Abstract：
:Quiescent hepatic stellate cell (HSC) activation and subsequent conversion into myofibroblasts is the central event in hepatic fibrosis pathogenesis. Epithelial-mesenchymal transition (EMT), another vital participant in liver fibrosis, has the potential to initiate HSC activation, which promotes abundant myofibroblast production. Previous studies suggest that Enhancer of Zeste Homolog 2 (EZH2) plays a significant role in myofibroblast transdifferentiation; however, the underlying mechanisms remain largely unaddressed. Carnosol (CS), a compound extracted from rosemary, displays multiple pharmacological activities. This study aimed to investigate the signaling mechanisms underlying EZH2 inhibition and the anti-fibrotic effect of CS in liver fibrosis. We found that CS significantly inhibited CCl4- and TGFβ1-induced liver fibrosis and reduced both HSC activation and EMT. EZH2 knockdown also prevented these processes induced by TGFβ1 in HSCs and AML-12 cells. Interestingly, the protective effect of CS was positively associated with Sirtuin 1 (SIRT1) activation and accompanied by EZH2 inhibition. SIRT1 knockdown attenuated the EZH2 inhibition induced by CS and increased EZH2 acetylation, which enhanced its stability. Conversely, upon TGFβ1 exposure, SIRT1 activation significantly reduced the level of EZH2 acetylation; however, EZH2 overexpression prevented the SIRT1 activation that primed myofibroblast inhibition, indicating that EZH2 is a target of SIRT1. Thus, SIRT1/EZH2 regulation could be used as a new therapeutic strategy for fibrogenesis. Together, this study provides evidence of activation of the SIRT1/EZH2 pathway by CS that inhibits myofibroblast generation, and thus, CS may represent an attractive candidate for anti-fibrotic clinical therapy.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Zhao H,Wang Z,Tang F,Zhao Y,Feng D,Li Y,Hu Y,Wang C,Zhou J,Tian X,Yao Jdoi
10.1016/j.phrs.2017.10.013subject
Has Abstractpub_date
2018-02-01 00:00:00pages
327-337eissn
1043-6618issn
1096-1186pii
S1043-6618(17)31157-Xjournal_volume
128pub_type
杂志文章abstract：:A growing number of evidences from clinical and preclinical studies have shown that dysregulation of microRNA (miRNA) function contributes to the progression of cancer and thus miRNA can be an effective target in therapy. Dietary phytochemicals, such as quercetin, are natural products that have potential anti-cancer p...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104346
更新日期：2019-09-01 00:00:00
abstract：:The effects of ethanol (EEP) and water (WSD) extracts of propolis collected from north China on blood glucose, blood lipid and free radicals in rats with diabetes mellitus were studied. The results show that EEP and WSD led to decreased levels of blood glucose (FBG), fructosamine (FRU), malonaldehyde (MDA), nitric oxi...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2004.06.011
更新日期：2005-02-01 00:00:00
abstract：:Cardiovascular baroreflex mechanisms and sympathetic tone could be involved in the arterial hypertension by coarctation of abdominal aorta artery (CoA). The present work analyzes the effect on the arterial pressure and heart rate (HR) of the clonidine, an alpha(2)-adrenergic central acting antihypertensive agent, afte...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：
更新日期：2003-07-01 00:00:00
abstract：:Autism-spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and repetitive patterns of behavior. ASD is, however, often associated with medical comorbidities and gastrointestinal (GI) dysfunction is among the most common. Studies have demonstrated a corr...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2018.03.020
更新日期：2018-06-01 00:00:00
abstract：:Despite the exploration of a large number of disparate drugs in animal models and clinical trials, no pharmacological intervention, with the exception of aggressive lipid lowering therapy has reduced late vein graft failure in man. The importance of devising more effective strategies is exemplified by the enormous eco...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2010.10.018
更新日期：2011-06-01 00:00:00
abstract：:The transparent bodies of see-through medaka fish has led to their use as models for in vivo cell and tissue imaging. However, these fish may also prove useful as models for pathological processes. Accumulating reports show that pathology in fish is similar to that in mammals, including humans. In this study, patholog...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2008.09.011
更新日期：2008-11-01 00:00:00
abstract：:A traditional Chinese medicine (TCM) formula (SL) comprising Sophorae Flos and Lonicerae Japonicae Flos was used for treating melanoma in ancient China. We have previously shown that an ethanolic extract of SL (SLE) possesses anti-melanoma effects and suppresses STAT3 signaling in vitro and in vivo. STAT3 has been lin...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2019.02.020
更新日期：2019-04-01 00:00:00
abstract：:PI3K was originally discovered as a lipid kinase involved in the phosphorylation of the inositol ring in position -3, leading to the synthesis of phosphatidyl-inositol-3-4 bisphosphate. The enzyme purified from rat liver is an heterodimer of two subunits of 85 and 110 KD respectively: it phosphorylates the D3 hydroxyl...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1997.0151
