Kang‐Xian Pills Inhibit Inflammatory Response and Decrease Gut Permeability to Treat Carbon Tetrachloride‐Induced Chronic Hepatic Injury through Modulating Gut Microbiota

Wang, Li; Cui, Huantian; Li, Yuting; Cao, Min; Man, Shanshan; Guo, Liying; Miao, Jing; Jia, Jianwei; Bian, Yuhong; Zhang, Zhaiyi

doi:10.1155/2020/8890182

Cited by 5 publications

(8 citation statements)

References 47 publications

(48 reference statements)

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“…Meanwhile, pathological change of liver histological also demonstrated that KXP treatment significantly alleviate CCL4-induced hepatocytes extensive edema and necrosis. In addition, our previous study demonstrated that KXP could alleviate the inflammation response of CCL4-induced CHI by regulating gut microbiota 7 . However, as an empirical formula, KXP consists of 12 Chinese medicines and contains multi-compounds, and it's tough to clarify the multi-molecular mechanisms with conventional experimental methods.…”

Section: Discussionmentioning

confidence: 95%

“…Our previous study showed that KXP exerted hepatic protective effect through decreasing levels of transaminase and raising activities of superoxide dismutase (SOD) and increasing contents of and glycogen (Gn) 6 . In addition, KXP could alleviate chronic liver injury through regulating gut microbiota to inhibit permeability of intestinal epithelial 7 . However, major hepatoprotective targets of KXP remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Target prediction of anti-chronic liver injury of Kangxian pill based on network pharmacology

Cao

Wang

et al. 2021

Preprint

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BackgroundThe present study aimed to validate the protect effect of Kangxian pill (KXP) on chronic hepatic injury (CHI) and investigate its potential mechanism by network pharmacology-based prediction and experimental verification in vivo . MethodsThe effect of KXP in the treatment of carbon tetrachloride (CCL 4 )-induced CHI is investigated by calculating liver index, measuring AST and ALT levels and performing HE staining. Targets of active ingredients of KXP were predicted in TCSMP and targets of chronic liver injury were searched in DisGeNET, OMIM and GeneCards databases. We obtain some pivotal targets of KXP for the treatment of CHI by intersecting the targets of KXP and CHI. Subsequently, we performed gene ontology (GO) functional and pathways enrichment analyses, as well as conducted networks based on potential targets to determine the core targets and representative pathways.We further validated expressions of IL-6, IL-1β, TNF-α, Bax, Bcl2, PI3K, Akt, and pAkt according to the potential molecular mechanisms analyzed based on network pharmacology analysis.ResultsThe results showed that the levels of AST and ALT in serum decreased after treatment with KXP. HE staining also revealed that KXP could improve hepatocyte abnormality in vivo . A total of 81 potential targets of KXP in the treatment of CHI were identified through network pharmacology analysis. After integrating potential targets, function enrichment, representative pathways and networks, we identified PI3K, AKT1,BCL2, TNF-α, IL-1β, and IL-6 as potential targets, which may play a vital role in the KXP treatment. The experimental results also showed that KXP could down-regulate the mRNA and protein expression of IL-1β, IL-6, TNF-α and Bax, and up-regulate the PI3K and p-Akt protein expression i n vivo .ConclusionsOur results suggest that KXP could alleviate CHI through regulating inflammation and apoptosis and provide deep insight into the hepato-protective mechanisms.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Target prediction of anti-chronic liver injury of Kangxian pill based on network pharmacology

Cao

Wang

et al. 2021

Preprint

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“…We established a liver fibrosis mouse model via intraperitoneal injection of CCl 4 , which was consistent with previous study (Wang et al, 2020). Briefly, CCl 4 was diluted with olive oil at a concentration of 2 ml/kg body weight and administered via intraperitoneal infusion twice per week over a six-week period.…”

Section: Induction Of Liver Fibrosis Mouse Modelmentioning

confidence: 92%

Geniposide Ameliorates Liver Fibrosis Through Reducing Oxidative Stress and Inflammatory Respose, Inhibiting Apoptosis and Modulating Overall Metabolism

Yang

Jin

et al. 2021

Front. Pharmacol.

