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    6259 results match your criteria Acta Pharmacologica Sinica[Journal]

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    Charactering the metabolism of cryptotanshinone by human P450 enzymes and uridine diphosphate glucuronosyltransferases in vitro.
    Acta Pharmacol Sin 2018 Feb 8. Epub 2018 Feb 8.
    Department of Clinical Pharmacology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
    Cryptotanshinone (CT) is the main active component in the root of Salvia miltiorrhiza Bunge (SMB) that displays antibacterial, anti-inflammatory and anticancer activities. In this study, we characterized phase I and phase II metabolism of CT in human liver microsomes in vitro and identified the metabolic enzymes (CYPs and UGTs) involved. The metabolites of CT generated by CYPs were detected using LC-MS/MS and the CYP subtypes involved in the metabolic reactions were identified using chemical inhibitors of CYP enzymes and recombinant human CYP enzymes (CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). Read More

    Different network pharmacology mechanisms of Danshen-based Fangjis in the treatment of stable angina.
    Acta Pharmacol Sin 2018 Feb 8. Epub 2018 Feb 8.
    Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
    Danshen (Salvia miltiorrhiza) preparations such as Danhong injection, Danshen injection, Salvianolate injection, compound Danshen injection and Sodium Tanshinone IIA Sulfonate (STS) injection are widely used in China to treat stable angina (angina pectoris) caused by coronary heart disease. In this study we compared the network pharmacological mechanisms of the 5 Danshen preparations. Following a literature search performed in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) database, China Biology Medicine (CBM) database, China Conference Paper Database, Wanfang Database, VIP Database and Conference Proceedings Citation Index (through January 2015), 444 randomized controlled trial publications detailing the use of the 5 Danshen-based injections for treating stable angina were identified, and their combined data were analyzed using a network meta-analysis. Read More

    Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools.
    Acta Pharmacol Sin 2018 Feb 8. Epub 2018 Feb 8.
    Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutic Sciences & Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
    Exosomes are nano-sized vesicles that serve as mediators for intercellular communication through the delivery of cargo, including protein, lipids, nucleic acids or other cellular components, to neighboring or distant cells. Exosomal cargo may vary in response to different physiological or pathological conditions. The endosomal sorting complex required for transport (ESCRT) family has been widely accepted as a key mechanism in biogenesis and cargo sorting. Read More

    MicroRNAs as biomarkers for human glioblastoma: progress and potential.
    Acta Pharmacol Sin 2018 Feb 8. Epub 2018 Feb 8.
    Department of Neurology, Department of Veterans Affairs Medical Center, San Francisco and University of California, San Francisco, CA 94121, USA.
    Glioblastoma multiforme (GBM) is the most common malignant glioma. Despite innovative research efforts in tumor therapy, the outcome for most diagnosed patients remains poor; therefore, early diagnosis of GBM is the most effective method for achieving better patient outcomes. In recent years, combined research efforts including cellular, molecular, genetic, and bioinformatics methods have been used to investigate GBM, and the results show that variations in miRNA expression occur in GBM tissues and biological fluids. Read More

    Emodin alleviates alternatively activated macrophage and asthmatic airway inflammation in a murine asthma model.
    Acta Pharmacol Sin 2018 Feb 8. Epub 2018 Feb 8.
    Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
    Alternatively activated macrophages (AAMs) are not only associated with asthma but also lead to asthmatic airway inflammation and remodeling. Inhibition of AAMs is an alternative therapeutic strategy for treating asthma. In this study we investigated whether emodin (1,3,8-trihydroxy-6-methylanthraquinone), isolated from the rhizome of Rheum palmatum, alleviated asthmatic airway inflammation and reduced AAM polarization in a murine asthma model. Read More

