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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Acta Pharmacol Sin 2018 Nov 16. 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

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

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

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

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

Acta Pharmacol Sin 2018 Oct 31. 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

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

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

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

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

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

Department of Pathology, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, China.

Fibronectin (FN) is a main component of extracellular matrix (ECM) in most adult tissues. Under pathological conditions, particularly inflammation, wound healing and tumors, an alternatively spliced exon extra domain A (EDA) is included in the FN protein (EDAFN), which facilitates cellular proliferation, motility, and aggressiveness in different lesions. In this study we investigated the effects of EDAFN on bone destruction in human radicular cysts and explored the possibility of editing FN gene or blocking the related paracrine signaling pathway to inhibit the osteoclastogenesis. Read More

Acta Pharmacol Sin 2018 Oct 26. Epub 2018 Oct 26.

Department of Pharmacology and Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.

Propofol is an intravenous anesthetic that can active γ-aminobutyric acid A (GABA) receptors and generate sedative-hypnotic effects. Propofol has been widely applied clinically to achieve sedation comparable to sleep in humans. The basal forebrain (BF) is a brain region that plays an important role in sleep-wake regulation. Read More

Acta Pharmacol Sin 2018 Oct 26. Epub 2018 Oct 26.

The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Recently, hepatic sinusoidal obstruction syndrome (HSOS) caused by herbal preparations containing pyrrolizidine alkaloids (PAs), such as Gynura Rhizoma (Tusanqi), has gained global attention. However, the lack of a reliable and reproducible animal model has greatly hampered mechanistic studies. Therefore, we aimed to establish a reproducible HSOS mouse model and investigate the hepatotoxic mechanism. Read More

Acta Pharmacol Sin 2018 Oct 17. Epub 2018 Oct 17.

Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao, 266021, China.

The α7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated Ca-permeable homopentameric ion channel implicated in cognition and neuropsychiatric disorders. Pharmacological enhancement of α7 nAChR function has been suggested for improvement of cognitive deficits. In the present study, we characterized a thiazolyl heterocyclic derivative, 6-(2-chloro-6-methylphenyl)-2-((3-fluoro-4-methylphenyl)amino)thiazolo[4,5-d]pyrimidin-7(6H)-one (JWX-A0108), as a novel type I α7 nAChR positive allosteric modulator (PAM), and evaluated its ability to reverse auditory gating and spatial working memory deficits in mice. Read More

Acta Pharmacol Sin 2018 Oct 17. Epub 2018 Oct 17.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Lysosomes are the terminal organelles of the autophagic-endocytic pathway and play a key role in the degradation of autophagic contents. We previously reported that a natural compound oblongifolin C (OC) increased the number of autophagosomes and impaired the degradation of P62, most likely via suppression of lysosomal function and blockage of autophagosome-lysosome fusion. However, the precise mechanisms of how OC inhibits the lysosome-autophagy pathway remain unclear. Read More

Acta Pharmacol Sin 2019 Mar 17;40(3):324-335. Epub 2018 Oct 17.

Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA.

The cannabinoid type-1 (CB) receptor, a G-protein-coupled receptor, is an attractive target for drug discovery due to its involvement in many physiological processes. Historically, drug discovery efforts targeting the CB receptor have focused on the development of orthosteric ligands that interact with the active site to which endogenous cannabinoids bind. Research performed over the last several decades has revealed substantial difficulties in translating CB orthosteric ligands into druggable candidates. Read More

Acta Pharmacol Sin 2018 Oct 16. Epub 2018 Oct 16.

Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

In order to maintain stable blood pressure and heart rate during surgery, anesthesiologists need to administer the appropriate amount of fluid with appropriate fluid type to the patient, then quantifying how fluid is distributed and eliminated from the body is useful for establishing a fluid administration strategy. In this study we characterized the volume kinetics of Ringer's lactate solution in patients undergoing open gastrectomy. When propofol and remifentanil reached a pseudosteady state at the target concentration and blood pressure was stabilized following surgical stimulation, enrolled patients were administered 1000 mL of Ringer's lactate solution for 20 min, followed by continuous infusion at a rate of 6 mL/kg/h until the time of the last blood collection for volume kinetic analysis. Read More

Acta Pharmacol Sin 2018 Oct 16. Epub 2018 Oct 16.

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

ShenMai, an intravenous injection prepared from steamed Panax ginseng roots (Hongshen) and Ophiopogon japonicus roots (Maidong), is used as an add-on therapy for coronary artery disease and cancer; saponins are its bioactive constituents. Since many saponins inhibit human organic anion-transporting polypeptides (OATP)1B, this investigation determined the inhibition potencies of circulating ShenMai saponins on the transporters and the joint potential of these compounds for ShenMai-drug interaction. Circulating saponins and their pharmacokinetics were characterized in rats receiving a 30-min infusion of ShenMai at 10 mL/kg. Read More

Acta Pharmacol Sin 2018 Oct 12. Epub 2018 Oct 12.

