6,484 results match your criteria Acta Pharmacologica Sinica[Journal]


Monocarbonyl curcumin analog A2 potently inhibits angiogenesis by inducing ROS-dependent endothelial cell death.

Acta Pharmacol Sin 2019 Apr 18. Epub 2019 Apr 18.

College of Bioengineering, Henan University of Technology, Zhengzhou, 450001, China.

Excessive and abnormal vessel growth plays a critical role in the pathogenesis of many diseases, such as cancer. Angiogenesis is one of the hallmarks of cancer growth, invasion, and metastasis. Discovery of novel antiangiogenic agents would provide new insights into the mechanisms of angiogenesis, as well as potential drugs for cancer treatment. Read More

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http://www.nature.com/articles/s41401-019-0224-x
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http://dx.doi.org/10.1038/s41401-019-0224-xDOI Listing
April 2019
1 Read

Nitazoxanide, an anti-parasitic drug, efficiently ameliorates learning and memory impairments in AD model mice.

Acta Pharmacol Sin 2019 Apr 18. Epub 2019 Apr 18.

Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

The pathogenesis of Alzheimer's disease (AD) is characterized by both accumulation of β-amyloid (Aβ) plaque and formation of neurofibrillary tangles in the brain. Recent evidence shows that autophagy activation may potently promote intracellular Aβ clearance. Thus targeting autophagy becomes a promising strategy for discovery of drug leads against AD. Read More

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http://dx.doi.org/10.1038/s41401-019-0220-1DOI Listing

Sevoflurane promotes migration, invasion, and colony-forming ability of human glioblastoma cells possibly via increasing the expression of cell surface protein 44.

Acta Pharmacol Sin 2019 Apr 9. Epub 2019 Apr 9.

Department of Anesthesiology, University of Virginia, Charlottesville, VA, 22901, USA.

Surgical resection of primary solid tumor under anesthesia remains a common practice. It has been concerned whether general anesthetics, especially volatile anesthetics, may promote the growth, migration, and invasion of cancer cells. In this study, we examined the effects of sevoflurane on human glioblastoma cells and determined the role of cluster of differentiation (CD) 44, a cell surface protein involved in cell growth, migration, and invasion, in sevoflurane's effects. Read More

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http://dx.doi.org/10.1038/s41401-019-0221-0DOI Listing

Donepezil, a drug for Alzheimer's disease, promotes oligodendrocyte generation and remyelination.

Acta Pharmacol Sin 2019 Mar 27. Epub 2019 Mar 27.

Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.

Myelin sheaths play important roles in neuronal functions. In the central nervous system (CNS), the myelin is formed by oligodendrocytes (OLs), which are differentiated from oligodendrocyte precursor cells (OPCs). In CNS demyelinating disorders such as multiple sclerosis (MS), the myelin sheaths are damaged and the remyelination process is hindered. Read More

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http://dx.doi.org/10.1038/s41401-018-0206-4DOI Listing
March 2019
4 Reads

Protective effects of specific cannabinoid receptor 2 agonist GW405833 on concanavalin A-induced acute liver injury in mice.

Acta Pharmacol Sin 2019 Mar 27. Epub 2019 Mar 27.

Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, China.

Cannabinoid receptor 2 (CB2R) is highly expressed in immune cells and plays an important role in regulating immune responses. In the current study, we investigated the effects of GW405833 (GW), a specific CB2R agonist, on acute liver injury induced by concanavalin A (Con A). In animal experiments, acute liver injury was induced in mice by injection of Con A (20 mg/kg, i. Read More

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http://dx.doi.org/10.1038/s41401-019-0213-0DOI Listing
March 2019
2 Reads

Eukaryotic elongation factor-2 kinase regulates the cross-talk between autophagy and pyroptosis in doxorubicin-treated human melanoma cells in vitro.

Acta Pharmacol Sin 2019 Mar 26. Epub 2019 Mar 26.

Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410008, China.

Eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, has been shown to play an important role in modulating autophagy and apoptosis in tumor cells under various stresses. In this study, we investigated the regulatory role of eEF-2K in pyroptosis (a new form of programmed necrosis) in doxorubicin-treated human melanoma cells. We found that doxorubicin (0. Read More

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http://dx.doi.org/10.1038/s41401-019-0222-zDOI Listing
March 2019
3 Reads
2.496 Impact Factor

Diabetes inhibits corneal epithelial cell migration and tight junction formation in mice and human via increasing ROS and impairing Akt signaling.

Acta Pharmacol Sin 2019 Mar 13. Epub 2019 Mar 13.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.

Corneal wounds usually heal quickly; but diabetic patients have more fragile corneas and experience delayed and painful healing. In the present study, we compared the healing capacity of corneal epithelial cells (CECs) between normal and diabetic conditions and the potential mechanisms. Primary murine CEC derived from wild-type and diabetic (db/db) mice, as well as primary human CEC were prepared. Read More

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http://dx.doi.org/10.1038/s41401-019-0223-yDOI Listing
March 2019
4 Reads

Temporal dynamics of immune response following prolonged myocardial ischemia/reperfusion with and without cyclosporine A.

