Abstract:
:Oral administration of curcumin has been shown to inhibit pulmonary fibrosis (PF) despite its extremely low bioavailability. In this study, we investigated the mechanisms underlying the anti-PF effect of curcumin in focus on intestinal endocrine. In bleomycin- and SiO2-treated mice, curcumin (75, 150 mg· kg-1 per day) exerted dose-dependent anti-PF effect when administered orally or rectally but not intravenously, implying an intestinal route was involved in the action of curcumin. We speculated that curcumin might promote the generation of gut-derived factors and the latter acted as a mediator subsequently entering the lungs to ameliorate fibrosis. We showed that oral administration of curcumin indeed significantly increased the expression of gut-derived hepatocyte growth factor (HGF) in colon tissues. Furthermore, in bleomycin-treated mice, the upregulated protein level of HGF in lungs by oral curcumin was highly correlated with its anti-PF effect, which was further confirmed by coadministration of c-Met inhibitor SU11274. Curcumin (5-40 μM) dose-dependently increased HGF expression in primary mouse fibroblasts, macrophages, CCD-18Co cells (fibroblast cell line), and RAW264.7 cells (monocyte-macrophage cell line), but not in primary colonic epithelial cells. In CCD-18Co cells and RAW264.7 cells, curcumin dose-dependently activated PPARγ and CREB, whereas PPARγ antagonist GW9662 (1 μM) or cAMP response element (CREB) inhibitor KG-501 (10 μM) significantly decreased the boosting effect of curcumin on HGF expression. Finally, we revealed that curcumin dose-dependently increased the production of 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2) in CCD-18Co cells and RAW264.7 cells, which was a common upstream of the two transcription factors. Moreover, both the in vitro and in vivo effects of curcumin were diminished by coadministration of HPGDS-inhibitor-1, an inhibitor of 15d-PGJ2 generation. Together, curcumin promotes the expression of HGF in colonic fibroblasts and macrophages by activating PPARγ and CREB via an induction of 15d-PGJ2, and the HGF enters the lungs giving rise to an anti-PF effect.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Miao YM,Zhang YJ,Qiao SM,Xia YF,Wei ZF,Dai Ydoi
10.1038/s41401-020-0469-4subject
Has Abstractpub_date
2020-07-21 00:00:00eissn
1671-4083issn
1745-7254pii
10.1038/s41401-020-0469-4pub_type
杂志文章abstract:AIM:to investigate the changing resistance to nondepolarizing muscle relaxants (NDMRs) during the first month after denervation. METHODS:the denervated and innervated skeletal muscle cells were examined on days 1, 4, 7, 14, 21, and 28 after denervation. Individual denervated and innervated cells were prepared from the...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.163
更新日期:2010-12-01 00:00:00
abstract:AIM:To investigate whether autologous transplantation of adult stem cells could improve post-infarcted heart function. METHODS:Bone marrow mononuclear cells (MNCs) were isolated from adult rabbits' tibias after coronary ligation. These cells were exposed to 5-azacytidine 10 micromol/L for 24 h on the third day of cult...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-07-01 00:00:00
abstract:AIM:The purpose of this study was to reveal the effects of hepatocyte growth factor (HGF) variants on human breast cancer cells and the differential signaling pathways of the variants in controlling cell proliferation and invasion. METHODS:Four HGF variants (NK1, NK2, NK3, and NK4) were created by gene engineering, an...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00799.x
更新日期:2008-06-01 00:00:00
abstract::Saw palmetto extract (SPE), an extract from the ripe berries of the American dwarf palm, has been widely used as a therapeutic remedy for urinary dysfunction due to benign prostatic hyperplasia (BPH) in Europe. Numerous mechanisms of action have been proposed for SPE, including the inhibition of 5alpha-reductase. Toda...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2009.1
更新日期:2009-03-01 00:00:00
abstract::Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2015.73
更新日期:2015-10-01 00:00:00
abstract:AIM:Diabetic nephropathy is one of the major complications of diabetes and the major cause of end-stage renal disease. In this study we investigated the insulin deficiency (ID) induced changes in renal mesangial cells (MCs) and in the kidney of STZ-induced diabetic rats. METHODS:Cultured rat renal MCs were incubated i...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.128
更新日期:2016-02-01 00:00:00
