Salvianolic acid B protects against ANIT-induced cholestatic liver injury through regulating bile acid transporters and enzymes, and NF-κB/IκB and MAPK pathways

Li, Shengnan; Wang, Rong; Wu, Bin; Wang, Yuanyuan; Song, Fuxing; Gu, Yanqiu; Yuan, Yongfang

doi:10.1007/s00210-019-01657-8

Cited by 16 publications

(5 citation statements)

References 62 publications

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“…BBR is known for its potent anti-inflammatory activities in liver disease [ 16 , 17 ]. Key pathways, such as NF-κB signaling pathway, MAPK pathways, and oxidative phosphorylation, are involved in inflammation-driven cholestatic liver injury [ 8 , 23 , 44 , 45 ]. Our RNA-seq gene analysis and pathway profiling showed that BBR significantly reduced inflammation in Mdr2 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of berberine in attenuating cholestatic liver injury: insights from a PSC mouse model

Wang,

Zhao,

et al. 2024

Cell Biosci

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Background and aims Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by progressive biliary inflammation and bile duct injury. Berberine (BBR) is a bioactive isoquinoline alkaloid found in various herbs and has multiple beneficial effects on metabolic and inflammatory diseases, including liver diseases. This study aimed to examine the therapeutic effect of BBR on cholestatic liver injury in a PSC mouse model (Mdr2−/− mice) and elucidate the underlying mechanisms. Methods Mdr2−/−mice (12–14 weeks old, both sexes) received either BBR (50 mg/kg) or control solution daily for eight weeks via oral gavage. Histological and serum biochemical analyses were used to assess fibrotic liver injury severity. Total RNAseq and pathway analyses were used to identify the potential signaling pathways modulated by BBR in the liver. The expression levels of key genes involved in regulating hepatic fibrosis, bile duct proliferation, inflammation, and bile acid metabolism were validated by qRT-PCR or Western blot analysis. The bile acid composition and levels in the serum, liver, small intestine, and feces and tissue distribution of BBR were measured by LC–MS/MS. Intestinal inflammation and injury were assessed by gene expression profiling and histological analysis. The impact on the gut microbiome was assessed using 16S rRNA gene sequencing. Results BBR treatment significantly ameliorated cholestatic liver injury, evidenced by decreased serum levels of AST, ALT, and ALP, and reduced bile duct proliferation and hepatic fibrosis, as shown by H&E, Picro-Sirius Red, and CK19 IHC staining. RNAseq and qRT-PCR analyses indicated a substantial inhibition of fibrotic and inflammatory gene expression. BBR also mitigated ER stress by downregulating Chop, Atf4 and Xbp-1 expression. In addition, BBR modulated bile acid metabolism by altering key gene expressions in the liver and small intestine, resulting in restored bile acid homeostasis characterized by reduced total bile acids in serum, liver, and small intestine and increased fecal excretion. Furthermore, BBR significantly improved intestinal barrier function and reduced bacterial translocation by modulating the gut microbiota. Conclusion BBR effectively attenuates cholestatic liver injury, suggesting its potential as a therapeutic agent for PSC and other cholestatic liver diseases.

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Section: Discussionmentioning

confidence: 99%

Therapeutic potential of berberine in attenuating cholestatic liver injury: insights from a PSC mouse model

Wang,

Zhao,

et al. 2024

Cell Biosci

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“…Thus far, no studies have reported the effects of these two organic acids on cholestasis. However, various studies have shown that many phenolic substances, such as apigenin, pterostilbene, and salvianolic acid B, have a preventive effect on cholestasis [ 15 , 46 , 47 ]. In the present study, the extracts of RCM contained different phenolic substances, which may also mainly contribute to the prevention of DDC-induced cholestasis in mice and their preventive effects might substantially depend on the phenolic compositions.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Rhus chinensis Mill. Fruits on 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine-Induced Cholestasis in Mice via Ameliorating Oxidative Stress and Inflammation