    Epicatechin potentiation of glucose-stimulated insulin secretion in INS-1 cells is not dependent on its antioxidant activity.
    Acta Pharmacol Sin 2018 Feb 8. Epub 2018 Feb 8.
    Department of Agricultural, Food and Nutritional Science, University of Alberta Edmonton, Alberta, T6G 2E1 Canada.
    Epicatechin (EC) is a monomeric flavan-3-ol. We have previously demonstrated that glucose-intolerant rats fed flavan-3-ols exhibit improved pancreatic islet function corresponding with an increase in circulating EC-derived metabolites. Thus, we speculate that EC may act as a cellular signaling molecule in vivo to modulate insulin secretion. Read More

    Inhibition of the G9a/GLP histone methyltransferase complex modulates anxiety-related behavior in mice.
    Acta Pharmacol Sin 2018 Feb 8. Epub 2018 Feb 8.
    Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
    Epigenetic gene-regulation abnormalities have been implicated in various neuropsychiatric disorders including schizophrenia and depression, as well as in the regulation of mood and anxiety. In addition, epigenetic mechanisms are involved in the actions of psychiatric drugs. Current anxiolytic drugs have significant shortcomings, and development of new medications is warranted. Read More

    Full genetic analysis for genome-wide association study of Fangji: a powerful approach for effectively dissecting the molecular architecture of personalized traditional Chinese medicine.
    Acta Pharmacol Sin 2018 Feb 8. Epub 2018 Feb 8.
    Institute of Bioinformatics, Zhejiang University, Hangzhou 310058, China.
    Elucidation of the systems biology foundation underlying the effect of Fangji, which are multi-herbal traditional Chinese medicine (TCM) formulas, is one of the major aims in the field. The numerous bioactive ingredients of a Fangji deal with the multiple targets of a complex disease, which is influenced by a number of genes and their interactions with the environment. Genome-wide association study (GWAS) is an unbiased approach for dissecting the genetic variants underlying complex diseases and individual response to a given treatment. Read More

    CTC clusters induced by heparanase enhance breast cancer metastasis.
    Acta Pharmacol Sin 2018 Feb 8. Epub 2018 Feb 8.
    Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    Aggregated metastatic cancer cells, referred to as circulating tumor cell (CTC) clusters, are present in the blood of cancer patients and contribute to cancer metastasis. However, the origin of CTC clusters, especially intravascular aggregates, remains unknown. Here, we employ suspension culture methods to mimic CTC cluster formation in the circulation of breast cancer patients. Read More

    Inverse changes in plasma tetranectin and titin levels in patients with type 2 diabetes mellitus: a potential predictor of acute myocardial infarction?
    Acta Pharmacol Sin 2018 Feb 8. Epub 2018 Feb 8.
    Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
    An early intervention using biomarkers to predict acute myocardial infarction (AMI) will effectively reduce global heart attack incidence, particularly among high-risk patients with type 2 diabetes mellitus (T2DM). This study attempted to identify potential biomarkers by detecting changes in the levels of plasma proteins in T2DM patients following onset of AMI in comparison with those without AMI. Volunteer T2DM patients without AMI (control; n=10) and T2DM patients with AMI (n=10) were recruited. Read More

    Apolipoprotein J as a predictive biomarker for restenosis after carotid endarterectomy: a retrospective study.
    Acta Pharmacol Sin 2018 Feb 8. Epub 2018 Feb 8.
    First Department of Surgery, Vascular Unit, Laiko General Hospital, National & Kapodistrian University of Athens, Greece.
    Carotid endarterectomy (CEA) is an effective surgical option for stroke prophylaxis in most patients. Restenosis after CEA can lead to re-intervention and adverse events, but the factors predicting restenosis are poorly understood. Apolipoprotein J (ApoJ) is considered to be a novel predictive factor of vascular restenosis and is associated with a large number of processes related to atherosclerosis and cell-cycle phases. Read More

    Salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers selectively suppress human CD20+ melanoma stem cells.
    Acta Pharmacol Sin 2018 Feb 14;39(2):261-274. Epub 2017 Dec 14.
    Department of Dermatology, Minhang Branch, Zhongshan Hospital, Fudan University/Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201199, China.
    Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Read More

