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Publisher: Elsevier   (Total: 3030 journals)

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Showing 1 - 200 of 3030 Journals sorted alphabetically
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 20, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 16, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 79, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 22, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 27, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 303, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 25, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription  
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 196, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 9, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 2)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 21, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 5, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 4)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 3)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 2)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 4)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 5)
Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 120, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 24, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 3)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 6, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 21, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 16, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 3, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 26, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 24, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 8, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 16, SJR: 0.223, h-index: 22)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 4)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Ecological Research     Full-text available via subscription   (Followers: 39, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 25, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 38, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 41, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 14)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 18, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 22)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 33, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 4)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 4)
Advances in Life Course Research     Hybrid Journal   (Followers: 7, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 5, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 6, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 3)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 7, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 20, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 14)
Advances in Pharmacology     Full-text available via subscription   (Followers: 13, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 7, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 8)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 4)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 17, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 56)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 1, SJR: 0.1, h-index: 2)
Advances in Space Research     Full-text available via subscription   (Followers: 332, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 7)
Advances in Surgery     Full-text available via subscription   (Followers: 6, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 28, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 14)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 12)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 42, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 304, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 4, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 7, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 390, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 29, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 36, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 1)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 48, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 3, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 9, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 5)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access  
Algal Research     Partially Free   (Followers: 7, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 6, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 45, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 5)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 3)
American Heart J.     Hybrid Journal   (Followers: 45, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 47, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 34, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 6, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 32, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 25, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 31, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 48, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 174, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 51, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 2)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 22, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 23, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 21, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 32, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 13, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 5)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 52, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 3)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 2, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 38, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 154, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 7, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 10)
Anesthésie & Réanimation     Full-text available via subscription  
Anesthesiology Clinics     Full-text available via subscription   (Followers: 21, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access  
Animal Behaviour     Hybrid Journal   (Followers: 143, SJR: 1.907, h-index: 126)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 5, SJR: 1.151, h-index: 83)
Animal Reproduction Science     Hybrid Journal   (Followers: 5, SJR: 0.711, h-index: 78)
Annales d'Endocrinologie     Full-text available via subscription   (SJR: 0.394, h-index: 30)
Annales d'Urologie     Full-text available via subscription  
Annales de Cardiologie et d'Angéiologie     Full-text available via subscription   (SJR: 0.177, h-index: 13)
Annales de Chirurgie de la Main et du Membre Supérieur     Full-text available via subscription  
Annales de Chirurgie Plastique Esthétique     Full-text available via subscription   (Followers: 2, SJR: 0.354, h-index: 22)
Annales de Chirurgie Vasculaire     Full-text available via subscription   (Followers: 1)

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Journal Cover Acta Pharmaceutica Sinica B
  [2 followers]  Follow
    
  This is an Open Access Journal Open Access journal
   ISSN (Print) 2211-3843 - ISSN (Online) 2211-3835
   Published by Elsevier Homepage  [3030 journals]
  • Salvianolic acid A alleviates renal injury in systemic lupus erythematosus
           induced by pristane in BALB/c mice

    • Authors: Yihuang Lin; Yu Yan; Huifang Zhang; Yucai Chen; Yangyang He; Shoubao Wang; Lianhua Fang; Yang Lv; Guanhua Du
      Pages: 159 - 166
      Abstract: Publication date: March 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 2
      Author(s): Yihuang Lin, Yu Yan, Huifang Zhang, Yucai Chen, Yangyang He, Shoubao Wang, Lianhua Fang, Yang Lv, Guanhua Du
      The purpose of this study was to investigate the effects of salvianolic acid A (SAA) in systemic lupus erythematosus (SLE) induced by pristane in BALB/c mice. Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane. Mice were then treated with daily oral doses of SAA for 5 months in parallel with mice treated with prednisone and aspirin as positive controls. The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin (H&E) and periodic acid–Schiff (PAS) staining. Western blot analysis of renal tissue was also employed. SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects. SAA treatment also significantly inhibited the phosphorylation of IKK, IκB and NFκB in renal tissues of lupus mice. In conclusion, the results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK, IκB and NFκB.
      Graphical abstract image