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Liver fibrosis is a progressive liver damage condition caused by various factors and may progress toward liver cirrhosis, and even hepatocellular carcinoma. Many studies have found that the disfunction in metabolism could contribute to the development of liver fibrosis. Geniposide, derived from Gardenia jasminoides J. Ellis, has been demonstrated with therapeutic effects on liver fibrosis. However, the exact molecular mechanisms of such liver-protection remain largely unknown. The aim of this study was to explored the effect of geniposide on metabolic regulations in liver fibrosis. We used carbon tetrachloride (CCl4) to construct a mouse model of liver fibrosis and subsequently administered geniposide treatment. Therapeutic effects of geniposide on liver fibrosis were accessed through measuring the levels of hepatic enzymes in serum and the pathological changes in liver. We also investigated the effects of geniposide on inflammatory response, oxidative stress and apoptosis in liver. Furthermore, serum untargeted metabolomics were used to explore the metabolic regulatory mechanisms behind geniposide on liver fibrosis. Our results demonstrated that geniposide could reduce the levels of hepatic enzymes in serum and ameliorate the pathological changes in liver fibrosis mice. Geniposide enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased methane dicarboxylic aldehyde (MDA) levels in liver. Geniposide treatment also decreased the levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-a) in liver tissue homogenate. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining demonstrated that geniposide could reduce the apoptosis of hepatocytes. Geniposide increased the protein expression of B-cell lymphoma-2 (Bcl-2) and downregulated the protein expression of Bcl-2 Associated X (Bax), cleaved-Caspase 3, and cleaved-Caspase 9. Serum untargeted metabolomics analysis demonstrated that geniposide treatment improved the metabolic disorders including glycerophospholipid metabolism, arginine and proline metabolism, and arachidonic acid (AA) metabolism. In conclusion, our study demonstrated the protective effects of geniposide on liver fibrosis. We found that geniposide could treat liver fibrosis by inhibiting oxidative stress, reducing inflammatory response and apoptosis in the liver, and modulating glycerophospholipid, and arginine, proline, and AA metabolism processes.

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“…We followed the methods of Wang et al 2020 [ 18 ]. Total RNAs were isolated from livers using the RNA extraction kit, and first-strand cDNAs were synthesized from 1 μ g of total RNAs according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…We followed the methods of Wang et al 2020 [ 18 ]. Briefly, rat colons were removed and fixed in paraffin, and the expression of occludin and tight junction protein-1 (ZO-1) in the colon was accessed via immunostaining.…”

Section: Methodsmentioning

confidence: 99%

Jian-Gan-Xiao-Zhi Decoction Alleviates Inflammatory Response in Nonalcoholic Fatty Liver Disease Model Rats through Modulating Gut Microbiota

Liao

Xie

Gao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Jian-Gan-Xiao-Zhi decoction (JGXZ), composed of Salvia miltiorrhiza Bunge, Panax notoginseng, Curcuma zedoaria, and other 9 types of herbs, has demonstrated beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the mechanisms behind JGXZ’s impact on NAFLD remain unknown. Methods. In this study, a NAFLD rat model induced by a high-fat diet (HFD) received oral treatment of JGXZ (8 or 16 g crude herb/kg) for 12 weeks. The therapeutic effects of JGXZ on NAFLD model rats were investigated through blood lipid levels and pathological liver changes. 16S rRNA analysis was used to study the changes in gut microbiota after JGXZ treatment. The expressions of occludin and tight junction protein 1 (ZO-1) in the colon were investigated using immunostaining to study the effects of JGXZ on gut permeability. The anti-inflammatory effects of JGXZ were also studied through measuring the levels of IL-1β, IL-6, and TNF-α in the serum and liver. Results. JGXZ treatment could decrease body weight and ameliorate dyslipidemia in NAFLD model rats. H&E and Oil Red O staining indicated that JGXZ reduced steatosis and infiltration of inflammatory cells in the liver. 16S rRNA analysis showed that JGXZ impacted the diversity of gut microbiota, decreasing the Firmicutes–to-Bacteroidetes ratio, and increasing the relative abundance of probiotics, such as Alloprevotella, Lactobacillus, and Turicibacter. Gut permeability evaluation found that the expressions of ZO-1 and occludin in the colon were increased after JGXZ treatment. Moreover, JGXZ treatment could decrease the levels of IL-1β, IL-6, and TNF-α in the serum and liver. Conclusions. Our study illustrated that JGXZ could ameliorate NAFLD through modulating gut microbiota, decreasing gut permeability, and alleviating inflammatory response.

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Kang‐Xian Pills Inhibit Inflammatory Response and Decrease Gut Permeability to Treat Carbon Tetrachloride‐Induced Chronic Hepatic Injury through Modulating Gut Microbiota

Cited by 5 publications

References 47 publications

Target prediction of anti-chronic liver injury of Kangxian pill based on network pharmacology

Target prediction of anti-chronic liver injury of Kangxian pill based on network pharmacology

Geniposide Ameliorates Liver Fibrosis Through Reducing Oxidative Stress and Inflammatory Respose, Inhibiting Apoptosis and Modulating Overall Metabolism

Jian-Gan-Xiao-Zhi Decoction Alleviates Inflammatory Response in Nonalcoholic Fatty Liver Disease Model Rats through Modulating Gut Microbiota

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