Acta Pharmacol Sin 2019 Mar 11. Epub 2019 Mar 11.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Laboratory of Molecular Cardiology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, China.

Understanding the dynamics of the immune response following late myocardial reperfusion is critical for the development of immunomodulatory therapy for myocardial infarction (MI). Cyclosporine A (CSA) possesses multiple therapeutic applications for MI, but its effects on the inflammation caused by acute MI are not clear. This study aimed to determine the dynamics of the immune response following myocardial ischemia/reperfusion (I/R) and the effects of CSA in a mouse model of prolonged myocardial ischemia designated to represent the human condition of late reperfusion. Read More

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http://dx.doi.org/10.1038/s41401-018-0197-1DOI Listing

Genetic variants in the PLS3 gene are associated with osteoporotic fractures in postmenopausal Chinese women.

Acta Pharmacol Sin 2019 Mar 5. Epub 2019 Mar 5.

Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Plastin 3 (PLS3) has been identified as a candidate gene for bone fragility in the Rotterdam study (RS) population. So far, however, whether PLS3 polymorphisms are genetic risk factors for osteoporosis in Asian population remains unclear. In order to investigate the association between genetic variants in PLS3 and the risk of fragility fracture and/or bone mineral density (BMD) in postmenopausal Chinese women, we conducted a case-control association study. Read More

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http://dx.doi.org/10.1038/s41401-019-0219-7DOI Listing
March 2019
3 Reads

Small molecule IVQ, as a prodrug of gluconeogenesis inhibitor QVO, efficiently ameliorates glucose homeostasis in type 2 diabetic mice.

Acta Pharmacol Sin 2019 Mar 4. Epub 2019 Mar 4.

State Key Laboratory Cultivation Base for TCM Quality and Efficacy, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Gluconeogenesis is a major source of hyperglycemia in patients with type 2 diabetes mellitus (T2DM), thus targeting gluconeogenesis to suppress glucose production is a promising strategy for anti-T2DM drug discovery. In our preliminary in vitro studies, we found that a small-molecule (E)-3-(2-(quinoline-4-yl)vinyl)-1H-indol-6-ol (QVO) inhibited the hepatic glucose production (HGP) in primary hepatocytes. We further revealed that QVO suppressed hepatic gluconeogenesis involving calmodulin-dependent protein kinase kinase β- and liver kinase B1-adenosine monophosphate-activated protein kinase (AMPK) pathways as well as AMPK-independent mitochondrial function-related signaling pathway. Read More

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http://dx.doi.org/10.1038/s41401-018-0208-2DOI Listing
March 2019
2 Reads

Nicotinamide phosphoribosyltransferase aggravates inflammation and promotes atherosclerosis in ApoE knockout mice.

Acta Pharmacol Sin 2019 Mar 4. Epub 2019 Mar 4.

Department of Pharmacology, Second Military Medical University, Shanghai, 200433, China.

Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme of nicotinamide adenine dinucleotide (NAD) salvage biosynthesis in mammals, and is involved in fundamental physiological processes and pathophysiology of many diseases. Thus far, however, the role of Nampt in atherosclerosis development is still in debate. In this study, we crossed global Nampt transgenic mice (Nampt-Tg) with a well-established atherosclerosis animal model (ApoE knockout mice, ApoE) to generate ApoE;Nampt-Tg mice and investigated the effects of Nampt overexpression on atherosclerosis development in ApoE mice. Read More

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http://dx.doi.org/10.1038/s41401-018-0207-3DOI Listing
March 2019
1 Read

Ligand-induced activation of ERK1/2 signaling by constitutively active G-coupled 5-HT receptors.

Acta Pharmacol Sin 2019 Mar 4. Epub 2019 Mar 4.

VARI-SIMM Center, Center for Structure and Function of Drug Targets, The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China.

5-HTR, 5-HTR, and 5-HTR are three constitutively active G-coupled 5-HT receptors that have key roles in brain development, learning, memory, cognition, and other physiological processes in the central nervous system. In addition to G signaling cascade mediated by these three 5-HT receptors, the ERK1/2 signaling which is dependent on cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) activation downstream of G signaling has also been widely studied. In this study, we investigated these two signaling pathways originating from the three G-coupled 5-HT receptors in AD293 cells. Read More

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http://dx.doi.org/10.1038/s41401-018-0204-6DOI Listing
March 2019
6 Reads

Structural insight into the serotonin (5-HT) receptor family by molecular docking, molecular dynamics simulation and systems pharmacology analysis.

Acta Pharmacol Sin 2019 Feb 27. Epub 2019 Feb 27.

Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Serotonin (5-HT) receptors are proteins involved in various neurological and biological processes, such as aggression, anxiety, appetite, cognition, learning, memory, mood, sleep, and thermoregulation. They are commonly associated with drug abuse and addiction due to their importance as targets for various pharmaceutical and recreational drugs. However, due to a high sequence similarity/identity among 5-HT receptors and the unavailability of the 3D structure of the different 5-HT receptor, no report was available so far regarding the systematical comparison of the key and selective residues involved in the binding pocket, making it difficult to design subtype-selective serotonergic drugs. Read More

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http://dx.doi.org/10.1038/s41401-019-0217-9DOI Listing
February 2019
5 Reads

mTORC1 inhibitor RAD001 (everolimus) enhances non-small cell lung cancer cell radiosensitivity in vitro via suppressing epithelial-mesenchymal transition.

Acta Pharmacol Sin 2019 Feb 22. Epub 2019 Feb 22.

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Resistance to radiotherapy causes non-small cell lung cancer (NSCLC) treatment failure associated with local recurrence and metastasis. Thus, understanding the radiosensitization of NSCLC cells is crucial for developing new treatments and improving prognostics. mTORC1 has been shown to regulate tumor cell radiosensitivity, but the underlying mechanisms are unclear. Read More

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http://dx.doi.org/10.1038/s41401-019-0215-yDOI Listing
February 2019

Predicted secreted protein analysis reveals synaptogenic function of Clstn3 during WAT browning and BAT activation in mice.

Acta Pharmacol Sin 2019 Feb 22. Epub 2019 Feb 22.

Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Promoting white adipose tissue (WAT) browning and enhancing brown adipose tissue (BAT) activity are attractive therapeutic strategies for obesity and its metabolic complications. Targeting sympathetic innervation in WAT and BAT represents a promising therapeutic concept. However, there are few reports on extracellular microenvironment remodeling, especially changes in nerve terminal connections. Read More

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http://dx.doi.org/10.1038/s41401-019-0211-2DOI Listing
February 2019
1 Read
2.496 Impact Factor

The inhibitory mechanism of aurintricarboxylic acid targeting serine/threonine phosphatase Stp1 in Staphylococcus aureus: insights from molecular dynamics simulations.

Acta Pharmacol Sin 2019 Feb 22. Epub 2019 Feb 22.

Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Serine/threonine phosphatase (Stp1) is a member of the bacterial Mg- or Mn- dependent protein phosphatase/protein phosphatase 2C family, which is involved in the regulation of Staphylococcus aureus virulence. Aurintricarboxylic acid (ATA) is a known Stp1 inhibitor with an IC50 of 1.03 μM, but its inhibitory mechanism has not been elucidated in detail because the Stp1-ATA cocrystal structure has not been determined thus far. Read More

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http://www.nature.com/articles/s41401-019-0216-x
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http://dx.doi.org/10.1038/s41401-019-0216-xDOI Listing
February 2019
3 Reads

Characteristics of β-oxidative and reductive metabolism on the acyl side chain of cinnamic acid and its analogues in rats.

Acta Pharmacol Sin 2019 Feb 21. Epub 2019 Feb 21.

Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.

Cinnamic acid and its analogues (pyragrel and ozagrel) undergo chain-shortened (β-oxidative) and reductive metabolism on acyl side chain. In this study, we characterized the β-oxidative and reductive metabolism on acyl side chain of cinnamic acid and its analogues using primary rat hepatocytes, hepatic mitochondrial, and microsomal systems. A compartmental model including parent compounds and metabolites was developed to characterize in vivo β-oxidative and reductive metabolism following an intravenous dose of parent compounds to rats. Read More

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http://dx.doi.org/10.1038/s41401-019-0218-8DOI Listing
February 2019
1 Read
2.496 Impact Factor

Minocycline protects against myocardial ischemia/reperfusion injury in rats by upregulating MCPIP1 to inhibit NF-κB activation.

Acta Pharmacol Sin 2019 Feb 21. Epub 2019 Feb 21.

Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 510182, China.

Minocycline is a tetracycline antibiotic and has been shown to play a protective role in cerebral and myocardial ischemia/reperfusion (I/R). However, the underlying mechanism remains unclear. Herein, we investigated whether monocyte chemotactic protein-induced protein-1 (MCPIP1), a negative regulator of inflammation, was involved in the minocycline-induced cardioprotection in myocardial I/R in vivo and in vitro models. Read More

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http://dx.doi.org/10.1038/s41401-019-0214-zDOI Listing
February 2019

Inhibition of G9a by a small molecule inhibitor, UNC0642, induces apoptosis of human bladder cancer cells.

Acta Pharmacol Sin 2019 Feb 14. Epub 2019 Feb 14.

Department of Urology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, China.