abstract:AIM:To investigate the pharmacokinetic profile and tissue distribution of a novel phosphodiesterase type 5 inhibitor, 5-ethyl-2-{5-[4-(2-hydroxy-ethyl)-piperazine-1-sulfonyl]-2-propoxy-phenyl}-7-propyl-3,5-dihydro-pyrrolo(3,2-d)pyrimidin-4-one (SK-3530), in rats after administration of the (14)C-labeled compound. METH...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00611.x
更新日期:2007-08-01 00:00:00
abstract:AIM:The changes of seizure susceptibility of transgenic mice overexpressing GABA transporter-1 (GAT-1) were studied to clarify the possible role of GABAergic transmission in epileptogenesis. METHODS:Seizures were induced by intraperitoneal administration of pentylenetetrazol (PTZ), picrotoxin (PIC), or kainic acid (KA...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract:AIM:To study the effects of cimetidine (Cim) on the production of interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha) by splenocytes in immune-derived aplastic anemic (AA) mice. METHODS:Aplastic anemic mice model was constructed first, and then the splenocytes were induced to secrete IFN gamma and...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract:AIM:To discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the mechanisms of inhibition in cancer cells. METHODS:Cell growth inhibition was detected by MTT assay, the cell cycle was analyzed by flow cytometry, and protein expression and phosphorylation was examined by Western blot analysis. RESUL...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2009.131
更新日期:2009-09-01 00:00:00
abstract:AIM:To investigate the effects of resveratrol on interleukin-1beta (IL-1beta) induced catabolism in bone marrow mesenchymal stem cell (MSC) derived chondrocytes cultured on chitosan-gelatin scaffolds (CGS). METHODS:The chondrogenesis of alginate-encapsulated MSCs was evaluated by toluidine blue staining, RT-PCR, and i...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00880.x
更新日期:2008-11-01 00:00:00
abstract::Monoclonal antibodies are believed to be magic bullets and hold great potential for lots of biological process. About 100 μg of mAb109 was expressed in 5 × 106 cells after 10 days' immunization. 64Cu-NOTA-mAb109 was synthesized with the specific activity of 0.74 MBq/μg and high in vitro stability. The binding affinity...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-019-0294-9
更新日期:2020-01-01 00:00:00
abstract:AIM:The substrate cocktail is frequently used to evaluate cytochrome P450 (CYP) enzyme-mediated drug interactions and potential interactions among the probe substrates. Here, we re-optimized the substrate cocktail method to increase the reliability and accuracy of screening for candidate compounds and expanded the meth...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.10
更新日期:2016-05-01 00:00:00
abstract::Cardiac amyloidosis (CA) comprises a heterogeneous group of medical conditions affecting the myocardium. It presents with proteinaceous infiltration with variable degrees of severity, prevalence and evolution. Despite this heterogeneity, erroneous protein folding is the common pathophysiologic process, yielding the fo...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2018.38
更新日期:2018-07-01 00:00:00
abstract:AIM:To discover novel ligands of estrogen receptor (ER) β using pharmacophore mapping and structure-based screening. METHODS:A computer-aided strategy combining pharmacophore mapping and structure-based screening was used to screen the Maybridge and Enamine databases. Yeast two-hybrid (Y2H) assay was used to detect th...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2014.69
更新日期:2014-10-01 00:00:00
abstract:AIM:To explore the action of doxorubicin on vascular smooth muscle cells. METHODS:Isometric tension of denuded or intact thoracic aortic vessels was recorded and [Ca(2+)](i) in isolated aortic smooth muscle cells was measured by using Fluo-3. RESULTS:Doxorubicin induced phasic and tonic contractions in denuded vessel...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2009.145
更新日期:2009-11-01 00:00:00
abstract:AIM:To study the effects of 3-n-butylphthalide (NBP) on the TREK-1 channel expressed in Chinese hamster ovary (CHO) cells. METHODS:Whole-cell patch-clamp recording was used to record TREK-1 channel currents. The effects of varying doses of l-NBP on TREK-1 currents were also observed. Current-clamp recordings were perf...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.210
更新日期:2011-02-01 00:00:00
abstract:AIM:To identify the genetic variants of angiotensin II type 2 receptor (AT2R) gene in a Chinese population and to determine whether the AT2R gene polymorphisms are associated with essential hypertension (EH). METHODS:The detection of single nucleotide polymorphisms (SNPs) was performed in 19 subjects by a direct DNA s...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-11-01 00:00:00
