Human pharmacology of positive GABA-A subtype-selective receptor modulators for the treatment of anxiety.
Abstract 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 anx...
Source: Acta Pharmacologica Sinica - December 5, 2018 Category: Drugs & Pharmacology Authors: Chen X, van Gerven J, Cohen A, Jacobs G Tags: Acta Pharmacol Sin Source Type: research

Human pharmacology of positive GABA-A subtype-selective receptor modulators for the treatment of anxiety
Human pharmacology of positive GABA-A subtype-selective receptor modulators for the treatment of anxiety, Published online: 05 December 2018; doi:10.1038/s41401-018-0185-5Human pharmacology of positive GABA-A subtype-selective receptor modulators for the treatment of anxiety (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - December 5, 2018 Category: Drugs & Pharmacology Authors: Xia Chen Joop van Gerven Adam Cohen Gabriel Jacobs Source Type: research

Influences of an NR1I2 polymorphism on heterogeneous antiplatelet reactivity responses to clopidogrel and clinical outcomes in acute ischemic stroke patients.
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. The selected SNPs were genotyped, and platelet function was measured. Modified Rankin Scale (mRS) scores and main adverse cardiovascular and cerebrovascular events (MACCE) were noted to assess the prognosis. We showed...
Source: Acta Pharmacologica Sinica - November 28, 2018 Category: Drugs & Pharmacology Authors: Chen YB, Zhou ZY, Li GM, Xiao CX, Yu WB, Zhong SL, Cai YF, Jin J, Huang M Tags: Acta Pharmacol Sin Source Type: research

C11, a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis.
Abstract 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 IC50 of 19 nM among a panel of 20 tyrosine kinases. C11 inhibited cell proliferation in various tumors, particularly bladder cancer and breast cancer. C11 also inhibited breast cancer MDA-MB-231 cell migration and invasion via suppression of FGFR1 phosphorylation and its downst...
Source: Acta Pharmacologica Sinica - November 28, 2018 Category: Drugs & Pharmacology Authors: Chen Z, Tong LJ, Tang BY, Liu HY, Wang X, Zhang T, Cao XW, Chen Y, Li HL, Qian XH, Xu YF, Xie H, Ding J Tags: Acta Pharmacol Sin Source Type: research

State-of-the-art: functional fluorescent probes for bioimaging and pharmacological research.
Abstract 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. Much attention now focuses on the real-time visualization of molecular disease events to yield new insights to the pathogenesis of the diseases. This review focuses on recent advances in the development of...
Source: Acta Pharmacologica Sinica - November 28, 2018 Category: Drugs & Pharmacology Authors: Lu L, Wu ZY, Li X, Han F Tags: Acta Pharmacol Sin Source Type: research

C11, a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis
C11, a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis, Published online: 28 November 2018; doi:10.1038/s41401-018-0191-7C11, a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor, suppresses breast cancer metastasis and angiogenesis (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - November 28, 2018 Category: Drugs & Pharmacology Authors: Zhuo Chen Lin-jiang Tong Bai-you Tang Hong-yan Liu Xin Wang Tao Zhang Xian-wen Cao Yi Chen Hong-lin Li Xu-hong Qian Yu-fang Xu Hua Xie Jian Ding Source Type: research

State-of-the-art: functional fluorescent probes for bioimaging and pharmacological research
State-of-the-art: functional fluorescent probes for bioimaging and pharmacological research, Published online: 28 November 2018; doi:10.1038/s41401-018-0190-8State-of-the-art: functional fluorescent probes for bioimaging and pharmacological research (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - November 28, 2018 Category: Drugs & Pharmacology Authors: Lu Lu Zhou-yue Wu Xin Li Feng Han Source Type: research