      PubDate: 2017-03-09T15:32:45Z
      DOI: 10.1016/j.apsb.2016.07.001
       
  • A set of interesting sequoiatones stereoisomers from a wetland
           soil-derived fungus Talaromyces flavus

    • Authors: Tianyu Sun; Jian Zou; Guodong Chen; Dan Hu; Bin Wu; Xingzhong Liu; Xinsheng Yao; Hao Gao
      Pages: 167 - 172
      Abstract: Publication date: March 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 2
      Author(s): Tianyu Sun, Jian Zou, Guodong Chen, Dan Hu, Bin Wu, Xingzhong Liu, Xinsheng Yao, Hao Gao
      Four interesting sequoiatones stereoisomers (1–4) were isolated from a wetland soil-derived fungus Talaromyces flavus by chiral HPLC. On the basis of comprehensive NMR and mass analyses, their planar structures were elucidated as the same as that of sequoiatone B. Among them, 1 and 3 (or 2 and 4) were a pair of enantiomers, and 1 and 2 (or 3 and 4) were a pair of stereoisomers with epimerization at C-12, which indicated that sequoiatione-type metabolites exist as enantiomers rather than as optically pure compounds in some strains. With the quantum chemical ECD calculations, the absolute configurations of C-8 in 1–4 were determined, which is the first report to establish the absolute configuration of C-8 in sequoiatones. However, the absolute configurations of C-12 in sequoiatones are still unsolved.
      Graphical abstract image

      PubDate: 2017-03-09T15:32:45Z
      DOI: 10.1016/j.apsb.2016.07.005
       
  • Four new phenolic glycosides from Baoyuan decoction

    • Authors: Xiaoli Ma; Xiaoyu Guo; Mingbo Zhao; Pengfei Tu; Yong Jiang
      Pages: 173 - 178
      Abstract: Publication date: March 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 2
      Author(s): Xiaoli Ma, Xiaoyu Guo, Mingbo Zhao, Pengfei Tu, Yong Jiang
      Four new phenolic glycosides, including two flavonoid glycosides (1 and 2) and two lignan glycosides (3 and 4), were isolated from the traditional Chinese medicine formula, Baoyuan decoction. Their structures were established by detailed analysis of the NMR and HR-ESI-MS spectroscopic data and their absolute configurations were determined by the experimental electronic circular dichroism data as well as chemical methods. Furthermore, the sources of the four new compounds were determined by the UPLC-Qtrap-MS method, which proved that 1 and 2 are originated from Glycyrrhiza uralensis, and 3 and 4 are from Cinnamomum cassia.
      Graphical abstract image

      PubDate: 2017-03-09T15:32:45Z
      DOI: 10.1016/j.apsb.2016.08.004
       
  • Cloning and characterization of squalene synthase and cycloartenol
           synthase from Siraitia grosvenorii

    • Authors: Huan Zhao; Qi Tang; Changming Mo; Longhua Bai; Dongping Tu; Xiaojun Ma
      Pages: 215 - 222
      Abstract: Publication date: March 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 2
      Author(s): Huan Zhao, Qi Tang, Changming Mo, Longhua Bai, Dongping Tu, Xiaojun Ma
      Mogrosides and steroid saponins are tetracyclic triterpenoids found in Siraitia grosvenorii. Squalene synthase (SQS) and cycloartenol synthase (CAS) are key enzymes in triterpenoid and steroid biosynthesis. In this study, full-length cDNAs of SgSQS and SgCAS were cloned by a rapid amplification of cDNA-ends with polymerase chain reaction (RACE-PCR) approach. The SgSQS cDNA has a 1254bp open reading frame (ORF) encoding 417 amino acids, and the SgCAS cDNA contains a 2298bp ORF encoding 765 amino acids. Bioinformatic analysis showed that the deduced SgSQS protein has two transmembrane regions in the C-terminal. Both SgSQS and SgCAS have significantly higher levels in fruits than in other tissues, suggesting that steroids and mogrosides are competitors for the same precursors in fruits. Combined in silico prediction and subcellular localization, experiments in tobacco indicated that SgSQS was probably in the cytoplasm or on the cytoskeleton, and SgCAS was likely located in the nucleus or cytosol. These results will provide a foundation for further study of SgSQS and SgCAS gene functions in S. grosvenorii, and may facilitate improvements in mogroside content in fruit by regulating gene expression.
      Graphical abstract image

