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Acta Pharmacologica Sinica

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https://www.readbyqxmd.com/read/28239160/insights-into-the-molecular-mechanisms-of-polygonum-multiflorum-thunb-induced-liver-injury-a-computational-systems-toxicology-approach
#1
Yin-Yin Wang, Jie Li, Zeng-Rui Wu, Bo Zhang, Hong-Bin Yang, Qin Wang, Ying-Chun Cai, Gui-Xia Liu, Wei-Hua Li, Yun Tang
An increasing number of cases of herb-induced liver injury (HILI) have been reported, presenting new clinical challenges. In this study, taking Polygonum multiflorum Thunb (PmT) as an example, we proposed a computational systems toxicology approach to explore the molecular mechanisms of HILI. First, the chemical components of PmT were extracted from 3 main TCM databases as well as the literature related to natural products. Then, the known targets were collected through data integration, and the potential compound-target interactions (CTIs) were predicted using our substructure-drug-target network-based inference (SDTNBI) method...
February 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28239159/sarsasapogenin-aa13-inhibits-lps-induced-inflammatory-responses-in-macrophage-cells-in-vitro-and-relieves-dimethylbenzene-induced-ear-edema-in-mice
#2
Dong Dong, Nan-Nan Zhou, Rui-Xuan Liu, Jia-Wei Xiong, Hui Pan, Si-Qi Sun, Lei Ma, Rui Wang
Sarsasapogenin-AA13 (AA13) is a novel synthetic derivative of sarsasapogenin extracted from the Chinese herb Rhizoma Anemarrhenae. In this study we investigated the effects of AA13 on lipopolysaccharide (LPS)-induced production of inflammatory factors in macrophage cells and the anti-inflammatory activity of AA13 in an inflammatory model of dimethylbenzene-induced ear edema. Macrophage cells (RAW264.7 cells and mouse peritoneal macrophages) were exposed to LPS (1 μg/mL); pretreatment with AA13 (5-20 μmol/L) dose-dependently inhibited LPS-induced production of NO, TNF-α and PGE2, and LPS-stimulated expression levels of COX-2 and iNOS...
February 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28239158/synthesis-of-the-novel-parp-1-inhibitor-ag-690-11026014-and-its-protective-effects-on-angiotensin-ii-induced-mouse-cardiac-remodeling
#3
Guo-Shuai Feng, Cui-Ge Zhu, Zhuo-Ming Li, Pan-Xia Wang, Yi Huang, Min Liu, Ping He, Lan-Lan Lou, Shao-Rui Chen, Pei-Qing Liu
We previously identified AG-690/11026014 (6014) as a novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor that effectively prevented angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. In the present study, we reported a new synthesis route for 6014, and investigated its protective effects on Ang II-induced cardiac remodeling and cardiac dysfunction and the underlying mechanisms in mice. We designed a new synthesis route to obtain a sufficient quantity of 6014 for this in vivo study. C57BL/6J mice were infused with Ang II and treated with 6014 (10, 30, 90 mg·kg(-1)·d(-1), ig) for 4 weeks...
February 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216625/endothelial-overexpression-of-endothelin-1-modulates-aortic-carotid-iliac-and-renal-arterial-responses-in-obese-mice
#4
Oliver Baretella, Sookja K Chung, Aimin Xu, Paul M Vanhoutte
Endothelin-1 (ET-1) is essential for mammalian development and life, but it has also been implicated in increased cardiovascular risk under pathophysiological conditions. The aim of this study was to determine the impact of endothelial overexpression of the prepro-endothelin-1 gene on endothelium-dependent and endothelium-independent responses in the conduit and renal arteries of lean and obese mice. Obesity was induced by high-fat-diet (HFD) consumption in mice with Tie-1 promoter-driven, endothelium-specific overexpression of the prepro-endothelin-1 gene (TET(het)) and in wild-type (WT) littermates on a C57BL/6N background...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216624/dual-targeted-hybrid-nanoparticles-of-synergistic-drugs-for-treating-lung-metastases-of-triple-negative-breast-cancer-in-mice
#5
Tian Zhang, Preethy Prasad, Ping Cai, Chunsheng He, Dan Shan, Andrew Michael Rauth, Xiao Yu Wu