Influences of an NR1I2 polymorphism on heterogeneous antiplatelet reactivity responses to clopidogrel and clinical outcomes in acute ischemic stroke patients
Influences of an NR1I2 polymorphism on heterogeneous antiplatelet reactivity responses to clopidogrel and clinical outcomes in acute ischemic stroke patients, Published online: 28 November 2018; doi:10.1038/s41401-018-0178-4Influences of an NR1I2 polymorphism on heterogeneous antiplatelet reactivity responses to clopidogrel and clinical outcomes in acute ischemic stroke patients (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - November 28, 2018 Category: Drugs & Pharmacology Authors: Yi-bei Chen Zi-yi Zhou Guo-min Li Can-xing Xiao Wei-bang Yu Shi-long Zhong Ye-feng Cai Jing Jin Min Huang Source Type: research

Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment.
Abstract 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. We hypothesize that Vitamin D3 ameliorates UFs by recovering the damaged DNA repair system, thus inhibits tumor progression. We compared the DNA damage status and Vitamin D receptor (VDR) expression between normal myometrial and UF primary cells. Unrepaired DNA double-strand breaks (DS...
Source: Acta Pharmacologica Sinica - November 26, 2018 Category: Drugs & Pharmacology Authors: Ali M, Shahin SM, Sabri NA, Al-Hendy A, Yang Q Tags: Acta Pharmacol Sin Source Type: research

Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment
Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment, Published online: 26 November 2018; doi:10.1038/s41401-018-0184-6Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - November 26, 2018 Category: Drugs & Pharmacology Authors: Mohamed Ali Sara Mahmoud Shahin Nagwa Ali Sabri Ayman Al-Hendy Qiwei Yang Source Type: research

THZ1 suppresses human non-small-cell lung cancer cells in vitro through interference with cancer metabolism.
In this study we elucidated the anticancer mechanism of THZ1 in human non-small-cell lung cancer (NSCLC) cells. We showed that treatment with THZ1 (10-1000 nM) dose-dependently suppressed the proliferation of human NSCLC cell lines H1299, A549, H292, and H23, and markedly inhibited the migration of these NSCLC cells. Furthermore, treatment with THZ1 (50 nM) arrested cell cycle at G2/M phase and induced apoptosis in these NSCLC cell lines. More importantly, we revealed that treatment with THZ1 (50 nM) blocked the glycolysis pathway but had no effect on glutamine metabolism. We further demonstrated that THZ1 treatment...
Source: Acta Pharmacologica Sinica - November 16, 2018 Category: Drugs & Pharmacology Authors: Cheng ZJ, Miao DL, Su QY, Tang XL, Wang XL, Deng LB, Shi HD, Xin HB Tags: Acta Pharmacol Sin Source Type: research

Endothelial cell-specific anticoagulation reduces inflammation in a mouse model of acute lung injury.
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. The expression of TF and PARs on the EC in lungs was upregulated after ALI. In the two strains of transgenic mice, expression ...
Source: Acta Pharmacologica Sinica - November 16, 2018 Category: Drugs & Pharmacology Authors: Lou J, Hu Y, Wu MD, Che LQ, Wu YF, Zhao Y, Tian BP, Bao ZQ, Zhu C, Wu YP, He LL, Bai CX, Zhou J, Ying SM, Li W, Chen ZH, Chen DX, Dorling A, Shen HH Tags: Acta Pharmacol Sin Source Type: research

Paeoniflorin-6'-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF- κB signaling: comparison with biological agents.
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. In CIA mice, we found that T cells and B cells exhibited abnormal proliferation; the percentages of CD19+ total B cells, CD19+CD27+-activated B cells, CD19+BAFFR+ and CD19+TACI+ cells were significantly increased in PBMCs and spleen lymphocytes. CP-25 suppressed the indicators of arthritis, alleviated histopathology, accompani...
Source: Acta Pharmacologica Sinica - November 16, 2018 Category: Drugs & Pharmacology Authors: Shu JL, Zhang XZ, Han L, Zhang F, Wu YJ, Tang XY, Wang C, Tai Y, Wang QT, Chen JY, Chang Y, Wu HX, Zhang LL, Wei W Tags: Acta Pharmacol Sin Source Type: research