      PubDate: 2017-03-09T15:32:45Z
      DOI: 10.1016/j.apsb.2016.06.012
       
  • Class I phosphatidylinositol 3-kinase inhibitors for cancer therapy

    • Authors: Wennan Zhao; Yuling Qiu; Dexin Kong
      Pages: 27 - 37
      Abstract: Publication date: January 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 1
      Author(s): Wennan Zhao, Yuling Qiu, Dexin Kong
      The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in human cancers. Class I PI3Ks are lipid kinases that phosphorylate phosphatidylinositol 4,5-bisphosphate (PIP2) at the 3-OH of the inositol ring to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), which in turn activates Akt and the downstream effectors like mammalian target of rapamycin (mTOR) to play key roles in carcinogenesis. Therefore, PI3K has become an important anticancer drug target, and currently there is very high interest in the pharmaceutical development of PI3K inhibitors. Idelalisib has been approved in USA and Europe as the first-in-class PI3K inhibitor for cancer therapy. Dozens of other PI3K inhibitors including BKM120 and ZSTK474 are being evaluated in clinical trials. Multifaceted studies on these PI3K inhibitors are being performed, such as single and combinational efficacy, resistance, biomarkers, etc. This review provides an introduction to PI3K and summarizes key advances in the development of PI3K inhibitors.
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      PubDate: 2017-01-22T11:15:03Z
      DOI: 10.1016/j.apsb.2016.07.006
       
  • Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against
           prostate cancer cells in vitro and in vivo

    • Authors: Guangyao Lv; Dengjun Sun; Jingwen Zhang; Xiaoxia Xie; Xiaoqiong Wu; Weishuo Fang; Jingwei Tian; Chunhong Yan; Hongbo Wang; Fenghua Fu
      Pages: 52 - 58
      Abstract: Publication date: January 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 1
      Author(s): Guangyao Lv, Dengjun Sun, Jingwen Zhang, Xiaoxia Xie, Xiaoqiong Wu, Weishuo Fang, Jingwei Tian, Chunhong Yan, Hongbo Wang, Fenghua Fu
      Tubulin has been shown to be an effective target for the development of cytotoxic agents against prostate cancer. Previously, we reported that Lx2-32c is an anti-tubulin agent with high binding affinity to tubulin. In this study, we investigated the potential of Lx2-32c to act as an effective cytotoxic agent in the treatment of prostate cancer. MTT assays showed that Lx2-32c was cytotoxic to all tested prostate cancer cell lines. The Lx2-32c-treated cells typically exhibited a rounded morphology associated with the onset of apoptosis, as evidenced by immunocytochemical staining. Human prostate cancer cell lines treated with Lx2-32c arrest in the G2/M phase of the cell cycle and the treatment is associated with an increased ratio of cells in the sub-G0/G1 phase as determined by flow cytometry. Furthermore, expression of the cleaved form of poly (ADP-ribose) polymerase in prostate cancer cell lines treated with Lx2-32c was shown by Western blotting assay. Xenograft implants of LNCaP and PC3-derived tumors in nude mice showed that Lx2-32c treatment significant inhibited tumor growth with effects equivalent to those of docetaxel. These findings demonstrate the potential of Lx2-32c as a candidate antitumor agent for the treatment of prostate cancer.
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      PubDate: 2017-01-22T11:15:03Z
      DOI: 10.1016/j.apsb.2016.06.005
       