Urinary bladder cancer (UBC) is characterized by frequent recurrence and metastasis despite the standard chemotherapy with gemcitabine and cisplatin combination. Histone modifiers are often dysregulated in cancer development, thus they can serve as an excellent drug targets for cancer therapy. Here, we investigated whether G9a, one of the histone H3 methyltransferases, was associated with UBC development. Read More

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http://dx.doi.org/10.1038/s41401-018-0205-5DOI Listing
February 2019
1 Read

Magnesium lithospermate B ameliorates microcirculation perfusion in rats by promoting vascular NO production via activating the PI3K/AKT pathway.

Acta Pharmacol Sin 2019 Feb 13. Epub 2019 Feb 13.

School of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China.

Microcirculation morphologically refers to the blood flow in vessels of less than 150 μm in diameter, including arterioles, capillaries and venules, which provides nutrients and removes metabolic byproducts within tissues. Microcirculation dysfunction is involved in the pathological progress of many diseases, such as obesity, hypertension, and insulin resistance. In this study we investigated the effects of magnesium lithospermate B (MLB), an active compound of the traditional Chinese medicine Slavia miltiorrhiza, on the microcirculation dysfunction in rats and the underlying molecular mechanisms. Read More

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http://dx.doi.org/10.1038/s41401-018-0203-7DOI Listing
February 2019

Low-intensity walking as mild medication for pressure control in prehypertensive and hypertensive subjects: how far shall we wander?

Acta Pharmacol Sin 2019 Feb 13. Epub 2019 Feb 13.

Hirakata Ryoikuen, Osaka, 573-0122, Japan.

Successful prevention and treatment of hypertension depend on the appropriate combination of antihypertensive drug therapy and nondrug lifestyle modification. While most hypertension guidelines recommend moderate- to high-intensity exercise, we decided to explore a mild yet effective type of exercise to add to hypertension management, especially in populations with complications or frailty. After comparing the short-term cardiovascular effects of low-speed walking versus high-speed walking for 3 kilometers (km) (3 km/h versus 6 km/h) in young, healthy volunteers, we delivered low-speed walking (low-intensity walking, 2. Read More

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http://dx.doi.org/10.1038/s41401-018-0202-8DOI Listing
February 2019
3 Reads

Simvastatin improves olanzapine-induced dyslipidemia in rats through inhibiting hepatic mTOR signaling pathway.

Acta Pharmacol Sin 2019 Feb 6. Epub 2019 Feb 6.

School of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.

Second-generation antipsychotic drug (SGA)-induced metabolic abnormalities, such as dyslipidemia, are a major clinical problem for antipsychotic therapy. Accumulated evidences have shown the efficacy of statins in reducing SGA-induced dyslipidemia, but the underlying mechanisms are unclear. In this study, we explored whether mTOR signaling was involved in olanzapine (OLZ)-induced dyslipidemia as well as the lipid-lowering effects of cotreatment of simvastatin (Sim) in rats. Read More

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http://dx.doi.org/10.1038/s41401-019-0212-1DOI Listing
February 2019

NLRP3 inflammasome pathway is involved in olfactory bulb pathological alteration induced by MPTP.

Acta Pharmacol Sin 2019 Feb 6. Epub 2019 Feb 6.

Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, China.

Olfactory bulb, as one of sensory organs opening to the outside, is susceptible to toxic environment and easy to deteriorate. Recent studies in Parkinson's disease (PD) patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys have shown that abnormal α-synuclein is accumulated in the olfactory glomeruli, suggesting that the lesions of PD are not only confined to the substantia nigra (SN) but also located in the olfactory bulb. Thus, olfactory bulb might be the region of onset in PD pathogenesis and a targeted region for diagnosis and treatment of PD. Read More

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http://www.nature.com/articles/s41401-018-0209-1
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http://dx.doi.org/10.1038/s41401-018-0209-1DOI Listing
February 2019
13 Reads

Cannabis, cannabinoid receptors, and endocannabinoid system: yesterday, today, and tomorrow.

Authors:
Jie Wu

Acta Pharmacol Sin 2019 Mar 22;40(3):297-299. Epub 2019 Jan 22.

Qingdao University Brain Science and Disease Institute, Qingdao, 266021, China.

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http://www.nature.com/articles/s41401-019-0210-3
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http://dx.doi.org/10.1038/s41401-019-0210-3DOI Listing
March 2019
6 Reads

Histone methyltransferase NSD2 mediates the survival and invasion of triple-negative breast cancer cells via stimulating ADAM9-EGFR-AKT signaling.

Acta Pharmacol Sin 2019 Jan 22. Epub 2019 Jan 22.

Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA, USA.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with a poor prognosis due to the lack of an effective targeted therapy. Histone lysine methyltransferases (KMTs) have emerged as attractive drug targets for cancer therapy. However, the function of the majority of KMTs in TNBC has remained largely unknown. Read More

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http://dx.doi.org/10.1038/s41401-018-0199-zDOI Listing
January 2019
1 Read

Costunolide alleviates HKSA-induced acute lung injury via inhibition of macrophage activation.

