Dopamine D<sub>2</sub> receptor signalling controls inflammation in acute pancreatitis <i>via</i> a PP2A‐dependent Akt/NF‐κB signalling pathway

Han, Xiao; Li, Bin; Ye, Xin; Mulatibieke, Tunike; Wu, Jianghong; Dai, Jing; Wu, Deqing; Ni, Jiahua; Zhang, Ruling; Xue, Jing; Wan, Rong; Wang, Xingpeng; Hu, Guoyong

doi:10.1111/bph.14057

Cited by 66 publications

(78 citation statements)

References 60 publications

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“…Conversely, liver dopamine (DA) levels were reduced in the same experimental condition ( Figure 3). Besides its crucial role as neurotransmitter in the central nervous system, recent findings suggest anti-inflammatory and protective effects that are induced by DA administration in experimental models of acute pancreatitis and hepatitis [55,56]. Consistent with the observed antiradical activity, both of the extracts reduced the LPS-induced levels of 3-HK ( Figure 2).…”

Section: Resultssupporting

confidence: 80%

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf

et al. 2020

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Bridelia species have been used in traditional African medicine for the management of diverse human ailments. In the current work, the detailed phytochemical profiles of the extracts of the stem bark of B. speciosa were evaluated and the antioxidant and enzyme inhibitory properties of the extracts were assessed. The anti-bacterial and anti-mycotic effects of the extracts were evaluated against selected pathogen strains. Additionally, the anti-proliferative effects were studied on the liver cancer HepG2 cell line. Finally, the putative protective effects were assessed on isolated rat liver that was challenged with lipopolysaccharide (LPS). The results revealed the presence of 36 compounds in the ethyl acetate extract, 44 in the methanol extract, and 38 in the water extract. Overall, the methanol extract showed the highest antioxidant activity, particularly in LPS-stimulated rat liver. Additionally, this extract exerted the highest antimycotic effect on C. albicans, whereas the water extract showed a promising anti-proliferative effect on liver cancer HepG2 cells. The methanol extract was also the most active as enzyme inhibitor, against acetylcholinesterase and butyrylcholinesterase. The current study appraises the antioxidant and enzyme inhibition properties of B. speciosa methanol extract and showed that this specie could be a promising source of biologically active phytochemicals, with potential health uses. Supplementary Materials: The following are available online at http://www.mdpi.com/2076-3921/9/2/128/s1. Supplementary Materials and Methods; CFF-strains. Author Contributions: Conceptualization, C.F. and G.Z.; methodology, G.O.; L.M.; software, L.M.; validation,: C.F.; G.Z.; L.M.; G.O.; formal analysis, C.F.; G.Z.; investigation, K.I.S.; K.B.; S.L.; L.R.; A.C. (Annalisa Chiavaroli); S.V.; P.A.; V.H.; S.C.; R.V.; L.D.L.; A.C. (Alessandro Cama); M.C.N.P.-A.; Z.C.; J.J.; M.F.M.; resources, C.F.; G.O.; L.M.; data curation, C.F.; G.Z.; writing-original draft preparation, M.F.M.; writing-review and editing, C.F., G.Z.; G.O.; L.M.; visualization, L.B.; supervision, L.B.; project administration, C.F.; L.M.; G.O.; G.Z.; funding acquisition, C.F.; G.O.; L.M. All authors have read and agreed to the published version of the manuscript.

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Section: Resultssupporting

confidence: 80%

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf

et al. 2020

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“…Moreover, dopamine or dopamine agonist was reported to inhibit the upregulation of proinflammatory cytokines in these immune cells . Additionally, stimulation of dopamine D 2 receptors reduces the increased expression of inflammatory cytokines of pancreatic acinar cells by inhibiting NF‐κB signaling in mice acute pancreatitis model in vitro . In this context, losartan may improve visceral function by activating peripheral dopamine D 2 receptors to suppress the cytokine signaling.…”

Section: Discussionmentioning

confidence: 99%

Losartan improves visceral sensation and gut barrier in a rat model of irritable bowel syndrome

