Fuzheng Huayu recipe prevents nutritional fibrosing steatohepatitis in mice

Jia, Yanhong; Wang, Rongqi; Mi, Hong-mei; Kong, Lingbo; Ren, Wei-Guang; Li, Wencong; Zhao, Suxian; Zhang, Yuguo; Wu, Wenjuan; Nan, Yuemin; Yu, Jun

doi:10.1186/1476-511x-11-45

Cited by 21 publications

(25 citation statements)

References 36 publications

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“…Nutritional factors such as high methionine-diet are associated with increased serum homocysteine levels. Extensive studies have shown that a high methionine-diet had awful effects on liver pathophysiology, for instance, oxidative stress, inflammation, lipid metabolism disorders and fibrosis [ 27 , 28 ]. Our observations are in line with previous studies reporting that methionine supplementation increased plasma Hcy levels, triggered oxidative stress of livers and impaired the anti-oxidative enzyme activity.…”

Section: Discussionmentioning

confidence: 99%

Homocysteine downregulates gene expression of heme oxygenase-1 in hepatocytes

et al. 2014

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BackgroundHyperhomocysteinemia (HHcy) is an independent risk factor for liver diseases, such as fatty liver and hepatic fibrosis. However, the mechanisms underlying this pro-oxidative effect of homocysteine (Hcy) in hepatocytes remain largely unknown. Thus, we investigated the effect of Hcy on the gene expression of heme oxygenase-1 (HO-1), the primary rate-limiting enzyme in heme catabolism and a key anti-oxidant detoxification enzyme in maintaining cellular redox homeostasis.MethodsIn vivo, twenty male C57BL/6 mice at 8 weeks of age were randomly divided into two groups. One group was fed a chow diet (chow group; n = 10), the other group of mice was fed a methionine-supplemented diet (Met group, 1 mg kg−1 day−1 L-methionine in drinking water; n = 10) for 4 weeks. In vitro, HepG2 cells were stimulated with different doses of homocysteine (Hcy).ResultsFour weeks’ methionine supplementation caused a significant increase of plasma Hcy concentration and a decrease of HO-1 expression in the liver of C57BL/6 mice than mice received chow diet. Besides, SOD enzyme activities were impaired and the level of oxidative stress markers, such as malondialdehyde (MDA) were elevated in the liver from mice supplemented with methionine compared with control mice. In cultured hepatocytes, Hcy treatment reduced both the mRNA and protein levels of HO-1 dose-dependently. However, Hcy had no effect on the gene expression of Nrf2, the major transcriptional regulator of HO-1. Instead, Hcy induced the expression of Bach1, a transcriptional repressor of HO-1. In addition, Hcy stimulated the nuclear localization of Bach1 but prevented that of Nrf2. Furthermore, we found that knockdown of Bach1 attenuated the suppression of the HO-1 expression by Hcy.ConclusionsCollectively, our results demonstrated that Bach1 plays an important role in Hcy-triggered ROS generations through inhibiting HO-1 expression, likely, resulting from the disturbed interplay between Bach1 and Nrf2.Electronic supplementary materialThe online version of this article (doi:10.1186/1743-7075-11-55) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Homocysteine downregulates gene expression of heme oxygenase-1 in hepatocytes

et al. 2014

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“…Identification of abnormally expressed miRNAs in the important pathologic state of NAFLD is helpful to further understand the molecular mechanism of nonalcoholic fibrosing steatohepatitis. In this study, we evaluated the differentially expressed miRNAs in nonalcoholic fibrosing steatohepatitis induced in mice fed with methionine-choline deficient (MCD) diet 15 16 17 and demonstrated for the first time that miR-146a-5p suppresses activation and proliferation of HSCs in the pathogenesis of nonalcoholic fibrosing steatohepatitis through targeting Wnt1 and Wnt5a and their consequent effectors alpha-smooth muscle actin (α-SMA) and type I collagen (Col-1).…”

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confidence: 99%

MiR-146a-5p suppresses activation and proliferation of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis through directly targeting Wnt1 and Wnt5a

