHXSD) for the treatment of jaundice as recorded in the Chinese traditional Chinese medicine book Jin Gui Yao Lue. In the clinic, SHCZF has been used to treat cholestasis-related liver disease by improving intrahepatic cholestasis, but the treatment mechanism has not been elucidated. In this study, 24 Sprague-Dawley (SD) rats were randomly assigned to the normal, acute intrahepatic cholestasis (AIC), SHCZF, and ursodeoxycholic acid (UDCA) groups. In addition, 36 SD rats were divided into dynamic groups, namely, normal 24 h, AIC 24 h, normal 48 h, AIC 48 h, normal 72 h, and AIC 72 h groups. Alpha-naphthylisothiocyanate (ANIT) was used to induce an AIC rat model. Serum biochemical indices and hepatic pathology were detected. Part of the hepatic tissues was used for sequencing, and others were used for subsequent experiments. Sequencing data combined with bioinformatics analysis were used to screen target genes and identify the mechanisms of SHCZF in treating AIC rats. Quantitative real-time PCR (qRT-PCR) and Western blotting (WB) were used to detect the RNA/Protein expression levels of screened genes. Rats in the dynamic group were used to determine the sequence of cholestasis and liver injury. High-performance liquid chromatography (HPLC) was used to determine the representative bioingredients of SHCZF. Sequencing and bioinformatics analysis suggested that IDI1 and SREBP2 are hub target genes of SHCZF to ameliorate ANTI-induced intrahepatic cholestasis in rats. The treatment mechanism is associated with the regulation of lipoprotein receptor (LDLr) to reduce cholesterol intake and 3-Hydroxy-3-Methylglutaryl-CoA reductase (HMGCR), and 3-Hydroxy-3-Methylglutaryl-CoA synthase 1 (HMGCS1) to decrease cholesterol synthesis. Animal experiments showed that SHCZF significantly reduced the expression levels of the above genes and proinflammatory cytokine lipocalin 2 (LCN2), inflammatory cytokines interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), thereby improving intrahepatic cholestasis and inflammation and liver injury.

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Da-Huang-Xiao-Shi decoction protects against3, 5-diethoxycarbonyl-1,4-dihydroxychollidine-induced chronic cholestasis by upregulating bile acid metabolic enzymes and efflux transporters

Cited by 11 publications

References 41 publications

Network pharmacology analysis and molecular docking to unveil the potential mechanisms of San-Huang-Chai-Zhu formula treating cholestasis

Network pharmacology analysis and molecular docking to unveil the potential mechanisms of San-Huang-Chai-Zhu formula treating cholestasis

Determination of multiple active constituents in Da‐Huang‐Xiao‐Shi decoction using HPLC–LTQ–Orbitrap mass spectrometry: Application in comparing the differences in the formula and its constituent herbs

The IDI1/SREBP2 axis drives intrahepatic cholestasis and is a treatment target of San-Huang-Cai-Zhu formula identified by sequencing and experiments

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