Acta Pharmacol Sin 2019 Jan 15. Epub 2019 Jan 15.

Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.

Staphylococcus aureus (S. aureus) infection leads to a severe inflammatory response and causes acute lung injury (ALI), eventually threatening human life. Therefore, it is of importance to find an agent to inhibit inflammation and reduce ALI. Read More

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http://dx.doi.org/10.1038/s41401-018-0192-6DOI Listing
January 2019
4 Reads

SHR-A1403, a novel c-Met antibody-drug conjugate, exerts encouraging anti-tumor activity in c-Met-overexpressing models.

Acta Pharmacol Sin 2019 Jan 14. Epub 2019 Jan 14.

Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China.

Emerging evidence demonstrates that a c-Met antibody-drug conjugate (ADC) has superior efficacy and safety profiles compared with those of currently available small molecules or antibody inhibitors for the treatment of c-Met-overexpressing cancers. Here we described both the in vitro and in vivo efficacies of SHR-A1403, a novel c-Met ADC composed of a humanized IgG2 monoclonal antibody against c-Met conjugated to a novel cytotoxic microtubule inhibitor. SHR-A1403 showed high affinity to c-Met proteins derived from human or monkey and potent inhibitory effects in cancer cell lines with high c-Met protein expression. Read More

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http://www.nature.com/articles/s41401-018-0198-0
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http://dx.doi.org/10.1038/s41401-018-0198-0DOI Listing
January 2019
13 Reads

CP-25 reverses prostaglandin E4 receptor desensitization-induced fibroblast-like synoviocyte dysfunction via the G protein-coupled receptor kinase 2 in autoimmune arthritis.

Acta Pharmacol Sin 2019 Jan 14. Epub 2019 Jan 14.

Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.

Paeoniflorin-6'-O-benzene sulfonate (CP-25) is a novel compound derived from paeoniflorin that has been demonstrated to have therapeutic effects in a rat model of rheumatoid arthritis (RA). However, the underlying mechanism has not been elucidated to date. We explored this mechanism in the present study by treating rats with adjuvant arthritis (AA) with CP-25. Read More

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http://dx.doi.org/10.1038/s41401-018-0196-2DOI Listing
January 2019
10 Reads

Discovery of β-arrestin-biased β-adrenoceptor agonists from 2-amino-2-phenylethanol derivatives.

Acta Pharmacol Sin 2019 Jan 14. Epub 2019 Jan 14.

State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking University, Beijing, 100871, China.

β-Arrestins are a small family of proteins important for signal transduction at G protein-coupled receptors (GPCRs). β-Arrestins are involved in the desensitization of GPCRs. Recently, biased ligands possessing different efficacies in activating the G protein- versus the β-arrestin-dependent signals downstream of a single GPCR have emerged, which can be used to selectively modulate GPCR signal transduction in such a way that desirable signals are enhanced to produce therapeutic effects while undesirable signals of the same GPCR are suppressed to avoid side effects. Read More

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http://dx.doi.org/10.1038/s41401-018-0200-xDOI Listing
January 2019
21 Reads

Magnesium lithospermate B protects the endothelium from inflammation-induced dysfunction through activation of Nrf2 pathway.

Acta Pharmacol Sin 2019 Jan 7. Epub 2019 Jan 7.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai, 201203, China.

Magnesium lithospermate B (MLB) is an active component of Salvia miltiorrhiza Radix, a traditional Chinese herb used in treating cardiovascular diseases. In this study, we investigated the protective effects of MLB against inflammation-induced endothelial dysfunction in vitro and in vivo, and the underlying mechanisms. Endothelial dysfunction was induced in human dermal microvascular endothelial cells (HMEC-1) in vitro by lipopolysaccharide (LPS, 1 μg/mL). Read More

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http://dx.doi.org/10.1038/s41401-018-0189-1DOI Listing
January 2019
1 Read

c-Myc promotes tubular cell apoptosis in ischemia-reperfusion-induced renal injury by negatively regulating c-FLIP and enhancing FasL/Fas-mediated apoptosis pathway.

Acta Pharmacol Sin 2018 Dec 28. Epub 2018 Dec 28.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

c-Myc plays an important role in cell proliferation, differentiation, and cell apoptosis. FasL/Fas pathway is a key regulator of cell apoptosis. This study was aimed to investigate the effects of c-Myc on the FasL/Fas pathway in ischemia-reperfusion (I/R)-induced renal injury. Read More

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http://dx.doi.org/10.1038/s41401-018-0201-9DOI Listing
December 2018
2 Reads
2.496 Impact Factor

A novel ASBT inhibitor, IMB17-15, repressed nonalcoholic fatty liver disease development in high-fat diet-fed Syrian golden hamsters.