Lung metastasis is the major cause of death in patients with triple negative breast cancer (TNBC), an aggressive subtype of breast cancer with no effective therapy at present. It has been proposed that dual-targeted therapy, ie, targeting chemotherapeutic agents to both tumor vasculature and cancer cells, may offer some advantages. The present work was aimed to develop a dual-targeted synergistic drug combination nanomedicine for the treatment of lung metastases of TNBC. Thus, Arg-Gly-Asp peptide (RGD)-conjugated, doxorubicin (DOX) and mitomycin C (MMC) co-loaded polymer-lipid hybrid nanoparticles (RGD-DMPLN) were prepared and characterized...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216623/development-of-a-novel-individualized-warfarin-dose-algorithm-based-on-a-population-pharmacokinetic-model-with-improved-prediction-accuracy-for-chinese-patients-after-heart-valve-replacement
#6
Yu-Bin Zhu, Xian-Hua Hong, Meng Wei, Jing Hu, Xin Chen, Shu-Kui Wang, Jun-Rong Zhu, Feng Yu, Jian-Guo Sun
The gene-guided dosing strategy of warfarin generally leads to over-dose in patients at doses lower than 2 mg/kg, and only 50% of individual variability in daily stable doses can be explained. In this study, we developed a novel population pharmacokinetic (PK) model based on a warfarin dose algorithm for Han Chinese patients with valve replacement for improving the dose prediction accuracy, especially in patients with low doses. The individual pharmacokinetic (PK) parameter - apparent clearance of S- and R-warfarin (CLs) was obtained after establishing and validating the population PK model from 296 recruited patients with valve replacement...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216622/effects-of-gene-polymorphisms-in-the-endoplasmic-reticulum-stress-pathway-on-clinical-outcomes-of-chemoradiotherapy-in-chinese-patients-with-nasopharyngeal-carcinoma
#7
Xiao-Bin Guo, Wan-le Ma, Li-Juan Liu, Yu-Ling Huang, Jing Wang, Li-Hua Huang, Xiang-Dong Peng, Ji-Ye Yin, Jin-Gao Li, Shao-Jun Chen, Guo-Ping Yang, Hui Wang, Cheng-Xian Guo
There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216621/dual-anti-ischemic-effects-of-rosmarinic-acid-n-butyl-ester-via-alleviation-of-dapk-p53-mediated-neuronal-damage-and-microglial-inflammation
#8
Lei Wu, Hong-Min Wang, Jin-Long Li, Hong-Xuan Feng, Wei-Min Zhao, Hai-Yan Zhang
The discovery of efficacious anti-ischemic drugs remains a challenge. Recently we have found that rosmarinic acid n-butyl ester (RABE), a derivative of rosmarinic acid, significantly protects SH-SY5Y cells against oxygen glucose deprivation (OGD)-induced cell death. In the present study we simultaneously investigated the effects of RABE on the two key players in the pathophysiology of cerebral ischemia, ischemic neuronal damage and microglial inflammation. Pretreatment with RABE (1, 10 μmol/L) dose-dependently attenuated OGD- or H2O2-induced reduction of the viability of SH-SY5Y neuroblastoma cells...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216620/aspirin-alleviates-cardiac-fibrosis-in-mice-by-inhibiting-autophagy
#9
Ping-Ping Liu, Hong-Hong Liu, Shu-Hong Sun, Xing-Xing Shi, Wan-Cheng Yang, Guo-Hai Su, Jing Zhao
Aspirin (ASA) is a cardioprotective drug with anti-cardiac fibrosis action in vivo. This study was aimed to clarify the anti-cardiac fibrosis action of ASA and the underlying mechanisms. Two heart injury models (injection of isoproterenol and ligation of the left anterior descending branch) were used in mice to induce cardiac fibrosis. The animals were treated with ASA (10 mg·kg(-1)·d(-1), ig) for 21 and 14 d, respectively. ASA administration significantly improved cardiac function, and ameliorated heart damage and fibrosis in the mice...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216619/15-deoxy-%C3%AE-12-14-prostaglandin-j2-alleviates-hepatic-ischemia-reperfusion-injury-in-mice-via-inducing-antioxidant-response-and-inhibiting-apoptosis-and-autophagy
#10
Kan Chen, Jing-Jing Li, Sai-Nan Li, Jiao Feng, Tong Liu, Fan Wang, Wei-Qi Dai, Yu-Jing Xia, Jie Lu, Ying-Qun Zhou, Chuan-Yong Guo
Hepatic ischemia-reperfusion (I/R) injury is a common clinical impairment that occurs in many circumstances and leads to poor prognosis. Both apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. 15-Deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) is one of the best-studied anti-inflammatory prostaglandins, which has been verified to exert anti-inflammatory and cell-protective functions in various types of cells and animal models. In this study we explored the effects of 15d-PGJ2 on both apoptosis and autophagy in mouse hepatic I/R injury and its possible mechanisms...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216618/1-2-5-6-dianhydrogalactitol-inhibits-human-glioma-cell-growth-in-vivo-and-in-vitro-by-arresting-the-cell-cycle-at-g2-m-phase
