Liver kinase B1/AMP‐activated protein kinase‐mediated regulation by gentiopicroside ameliorates P2X7 receptor‐dependent alcoholic hepatosteatosis

Li, Xia; Zhang, Yu; Jin, Quan; Xia, Kai-Li; Jiang, Min; Cui, Ben-Wen; Wu, Yan-Ling; Shen, Song; Lian, Li-Hua; Nan, Ji‐Xing

doi:10.1111/bph.14145

Cited by 80 publications

(77 citation statements)

References 59 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7 Furthermore, GPS had been reported for regulating P2X7R-mediated inflammatory response via LKB1 and AMPK. 8 Our results demonstrated that GPS inhibited pain and pruritus in an anti-inflammatory manner in vivo, and the effect of GPS on dermatitis had no report in the previous studies. Moreover, the GPS exhibited repair function during the skin damage.…”

contrasting

confidence: 52%

Gentiopicroside Reduces Pain, Pruritus, and Corticosteroid Addictive Dermatitis

Zhou

Deng²,

Xiang³

et al. 2019

Natural Product Communications

View full text Add to dashboard Cite

Corticosteroid addictive dermatitis (CAD) has rapidly emerged as a health problem which is difficult to cure. The dermatitis control is general with the tacrolimus, pimecrolimus, and antihistamines, and these synthetic drugs are likely to have some side effects, and how to use the nonirritating natural product to reduce the CAD has been rarely reported. Strong evidence indicates that gentiopicroside (GPS) has been reported to have anti-inflammation and anticancer properties. In the present study, we invented a device to collect GPS to study the effect of GPS on pain, pruritus, and CAD repair in model animals. Our results showed that the data on antipain and antipruritus treated with GPS were better than those of control group, and the inflammation of rabbit skin upon 2,4-dinitrochlorobenzene exposure reduced by GPS. In conclusion, GPS could be a factor for antipain, antipruritus, and CAD repair; hence, these findings suggest that it can act as a protective factor for CAD.

show abstract

contrasting

confidence: 52%

Gentiopicroside Reduces Pain, Pruritus, and Corticosteroid Addictive Dermatitis

Zhou

Deng²,

Xiang³

et al. 2019

Natural Product Communications

View full text Add to dashboard Cite

show abstract

“…It was considered to be one of the various mechanisms of Gentiopicroside exerting analgesic effects. Furthermore，in the previous research we conducted on DPN rat models, Gentiopicroside was found to effectively regulate dyslipidemia [17], which we suspected to be one of the important mechanisms of Gentiopicroside in the treatment of DPN. The current research aimed to further investigate the analgesic effect and the probable mechanism of Gentiopicroside on DPN, and to figure out the association among Gentiopicroside, dyslipidemia and PPAR-γ/AMPK/ACC signaling pathway through a series of experiments in vivo and in vitro.…”

Section: Introductionmentioning

confidence: 91%

Gentiopicroside Ameliorates Diabetic Peripheral Neuropathy by Modulating PPAR- Γ/AMPK/ACC Signaling Pathway

Yao

Gong

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Gentiopicroside is promising as an important secoiridoid compound against pain. The present study aimed to investigate the analgesic effect and the probable mechanism of Gentiopicroside on Diabetic Peripheral Neuropathy (DPN), and to figure out the association among Gentiopicroside, dyslipidemia and PPAR- γ/AMPK/ACC signaling pathway. Methods: DPN rat models were established by streptozotocin and RSC96 cells were cultured. Hot, cold and mechanical tactile allodynia were conducted. Blood lipids, nerve blood flow, Motor Nerve Conduction Velocity (MNCV) and Sensory Nerve Conduction Velocity (SNCV) were detected. Gene and protein expression of PPAR- γ/AMPK/ACC pathway was analyzed by reverse transcription-quan titative polymerase chain reaction (RT-qPCR) and Westernblot. Besides, PPAR-γ antagonist GW9662 and agonist rosiglitazone, AMPK antagonist compound C and activator AICAR as well as ACC inhibitor TOFA were used to further confirm the relationship between PPAR-γ and AMPK. Results: The results demonstrated that Gentiopicroside markedly ameliorated hyperalgesia with prolonged paw withdrawal latency to heat and cold stimuli and fewer responses to mechanical allodynia compared with DPN model group. Gentiopicroside regulated dyslipidemia, enhanced nerve blood flow and improved MNCV as well as SNCV. Gentiopicroside suppressed ACC expression through the activation of AMPK and PPAR-γ mediated the activation of AMPK and subsequent inhibition of ACC expression. Conclusion: In conclusion, the present study demon strated that Gentiopicroside exerted nerve-protective effect and attenuated experimental DPN by restoring dyslipidmia and improved nerve blood flow through regulating PPAR-γ/AMPK/ACC signal pathway. These results provided a promising potential treatment of DPN.