Nozu

Miyagishi

Nozu

et al. 2020

Neurogastroenterology Motil

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Background: Lipopolysaccharide (LPS) or repeated water avoidance stress (WAS) induces visceral allodynia and colonic hyperpermeability via corticotropin-releasing factor (CRF) and proinflammatory cytokines, which is considered to be a rat irritable bowel syndrome (IBS) model. As losartan is known to inhibit proinflammatory cytokine release, we hypothesized that it improves these visceral changes. Methods:The threshold of visceromotor response (VMR), that is, abdominal muscle contractions induced by colonic balloon distention was electrophysiologically measured in rats. Colonic permeability was determined in vivo by quantifying the absorbed Evans blue in colonic tissue for 15 minutes spectrophotometrically. Key Results: Lipopolysaccharide (1 mg kg −1 ) subcutaneously (s.c.) reduced the threshold of VMR and increased colonic permeability. Losartan (5-25 mg kg −1 s.c.) for 3 days inhibited these changes in a dose-dependent manner. Moreover, repeated WAS (1 hour daily for 3 days) or intraperitoneal injection of CRF (50 µg kg −1 ) induced the similar visceral changes as LPS, which were also eliminated by losartan. These effects by losartan in LPS model were reversed by GW9662 (a peroxisome proliferator-activated receptor-γ [PPAR-γ] antagonist), N G -nitro-L-arginine methyl ester (a nitric oxide [NO] synthesis inhibitor), or naloxone (an opioid receptor antagonist). Moreover, it also inhibited by sulpiride (a dopamine D 2 receptor antagonist) or domperidone (a peripheral dopamine D 2 antagonist). Conclusion & Inferences:Losartan prevented visceral allodynia and colonic hyperpermeability in rat IBS models. These actions may be PPAR-γ-dependent and also mediated by the NO, opioid, and dopamine D 2 pathways. Losartan may be useful for IBS treatment. K E Y W O R D Sangiotensin II type 1 receptor, gut barrier, irritable bowel syndrome, lipopolysaccharide, visceral sensation

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“…Further investigation on intracellular signaling pathways demonstrated that DSC suppressed inflammatory responses by enhancing SOCS3 expression and suppressing activation of NF-κB and STAT3. NF-κB activation in acinar cells is a key intracellular event in AP and modulates a variety of inflammatory genes ( 24 ). STAT3 is activated by IL-6 trans-signaling and involved in pancreatic damage in AP ( 9 , 10 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Derivative of the Natural Product Danshensu Suppresses Inflammatory Responses to Alleviate Caerulein-Induced Acute Pancreatitis

et al. 2018

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Acute pancreatitis (AP), a common abdominal inflammatory disorder, is characterized by premature intracellular activation of digestive proteases within pancreatic acini and a consecutive systemic inflammatory response. Although the mechanism remains to be fully understood, inflammation is the main cause of pancreatic damage in AP. A novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-1-oxopropan-2-ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)], derived from danshensu, exhibits anti-inflammatory and anti-apoptotic properties in vitro. However, its potential beneficial effect in AP has not been demonstrated. This study aimed to investigate the effects and underlying mechanisms of DSC in experimental AP in mice. We found that DSC suppressed inflammatory responses in AP by inhibiting the activation of nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3) and nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome. Furthermore, treatment with DSC modulated the infiltration of neutrophils and the phenotypes of macrophages in mice induced with AP. Interestingly, we found that the expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and its regulated antioxidant enzyme heme oxygenase-1 (HO-1), which modulate inflammatory activities, was significantly increased in DSC-treated groups. Together, our findings demonstrate that DSC alleviates pancreatic inflammation and damage in AP by inhibiting the activation of NF-κB, STAT3, and NLRP3 inflammasome and modulating immune cell responses.

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Dopamine D₂ receptor signalling controls inflammation in acute pancreatitis via a PP2A‐dependent Akt/NF‐κB signalling pathway

Abstract: D receptors control pancreatic inflammation in AP by inhibiting NF-κB activation via a PP2A-dependent Akt signalling pathway.

Cited by 66 publications

References 60 publications

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf

Losartan improves visceral sensation and gut barrier in a rat model of irritable bowel syndrome

A Novel Derivative of the Natural Product Danshensu Suppresses Inflammatory Responses to Alleviate Caerulein-Induced Acute Pancreatitis

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Dopamine D2 receptor signalling controls inflammation in acute pancreatitis via a PP2A‐dependent Akt/NF‐κB signalling pathway

Abstract: D receptors control pancreatic inflammation in AP by inhibiting NF-κB activation via a PP2A-dependent Akt signalling pathway.

Cited by 66 publications

References 60 publications

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf

Losartan improves visceral sensation and gut barrier in a rat model of irritable bowel syndrome

A Novel Derivative of the Natural Product Danshensu Suppresses Inflammatory Responses to Alleviate Caerulein-Induced Acute Pancreatitis

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Dopamine D₂ receptor signalling controls inflammation in acute pancreatitis via a PP2A‐dependent Akt/NF‐κB signalling pathway