Platelet microparticles contribute to aortic vascular endothelial injury in diabetes via the mTORC1 pathway.
Abstract 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. PMP levels in the circulation and aorta tissues were time-dependently increased in streptozotocin-induced diabetic rats at weeks 4, 8, and 12 (P 
Source: Acta Pharmacologica Sinica - November 16, 2018 Category: Drugs & Pharmacology Authors: Wang GH, Ma KL, Zhang Y, Hu ZB, Liu L, Lu J, Chen PP, Lu CC, Ruan XZ, Liu BC Tags: Acta Pharmacol Sin Source Type: research

Platelet microparticles contribute to aortic vascular endothelial injury in diabetes via the mTORC1 pathway
Platelet microparticles contribute to aortic vascular endothelial injury in diabetes via the mTORC1 pathway, Published online: 16 November 2018; doi:10.1038/s41401-018-0186-4Platelet microparticles contribute to aortic vascular endothelial injury in diabetes via the mTORC1 pathway (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - November 16, 2018 Category: Drugs & Pharmacology Authors: Gui-hua Wang Kun-ling Ma Yang Zhang Ze-bo Hu Liang Liu Jian Lu Pei-pei Chen Chen-chen Lu Xiong-zhong Ruan Bi-cheng Liu Source Type: research

Paeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents
Paeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agentsPaeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents, Published online: 16 November 2018; doi:10.1038/s41401-018-0169-5Paeoniflorin-6′-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - November 16, 2018 Category: Drugs & Pharmacology Authors: Jin-ling Shu Xian-zheng Zhang Le Han Feng Zhang Yu-jing Wu Xiao-yu Tang Chen Wang Yu Tai Qing-tong Wang Jing-yu Chen Yan Chang Hua-xun Wu Ling-ling Zhang Wei Wei Source Type: research

Endothelial cell-specific anticoagulation reduces inflammation in a mouse model of acute lung injury
Endothelial cell-specific anticoagulation reduces inflammation in a mouse model of acute lung injury, Published online: 16 November 2018; doi:10.1038/s41401-018-0175-7Endothelial cell-specific anticoagulation reduces inflammation in a mouse model of acute lung injury (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - November 16, 2018 Category: Drugs & Pharmacology Authors: Jian Lou Yue Hu Min-dan Wu Luan-qing Che Yin-fang Wu Yun Zhao Bao-ping Tian Zheng-qiang Bao Chen Zhu Yan-ping Wu Lu-lu He Chun-xue Bai Jian Zhou Song-min Ying Wen Li Zhi-hua Chen Da-xin Chen Anthony Dorling Hua-hao Shen Source Type: research

THZ1 suppresses human non-small-cell lung cancer cells in vitro through interference with cancer metabolism
THZ1 suppresses human non-small-cell lung cancer cells in vitro through interference with cancer metabolism, Published online: 16 November 2018; doi:10.1038/s41401-018-0187-3THZ1 suppresses human non-small-cell lung cancer cells in vitro through interference with cancer metabolism (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - November 16, 2018 Category: Drugs & Pharmacology Authors: Zhu-Jun Cheng Du-Ling Miao Qiu-Yun Su Xiao-Li Tang Xiao-Lei Wang Li-Bin Deng Hui-Dong Shi Hong-Bo Xin Source Type: research

Different structures of berberine and five other protoberberine alkaloids that affect P-glycoprotein-mediated efflux capacity.
Abstract 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 ...
Source: Acta Pharmacologica Sinica - November 15, 2018 Category: Drugs & Pharmacology Authors: Zhang YT, Yu YQ, Yan XX, Wang WJ, Tian XT, Wang L, Zhu WL, Gong LK, Pan GY Tags: Acta Pharmacol Sin Source Type: research

Different structures of berberine and five other protoberberine alkaloids that affect P-glycoprotein-mediated efflux capacity
Different structures of berberine and five other protoberberine alkaloids that affect P-glycoprotein-mediated efflux capacity, Published online: 15 November 2018; doi:10.1038/s41401-018-0183-7Different structures of berberine and five other protoberberine alkaloids that affect P-glycoprotein-mediated efflux capacity (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - November 15, 2018 Category: Drugs & Pharmacology Authors: Yi-ting Zhang Yu-qi Yu Xiao-xia Yan Wen-jie Wang Xiao-ting Tian Le Wang Wei-liang Zhu Li-kun Gong Guo-yu Pan Source Type: research