et al. 2022

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This study focused on the preventive effects of the extracts of Rhus chinensis Mill. (RCM) fruits on cholestasis induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in mice. The results showed that RCM extracts could significantly ameliorate DDC-induced cholestasis via multiple mechanisms, including (1) alleviating liver damage via enhancing antioxidant capacity, such as increasing the contents of glutathione, superoxide dismutase, and catalase and inhibiting the levels of malondialdehyde; (2) preventing liver inflammation by suppressing NF-κB pathway and reducing proinflammatory cytokines secretion (e.g., tumor necrosis factor-α, interleukin-1β, and interleukin-6); (3) inhibiting liver fibrosis and collagen deposition by regulating the expression of transforming growth factor-β and α-smooth muscle actin; (4) modulating abnormal bile acid metabolism through increasing the expression of bile salt export pump and multidrug resistance-associated protein 2. This study was the first to elucidate the potential preventive effect of RCM extracts on DDC-induced cholestasis in mice from multiple pathways, which suggested that RCM fruits could be considered as a potential dietary supplement to prevent cholestasis.

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“…Rosmarinic acid is contained mainly in the family Lamiaceae, and numerous studies have demonstrated its health benefits, especially in management of inflammatory diseases via inhibition of oxidative stress, apoptosis, and inflammation (Joardar et al, 2019;Luo et al, 2020). Salvianolic acid B was remarkably abundant in OSB, and several studies indicated that it had strong antiinflammatory and anti-fibrotic effects through targeting the MAPK and NF-κB pathways (Li et al, 2019;Wu et al, 2019). Polymethoxylated flavonoids, such as sinensetin, have been widely reported with anti-inflammatory, anti-oxidant, antidementia, and vasorelaxant activities and the action mechanisms could be involved in the regulation of different targets and signaling pathways including AKT and NF-κB signaling pathways (Lee et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

A New Strategy to Investigate the Efficacy Markers Underlying the Medicinal Potentials of Orthosiphon stamineus Benth.

Zhou

et al. 2021

Front. Pharmacol.

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Orthosiphon stamineus Benth. (OSB) is a well-known herbal medicine exerting various pharmacological effects and medicinal potentials. Owing to its complex of phytochemical constituents, as well as the ambiguous relationship between phytochemical constituents and varied bioactivities, it is a great challenge to explore which constituents make a core contribution to the efficacy of OSB, making it difficult to determine the efficacy makers underlying the varied efficacies of OSB. In our work, a new strategy was exploited and applied for investigating efficacy markers of OSB consisting of phytochemical analysis, in vivo absorption analysis, bioactive compound screening, and bioactive compound quantification. Using liquid chromatography coupled with mass spectrometry, a total of 34 phytochemical components were detected in the OSB extract. Subsequently, based on in vivo absorption analysis, 14 phytochemical constituents in the form of prototypes were retained as potential bioactive compounds. Ten diseases were selected as the potential indications of OSB based on previous reports, and then the overall interaction between compounds, action targets, action pathways, and diseases was revealed based on bioinformatic analysis. After refining key pathways and targets, the interaction reversing from pathways, targets to constituents was deduced, and the core constituents, including tanshinone IIA, sinensetin, salvianolic acid B, rosmarinic acid, and salvigenin, were screened out as the efficacy markers of OSB. Finally, the contents of these five constituents were quantified in three different batches of OSB extracts. Among them, the content of salvianolic acid B was the highest while the content of tanshinone IIA was the lowest. Our work could provide a promising direction for future research on the quality control and pharmacological mechanism of OSB.

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Salvianolic acid B protects against ANIT-induced cholestatic liver injury through regulating bile acid transporters and enzymes, and NF-κB/IκB and MAPK pathways

Cited by 16 publications

References 62 publications

Therapeutic potential of berberine in attenuating cholestatic liver injury: insights from a PSC mouse model

Therapeutic potential of berberine in attenuating cholestatic liver injury: insights from a PSC mouse model

Protective Effect of Rhus chinensis Mill. Fruits on 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine-Induced Cholestasis in Mice via Ameliorating Oxidative Stress and Inflammation

A New Strategy to Investigate the Efficacy Markers Underlying the Medicinal Potentials of Orthosiphon stamineus Benth.

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