show abstract

“…Previously, we reported that the inhibition of the P2X7 receptor–NLRP3 inflammasome axis could prevent extracellular matrix deposition and liver fibrosis (Jiang et al, ). Additionally, inhibition of IL‐1β secretion by macrophages using low MW compounds might be beneficial to the steatotic phenotype of hepatocytes (Li et al, ). However, whether and how P2X7 receptors affect the crosstalk between hepatocytes and macrophages during alcoholic hepatosteatosis is not known.…”

Section: Introductionmentioning

confidence: 99%

“…This glucoside exhibits a wide range of pharmacological effects, including anti‐aging (Cheung, Leung, Liu, & Che, ), anti‐oxidation (Wang, Zhao, Han, Chen, & Wang, ), and anticancer (Lin et al, ) effects, without toxic side effects. Although 2354glu is known to attenuate the non‐alcoholic fatty liver disease induced by a methionine and choline‐deficient diet (Li et al, ; Lou et al, ), whether and how 2354glu could regulate hepatic steatosis and inflammation induced by binge alcohol consumption had not been studied. Previously, we reported the potential reversal of alcoholic hepatosteatosis via regulation of P2X7 receptors (Li et al, ).…”

Section: Introductionmentioning

confidence: 99%

P2X7 receptor‐targeted regulation by tetrahydroxystilbene glucoside in alcoholic hepatosteatosis: A new strategy towards macrophage–hepatocyte crosstalk

Zhang

Jiang

Cui

et al. 2020

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

Background and Purpose:Regulating macrophage-hepatocyte crosstalk through P2X7 receptors has led to new pharmacological strategies to reverse alcoholic hepatosteatosis. We investigated how tetrahydroxystilbene glucoside (2354glu), isolated from Polygonum multiflorum, modulates macrophage-hepatocyte crosstalk during alcoholic hepatosteatosis.Experimental Approach: A model of alcoholic hepatosteatosis was established by giving ethanol intragastrically to C57BL/6 mice. HepG2 cells were incubated in conditioned medium from LPS+ATP-activated THP-1 human macrophages with silenced or overexpressed P2X7 receptors. THP-1 macrophages or mouse peritoneal macrophages were pretreated with 2354glu for 1 hr prior to LPS+ATP stimulation.Western blots, RT-PCR and immunohistochemical analysis were used, along with over-expression and silencing of P2X7 receptors.Key Results: Knockdown or overexpression of P2X7 receptors in THP-1 macrophages affected release of mature IL-1β and, subsequently, modulated lipid metabolism in HepG2 cells via the LKB-AMPK pathway. 2354glu ameliorated alcoholic hepatosteatosis in mice by regulating LKB1-AMPK-SREBP1 pathway and its target genes. Suppression of P2X7 receptor activation by 2354glu inhibited IL-1β release and reduced macrophage and neutrophil infiltration. In macrophages stimulated with LPS+ATP, expression of P2X7 receptors, caspase-1 and NF-κB, release of IL-1β, calcium influx and PI uptake were reduced by 2354glu. SIRT1-LKB1-AMPK-SREBP1 axis-mediated lipid accumulation in HepG2 cells was reduced when they were cultured with conditioned media from LPS+ATP-activated THP-1 macrophages pretreated with 2354glu.Abbreviations: 2345glu, tetrahydroxystilbene glucoside, 2,3,5,4 0 -tetrahydroxy-stilbene-2-O-β-D-glucoside; AMPK, AMP-activated protein kinase; LKB1, liver kinase B1; NLRP3, nucleotidebinding oligomerization domain-like receptor protein 3; SIRT1, sirtuin 1; SREBP1, sterol regulatory element-binding protein 1; TLRs, toll like receptors.

show abstract

Liver kinase B1/AMP‐activated protein kinase‐mediated regulation by gentiopicroside ameliorates P2X7 receptor‐dependent alcoholic hepatosteatosis

Abstract: Activation of LKB1/AMPK signalling by gentiopicroside was mediated by the P2X7 receptor-NLRP3 inflammasome, suggesting the therapeutic value of blocking P2X7 receptors in the treatment of alcoholic hepatosteatosis.

Cited by 80 publications

References 59 publications

Gentiopicroside Reduces Pain, Pruritus, and Corticosteroid Addictive Dermatitis

Gentiopicroside Reduces Pain, Pruritus, and Corticosteroid Addictive Dermatitis

Gentiopicroside Ameliorates Diabetic Peripheral Neuropathy by Modulating PPAR- Γ/AMPK/ACC Signaling Pathway

P2X7 receptor‐targeted regulation by tetrahydroxystilbene glucoside in alcoholic hepatosteatosis: A new strategy towards macrophage–hepatocyte crosstalk

Contact Info

Product

Resources

About