#11
Chun Peng, Xin-Ming Qi, Ling-Ling Miao, Jin Ren
1,2:5,6-dianhydrogalactitol (DAG) is a hexitol epoxide with marked antitumor activity against multiple types of cancer cells, but the molecular mechanisms by which DAG functions as an antitumor agent is largely unknown. In this study, we investigated the inhibitory effects of DAG on human glioma cell growth in vitro and in vivo and uncovered the underlying molecular mechanisms. Treatment with DAG (120 μmol/L) dose-dependently inhibited the proliferation and colony formation in human glioma cell lines LN229, U251, and U87MG in vitro...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28112185/lyrm03-an-ubenimex-derivative-attenuates-lps-induced-acute-lung-injury-in-mice-by-suppressing-the-tlr-4-signaling-pathway
#12
Hui-Qiong He, Ya-Xian Wu, Yun-Juan Nie, Jun Wang, Mei Ge, Feng Qian
Toll-like receptor 4 (TLR4)-mediated signaling plays a critical role in sepsis-induced acute lung injury (ALI). LYRM03 (3-amino-2-hydroxy-4-phenyl-valyl-isoleucine) is a novel derivative of ubenimex, a widely used antineoplastic medicine. We previously found that LYRM03 has anti-inflammatory effects in cecal ligation puncture mouse model. In this study we determined whether LYRM03 attenuated LPS-induced ALI in mice. LPS-induced ALI mouse model was established by challenging the mice with intratracheal injection of LPS (5 mg/kg), which was subsequently treated with LYRM03 (10 mg/kg, ip)...
January 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28112184/marine-derive-chromopeptide-a-a-novel-class-i-hdac-inhibitor-suppresses-human-prostate-cancer-cell-proliferation-and-migration
#13
Jing-Ya Sun, Ji-Dong Wang, Xin Wang, Hong-Chun Liu, Min-Min Zhang, Yu-Chih Liu, Chen-Hua Zhang, Yi Su, Yan-Yan Shen, Yue-Wei Guo, Ai-Jun Shen, Mei-Yu Geng
Histone deacetylases (HDACs), especially HDAC1, 2, 3 and 4, are abundantly expressed and over-activated in prostate cancer that is correlated with the poor prognosis. Thus, inhibition of HDAC activity has emerged as a potential alternative option for prostate cancer therapy. Chromopeptide A is a depsipeptide isolated from the marine sediment-derived bacterium Chromobacterium sp. HS-13-94; it has a chemical structure highly similar to FK228, a class I HDAC inhibitor that is approved by FDA for treating T-cell lymphoma...
January 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28112183/soluplus-micelles-for-improving-the-oral-bioavailability-of-scopoletin-and-their-hypouricemic-effect-in-vivo
#14
Ying-Chun Zeng, Sha Li, Chang Liu, Tao Gong, Xun Sun, Yao Fu, Zhi-Rong Zhang
Scopoletin is an active coumarin possessing a variety of pharmacological activities, including anti-hyperuricemic effect, but with poor solubility. To improve its oral bioavailability, we attempted to encapsulate scopoletin into Soluplus micelles (Soluplus-based scopoletin micelles, Sco-Ms) and evaluated the hypouricemic action of Sco-Ms. Sco-Ms were prepared using a thin-film hydration method. Sco-Ms displayed near spherical shapes with an average size of 59.4±2.4 nm (PDI=0.08±0.02). The encapsulation efficiency of scopoletin was 87...
January 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28112182/hippocampal-cyslt1r-knockdown-or-blockade-represses-lps-induced-depressive-behaviors-and-neuroinflammatory-response-in-mice
#15
Jing-Ran Lin, Shun-Chang Fang, Su-Su Tang, Mei Hu, Yan Long, Arijit Ghosh, Hong-Bin Sun, Ling-Yi Kong, Hao Hong
Evidence suggests that neuroinflammation is involved in depression and that the cysteinyl leukotriene receptor 1 (CysLT1R) plays a potential pathophysiological role in several types of CNS disorders. Our previous study has shown that knockdown of hippocampal CysLT1R in mice prevents the depressive-like phenotype and neuroinflammation induced by chronic mild stress (CMS). Here, we examined the effects of hippocampal CysLT1R knockdown and CysLT1R blockade on LPS-induced depressive-like behavior in mice. We found that injection of LPS (0...