Acta Pharmacol Sin 2018 Dec 20. Epub 2018 Dec 20.

NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, 100050, China.

The manipulation of bile acid (BA) homeostasis by blocking the ileal apical Na-dependent bile salt transporter (ASBT/SLC10A2) may have therapeutic effects in nonalcoholic fatty liver disease. We developed a novel ASBT inhibitor, an N-(3,4-o-dichlorophenyl)-2-(3-trifluoromethoxy) benzamide derivative referred to as IMB17-15, and investigated its therapeutic effects and the molecular mechanisms underlying the effects. Syrian golden hamsters were challenged with high-fat diet (HFD) to induce NAFLD and were subsequently administered 400 mg/kg IMB17-15 by gavage daily for 21 days. Read More

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http://www.nature.com/articles/s41401-018-0195-3
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http://dx.doi.org/10.1038/s41401-018-0195-3DOI Listing
December 2018
18 Reads

Magnesium isoglycyrrhizinate ameliorates high fructose-induced liver fibrosis in rat by increasing miR-375-3p to suppress JAK2/STAT3 pathway and TGF-β1/Smad signaling.

Acta Pharmacol Sin 2018 Dec 19. Epub 2018 Dec 19.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.

Increasing evidence has demonstrated that excessive fructose intake induces liver fibrosis. Epithelial-mesenchymal transition (EMT) driven by transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog (Smad) signaling activation promotes the occurrence and development of liver fibrosis. Magnesium isoglycyrrhizinate is clinically used as a hepatoprotective agent to treat liver fibrosis, but its underlying molecular mechanism has not been identified. Read More

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http://dx.doi.org/10.1038/s41401-018-0194-4DOI Listing
December 2018
3 Reads
2.496 Impact Factor

Sulfuretin protects hepatic cells through regulation of ROS levels and autophagic flux.

Acta Pharmacol Sin 2018 Dec 18. Epub 2018 Dec 18.

State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai, China.

Palmitate (PA) exposure induces stress conditions featuring ROS accumulation and upregulation of p62 expression, resulting in autophagic flux blockage and cell apoptosis. Sulfuretin (Sul) is a natural product isolated from Rhus verniciflua Stokes; the cytoprotective effect of Sul on human hepatic L02 cells and mouse primary hepatocytes under PA-induced stress conditions was investigated in this study. Sul induced mitophagy by activation of p-TBK1 and LC3 and produced a concomitant decline in p62 expression. Read More

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http://dx.doi.org/10.1038/s41401-018-0193-5DOI Listing
December 2018
1 Read

Profiling and targeting of cellular mitochondrial bioenergetics: inhibition of human gastric cancer cell growth by carnosine.

Acta Pharmacol Sin 2018 Dec 18. Epub 2018 Dec 18.

Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, China.

L-Carnosine (β-alanyl-L-histidine) is a naturally occurring dipeptide distributed in various organs of mammalians. We previously showed that carnosine inhibited proliferation of human gastric cancer cells through targeting both mitochondrial bioenergetics and glycolysis pathway. But the mechanism underlying carnosine action on mitochondrial bioenergetics of tumor cells remains unclear. Read More

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http://dx.doi.org/10.1038/s41401-018-0182-8DOI Listing
December 2018
4 Reads

Human pharmacology of positive GABA-A subtype-selective receptor modulators for the treatment of anxiety.

Acta Pharmacol Sin 2018 Dec 5. Epub 2018 Dec 5.

Centre for Human Drug Research, Leiden, 2333 CL, The Netherlands.

Anxiety disorders arise from disruptions among the highly interconnected circuits that normally serve to process the streams of potentially threatening stimuli. The resulting imbalance among these circuits can cause a fundamental misinterpretation of neural sensory information as threatening and can lead to the inappropriate emotional and behavioral responses observed in anxiety disorders. There is considerable preclinical evidence that the GABAergic system, in general, and its α2- and/or α5-subunit-containing GABA(A) receptor subtypes, in particular, are involved in the pathophysiology of anxiety disorders. Read More

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http://dx.doi.org/10.1038/s41401-018-0185-5DOI Listing
December 2018
4 Reads

State-of-the-art: functional fluorescent probes for bioimaging and pharmacological research.

Acta Pharmacol Sin 2018 Nov 28. Epub 2018 Nov 28.

Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.

Cardiovascular diseases, neuropsychiatric disorders, and cancers seriously endanger human health. Mechanistic and pharmacological mechanisms of candidate drugs are central to the translational paradigm. Since many signal transduction and molecular events are implicated in these diseases, a novel method to interrogate the key pharmacological mechanisms is required to accelerate innovative drug discovery. Read More

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http://www.nature.com/articles/s41401-018-0190-8
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http://dx.doi.org/10.1038/s41401-018-0190-8DOI Listing
November 2018
22 Reads

C11, a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis.

