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[Display omitted] • The hepatoprotective effects of C. spinosa fruit extract (CSE) on triptolide (TP)-induced hepatotoxicity was found. • 19 metabolites identified were associated with TP treatment and 13 metabolites were altered relative to CSE intervention. • CSE-H inhibited the activities of arachidonate 5-lipoxygenase-activating protein and choline kinase alpha in the liver. The study aimed to investigate the hepatoprotective effects of Capparis spinosa fruit extract (CSE) on triptolide (TP)-induced hepatotoxicity in vitro and in vivo. In vitro, we used a TP-induced AML-12 cell injury model and flow cytometry to determine the cell survival rate after intervention with CSE. In vivo, acute liver injury was induced by intragastric administration of TP (1000 μg/kg) to C57BL/6 mice. Two experimental groups received CSE treatment at 0.9 g/kg (CSE-Low (L)) or 2.8 g/kg (CSE-high (H)). CSE-H can significantly decrease liver cell apoptosis and ameliorated TP-induced liver injury. Furthermore, 19 metabolites identified in serum were associated with TP treatment and the levels of 13 metabolites were altered relative to TP treatment after CSE-H intervention. TP increased the activities of arachidonate 5-lipoxygenase-activating protein and choline kinase alpha in the liver, while CSE-H inhibited their activity. In conclusion, the CSE has good hepatoprotective effects on TP-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Aim: To investigate the mechanism of action of Fuzheng Huayu recipe (FZHY) and vitamin E (Vit E) against renal interstitial fibrosis related to transforming growth factor-beta1 (TGF-β1) mediated tubular epithelial-to-mesenchymal transition. Materials and methods: Renal interstitial fibrosis was induced by administration of HgCl2 at a dose of 8mg/kg body weight once a day for 9 weeks. Rats were randomly divided into four groups: normal, model, FZHY, and Vit E group. Rats in the latter two groups were treated with the FZHY recipe and Vit E respectively. HK-2 cells were treated with TGF-β1 for 24h, followed by incubation with either SB-431542 (a potent and specific inhibitor of TβR-I kinase) or FZHY drug-containing serum for another 24h. Hyp content in rat kidney tissue was assayed with Jamall''s method and collagen deposition in kidney was visualized using Masson stain. Protein expression of TGF-β1, TβR-I, Smad2, p-Smad2, Smad3, and p-Smad3 was analyzed by Western blotting. Protein expression and the location of Smad3 in kidney was assayed by immunohistochemistry, E-cadherin, cytokeratin 18 (CK-18), α-SMA and TGF-β1 by immunofluorescent stain. Results: FZHY and Vit E inhibited renal collagen deposition and reduced Hyp content significantly. They upregulated E-cadherin protein expression and down-regulated the protein expression of α-SMA, TGF-β1, p-Smad2, p-Smad3, and TβR-I. Lastly, they inhibited the nuclear translocation of Smad3 in fibrotic kidney tissue. FZHY drug-containing serum significantly upregulated the expression of CK-18 and down-regulated the expression of α-SMA, TβR-I, p-Smad2/3 in TGF-β1 stimulated HK-2 cells. Conclusion: The mechanism of action of FZHY and Vit E against renal interstitial fibrosis is related to the reversal of tubular EMT induced by TGF-β1. [Copyright &y& Elsevier]

Ethnopharmacological relevance Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. Aim of the study To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Materials and methods Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC–MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. Results A rapid, sensitive and convenient UHPLC–MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15 g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC (0- t ) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly ( P <0.05). Tissue distribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point ( P <0.05). Meanwhile, the result also reveals that the hepatic fibrosis could delay the peak time of lignans in liver. Conclusion The results proved that the established UHPLC–MS/MS method could be applied to the comparative study on pharmacokinetics and tissue distribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacology: Fuzheng Huayu recipe (FZHY) was formulated on the basis of Chinese medicine theory in treating liver fibrosis. It has a significant efficacy against liver fibrosis caused by chronic hepatitis B, with the action mechanisms of inhibition of hepatic stellate cell activation, protection of hepatocyte oxidative injury and regulations of hepatic matrix remodeling etc. Aim of the study: To identify the absorbed components and metabolites of Danshen in FZHY in rat serum, and find their active components for anti-liver fibrosis. Material and methods: A valid high performance liquid chromatography–electrospray ionization ion trap mass spectrometry (HPLC-ESI/MSn) method was established to investigate the absorbed and metabolized compounds of Danshen in FZHY in rat serum after oral administration. Mass spectra were acquired in both negative and positive modes. Otherwise, to evaluate the anti-hepatic fibrosis efficacies of absorbed and metabolized compounds, the LX-2 cell line of hepatic stellate cell (HSC), which was crucial cellular basis of fibrogenesis, was cultured and incubated with absorbed compounds, the cytotoxicity was determined with the cellomics Multiparameter Cytotoxicity Kit 1 by High Content Screening (HCS), the cell proliferation was assayed with EdU-DNA incorporation, and the cell activation was analyzed through α-smooth muscle actin (α–SMA) expression with high content screening technology. Results: More than 11 compounds and 2 metabolites from Danshen were identified in the serum after oral administration of FZHY by comparing their mass spectra and retention behavior with reference compounds or literature data. Among these compounds, there were no obvious changes in nuclear morphology, membrane permeability with blow 96μM of six polar compounds treatment in comparison with control cells, respectively. And the salvianolic acid B (6μM, 48μM), caffeic acid (6μM, 48μM) and rosmarinic acid (48μM) could obviously inhibit LX-2 cells proliferation, down-regulate α–SMA expression. Conclusion: The results proved that the established method could be applied to analyze the absorbed into blood compounds of Danshen after oral administration FZHY. These absorbed compounds included 11 compounds and 2 metabolites of Danshen. Among them, the salvianolic acid B, caffeic acid and rosmarinic acid were the effective components of FZHY to anti-hepatic fibrosis effects. [Copyright &y& Elsevier]