  • Euphorbia factor L2 induces apoptosis in A549 cells through the
           mitochondrial pathway

    • Authors: Minting Lin; Sili Tang; Chao Zhang; Hubiao Chen; Wenjing Huang; Yun Liu; Jianye Zhang
      Pages: 59 - 64
      Abstract: Publication date: January 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 1
      Author(s): Minting Lin, Sili Tang, Chao Zhang, Hubiao Chen, Wenjing Huang, Yun Liu, Jianye Zhang
      Euphorbia factor L2, a lathyrane diterpenoid isolated from caper euphorbia seed (the seeds of Euphorbia lathyris L.), has been traditionally applied to treat cancer. This article focuses on the cytotoxic activity of Euphorbia factor L2 against lung carcinoma A549 cells and the mechanism by which apoptosis is induced. We analyzed the cytotoxicity and related mechanism of Euphorbia factor L2 with an MTT assay, an annexin V-FITC/PI test, a colorimetric assay, and immunoblotting. Euphorbia factor L2 showed potent cytotoxicity to A549 cells. Euphorbia factor L2 led to an increase in reactive oxygen species (ROS) generation, a loss of mitochondrial electrochemical potential, release of cytochrome c, activation of caspase-9 and caspase-3, and cleavage of poly(ADP-ribose) polymerase, suggesting that Euphorbia factor L2 induced apoptosis through a mitochondrial pathway. The cytotoxic activity of Euphorbia factor L2 in A549 cells and the related mechanisms of apoptotic induction provide support for the further investigation of caper euphorbia seeds.
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      PubDate: 2017-01-22T11:15:03Z
      DOI: 10.1016/j.apsb.2016.06.008
       
  • Asiatic acid inhibits lung cancer cell growth in vitro and in vivo by
           destroying mitochondria

    • Authors: Tiancong Wu; Ji Geng; Wenjie Guo; Jing Gao; Xixu Zhu
      Pages: 65 - 72
      Abstract: Publication date: January 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 1
      Author(s): Tiancong Wu, Ji Geng, Wenjie Guo, Jing Gao, Xixu Zhu
      Asiatic acid (AA), a pentacyclic triterpene found in Centella asiatica, displays significant anti-proliferative effects on cancer cells in vitro although the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer both in vivo and in vitro. Using the MTT assay, AA was found to induce apoptosis in a dose- and time-dependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3 (LC3) and decreased the expression of p62. Furthermore, exposure to AA resulted in collapse of the mitochondrial membrane potential and generation of reactive oxygen species (ROS), suggesting mitochondria are the target of AA. In the mouse lung cancer xenograft model, oral administration of AA significantly inhibited tumor volume and weight accompanied by significant apoptosis of lung cancer cells. In addition, it led to a significant decrease in the expression of proliferating cell nuclear antigen (PCNA). In summary, the results show that AA significantly reduces lung cancer cell growth both in vitro and in vivo and that the associated apoptosis is mediated through mitochondrial damage.
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      PubDate: 2017-01-22T11:15:03Z
      DOI: 10.1016/j.apsb.2016.04.003
       
  • 2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer
           and anti-inflammatory agents

    • Authors: Erin Marie Kirwen; Tarun Batra; Chandrabose Karthikeyan; Girdhar Singh Deora; Vandana Rathore; Chaitanya Mulakayala; Naveen Mulakayala; Amy Catherine Nusbaum; Joel Chen; Haneen Amawi; Kyle McIntosh; Sahabjada; Neelam Shivnath; Deepak Chowarsia; Nisha Sharma; Md Arshad; Piyush Trivedi; Amit K. Tiwari
      Pages: 73 - 79
      Abstract: Publication date: January 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 1
      Author(s): Erin Marie Kirwen, Tarun Batra, Chandrabose Karthikeyan, Girdhar Singh Deora, Vandana Rathore, Chaitanya Mulakayala, Naveen Mulakayala, Amy Catherine Nusbaum, Joel Chen, Haneen Amawi, Kyle McIntosh, Sahabjada, Neelam Shivnath, Deepak Chowarsia, Nisha Sharma, Md Arshad, Piyush Trivedi, Amit K. Tiwari
      In this study we examined the suitability of the 3H-imidazo[4,5-b]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against MCF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity in vitro. The results showed that compound 3f exhibited 2-fold selectivity with IC50 values of 9.2 and 21.8 µmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound 3f revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.
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      PubDate: 2017-01-22T11:15:03Z
      DOI: 10.1016/j.apsb.2016.05.003
       