Bevacizumab or fibronectin gene editing inhibits the osteoclastogenic effects of fibroblasts derived from human radicular cysts.
In this study we investigated the effects of EDA+FN 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. The specimens of radicular cysts were obtained from 20 patients. We showed that the vessel density was positively associated with both the lesion size (R = 0.49, P = 0.001) and EDA+FN staining (R = 0.26, P = 0.022) in the specimens. We isolated fibroblasts from surgical specimens, and used the CRISPR/Cas system to knockout the EDA exon, or ...
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Wang HC, Wang P, Chen YW, Zhang Y Tags: Acta Pharmacol Sin Source Type: research

Drug addiction: a curable mental disorder?
Abstract Drug addiction is a chronic, relapsing brain disorder. Multiple neural networks in the brain including the reward system (e.g., the mesocorticolimbic system), the anti-reward/stress system (e.g., the extended amygdala), and the central immune system, are involved in the development of drug addiction and relapse after withdrawal from drugs of abuse. Preclinical and clinical studies have demonstrated that it is promising to control drug addiction by pharmacologically targeting the addiction-related systems in the brain. Here we review the pharmacological targets within the dopamine system, glutamate system,...
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Liu JF, Li JX Tags: Acta Pharmacol Sin Source Type: research

Caspase-11 promotes renal fibrosis by stimulating IL-1 β maturation via activating caspase-1.
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). The mice were treated with either caspase-11 inhibitor wedelolactone (Wed, 30 mg/kg/day, ig) for 7 days or caspase-11 siRNA (10 nmol/20 g body weight per day, iv) for 14 days. The mice were euthanized on day 14, their renal tissue and blood sample were collected. We found that the obstructed kidney had significantly higher caspase-11 levels and obvious tubular injury...
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Miao NJ, Xie HY, Xu D, Yin JY, Wang YZ, Wang B, Yin F, Zhou ZL, Cheng Q, Chen PP, Zhou L, Xue H, Zhang W, Wang XX, Liu J, Lu LM Tags: Acta Pharmacol Sin Source Type: research

µ-TRTX-Ca1a: a novel neurotoxin from Cyriopagopus albostriatus with analgesic effects.
µ-TRTX-Ca1a: a novel neurotoxin from Cyriopagopus albostriatus with analgesic effects. Acta Pharmacol Sin. 2018 Oct 31;: Authors: Zhang YX, Peng DZ, Zhang QF, Huang B, Yang QC, Tang DF, Chen MZ, Rong MQ, Liu ZH Abstract 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 0.01% of such spider toxins has been explored, and thus there is a great potential for discovery of novel VGSC modulators as useful p...
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Zhang YX, Peng DZ, Zhang QF, Huang B, Yang QC, Tang DF, Chen MZ, Rong MQ, Liu ZH Tags: Acta Pharmacol Sin Source Type: research

Metabolism and disposition of pyrotinib in healthy male volunteers: covalent binding with human plasma protein.
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 [14C]pyrotinib. At 240 h postdose, the mean cumulative excretion of the dose radioactivity was 92.6%, including 1.7% in urine and 90.9% in feces. In feces, oxidative metabolites were detected as major drug-related materials and the primary metabolic pathways were O-depicoline (M1), oxidation of pyrrolidine (M5), and oxidation of pyridine (M6-1, M6-2, M6-3, and M6-4). In plasma, the major circulating entities identified were pyrotinib, SHR150980 (M1), SHR151468 (M2), and SH...
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Meng J, Liu XY, Ma S, Zhang H, Yu SD, Zhang YF, Chen MX, Zhu XY, Liu Y, Yi L, Ding XL, Chen XY, Miao LY, Zhong DF Tags: Acta Pharmacol Sin Source Type: research