    Pure mechanistic analysis of additive neuroprotective effects between baicalin and jasminoidin in ischemic stroke mice.
    Acta Pharmacol Sin 2018 Jan 18. Epub 2018 Jan 18.
    Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
    Both baicalin (BA) and jasminoidin (JA) are active ingredients in Chinese herb medicine Scutellaria baicalensis and Fructus gardeniae, respectively. They have been shown to exert additive neuroprotective action in ischemic stroke models. In this study we used transcriptome analysis to explore the pure therapeutic mechanisms of BA, JA and their combination (BJ) contributing to phenotype variation and reversal of pathological processes. Read More

    The mTOR inhibitor AZD8055 overcomes tamoxifen resistance in breast cancer cells by down-regulating HSPB8.
    Acta Pharmacol Sin 2018 Jan 18. Epub 2018 Jan 18.
    Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    Tamoxifen, an important endocrine therapeutic agent, is widely used for the treatment of estrogen receptor positive (ER) breast cancer. However, de novo or acquired resistance prevents patients from benefitting from endocrine approaches and necessitates alternative treatments. In this study, we report that small heat protein beta-8 (HSPB8) may serve as an important molecule in tamoxifen resistance. Read More

    3-Acetyl-oleanolic acid ameliorates non-alcoholic fatty liver disease in high fat diet-treated rats by activating AMPK-related pathways.
    Acta Pharmacol Sin 2018 Jan 18. Epub 2018 Jan 18.
    Jiangsu Key Lab of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
    3-Acetyl-oleanolic acid (3Ac-OA) is a derivative of oleanolic acid (OA), which has shown therapeutic beneficial effects on diabetes and metabolic syndrome. In this study we investigated whether 3Ac-OA exerted beneficial effect on non-alcoholic fatty liver disease (NAFLD) in rats and its potential underlying mechanisms. Treatment with 3Ac-OA (1-100 μmol/L) dose-dependently decreased the intracellular levels of total cholesterol (TC) and triglyceride (TG) in FFA-treated primary rat hepatocytes and human HepG2 cell lines in vitro. Read More

    Ulinastatin attenuates LPS-induced inflammation in mouse macrophage RAW264.7 cells by inhibiting the JNK/NF-κB signaling pathway and activating the PI3K/Akt/Nrf2 pathway.
    Acta Pharmacol Sin 2018 Jan 11. Epub 2018 Jan 11.
    School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou 510006, China.
    Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor isolated and purified from human urine with strong anti-inflammatory and cytoprotective actions, which is widely used for the treatment of various diseases, such as pancreatitis and sepsis. Although the therapeutic effects of UTI are reported to be associated with a variety of mechanisms, the signaling pathways mediating the anti-inflammatory action of UTI remain to be elucidated. In the present study we carried out a systematic study on the anti-inflammatory and anti-oxidative mechanisms of UTI and their relationships in LPS-treated RAW264. Read More

    Regulatory T cells as a new therapeutic target for atherosclerosis.
    Acta Pharmacol Sin 2018 Jan 11. Epub 2018 Jan 11.
    Clinical Anatomy & Reproductive Medicine Application Institute, Department of Histology and Embryology, University of South China, Hengyang 421001, China.
    Atherosclerosis is an autoimmune disease caused by self- and non-self-antigens contributing to excessive activation of T and B cell immune responses. These responses further aggravate vascular inflammation and promote progression of atherosclerosis and vulnerability to plaques via releasing pro-inflammatory cytokines. Regulatory T cells (Tregs) as the major immunoregulatory cells, in particular, induce and maintain immune homeostasis and tolerance by suppressing the immune responses of various cells such as T and B cells, natural killer (NK) cells, monocytes, and dendritic cells (DCs), as well as by secreting inhibitory cytokines interleukin (IL)-10, IL-35 and transcription growth factor β (TGF-β) in both physiological and pathological states. Read More