Acta Pharmacol Sin 2018 Nov 28. Epub 2018 Nov 28.

Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis. Here, we identified a new selective FGFR inhibitor, C11, and assessed its antitumor activities. C11 was a selective FGFR1 inhibitor with an IC of 19 nM among a panel of 20 tyrosine kinases. Read More

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http://dx.doi.org/10.1038/s41401-018-0191-7DOI Listing
November 2018
5 Reads

Influences of an NR1I2 polymorphism on heterogeneous antiplatelet reactivity responses to clopidogrel and clinical outcomes in acute ischemic stroke patients.

Acta Pharmacol Sin 2018 Nov 28. Epub 2018 Nov 28.

Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.

Pregnane X receptor (PXR) is a member of nuclear receptor subfamily 1 (NR1I2) that is a transcriptional regulator of several metabolic enzymes involved in clopidogrel metabolism. In this study we identified and evaluated the contributions of single nucleotide polymorphisms (SNPs) in NR1I2 and cytochrome P450 (CYP) 2C19 alleles to clopidogrel resistance (CR) and long-term clinical outcomes in acute ischemic stroke (IS) patients. A total of 634 patients with acute IS were recruited, who received antiplatelet medication (clopidogrel or aspirin) every day and completed a 1-year follow-up. Read More

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http://dx.doi.org/10.1038/s41401-018-0178-4DOI Listing
November 2018
8 Reads

Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment.

Acta Pharmacol Sin 2018 Nov 26. Epub 2018 Nov 26.

Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL, 60612, USA.

Uterine fibroids (UFs) are the most common benign neoplastic threat to women's health and associated with DNA damage and genomic instability. Hypovitaminosis D is a known risk factor for UFs, especially among African Americans. Vitamin D3 has been shown to effectively inhibit UF phenotype, but its mechanisms remain unclear. Read More

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http://dx.doi.org/10.1038/s41401-018-0184-6DOI Listing
November 2018
2 Reads
2.496 Impact Factor

Platelet microparticles contribute to aortic vascular endothelial injury in diabetes via the mTORC1 pathway.

Acta Pharmacol Sin 2019 Apr 16;40(4):468-476. Epub 2018 Nov 16.

Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.

Platelet microparticles (PMPs) are closely associated with diabetic macrovascular complications. The present study aimed to investigate the effects of PMPs in diabetes on aortic vascular endothelial injury and to explore the underlying mechanisms. Peritoneal injection of streptozotocin was used to generate a diabetic rat model in vivo, and human umbilical vein endothelial cells (HUVECs) treated with PMPs were used in vitro. Read More

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http://www.nature.com/articles/s41401-018-0186-4
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http://dx.doi.org/10.1038/s41401-018-0186-4DOI Listing
April 2019
18 Reads

Paeoniflorin-6'-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents.

Acta Pharmacol Sin 2018 Nov 16. Epub 2018 Nov 16.

Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Anti-Inflammatory Immune Drugs Collaborative Innovation Center, Hefei, 230032, China.

Paeoniflorin-6'-O-benzene sulfonate (CP-25) is a new ester derivative of paeoniflorin with improved lipid solubility and oral bioavailability, as well as better anti-inflammatory activity than its parent compound. In this study we explored whether CP-25 exerted therapeutic effects in collagen-induced arthritis (CIA) mice through regulating B-cell activating factor (BAFF)-BAFF receptors-mediated signaling pathways. CIA mice were given CP-25 or injected with biological agents rituximab or etanercept for 40 days. Read More

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http://dx.doi.org/10.1038/s41401-018-0169-5DOI Listing
November 2018
2 Reads

Endothelial cell-specific anticoagulation reduces inflammation in a mouse model of acute lung injury.

Acta Pharmacol Sin 2018 Nov 16. Epub 2018 Nov 16.

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.

Tissue factor (TF)-dependent coagulation contributes to lung inflammation and the pathogenesis of acute lung injury (ALI). In this study, we explored the roles of targeted endothelial anticoagulation in ALI using two strains of transgenic mice expressing either a membrane-tethered human tissue factor pathway inhibitor (hTFPI) or hirudin fusion protein on CD31 cells, including vascular endothelial cells (ECs). ALI was induced by intratracheal injection of LPS, and after 24 h the expression of TF and protease-activated receptors (PARs) on EC in lungs were assessed, alongside the extent of inflammation and injury. Read More

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http://dx.doi.org/10.1038/s41401-018-0175-7DOI Listing
November 2018
21 Reads

THZ1 suppresses human non-small-cell lung cancer cells in vitro through interference with cancer metabolism.

Acta Pharmacol Sin 2018 Nov 16. Epub 2018 Nov 16.

Institute of Translational Medicine, Nanchang University, 330031, Nanchang, China.