CZ-7, a new derivative of Claulansine F, ameliorates 2VO-induced vascular dementia in rats through a Nrf2-mediated antioxidant responses.
In conclusion, CZ-7 has therapeutic potential for VD by alleviating oxidative stress injury through Nrf2-mediated antioxidant responses. PMID: 30382185 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Liu DD, Yuan X, Chu SF, Chen C, Ren Q, Luo P, Lin MY, Wang SS, Zhu TB, Ai QD, Zang YD, Zhang DM, He X, Huang ZH, Sun HS, Feng ZP, Chen NH Tags: Acta Pharmacol Sin Source Type: research

CZ-7, a new derivative of Claulansine F, ameliorates 2VO-induced vascular dementia in rats through a Nrf2-mediated antioxidant responses
CZ-7, a new derivative of Claulansine F, ameliorates 2VO-induced vascular dementia in rats through a Nrf2-mediated antioxidant responses, Published online: 31 October 2018; doi:10.1038/s41401-018-0078-7CZ-7, a new derivative of Claulansine F, ameliorates 2VO-induced vascular dementia in rats through a Nrf2-mediated antioxidant responses (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Dan-dan Liu Xia Yuan Shi-feng Chu Chen Chen Qian Ren Piao Luo Mei-yu Lin Sha-sha Wang Tian-bi Zhu Qi-di Ai Ying-da Zang Dong-ming Zhang Xin He Zhi-hua Huang Hong-shuo Sun Zhong-ping Feng Nai-hong Chen Source Type: research

Caspase-11 promotes renal fibrosis by stimulating IL-1β maturation via activating caspase-1
Caspase-11 promotes renal fibrosis by stimulating IL-1β maturation via activating caspase-1Caspase-11 promotes renal fibrosis by stimulating IL-1β maturation via activating caspase-1, Published online: 31 October 2018; doi:10.1038/s41401-018-0177-5Caspase-11 promotes renal fibrosis by stimulating IL-1β maturation via activating caspase-1 (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Nai-jun Miao Hong-yan Xie Dan Xu Jian-yong Yin Yan-zhe Wang Bao Wang Fan Yin Zhuan-li Zhou Qian Cheng Pan-pan Chen Li Zhou Hong Xue Wei Zhang Xiao-xia Wang Jun Liu Li-min Lu Source Type: research

Drug addiction: a curable mental disorder?
Drug addiction: a curable mental disorder?, Published online: 31 October 2018; doi:10.1038/s41401-018-0180-xDrug addiction: a curable mental disorder? (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Jian-feng Liu Jun-xu Li Source Type: research

µ-TRTX-Ca1a: a novel neurotoxin from Cyriopagopus albostriatus with analgesic effects
µ-TRTX-Ca1a: a novel neurotoxin from Cyriopagopus albostriatus with analgesic effectsµ-TRTX-Ca1a: a novel neurotoxin from Cyriopagopus albostriatus with analgesic effects, Published online: 31 October 2018; doi:10.1038/s41401-018-0181-9µ-TRTX-Ca1a: a novel neurotoxin from Cyriopagopus albostriatus with analgesic effects (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Yun-xiao Zhang De-zheng Peng Qing-feng Zhang Biao Huang Qiu-chu Yang Dong-fang Tang Min-zhi Chen Ming-qiang Rong Zhong-hua Liu Source Type: research

Metabolism and disposition of pyrotinib in healthy male volunteers: covalent binding with human plasma protein
Metabolism and disposition of pyrotinib in healthy male volunteers: covalent binding with human plasma protein, Published online: 31 October 2018; doi:10.1038/s41401-018-0176-6Metabolism and disposition of pyrotinib in healthy male volunteers: covalent binding with human plasma protein (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Jian Meng Xiao-yun Liu Sheng Ma Hua Zhang Song-da Yu Yi-fan Zhang Mei-xia Chen Xiao-yu Zhu Yi Liu Ling Yi Xiao-liang Ding Xiao-yan Chen Li-yan Miao Da-fang Zhong Source Type: research