    Schisandrin ameliorates cognitive impairment and attenuates Aβ deposition in APP/PS1 transgenic mice: involvement of adjusting neurotransmitters and their metabolite changes in the brain.
    Acta Pharmacol Sin 2018 Jan 11. Epub 2018 Jan 11.
    School of Pharmacy, China Medical University, Shenyang 110122, China.
    Neurotransmitters (NTs) in the brain are involved in neurodegenerative diseases, such as Alzheimer's disease (AD). Schisandrin is a major ingredient of Schisandra chinensis (Turcz.) Baill and has been used for the treatment of AD. Read More

    Tanshinol alleviates impaired bone formation by inhibiting adipogenesis via KLF15/PPARγ2 signaling in GIO rats.
    Acta Pharmacol Sin 2018 Jan 11. Epub 2018 Jan 11.
    Department of Pharmacology, Guangdong Medical University, Zhanjiang 524023, China.
    Glucocorticoid (GC)-induced osteoporosis (GIO) is characterized by impaired bone formation, which can be alleviated by tanshinol, an aqueous polyphenol isolated from Salvia miltiorrhiza Bunge. In this study we investigated the molecular mechanisms underlying GC-induced modulation of osteogenesis as well as the possibility of using tanshinol to interfere with GIO. Female SD rats aged 4 months were orally administered distilled water (Con), prednisone (GC, 5 mg·kg·d), GC plus tanshinol (Tan, 16 mg·kg·d) or GC plus resveratrol (Res, 5 mg·kg·d) for 14 weeks. Read More

    EBP50 suppresses the proliferation of MCF-7 human breast cancer cells via promoting Beclin-1/p62-mediated lysosomal degradation of c-Myc.
    Acta Pharmacol Sin 2017 Dec 28. Epub 2017 Dec 28.
    Key Laboratory of Biotechnology of Antibiotics of National Health and Family Planning Commission (NHFPC), Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050, China.
    c-Myc, a key activator of cell proliferation and angiogenesis, promotes the development and progression of breast cancer. Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) is a multifunctional scaffold protein that suppresses the proliferation of breast cancer cells. In this study we investigated whether the cancer-suppressing effects of EBP50 resulted from its regulation of c-Myc signaling in human breast cancer MCF-7 cells in vitro and in vivo. Read More

    CYP3A4 inducer and inhibitor strongly affect the pharmacokinetics of triptolide and its derivative in rats.
    Acta Pharmacol Sin 2017 Dec 28. Epub 2017 Dec 28.
    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    Triptolide is the most active ingredient of Tripterygium wilfordii Hook F, which is used to treat rheumatoid arthritis. (5R)-5-Hydroxytriptolide is a hydroxylation derivative of triptolide with a reduced toxicity. To investigate the metabolic enzymes of the two compounds and the drug-drug interactions with enzyme inducers or inhibitors, a series of in vitro and in vivo experiments were conducted. Read More

    Humanin decreases mitochondrial membrane permeability by inhibiting the membrane association and oligomerization of Bax and Bid proteins.
    Acta Pharmacol Sin 2017 Dec 21. Epub 2017 Dec 21.
    Department of Pharmacology III, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    Humanin (HN) is a 24-residue peptide identified from the brain of a patient with Alzheimer's disease (AD). HN has been found to protect against neuronal insult caused by Aβ peptides or transfection of familial AD mutant genes. In order to elucidate the molecular mechanisms of HN neuroprotection, we explored the effects of HN on the association of Bax or Bid with lipid bilayers and their oligomerization in the membrane. Read More

    Prefrontal AMPA receptors are involved in the effect of methylphenidate on response inhibition in rats.
    Acta Pharmacol Sin 2017 Dec 21. Epub 2017 Dec 21.
    Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
    Response inhibition is a critical executive control function in many species. Deficits in response inhibition have been observed in many disorders, eg, attention deficit/hyperactivity disorder (ADHD). The stop-signal task (SST) is a unique behavior task for evaluating response inhibition via measuring the covert latency of a stop process, and it is widely used in studies of humans, nonhuman primates and rodents. Read More

