Dasatinib ameliorates chronic pancreatitis induced by caerulein via anti-fibrotic and anti-inflammatory mechanism

Zeng, Xiang-Peng; Wang, Limin; Guo, Hong-Lei; He, Lin; Bi, Yang; Xu, Zefeng; Li, Zhao‐Shen; Hu, Liang‐Hao

doi:10.1016/j.phrs.2019.104357

Cited by 32 publications

(28 citation statements)

References 41 publications

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“…injections of caerulein (Cae, 50 μg/kg) were performed in C57BL/6 male mice, 3 days per week, for a total of 6 weeks. Mice were killed 5 days after the last caerulein injection 24 . Upon Cae injection, mice in Cae group and Cae + ILG group were orally administered with either vehicle solution (0.5% Na‐CMC) or ILG (20, 40 mg/kg/day) solution, respectively, from the first day of the 4th week till the day before killing (Figure 1A).…”

Section: Methodsmentioning

confidence: 99%

“…Human pancreatic stellate cells (hPSCs) were obtained as a gift from Prof. Logsdon CD (Department of Cancer Biology, University of Texas MD Anderson Cancer Centre, Houston, Texas, USA) and cultured in Dulbecco's modified eagle medium (DMEM, Hyclone Laboratories), supplemented with 15% foetal bovine serum (FBS, Gibco, USA) and 1% penicillin/streptomycin (Gibco, USA), and the medium was replaced every other day 24 . RAW 264.7 cells, a mouse peritoneal macrophage cell line, were obtained from American Type Culture Collection (ATCC, VA, USA) and were cultured in DMEM (supplemented with 10% FBS, and 1% penicillin/streptomycin).…”

Section: Methodsmentioning

confidence: 99%

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Isoliquiritigenin ameliorates caerulein‐induced chronic pancreatitis by inhibiting the activation of PSCs and pancreatic infiltration of macrophages

Wang

Liang

et al. 2020

J Cellular Molecular Medi

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Chronic pancreatitis (CP) is characterized by persistent inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Currently, the clinical therapeutic scheme of CP is mainly symptomatic treatment including pancreatic enzyme replacement, glycaemic control and nutritional support therapy, lacking of specific therapeutic drugs for prevention and suppression of inflammation and fibrosis aggravating in CP. Here, we investigated the effect of isoliquiritigenin (ILG), a chalcone‐type dietary compound derived from licorice, on pancreatic fibrosis and inflammation in a model of caerulein‐induced murine CP, and the results indicated that ILG notably alleviated pancreatic fibrosis and infiltration of macrophages. Further in vitro studies in human pancreatic stellate cells (hPSCs) showed that ILG exerted significant inhibition on the proliferation and activation of hPSCs, which may be due to negative regulation of the ERK1/2 and JNK1/2 activities. Moreover, ILG significantly restrained the M1 polarization of macrophages (RAW 264.7) via attenuation of the NF‐κB signalling pathway, whereas the M2 polarization was hardly affected. These findings indicated that ILG might be a potential anti‐inflammatory and anti‐fibrotic therapeutic agent for CP.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Isoliquiritigenin ameliorates caerulein‐induced chronic pancreatitis by inhibiting the activation of PSCs and pancreatic infiltration of macrophages

Wang

Liang

et al. 2020

J Cellular Molecular Medi

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“…It had been reported that pancreatitis could be alleviated via reducing the production of TNF-α, IL-6, IL-1β which was associated with regulating the MAPK signaling way [27]. Xiang-Peng Zeng et al found that inhibiting the MAPK cascade including MAPK3 might be a potential anti-in ammatory strategy for pancreatitis [28]. IL-6 was one of the most biologically active cytokines, had many biological functions and was considered as the reliable marker for severity in acute pancreatitis [29].…”

Section: Discussionmentioning

confidence: 99%

Uncovering the Pharmacological of Xiaochaihu Decoction in the Treatment of Pancreatitis Based on the Network Pharmacology