Bevacizumab or fibronectin gene editing inhibits the osteoclastogenic effects of fibroblasts derived from human radicular cysts
Bevacizumab or fibronectin gene editing inhibits the osteoclastogenic effects of fibroblasts derived from human radicular cysts, Published online: 31 October 2018; doi:10.1038/s41401-018-0172-xBevacizumab or fibronectin gene editing inhibits the osteoclastogenic effects of fibroblasts derived from human radicular cysts (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 31, 2018 Category: Drugs & Pharmacology Authors: Hai-Cheng Wang Peng Wang Yuan-wei Chen Yan Zhang Source Type: research

Gynura Rhizoma containing pyrrolizidine alkaloids induces the hepatic sinusoidal obstruction syndrome in mice via upregulating fibrosis-related factors.
Abstract 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. The model was established by intragastrical administration of Gynura Rhizoma extract, i.e., 1.0 g extract/kg per day (equal to 16.7 g crude drug/kg per day based on extraction rate...
Source: Acta Pharmacologica Sinica - October 26, 2018 Category: Drugs & Pharmacology Authors: Zhang F, Zhou Y, Yang X, Xiong AZ, Wang ZT, Yang L Tags: Acta Pharmacol Sin Source Type: research

Propofol decreases the excitability of cholinergic neurons in mouse basal forebrain via GABAA receptors.
Abstract Propofol is an intravenous anesthetic that can active γ-aminobutyric acid A (GABAA) 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. Previous studies suggest that propofol affects the sleep-wake circuit via the BF; however, the mechanism remains elusive. In the current study we investigated the effects of propofol on the inherent properties of cholinergic neurons and their ability to convert excitatory inputs...
Source: Acta Pharmacologica Sinica - October 26, 2018 Category: Drugs & Pharmacology Authors: Chen L, Yang ZL, Cheng J, Zhang PP, Zhang LS, Liu XS, Wang LC Tags: Acta Pharmacol Sin Source Type: research

Propofol decreases the excitability of cholinergic neurons in mouse basal forebrain via GABAA receptors
Propofol decreases the excitability of cholinergic neurons in mouse basal forebrain via GABAA receptors, Published online: 26 October 2018; doi:10.1038/s41401-018-0168-6Propofol decreases the excitability of cholinergic neurons in mouse basal forebrain via GABAA receptors (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 26, 2018 Category: Drugs & Pharmacology Authors: Lei Chen Zhi-lai Yang Juan Cheng Ping-ping Zhang Le-sha Zhang Xue-sheng Liu Lie-cheng Wang Source Type: research

Gynura Rhizoma containing pyrrolizidine alkaloids induces the hepatic sinusoidal obstruction syndrome in mice via upregulating fibrosis-related factors
Gynura Rhizoma containing pyrrolizidine alkaloids induces the hepatic sinusoidal obstruction syndrome in mice via upregulating fibrosis-related factors, Published online: 26 October 2018; doi:10.1038/s41401-018-0155-yGynura Rhizoma containing pyrrolizidine alkaloids induces the hepatic sinusoidal obstruction syndrome in mice via upregulating fibrosis-related factors (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 26, 2018 Category: Drugs & Pharmacology Authors: Fang Zhang Yue Zhou Xiao Yang Ai-zhen Xiong Zheng-tao Wang Li Yang Source Type: research

Translational potential of allosteric modulators targeting the cannabinoid CB1 receptor.
Abstract The cannabinoid type-1 (CB1) 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 CB1 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 CB1 orthosteric ligands into druggable candidates. The difficulty is mainly due to the adverse effects associated with orthosteric CB1 ligands. Recen...
Source: Acta Pharmacologica Sinica - October 17, 2018 Category: Drugs & Pharmacology Authors: Lu D, Immadi SS, Wu Z, Kendall DA Tags: Acta Pharmacol Sin Source Type: research

Oblongifolin C suppresses lysosomal function independently of TFEB nuclear translocation.
Abstract 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. In the present study, we investigated the effect of OC on transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, lys...
Source: Acta Pharmacologica Sinica - October 17, 2018 Category: Drugs & Pharmacology Authors: Wu M, Lao YZ, Tan HS, Lu G, Ren Y, Zheng ZQ, Yi J, Fu WW, Shen HM, Xu HX Tags: Acta Pharmacol Sin Source Type: research