更新日期：1997-04-01 00:00:00
abstract：:The effect of flumazenil (FLU) on plasma protein binding of diazepam (DZ), nordiazepam (ND) and oxazepam (OX) was determined in plasma from drug-naive dogs to which graded concentrations of tested drugs alone and in combination were added. The results revealed that as the concentration of FLU added to plasma alone was...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(05)80018-0
更新日期：1995-11-01 00:00:00
abstract：:The vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase receptor for VEGF-A, VEGF-B, and placental growth factor (PlGF) ligands that is expressed in endothelial, myelomonocytic and tumor cells. VEGF-B and PlGF exclusively bind to VEGFR-1, whereas VEGF-A also binds to VEGFR-2. At variance with ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2018.08.023
更新日期：2018-10-01 00:00:00
abstract：:The pharmacokinetics of doxycycline hydrochloride (DoxHcl) at a dose of 5 mg kg-1 BW was studied after an intravenous (i.v.) bolus and intramuscular (i.m.) injections in non lactating goats. A microbiological assay employing Bacillus subtilis as the test organism was used to measure its concentrations in serum and uri...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2003.10.012
更新日期：2004-05-01 00:00:00
abstract：:Vascular responses to hypoxia are heterogeneous and involve the release of vasodilators substances such as nitric oxide (NO) and prostacyclin (PGI(2)). In vitro studies have shown that Vitamin K(1) modulates the release of arachidonic acid (AA) in vascular cells, and thus inhibits the capacity of blood vessels to synt...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s104366180200227x
更新日期：2002-12-01 00:00:00
abstract：:Atropine (5 mg/kg, s.c., twice daily) had no significant effect on 24-h water consumption on day 1 of treatment; on subsequent days the rats showed a significant increase. Procyclidine (5 mg/kg, s.c., twice daily) had a similar effect, except that the increase in daily water consumption began on the third day of treat...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/1043-6618(90)90745-y
更新日期：1990-01-01 00:00:00
abstract：:Targeting on the IKKβ to discover anti-inflammatory drugs has been launched for ten years, due to its predominant role in canonical NF-κB signaling. In the current study, we identified a novel IKKβ inhibitor, ellipticine (ELL), an alkaloid isolated from Ochrosia elliptica and Rauvolfia sandwicensis. We found that ELL ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2019.104440
更新日期：2019-11-01 00:00:00
abstract：:As the body's first line of defense, the skin is the organ most frequently exposed to chemicals present in personal hygiene products, household products, or materials used in the work environment. In this context, skin disorders account for more than 40 % of all occupational and work-related diseases, constituting a s...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.105282
更新日期：2020-12-01 00:00:00
abstract：:Diabetic nephropathy (DN) is a common and serious complication of diabetes and causes kidney failure. Ginsenoside Rg5 (Rg5) is an important monomer in the main protopanaxadiol component of black ginseng. Rg5 has exhibited some beneficial biological effects, such as anti-cancer, neuroprotection, and anti-depression, bu...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.104746
更新日期：2020-05-01 00:00:00
abstract：:Duchenne muscular dystrophy (DMD) is a severe muscle disease of known etiology without effective, or generally applicable therapy. Mitochondria are affected by the disease in animal models but whether mitochondrial dysfunction is part of the pathogenesis in patients remains unclear. We show that primary cultures obtai...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2017.09.001
更新日期：2017-11-01 00:00:00
abstract：:Injury to the bronchial epithelium in respiratory diseases such as asthma and COPD results in the loss of barrier function and an elevated sensitivity to environmental insults. An increased release of the endogenous cannabinoid, anandamide in response to inhalation of allergen in asthmatic patients has been reported. ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.01.023
更新日期：2016-03-01 00:00:00
abstract：:Cannabinoids have emerged as promising neuroprotective agents due to their capability to activate specific targets, which are involved in the control of neuronal homeostasis and survival. Specifically, those ligands that selectively target and activate the CB2 receptor may be useful for their anti-inflammatory and neu...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.03.021
更新日期：2016-08-01 00:00:00
abstract：:Pharmacokinetic of methyldopa (50 mg kg(-1)i.p.) was studied in anesthetized sham operated and sinoaortic denervated (SAD) rats by using the microdialysis technique. Vascular shunt probe was inserted into the carotid artery and concentric probe was placed in the striatum. Levels of methyldopa were measured by HPLC-EC....