    Association of serum uric acid levels with osteoporosis and bone turnover markers in a Chinese population.
    Acta Pharmacol Sin 2017 Dec 14. Epub 2017 Dec 14.
    Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
    Recent evidence shows that uric acid is protective against some neurological diseases, but can be detrimental in many metabolic and cardiovascular disorders. In this study, we examined the association between serum uric acid levels and bone metabolism in Chinese males and postmenopausal females. A total of 943 males and 4256 postmenopausal females were recruited in Shanghai. Read More

    Suppression of eEF-2K-mediated autophagy enhances the cytotoxicity of Raddeanin A against human breast cancer cells in vitro.
    Acta Pharmacol Sin 2017 Dec 14. Epub 2017 Dec 14.
    Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410008, China.
    Recent evidence shows that raddeanin A (RA), an oleanane-type triterpenoid saponin extracted from Anemone raddeana Regel, exerts remarkable cytotoxicity against cancer cells in vitro and in vivo. In addition, RA has also been found to activate autophagy in human gastric cancer cells. In this study, we investigated the molecular mechanisms underlying RA-induced autophagy as well as the relationship between RA-induced autophagy and its cytotoxicity in human breast cancer cells in vitro. Read More

    Influences of Ivabradine treatment on serum levels of cardiac biomarkers sST2, GDF-15, suPAR and H-FABP in patients with chronic heart failure.
    Acta Pharmacol Sin 2017 Dec 14. Epub 2017 Dec 14.
    Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology and Intensive Medical Care, University Hospital Jena, Friedrich Schiller University Jena, Germany.
    Chronic heart failure (CHF) represents a major cause of hospitalization and death. Recent evidence shows that novel biomarkers such as soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) are correlated with inflammatory and ischemic responses in CHF patients. In this study we examined the effects of Ivabradine that inhibited the hyperpolarization-activated cyclic nucleotide-gated channel (HCN channel, also called funny current I), thereby leading to selective heart rate reduction and improved myocardial oxygen supply on the cardiac biomarkers sST2, GDF-15, suPAR and H-FABP in 50 CHF patients at the University Hospital of Jena. Read More

    Exosomes: new molecular targets of diseases.
    Acta Pharmacol Sin 2017 Dec 7. Epub 2017 Dec 7.
    Cardiovascular Research Institute, Division of Cardiovascular Diseases, Department of Internal Medicine.
    Extracellular vesicles (EVs) comprise apoptotic bodies, microvesicles and exosomes, and they perform as key regulators in cell-to-cell communication in normal as well as diseased states. EVs contain natural cargo molecules, such as miRNA, mRNA and proteins, and transfer these functional cargos to neighboring cells or more distant cells through circulation. These functionally active molecules then affect distinct signaling cascades. Read More

    A micRNA-200c/cathepsin L feedback loop determines paclitaxel resistance in human lung cancer A549 cells in vitro through regulating epithelial-mesenchymal transition.
    Acta Pharmacol Sin 2017 Dec 7. Epub 2017 Dec 7.
    Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
    Cathepsin L (CTSL), a cysteine protease, is closely related to tumor occurrence, development, and metastasis, and possibly regulates cancer cell resistance to chemotherapy. miRNAs, especially the miR-200 family, have been implicated in drug-resistant tumors. In this study we explored the relationship of CTSL, micRNA-200c and drug resistance, and the potential regulatory mechanisms in human lung cancer A549 cells and A549/TAX cells in vitro. Read More