Pharmacological characterization of JWX-A0108 as a novel type I positive allosteric modulator of α7 nAChR that can reverse acoustic gating deficits in a mouse prepulse inhibition model.
Pharmacological characterization of JWX-A0108 as a novel type I positive allosteric modulator of α7 nAChR that can reverse acoustic gating deficits in a mouse prepulse inhibition model. Acta Pharmacol Sin. 2018 Oct 17;: Authors: Sun LL, Yang TY, Wei NN, Lu W, Jiao WX, Zhou QQ, Miao YZ, Gao Q, Wang XT, Sun Q, Wang K Abstract The α7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated Ca2+-permeable homopentameric ion channel implicated in cognition and neuropsychiatric disorders. Pharmacological enhancement of α7 nAChR function has been suggested for improvement of cogn...
Source: Acta Pharmacologica Sinica - October 17, 2018 Category: Drugs & Pharmacology Authors: Sun LL, Yang TY, Wei NN, Lu W, Jiao WX, Zhou QQ, Miao YZ, Gao Q, Wang XT, Sun Q, Wang K Tags: Acta Pharmacol Sin Source Type: research

Translational potential of allosteric modulators targeting the cannabinoid CB1 receptor
Translational potential of allosteric modulators targeting the cannabinoid CB1 receptor, Published online: 17 October 2018; doi:10.1038/s41401-018-0164-xTranslational potential of allosteric modulators targeting the cannabinoid CB1 receptor (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 17, 2018 Category: Drugs & Pharmacology Authors: Dai Lu Sri Sujana Immadi Zhixing Wu Debra A. Kendall Source Type: research

Oblongifolin C suppresses lysosomal function independently of TFEB nuclear translocation
Oblongifolin C suppresses lysosomal function independently of TFEB nuclear translocation, Published online: 17 October 2018; doi:10.1038/s41401-018-0167-7Oblongifolin C suppresses lysosomal function independently of TFEB nuclear translocation (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 17, 2018 Category: Drugs & Pharmacology Authors: Man Wu Yuan-zhi Lao Hong-sheng Tan Guang Lu Yi Ren Zhao-qing Zheng Juan Yi Wen-wei Fu Han-ming Shen Hong-xi Xu Source Type: research

Pharmacological characterization of JWX-A0108 as a novel type I positive allosteric modulator of α7 nAChR that can reverse acoustic gating deficits in a mouse prepulse inhibition model
Pharmacological characterization of JWX-A0108 as a novel type I positive allosteric modulator of α7 nAChR that can reverse acoustic gating deficits in a mouse prepulse inhibition modelPharmacological characterization of JWX-A0108 as a novel type I positive allosteric modulator of α7 nAChR that can reverse acoustic gating deficits in a mouse prepulse inhibition model, Published online: 17 October 2018; doi:10.1038/s41401-018-0163-yPharmacological characterization of JWX-A0108 as a novel type I positive allosteric modulator of α7 nAChR that can reverse acoustic gating deficits in a mouse prepulse inhibition...
Source: Acta Pharmacologica Sinica - October 17, 2018 Category: Drugs & Pharmacology Authors: Li-lan Sun Tao-yi Yang Ning-ning Wei Wei Lu Wen-xuan Jiao Qi-qi Zhou Yong-zhen Miao Qin Gao Xin-tong Wang Qi Sun KeWei Wang Source Type: research

Multiple circulating saponins from intravenous ShenMai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions.
Abstract 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 She...
Source: Acta Pharmacologica Sinica - October 16, 2018 Category: Drugs & Pharmacology Authors: Olaleye OE, Niu W, Du FF, Wang FQ, Xu F, Pintusophon S, Lu JL, Yang JL, Li C Tags: Acta Pharmacol Sin Source Type: research

Population-based volume kinetics of Ringer's lactate solution in patients undergoing open gastrectomy.
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. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. The change in hem...
Source: Acta Pharmacologica Sinica - October 16, 2018 Category: Drugs & Pharmacology Authors: Lee JH, Choo YJ, Lee YH, Rhim JH, Lee SH, Choi BM, Oh ST, Choi KT, Noh GJ Tags: Acta Pharmacol Sin Source Type: research