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1999.0610
更新日期：2000-04-01 00:00:00
abstract：:The antioxidant properties of a novel water-soluble antioxidant of the benzofuran family (5-hydroxy-4,6,7-trimethyl-2,3-dihydrobenzofuran-2-acetic acid, BFA) were studied. In rat liver mitochondria BFA increases the lag-time and decreases the extent of lipid peroxidation induced by ascorbate/Fe2+; an IC50 value of abo...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/1043-6618(91)90041-u
更新日期：1991-12-01 00:00:00
abstract：:Cardiovascular disease (CVD) is the leading cause of death worldwide and the prevalence of obesity and diabetes are increasing. In obesity, adipose tissue increases the secretion of bioactive mediators (adipokines) that may represent a key mechanism linking obesity to CVD. Adiponectin, extensively studied in metabolic...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2014.03.003
更新日期：2014-04-01 00:00:00
abstract：:In this study, we have addressed the pharmacogenomic basis of the response of gastrointestinal tumors to six anticancer drugs using a panel of fifteen cell lines derived from pancreatic, stomach and biliary tract cancers. We determined the constitutive expression levels of 96 genes, whose encoded proteins contribute t...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.09.007
更新日期：2016-11-01 00:00:00
abstract：BACKGROUND:Overexpression of heat shock proteins (Hsps) is associated to myocardial protection and it has been suggested that they could be a marker of cardiac preservation in conditions such as extracorporeal circulation. Aim of this study was to evaluate if cardioplegic arrest can modify the expression of Hsps in the...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(03)00193-2
更新日期：2003-11-01 00:00:00
abstract：:Advanced glycation end products (AGEs) and their receptor (RAGE) axis contributes to diabetic nephropathy. An oral hypoglycemic agent, metformin may have a potential effect on the inhibition of glycation reactions. Further, since a pathophysiological crosstalk between renin-angiotensin system (RAS) and AGEs-RAGE axis ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2011.11.001
更新日期：2012-03-01 00:00:00
abstract：:Cicletanine [(+/-)-C] is a racemic furopyridine derivative used as an antihypertensive agent. Pharmacokinetic and metabolic studies have shown that cicletanine is rapidly and almost fully metabolized into sulfo- and glucuro-conjugated metabolites. However, the stereoselective metabolism of cicletanine is not well-know...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2000.0660
更新日期：2000-07-01 00:00:00
abstract：:Novel therapeutic strategies are needed to address and to solve the emerging problem of hypoxia-induced resistance to anticancer drugs. N-(4-Hydroxyphenyl)retinamide (4-HPR) exhibits potent anticancer and chemopreventive activities, but its inefficiency under hypoxia, through undetermined mechanisms, may contribute to...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2010.07.002
更新日期：2010-11-01 00:00:00
abstract：:The effect of different L-histidine concentrations on human mammary tumour cell (CG5) proliferation was studied to test the hypothesis of a role of histidine in modulating sex steroid-regulated cell proliferation. Cell growth was only possible in the 10(-5) M and 10(-2) M range, while its inhibition by medroxyprogeste...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1996.0126
更新日期：1997-02-01 00:00:00
abstract：:In the last decade, the prevalence of autism spectrum disorders (ASD) has dramatically escalated worldwide. Currently available drugs mainly target some co-occurring symptoms of ASD, but are not effective on the core symptoms, namely impairments in communication and social interaction, and the presence of restricted a...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104579
更新日期：2020-02-01 00:00:00
abstract：OBJECTIVES:There is still a need to develop new effective medications for the treatment of ulcerative colitis, particularly for patients who are intolerant or resistant to first line therapies. This article compared the efficacy and safety of etrolizumab and infliximab in moderate to severe ulcerative colitis. METHODS...
journal_title：Pharmacological research
pub_type： 杂志文章,meta分析
doi：10.1016/j.phrs.2018.11.003
更新日期：2019-01-01 00:00:00