    Asperosaponin VI promotes angiogenesis and accelerates wound healing in rats via up-regulating HIF-1α/VEGF signaling.
    Acta Pharmacol Sin 2017 Dec 7. Epub 2017 Dec 7.
    Department of Orthopedics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.
    Wound therapy remains a clinical challenge due to the complexity of healing pathology and high demand of achieving functional and aesthetically satisfactory scars. Newly formed blood vessels are essential for tissue repair since they can support cells at the wound site with nutrition and oxygen. In this study, we investigated the effects of Asperosaponin VI (ASA VI) isolated from a traditional Chinese medicine, the root of Dipsacus asper Wall, in promoting angiogenesis, as well as its function in wound therapeutics. Read More

    Dendritic cell nuclear protein-1 regulates melatonin biosynthesis by binding to BMAL1 and inhibiting the transcription of N-acetyltransferase in C6 cells.
    Acta Pharmacol Sin 2017 Dec 7. Epub 2017 Dec 7.
    Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
    Dendritic cell nuclear protein-1 (DCNP1) is a protein associated with major depression. In the brains of depression patients, DCNP1 is up-regulated. However, how DCNP1 participates in the pathogenesis of major depression remains unknown. Read More

    C1206, a novel curcumin derivative, potently inhibits Hsp90 and human chronic myeloid leukemia cells in vitro.
    Acta Pharmacol Sin 2017 Dec 7. Epub 2017 Dec 7.
    School of Pharmacy, Fujian Medical University, Fuzhou 350108, China.
    4-(4-Pyridinyl methylene) curcumin (C1206) is a new derivative of curcumin that is more active than curcumin in inhibition of heat shock protein 90 (Hsp90) and antitumor action. In this study we investigated the relationship between C1206-induced inhibition of Hsp90 and its anti-leukemic effects. The fluorescence quenching experiments showed that C1206 seemed to bind the middle dimerization domain of Hsp90. Read More

    Activation of human smooth muscle BK channels by hydrochlorothiazide requires cell integrity and the presence of BK βsubunit.
    Acta Pharmacol Sin 2017 Nov 30. Epub 2017 Nov 30.
    IIFP, UNLP, CONICET - Instituto de estudios Inmunológicos y Fisiopatológicos, Universidad Nacional de La Plata, Consejo Nacional de Investigaciones Científicas y Tecnológicas, La Plata, Argentina. 47 y 115 S/N, La Plata (1900), Buenos Aires, Argentina.
    Thiazide-like diuretics are the most commonly used drugs to treat arterial hypertension, with their efficacy being linked to their chronic vasodilatory effect. Previous studies suggest that activation of the large conductance voltage- and Ca-dependent K(BK) channel (Slo 1, MaxiK channel) is responsible for the thiazide-induced vasodilatory effect. But the direct electrophysiological evidence supporting this claim is lacking. Read More

    The LPI/GPR55 axis enhances human breast cancer cell migration via HBXIP and p-MLC signaling.
    Acta Pharmacol Sin 2017 Nov 30. Epub 2017 Nov 30.
    Public R&D Center of Bio-Manufacture, Hebei University of Science and Technology, Shijiazhuang 050018, China.
    The G protein-coupled receptor 55 (GPR55) is expressed in multiple tissues, and has been implicated in cancer pathogenesis, but little is known about its role in the migratory behavior of cancer cells, particularly breast cancer cells. In this study we first showed that GPR55 expression levels in 38 metastatic lymph nodes of breast cancer patients were profoundly elevated, and were positively associated in human breast cancer cells with their migratory ability. Moreover, the plasma levels of GPR55 endogenous agonist L-a-lysophosphatidylinositol (LPI) were significantly increased in breast cancer patients compared with healthy individuals. Read More

    Pharmacokinetic and pharmacodynamic evidence for developing an oral formulation of octreotide against gastric mucosal injury.
    Acta Pharmacol Sin 2017 Nov 30. Epub 2017 Nov 30.
    Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
    Among the somatostatin analogues, octreotide (OCT) is the most commonly used in clinic via intravenous or subcutaneous injection to treat various diseases caused by increased secretion of growth hormone, gastrin or insulin. In order to assesse the feasibility of developing oral formulations of OCT, we conducted systematical pharmacokinetic and pharmacodynamic analyses of OCT in several animal models. The pharmacokinetic studies in rats showed that intragastric administration of OCT had extremely low bioavailability (<0. Read More