Cancer cells always require more nutrients, energy, and biosynthetic activity to sustain their rapid proliferation than normal cells. Previous studies have shown the impact of THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), on transcription regulation and cell-cycle arrest in numerous cancers, but its effects on cellular metabolism in cancer cells remain unknown. In this study we elucidated the anticancer mechanism of THZ1 in human non-small-cell lung cancer (NSCLC) cells. Read More

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http://www.nature.com/articles/s41401-018-0187-3
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http://dx.doi.org/10.1038/s41401-018-0187-3DOI Listing
November 2018
17 Reads

Different structures of berberine and five other protoberberine alkaloids that affect P-glycoprotein-mediated efflux capacity.

Acta Pharmacol Sin 2019 Jan 15;40(1):133-142. Epub 2018 Nov 15.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Berberine, berberrubine, thalifendine, demethyleneberberine, jatrorrhizine, and columbamine are six natural protoberberine alkaloid (PA) compounds that display extensive pharmacological properties and share the same protoberberine molecular skeleton with only slight substitution differences. The oral delivery of most PAs is hindered by their poor bioavailability, which is largely caused by P-glycoprotein (P-gp)-mediated drug efflux. Meanwhile, P-gp undergoes large-scale conformational changes (from an inward-facing to an outward-facing state) when transporting substrates, and these changes might strongly affect the P-gp-binding specificity. Read More

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http://dx.doi.org/10.1038/s41401-018-0183-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318324PMC
January 2019
17 Reads

CZ-7, a new derivative of Claulansine F, ameliorates 2VO-induced vascular dementia in rats through a Nrf2-mediated antioxidant responses.

Acta Pharmacol Sin 2019 Apr 31;40(4):425-440. Epub 2018 Oct 31.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Vascular dementia (VD) results from accumulated damage in the vascular system, which is characterized by progressive impairments in memory and cognition and is second only to Alzheimer's disease (AD) in prevalence among all types of dementia. In contrast to AD, there is no FDA-approved treatment for VD owing to its multiple etiologies. In this study, we investigated whether CZ-7, a new derivative of Claulansine F (Clau F) with verified neuroprotective activity in vitro, could ameliorate the cognitive impairment of rats with permanent occlusion of bilateral common carotid arteries (2VO) and its potential mechanisms of action. Read More

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http://dx.doi.org/10.1038/s41401-018-0078-7DOI Listing
April 2019
11 Reads

Metabolism and disposition of pyrotinib in healthy male volunteers: covalent binding with human plasma protein.

Acta Pharmacol Sin 2018 Oct 31. Epub 2018 Oct 31.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201210, China.

Pyrotinib is a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor that is used to treat HER2-positive breast cancer. In this study we investigated the metabolism and disposition of pyrotinib in six healthy Chinese men after a single oral dose of 402 mg of [C]pyrotinib. At 240 h postdose, the mean cumulative excretion of the dose radioactivity was 92. Read More

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http://www.nature.com/articles/s41401-018-0176-6
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http://dx.doi.org/10.1038/s41401-018-0176-6DOI Listing
October 2018
15 Reads

µ-TRTX-Ca1a: a novel neurotoxin from Cyriopagopus albostriatus with analgesic effects.

Acta Pharmacol Sin 2018 Oct 31. Epub 2018 Oct 31.

The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China.

Human genetic and pharmacological studies have demonstrated that voltage-gated sodium channels (VGSCs) are promising therapeutic targets for the treatment of pain. Spider venom contains many toxins that modulate the activity of VGSCs. To date, only 0. Read More

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http://www.nature.com/articles/s41401-018-0181-9
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http://dx.doi.org/10.1038/s41401-018-0181-9DOI Listing
October 2018
8 Reads

Caspase-11 promotes renal fibrosis by stimulating IL-1β maturation via activating caspase-1.

Acta Pharmacol Sin 2018 Oct 31. Epub 2018 Oct 31.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

Caspase-11 is a key upstream modulator for activation of inflammatory response under pathological conditions. In this study, we investigated the roles of caspase-11 in the maturation of interleukin-1β (IL-1β) and development of renal interstitial fibrosis in vivo and in vitro. Mice were subjected to unilateral ureteral obstruction (UUO). Read More

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http://www.nature.com/articles/s41401-018-0177-5
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http://dx.doi.org/10.1038/s41401-018-0177-5DOI Listing
October 2018
9 Reads
2.500 Impact Factor

Drug addiction: a curable mental disorder?

Acta Pharmacol Sin 2018 Dec 31;39(12):1823-1829. Epub 2018 Oct 31.

Department of Pharmacology and Toxicology, University at Buffalo, The State University of New York, Buffalo, NY, 14203, USA.

Drug addiction is a chronic, relapsing brain disorder. Multiple neural networks in the brain including the reward system (e.g. Read More

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http://dx.doi.org/10.1038/s41401-018-0180-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289334PMC
December 2018
1 Read