  • C0818, a novel curcumin derivative, interacts with Hsp90 and inhibits
           Hsp90 ATPase activity

    • Authors: Yingjuan Fan; Yang Liu; Lianru Zhang; Fang Cai; Liping Zhu; Jianhua Xu
      Pages: 91 - 96
      Abstract: Publication date: January 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 1
      Author(s): Yingjuan Fan, Yang Liu, Lianru Zhang, Fang Cai, Liping Zhu, Jianhua Xu
      The aims of the present study were to estimate the affinity between 3,5-(E)-bis(3-methoxy-4-hydroxybenzal)-4-piperidinone hydrochloride (C0818) and heat shock protein 90 (Hsp90) and to investigate the inhibitory effects of this compound on Hsp90 ATPase activity. Fluorescence spectroscopy was used to examine the affinity between varying concentrations of C0818 and Hsp90, N-Hsp90, M-Hsp90 and C-Hsp90. Fluorescence intensities were recorded in the range of 290–510nm at 293, 303 and 310K, respectively. A colorimetric assay for inorganic phosphate (based on the formation of a phosphomolybdate complex and the subsequent reaction with malachite green) were used to examine the inhibitory effects of C0818 on Hsp90 ATPase activity. The equilibrium dissociation constant K D value of C0818 was found to be 23.412±0.943μmol/L. The interaction between C0818 and Hsp90 was driven mainly by electrostatic interactions. C0818 showed the strongest affinity with C-Hsp90. These results conclusively demonstrate the inhibitory activity of C0818 on the activity of Hsp90 ATPase.
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      PubDate: 2017-01-22T11:15:03Z
      DOI: 10.1016/j.apsb.2016.05.014
       
  • Synthesis of hydroxycinnamic acid derivatives as mitochondria-targeted
           antioxidants and cytotoxic agents

    • Authors: Jiyu Li; Dian He; Baitao Wang; Ling Zhang; Kun Li; Qinjian Xie; Lifang Zheng
      Pages: 106 - 115
      Abstract: Publication date: January 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 1
      Author(s): Jiyu Li, Dian He, Baitao Wang, Ling Zhang, Kun Li, Qinjian Xie, Lifang Zheng
      In order to develop agents with superior chemopreventive and chemotherapeutic properties against hepatocellular carcinomas, mitochondria-targeted hydroxycinnamic acids (MitoHCAs) were synthesized by conjugation with a triphenylphosphonium cation. These synthetic compounds were evaluated for their antioxidant activities in hepatic mitochondria, including against OH∙− and ROO∙− induced lipid peroxidation. H2O2 production was decreased significantly by increasing glutathione peroxidase and catalase activities. In addition, cell proliferation data from three cell lines (HepG2, L02 and WI38) indicated that the MitoHCAs were selective for cancer cells. Interestingly, the MitoHCAs both with or without Ca2+ triggered mitochondrial dysfunction by inducing mitochondrial swelling, collapsing the mitochondrial membrane potential and causing cytochrome c release. In particular, an inhibitor of the mitochondrial permeability transition pore (mPTP), cyclosporin A, attenuated mitochondrial damage and cell apoptosis, indicating that mPTP may be involved in the antiproliferative activity of MitoHCAs. Further studies focused on structural optimization of these compounds are onging.
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      PubDate: 2017-01-22T11:15:03Z
      DOI: 10.1016/j.apsb.2016.05.002
       