    Chip-based digital PCR as a novel detection method for quantifying microRNAs in acute myocardial infarction patients.
    Acta Pharmacol Sin 2017 Nov 30. Epub 2017 Nov 30.
    Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany.
    miRNAs have shown promise as potential biomarkers for acute myocardial infarction (AMI). However, the current used quantitative real-time PCR (qRT-PCR) allows solely for relative expression of nucleic acids and it is susceptible to day-to-day variability, which has limited the validity of using the miRNAs as biomarkers. In this study we explored the technical qualities and diagnostic potential of a new technique, chip-based digital PCR, in quantifying the miRNAs in patients with AMI and ischaemia-reperfusion injury (I/R). Read More

    Computational insights into the G-protein-biased activation and inactivation mechanisms of the μ opioid receptor.
    Acta Pharmacol Sin 2018 Jan 30;39(1):154-164. Epub 2017 Nov 30.
    Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
    The μ opioid receptor (OR), a member of the class A subfamily of G-protein coupled receptors (GPCRs), is a major target for the treatment of pain. G-protein biased μ-OR agonists promise to be developed as analgesics. Thus, TRV130, the first representative μ-OR ligand with G-protein bias, has entered into phase III clinical trials. Read More

    Capsaicin enhances the antitumor activity of sorafenib in hepatocellular carcinoma cells and mouse xenograft tumors through increased ERK signaling.
    Acta Pharmacol Sin 2017 Nov 30. Epub 2017 Nov 30.
    Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, China.
    Sorafenib, a small inhibitor of tyrosine protein kinases, is currently the standard chemotherapy drug for the treatment of advanced hepatocellular carcinoma (HCC). Although sorafenib improves the survival of HCC patients, its efficacy is not optimal and requires further improvement. Capsaicin, the major active component of chili peppers from the genus Capsicum, is not only the agonist of TRPV1 channel, but also displays antitumor activity and enhances the sensitivity of cancer cells to cytotoxic drugs. Read More

    Yangxin Tongmai formula ameliorates impaired glucose tolerance in children with Graves' disease through upregulation of the insulin receptor levels.
    Acta Pharmacol Sin 2017 Nov 23. Epub 2017 Nov 23.
    Children's Hospital Chongqing Medical University, Chongqing 400000, China.
    Graves' disease (GD) is the leading cause of hyperthyroidism, and the majority of GD patients eventually develop disorders of glucose handling, which further affects their quality of life. Yangxin Tongmai formula (YTF) is modified from a famous formula of traditional Chinese medicine for the treatment of cardiovascular diseases. In this study we investigated the potential effects of YTF in the treatment of pediatric GD patients with impaired glucose tolerance. Read More

    Characterization of naturally occurring pentacyclic triterpenes as novel inhibitors of deubiquitinating protease USP7 with anticancer activity in vitro.
    Acta Pharmacol Sin 2017 Nov 23. Epub 2017 Nov 23.
    Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
    Deubiquitinating protease USP7 is a promising therapeutic target for cancer treatment, and interest in developing USP7 inhibitors has greatly increased. In the present study, we reported a series of natural pentacyclic triterpenes with USP7 inhibitory activity in vitro. Among them, both the ursane triterpenes and oleanane triterpenes were more active than the lupine triterpenes, whereas ursolic acid was the most potent with ICof 7. Read More