abstract::Kushen (Radix Sophorae Flavescentis) has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling (Rhizoma Smilacis Glabrae). The main principles of CKI are m...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2015.24
更新日期:2015-06-01 00:00:00
abstract:AIM:To investigate the mitochondria-initiated apoptosis pathway involved in Carbon tetrachloride (CCl4) hepatotoxicity in vitro. METHODS:Several cytotoxicity endpoints, including WST-8 metabolism, lactate dehydrogenase leakage and morphological changes, were examined. The 5,5'-dithio-bis(2-nitrobenzoic acid) reaction ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00143.x
更新日期:2005-08-01 00:00:00
abstract::Type capital I, Ukrainian natural killer T cells (NKT cells), a subset of CD1d-restricted T cells with invariant Valphabeta TCR, are characterized by prompt production of large amounts of Th1 and/or Th2 cytokines upon primary stimulation through the TCR complex. The rapid release of cytokines implies that type capital...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2010.119
更新日期:2010-09-01 00:00:00
abstract:AIM:To study the association between APOE polymorphisms and cerebral infarction through a case-control study among the Chinese Han population. METHODS:First-ever cerebral infarction patients (n=226) whose ages ranged from 40 to 60 years old were recruited from Department of Neurology, Zhongshan Hospital, Shanghai, and...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract:AIM:To isolate the G4 and G1 molecular forms of acetylcholinesterase in rat cortex for interpreting the therapeutical effect of the AChE inhibitor drugs. METHODS:Size exclusion chromatography and ultracentrifugation were used to isolate and ascertain the G4 and G1 molecular forms of AChE. RESULTS:After size exclusion...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
abstract:AIM:The responses of the intracellular calcium ([Ca2+]i) and the intracellular pH (pHi) to kappa-opioid receptor stimulation were determined in the single right ventricular myocytes isolated from the hearts of chronically hypoxic rats which exhibited right ventricular hypertrophy (RVH). METHODS:With the spectrofluorom...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract:AIM:To study the alterations of myocardial taurine transport function, taurine transporter (TAUT), and cysteine sulfinate decarboxylase (CSD) mRNA as well as effect of exogenous taurine in rats with isoproterenol (ISO)-induced cardiomegaly. METHODS:[3H]-Taurine uptake and release on myocardium were determined. Binding...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
abstract:AIM:To explore the anti-diabetic effects of berberine and its influence on insulin secretion. METHODS:Impaired glucose tolerance rats induced by iv injection of streptozotocin 30 mg/kg were treated with berberine 187.5 and 562.5 mg/kg while fed with high fat laboratory chow. After rats were treated for 4 weeks, oral g...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-04-01 00:00:00
abstract:AIM:To express dopamine D1 receptor in baculovirus-Sf9 cell system, and to investigate the effects of l-12-chloroscoulerine (l-CSL) on the recombinant D1 receptor (D1R). METHODS:The recombinant baculovirus, Autographa californica nuclear polyhedrosis virus bearing D1R (AcNPV- D1R) was generated, and then was used to p...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-03-01 00:00:00
abstract:AIM:To investigate the effect of aluminum (Al) on high voltage-dependent calcium current (I(HVA)) and its modulation by ginkgolide B (Gin B). METHODS:The whole-cell, patch-clamp technique was used to record IHVA from acutely isolated hippocampal CA1 pyramydal neurons in rats. RESULTS:Al 0.1 mmol/L (low concentration)...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00073.x
更新日期:2005-05-01 00:00:00
abstract:AIM:To investigate the expression of advanced glycation end products (AGEs) and their receptor RAGE in the livers and blood vessels of rats with non-alcoholic steatohepatitis (NASH) and the effect of pentoxifylline (PTX) on liver and artery function in rats with NASH. METHODS:Sprague-Dawley rats were fed a high-fat di...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.110
更新日期:2010-10-01 00:00:00
abstract:AIM:Fibroblast growth factor 7 (FGF7) is involved in a number of physiological and pathological processes, including lung disease. However, relatively little is known about the effect of FGF7 gene polymorphisms on chronic obstructive pulmonary disease (COPD) susceptibility. This study aimed to investigate the associati...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.69
更新日期:2012-08-01 00:00:00