Population-based volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomy
Population-based volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomyPopulation-based volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomy, Published online: 16 October 2018; doi:10.1038/s41401-018-0179-3Population-based volume kinetics of Ringer’s lactate solution in patients undergoing open gastrectomy (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 16, 2018 Category: Drugs & Pharmacology Authors: Joo-Hyun Lee Yeong-Jin Choo Yong-Hun Lee Jin-Ho Rhim Soo-Han Lee Byung-Moon Choi Sung-Tae Oh Kyu-Taek Choi Gyu-Jeong Noh Source Type: research

Multiple circulating saponins from intravenous ShenMai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions
Multiple circulating saponins from intravenous ShenMai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions, Published online: 16 October 2018; doi:10.1038/s41401-018-0173-9Multiple circulating saponins from intravenous ShenMai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - October 16, 2018 Category: Drugs & Pharmacology Authors: Olajide E. Olaleye Wei Niu Fei-fei Du Feng-qing Wang Fang Xu Salisa Pintusophon Jun-lan Lu Jun-ling Yang Chuan Li Source Type: research

Identification and characterization of a series of novel HCN channel inhibitors.
In this study, we designed and synthesized eight alkanol amine derivatives, and assessed their effects on HCN channels expressed in COS7 cells using a whole-cell patch clamp method. Among them, compound 4e displayed the most potent inhibitory activity with an IC50 of 2.9 ± 1.2 µM at - 120 mV on HCN2 channel expressed in COS7 cells. Further analysis revealed that application of compound 4e (10 μM) caused a slowing of activation and a hyperpolarizing shift (ΔV1/2 = - 30.2 ± 2.9 mV, n = 5) in the volt...
Source: Acta Pharmacologica Sinica - October 12, 2018 Category: Drugs & Pharmacology Authors: Chen SJ, Xu Y, Liang YM, Cao Y, Lv JY, Pang JX, Zhou PZ Tags: Acta Pharmacol Sin Source Type: research

Tubeimoside-1, a triterpenoid saponin, induces cytoprotective autophagy in human breast cancer cells in vitro via Akt-mediated pathway.
Abstract 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. Tubeimoside-1 (TBMS1), a triterpenoid saponin extract...
Source: Acta Pharmacologica Sinica - October 12, 2018 Category: Drugs & Pharmacology Authors: Jiang SL, Guan YD, Chen XS, Ge P, Wang XL, Lao YZ, Xiao SS, Zhang Y, Yang JM, Xu XJ, Cao DS, Cheng Y Tags: Acta Pharmacol Sin Source Type: research

CID1067700, a late endosome GTPase Rab7 receptor antagonist, attenuates brain atrophy, improves neurologic deficits and inhibits reactive astrogliosis in rat ischemic stroke.
Abstract 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). Primary astrocytes were subjected to an oxygen and glucose deprivation and reoxygenation (OGD/Re) procedure; CID was added to the cell culture media. We found that Rab7 was significantly elev...
Source: Acta Pharmacologica Sinica - October 12, 2018 Category: Drugs & Pharmacology Authors: Qin Y, He Y, Zhu YM, Li M, Ni Y, Liu J, Zhang HL Tags: Acta Pharmacol Sin Source Type: research

Osthole prevents tamoxifen-induced liver injury in mice.
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. Mice were injected with osthole (100 mg/kg, ip) or vehicle, followed by TMX (90 mg/kg, ip) 24 h later. We showed that a single injection of TMX-induced liver injury and oxidative stress. Pretreatment with osthole attenuated TMX-induced liver injury evidenced by dose-dependent reduction of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Pretreatment with osthole also blunted TMX-induced oxidative stre...
Source: Acta Pharmacologica Sinica - October 12, 2018 Category: Drugs & Pharmacology Authors: Zhou WB, Zhang XX, Cai Y, Sun W, Li H Tags: Acta Pharmacol Sin Source Type: research