    Hispidulin mediates apoptosis in human renal cell carcinoma by inducing ceramide accumulation.
    Acta Pharmacol Sin 2017 Dec 9;38(12):1618-1631. Epub 2017 Nov 9.
    Medical College, Qingdao University, Qingdao 266071, China.
    Hispidulin, a polyphenolic flavonoid extracted from the traditional Chinese medicinal plant S involucrata, exhibits anti-tumor effects in a wide array of human cancer cells, mainly through growth inhibition, apoptosis induction and cell cycle arrest. However, its precise anticancer mechanisms remain unclear. In this study, we investigated the molecular mechanisms that contribute to hispidulin-induced apoptosis of human clear-cell renal cell carcinoma (ccRCC) lines Caki-2 and ACHN. Read More

    Tumor-targeting efficacy of a BF211 prodrug through hydrolysis by fibroblast activation protein-α.
    Acta Pharmacol Sin 2017 Nov 9. Epub 2017 Nov 9.
    Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China.
    BF211, a bufalin (BF) derivative, exhibits stronger anti-cancer activity than BF but with potential cardiotoxicity. Fibroblast activation protein-α (FAPα) is a membrane-bound protease specifically expressed by carcinoma-associated fibroblasts, thus has been used for the selective delivery of anticancer agents. In this study, we used a FAPα-based prodrug strategy to synthesize a dipeptide (Z-Gly-Pro)-conjugated BF211 prodrug named BF211-03. Read More

    Time-dependent pharmacokinetics of dexamethasone and its efficacy in human breast cancer xenograft mice: a semi-mechanism-based pharmacokinetic/pharmacodynamic model.
    Acta Pharmacol Sin 2017 Nov 9. Epub 2017 Nov 9.
    Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
    Dexamethasone (DEX) is the substrate of CYP3A. However, the activity of CYP3A could be induced by DEX when DEX was persistently administered, resulting in auto-induction and time-dependent pharmacokinetics (pharmacokinetics with time-dependent clearance) of DEX. In this study we investigated the pharmacokinetic profiles of DEX after single or multiple doses in human breast cancer xenograft nude mice and established a semi-mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for characterizing the time-dependent PK of DEX as well as its anti-cancer effect. Read More

    Rhynchophylla total alkaloid rescues autophagy, decreases oxidative stress and improves endothelial vasodilation in spontaneous hypertensive rats.
    Acta Pharmacol Sin 2017 Nov 9. Epub 2017 Nov 9.
    Shandong University of Traditional Chinese Medicine, Ji-nan 250000, China.
    Autophagy plays an important role in alleviating oxidative stress and stabilizing atherosclerotic plaques. However, the potential role of autophagy in endothelial vasodilation function has rarely been studied. This study aimed to investigate whether rhynchophylla total alkaloid (RTA) has a positive role in enhancing autophagy through decreasing oxidative stress, and improving endothelial vasodilation. Read More

    Cucurbitacin I inhibits STAT3, but enhances STAT1 signaling in human cancer cells in vitro through disrupting actin filaments.
    Acta Pharmacol Sin 2017 Nov 9. Epub 2017 Nov 9.
    Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    STAT1 and STAT3 are two important members of the STAT (signal transducers and activators of transcription) protein family and play opposing roles in regulating cancer cell growth. Suppressing STAT3 and/or enhancing STAT1 signaling are considered to be attractive anticancer strategies. Cucurbitacin I (CuI) isolated from the cucurbitacin family was reported to be an inhibitor of STAT3 signaling and a disruptor of actin cytoskeleton. Read More

    Chinese herbal formula Fuzheng Huayu alleviates CCl-induced liver fibrosis in rats: a transcriptomic and proteomic analysis.
    Acta Pharmacol Sin 2017 Nov 2. Epub 2017 Nov 2.
    Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
    Liver fibrosis is a consequence of chronic liver disease that can progress to liver cirrhosis or even hepatocarcinoma. Fuzheng Huayu (FZHY), a Chinese herbal formula, has been shown to exert anti-fibrotic effects. To better understand the molecular mechanisms underlying the anti-fibrotic effects of FZHY, we analyzed transcriptomic and proteomic combination profiles in CCl-induced liver fibrosis in rats, which were treated with extracted FZHY powder (0. Read More

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