Zhan

et al. 2020

Preprint

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BackgroundXiaochaihu Decoction (XD) was a traditional prescription, has been demonstrated the pharmacodynamic on pancreatitis. But the underline mechanism remained to be explored. Therefore, this study was aimed to combined network pharmacology method and molecular docking technology to demonstrate the potential mechanism of XD treated with pancreatitis.MethodsFirstly, compounds of seven herbs containing XD were collected from TCMSP Database and the putative targets of Pancreatitis were obtained from OMIM, TTD, Genecards Database. Then PPI network was constructed according to the matching results between XD potential targets and pancreatic neoplasms targets. Furthermore, enrichment analysis on GO and KEGG by DAVID utilized bioinformatics resources. Finally, Molecular Docking was performed to simulate the interaction between the active compound of XD and putative targets.ResultsA total of 196 active ingredients and 91 putative targets were selected out. The PPI interaction network analysis demonstrated that Quercetin was the candidate agents and MAPK3, IL-6 and TP53 were the potential targets for the XD treatment of pancreatitis. The KEGG analysis revealed that pathways in cancers, TNF signaling way, MAPK signaling way might play an important role in pancreatitis therapy. And Molecular Docking results showed that Quercetin combined well with MAPK3, IL-6 and TP53.ConclusionThis study illustrated that Quercetin containing in XD might played an important role in pancreatitis therapy by acting the key genes of MPAK3, IL-6 and TP53. And it also provided a strategy to elucidate the mechanisms of Traditional Chinese Medicine (TCM) at the level of network pharmacology.

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“…It had been reported that pancreatitis could be alleviated via reducing the production of TNF-α, IL-6, IL-1β which was associated with regulating the MAPK signaling way [28]. Xiang-Peng Zeng et al found that inhibiting the MAPK cascade including MAPK3 might be a potential anti-in ammatory strategy for pancreatitis [29].…”

Section: Discussionmentioning

confidence: 99%

Uncovering the Pharmacological of Xiaochaihu Decoction in the Treatment of Pancreatitis Based on the Network Pharmacology

Zhan

et al. 2020

Preprint

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BackgroundXiaochaihu Decoction (XD) has been demonstrated the pharmacodynamic on pancreatitis. This study was aimed to investigate the material and molecular basis of Xiaochaihu Decoction.MethodsFirstly, compounds of seven herbs containing XD were collected from TCMSP Database and the putative targets of Pancreatitis were obtained from OMIM, TTD, Genecards Database. Then PPI network was constructed according to the matching results between XD potential targets and pancreatic neoplasms targets. Furthermore, enrichment analysis on GO and KEGG by DAVID utilized bioinformatics resources. Finally, Molecular Docking was performed to simulate the interaction between the active compound of XD and putative targets. In vitro experiment, AR42J cells were induced by LPS and then treated with Quercetin (25, 50, 100 μM). The IL-6, TNF-α, IL-1β levels were detected by Elisa kit and MAPK3, TP53 mRNA expressions were measured by RT-PCR.ResultsA total of 196 active ingredients and 91 putative targets were selected out. The PPI interaction network analysis demonstrated that Quercetin was the candidate agents and MAPK3, IL-6 and TP53 were the potential targets for the XD treatment of pancreatitis. The KEGG analysis revealed that pathways in cancers, TNF signaling way, MAPK signaling way might play an important role in pancreatitis therapy. And Molecular Docking results showed that Quercetin combined well with MAPK3, IL-6 and TP53. In vitro experiment indicated that, Quercetin inhibited the IL-6, TNF-α, IL-1β levels and MAPK3, TP53 mRNA. ConclusionThis study illustrated that Quercetin containing in XD might played an important role in pancreatitis therapy by acting the key genes of MPAK3, IL-6 and TP53 which were associating with inflammation and apoptosis.

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Dasatinib ameliorates chronic pancreatitis induced by caerulein via anti-fibrotic and anti-inflammatory mechanism

Cited by 32 publications

References 41 publications

Isoliquiritigenin ameliorates caerulein‐induced chronic pancreatitis by inhibiting the activation of PSCs and pancreatic infiltration of macrophages

Isoliquiritigenin ameliorates caerulein‐induced chronic pancreatitis by inhibiting the activation of PSCs and pancreatic infiltration of macrophages

Uncovering the Pharmacological of Xiaochaihu Decoction in the Treatment of Pancreatitis Based on the Network Pharmacology

Uncovering the Pharmacological of Xiaochaihu Decoction in the Treatment of Pancreatitis Based on the Network Pharmacology

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