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

Human liver or hepatocyte transplantation is limited by a severe shortage of donor organs. Direct reprogramming of other adult cells into hepatic cells may offer a solution to this problem. In a previous study, we have generated hepatocyte-like cells from mouse fibroblasts using only one transcription factor (TF) plus a chemical cocktail. Read More

Acta Pharmacol Sin 2018 Oct 12. Epub 2018 Oct 12.

Department of Integrative Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.

The traditional Chinese medicine "Fuzi" (Aconiti Lateralis Radix Praeparata) and its three representative alkaloids, aconitine (AC), benzoylaconine (BAC), and aconine, have been shown to increase mitochondrial mass. Whether Fuzi has effect on mitochondrial biogenesis and the underlying mechanisms remain unclear. In the present study, we focused on the effect of BAC on mitochondrial biogenesis and the underlying mechanisms. Read More

Acta Pharmacol Sin 2018 Oct 12. Epub 2018 Oct 12.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Department of Pathophysiology, Nanjing Medical University, Nanjing, 211166, China.

Tamoxifen (TMX) is an antiestrogen drug that is used in the treatment and prevention of all stages of estrogen-dependent breast cancer. Adverse effects of TMX include hepatotoxicity. In this study, we investigated the therapeutic effects of osthole, isolated from medicinal plants especially Fructus Cnidii, on TMX-induced acute liver injury in mice. Read More

Acta Pharmacol Sin 2018 Oct 12. Epub 2018 Oct 12.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences; Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, 215123, China.

Increasing evidence suggests that Ras-related in brain 7 (Rab7), an endosome-localized small GTPase contributes to cerebral ischemic brain injury. In the present study, we investigated the role of Rab7 in ischemic stroke-induced formation of astrogliosis and glial scar. Rats were subjected to transient middle cerebral artery occlusion (tMCAO); the rats were injected with the Rab7 receptor antagonist CID1067700 (CID). Read More

Acta Pharmacol Sin 2018 Oct 12. Epub 2018 Oct 12.

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

Autophagy, a form of cellular self-digestion by lysosome, is associated with various disease processes including cancers, and modulating autophagy has shown promise in the treatment of various malignancies. A number of natural products display strong antitumor activity, yet their mechanisms of action remain unclear. To gain a better understanding of how traditional Chinese medicine agents exert antitumor effects, we screened 480 natural compounds for their effects on autophagy using a high content screening assay detecting GFP-LC3 puncta in HeLa cells. Read More

Acta Pharmacol Sin 2018 Oct 12. Epub 2018 Oct 12.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a critical role in controlling pacemaker activity in both heart and nervous system. Developing HCN channel inhibitors has been proposed to be an important strategy for the treatment of pain, heart failure, arrhythmias, and epilepsy. One HCN channel inhibitor, ivabradine, has been clinically approved for the treatment of angina pectoris and heart failure. Read More

Acta Pharmacol Sin 2018 Dec 8;39(12):1894-1901. Epub 2018 Oct 8.

Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

Although the treatment of adult T-cell acute lymphoblastic leukemia (T-ALL) has been significantly improved, the heterogeneous genetic landscape of the disease often causes relapse. Aberrant activation of mammalian target of rapamycin (mTOR) pathway in T-ALL is responsible for treatment failure and relapse, suggesting that mTOR inhibition may represents a new therapeutic strategy. In this study, we investigated whether the mTOR complex 1 (mTORC1) inhibitor everolimus could be used as a therapeutic agent against human T-ALL. Read More

Acta Pharmacol Sin 2018 Oct 10;39(10):1661-1669. Epub 2018 May 10.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 100050.

NF-E2-related factor 2 (Nrf2) is a transcription factor and a pivotal factor in the induction of the cell defense system. Recent reports show that Nrf2 plays critical roles in tumor heterogeneity and drug resistance. In the present study we investigated whether and how Nrf2 mediated the resistance of human cancer cells to boningmycin (BON), a new antitumor antibiotic of the bleomycin family. Read More

Acta Pharmacol Sin 2018 Nov;39(11):1706-1715

Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Berberine is a natural medicine with multiple beneficial biological activities. In this study, we explored the mechanisms underlying the neuroprotective action of berberine in mice subjected transient middle cerebral artery occlusion (tMCAO). Read More

Acta Pharmacol Sin 2019 Jan 27;40(1):13-25. Epub 2018 Sep 27.

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.

Ginsenoside Rg1 (Rg1), a saponin extracted from Panax ginseng, has been well documented to be effective against ischemic/reperfusion (I/R) neuronal injury. However, the underlying mechanisms remain obscure. In the present study, we investigated the roles of Nrf2 and miR-144 in the protective effects of Rg1 against I/R-induced neuronal injury. Read More