January 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28112181/il-3-and-ctla4-gene-polymorphisms-may-influence-the-tacrolimus-dose-requirement-in-chinese-kidney-transplant-recipients
#16
Mou-Ze Liu, Hai-Yan He, Yue-Li Zhang, Yong-Fang Hu, Fa-Zhong He, Jian-Quan Luo, Zhi-Ying Luo, Xiao-Ping Chen, Zhao-Qian Liu, Hong-Hao Zhou, Ming-Jie Shao, Ying-Zi Ming, Hua-Wen Xin, Wei Zhang
The highly variable pharmacokinetics and narrow therapeutic window of tacrolimus (TAC) has hampered its clinical use. Genetic polymorphisms may contribute to the variable response, but the evidence is not compelling, and the explanation is unclear. In this study we attempted to find previously unknown genetic factors that may influence the TAC dose requirements. The association of 105 pathway-related single nucleotide polymorphisms (SNPs) with TAC dose-adjusted concentrations (C0/D) was examined at 7, 30 and 90 d post-operation in 382 Chinese kidney transplant recipients...
January 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28112180/lowering-serum-lipids-via-pcsk9-targeting-drugs-current-advances-and-future-perspectives
#17
REVIEW
Ni-Ya He, Qing Li, Chun-Yan Wu, Zhong Ren, Ya Gao, Li-Hong Pan, Mei-Mei Wang, Hong-Yan Wen, Zhi-Sheng Jiang, Zhi-Han Tang, Lu-Shan Liu
Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as neural apoptosis regulated convertase (NARC1), is a key modulator of cholesterol metabolism. PCSK9 increases the serum concentration of low-density lipoprotein cholesterol by escorting low-density lipoprotein receptors (LDLRs) from the membrane of hepatic cells into lysosomes, where the LDLRs are degraded. Owing to the importance of PCSK9 in lipid metabolism, considerable effort has been made over the past decade in developing drugs targeting PCSK9 to lower serum lipid levels...
January 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28112179/dicer1-mir-29-hmgcr-axis-contributes-to-hepatic-free-cholesterol-accumulation-in-mouse-non-alcoholic-steatohepatitis
#18
Ming-Xia Liu, Man Gao, Chun-Zhu Li, Cun-Zhi Yu, Hong Yan, Chun Peng, Yu Li, Cheng-Gang Li, Ze-Long Ma, Yang Zhao, Meng-Fan Pu, Ling-Ling Miao, Xin-Ming Qi, Jin Ren
Dicer1 is an enzyme essential for microRNA (miRNA) maturation. The loss of miRNAs resulted from Dicer1 deficiency greatly contributes to the progression of many diseases, including lipid dysregulation, but its role in hepatic accumulation of free cholesterol (FC) that is critical in the development of non-alcoholic steatohepatitis (NASH) remains elusive. In this study, we used the liver-specific Dicer1-knockout mice to identify the miRNAs involved in hepatic FC accumulation. In a widely used dietary NASH model, mice were fed a methionine-choline-deficient (MCD) diet for 3 weeks, which resulted in significant increase in hepatic FC levels as well as decrease of Dicer1 mRNA levels in livers...
January 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28112178/benzyl-isothiocyanate-induces-protective-autophagy-in-human-lung-cancer-cells-through-an-endoplasmic-reticulum-stress-mediated-mechanism
#19
Qi-Cheng Zhang, Zhen-Hua Pan, Bo-Ning Liu, Zhao-Wei Meng, Xiang Wu, Qing-Hua Zhou, Ke Xu
Isothiocyanates, such as allyl isothiocya¬nate (AITC), benzyl isothiocyanate (BITC), phenethyl isothio¬cyanate (PEITC) and sulforaphane (SFN), are natural compounds abundant in cruciferous vegetables, which have substantial chemopreventive activities against various human malignancies. However, the mechanisms underlying the inhibition of tumor cell growth by isothiocyanates are not fully understood. Since autophagy has dual functions in cancer, in the present study we investigated the effects of BITC on autophagy induction in human lung cancer cells in vitro and in vivo...
January 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28112177/adenosine-a2a-receptor-deficiency-attenuates-the-somnogenic-effect-of-prostaglandin-d2-in-mice
#20
Bin-Jia Zhang, Zhi-Li Huang, Jiang-Fan Chen, Yoshihiro Urade, Wei-Min Qu
Prostaglandin D2 (PGD2) is one of the most potent endogenous sleep promoting substances. PGD2 activates the PGD2 receptor (DPR) and increases the extracellular level of adenosine in wild-type (WT) mice but not DPR knockout (KO) mice, suggesting that PGD2-induced sleep is DPR-dependent, and adenosine may be the signaling molecule that mediates the somnogenic effect of PGD2. The aim of this study was to determine the involvement of the adenosine A2A receptor (A2AR) in PGD2-induced sleep.We infused PGD2 into the lateral ventricle of WT and A2AR KO mice between 20:00 and 2:00 for 6 h, and electroencephalograms and electromyograms were simultaneously recorded...
January 23, 2017: Acta Pharmacologica Sinica
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