Niu

Wang

et al. 2015

Sci Rep

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Nonalcoholic fibrosing steatohepatitis is a uniform process throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been suggested to modulate cellular processes in liver diseases. However, the functional role of miRNAs in nonalcoholic fibrosing steatohepatitis is largely unclear. In this study, we systematically analyzed the hepatic miRNAs by microarray analysis in nonalcoholic fibrosing steatohepatitis in C57BL/6J mice induced by methionine-choline deficient (MCD) diet. We identified 19 up-regulated and 18 down-regulated miRNAs in liver with fibrosis. Among these dysregulated miRNAs, miR-146a-5p was the most significant down-regulated miRNA. Luciferase activity assay confirmed that Wnt1 and Wnt5a were both the target genes of miR-146a-5p. Hepatic miR-146a-5p was down-regulated in fibrosing steatohepatitis, but its target genes Wnt1 and Wnt5a and their consequent effectors α-SMA and Col-1 were significantly up-regulated. In addition, miR-146a-5p was downregulated, whilst Wnt1 and Wnt5a were up-regulated in the activated primary hepatic stellate cells (HSCs) compared to the quiescent primary HSCs. Overexpression of miR-146a-5p in HSCs inhibited HSC activation and proliferation, which concomitant with the decreased expressions of Wnt1, Wnt5a, α-SMA and Col-1. In conclusion, miR-146a-5p suppresses activation and proliferation of HSCs in the progress of nonalcoholic fibrosing steatohepatitis through targeting Wnt1 and Wnt5a and consequent effectors α-SMA and Col-1.

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“…Many previous studies also proved the usefulness of network pharmacology in investigating the synergistic molecular mechanisms of the TCM formula [6][7][8]. However, false positive probability of network pharmacology approaches is relatively large, which results in hundreds of active components and their potential target proteins for a TCM formula [9][10][11]. us, we try to combine the network pharmacology approach with known proteomics results in order to reduce the false positive probability.…”

Section: Introductionmentioning

confidence: 99%

The Active Compounds of Yixin Ningshen Tablet and Their Potential Action Mechanism in Treating Coronary Heart Disease‐ A Network Pharmacology and Proteomics Approach

Lv¹,

Wang

Wu³

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Yixin Ningshen tablet is a CFDA-approved TCM formula for treating coronary heart disease (CHD) clinically. However, its active compounds and mechanism of action in treating CHD are unknown. In this study, a novel strategy with the combination of network pharmacology and proteomics was proposed to identify the active components of Yixin Ningshen tablet and the mechanism by which they treat CHD. With the application of network pharmacology, 62 active compounds in Yixin Ningshen tablet were screened out by text mining, and their 313 potential target proteins were identified by a tool in SwissTargetPrediction. These data were integrated with known CHD-related proteomics results to predict the most possible targets, which reduced the 313 potential target proteins to 218. The STRING database was retrieved to find the enriched pathways and related diseases of these target proteins, which indicated that the Calcium, MAPK, PI3K-Akt, cAMP, Rap1, AGE-RAGE, Relaxin, HIF-1, Prolactin, Sphingolipid, Estrogen, IL-17, Jak-STAT signaling pathway, necroptosis, arachidonic acid metabolism, insulin resistance, endocrine resistance, and steroid hormone biosynthesis might be the main pathways regulated by Yixin Ningshen tablet for the treatment of CHD. Through further enrichment analysis and literature study, EGFR, ERBB2, VGFR2, FGF1, ESR1, LOX15, PGH2, HMDH, ADRB1, and ADRB2 were selected and then validated to be the target proteins of Yixin Ningshen tablet by molecular docking, which indicated that Yixin Ningshen tablet might treat CHD mainly through promoting heart regeneration, new vessels’ formation, and the blood supply of the myocardial region and reducing cardiac output, oxygen demand, and inflammation as well as arteriosclerosis (promoting vasodilation and intraplaque neoangiogenesis, lowering blood lipid). This study is expected to benefit the clinical application of Yixin Ningshen tablet for the treatment of CHD.

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Fuzheng Huayu recipe prevents nutritional fibrosing steatohepatitis in mice

Cited by 21 publications

References 36 publications

Homocysteine downregulates gene expression of heme oxygenase-1 in hepatocytes

Homocysteine downregulates gene expression of heme oxygenase-1 in hepatocytes

MiR-146a-5p suppresses activation and proliferation of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis through directly targeting Wnt1 and Wnt5a

The Active Compounds of Yixin Ningshen Tablet and Their Potential Action Mechanism in Treating Coronary Heart Disease‐ A Network Pharmacology and Proteomics Approach

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