  • Cloning and expression of three thaumatin-like protein genes from
           Polyporus umbellatus

    • Authors: Mengmeng Liu; Dawei Zhang; Yongmei Xing; Shunxing Guo
      Abstract: Publication date: Available online 11 April 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Mengmeng Liu, Dawei Zhang, Yongmei Xing, Shunxing Guo
      Genes encoding thaumatin-like protein (TLPs) are frequently found in fungal genomes. However, information on TLP genes in Polyporus umbellatus is still limited. In this study, three TLP genes were cloned from P. umbellatus. The full-length coding sequence of PuTLP1, PuTLP2 and PuTLP3 were 768, 759 and 561bp long, respectively, encoding for 256, 253 and 187 amino acids. Phylogenetic trees showed that P. umbellatus PuTLP1, PuTLP2 and PuTLP3 were clustered with sequences from Gloeophyllum trabeum, Trametes versicolor and Stereum hirsutum, respectively. The expression patterns of the three TLP genes were higher in P. umbellatus with Armillaria mellea infection than in the sclerotia without A. mellea. Furthermore, over-expression of three PuTLPs were carried out in Escherichia coli BL21 (DE3) strain, and high quality proteins were obtained using Ni-NTA resin that can be used for preparation of specific antibodies. These results suggest that PuTLP1, PuTLP2 and PuTLP3 in P. umbellatus may be involved in the defense response to A. mellea infections.
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      PubDate: 2017-04-19T19:14:27Z
      DOI: 10.1016/j.apsb.2017.03.001
       
  • A preliminary study on the interaction between Asn-Gly-Arg (NGR)-modified
           multifunctional nanoparticles and vascular epithelial cells

    • Authors: Chunxi Liu; Tingxian Liu; Xiaoyue Yu; Yizhu Gu
      Abstract: Publication date: Available online 1 April 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Chunxi Liu, Tingxian Liu, Xiaoyue Yu, Yizhu Gu
      Previously developed Asn-Gly-Arg (NGR) peptide-modified multifunctional poly(ethyleneimine)–poly(ethylene glycol) (PEI–PEG)-based nanoparticles (TPIC) have been considered to be promising carriers for the co-delivery of DNA and doxorubicin (DOX). As a continued effort, the aim of the present study was to further evaluate the interaction between TPIC and human umbilical vein endothelial cells (HUVEC) to better understand the cellular entry mechanism. In the present investigation, experiments relevant to co-localization, endocytosis inhibitors and factors influencing the internalization were performed. Without any treatment, there was no co-localization between aminopeptidase N/CD13 (APN/CD13) and caveolin 1 (CAV1). However, co-localization between CD13 and CAV1 was observed when cells were incubated with an anti-CD13 antibody or TPIC. As compared with antibody treatment, TPIC accelerated the speed and enhanced the degree of co-localization. TPIC entered HUVEC not only together with CD13 but also together with CAV1. However, this internalization was not dependent on the enzyme activity of CD13 but could be inhibited by methyl-β-eyclodextfin (MβCD), further identifying the involvement of caveolae-mediated endocytosis (CvME). This conclusion was also verified by endocytosis inhibitor experiments.
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      PubDate: 2017-04-04T18:10:04Z
      DOI: 10.1016/j.apsb.2017.02.003
       
  • Advances in ultrasound-targeted microbubble–mediated gene therapy
           for liver fibrosis

    • Authors: Cuiyuan Huang; Hong Zhang; Ruidan Bai
      Abstract: Publication date: Available online 15 March 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Cuiyuan Huang, Hong Zhang, Ruidan Bai
      Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble–mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.
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      PubDate: 2017-03-17T16:42:06Z
      DOI: 10.1016/j.apsb.2017.02.004
       
  • The effect of 8-OH-DPAT and dapoxetine on gene expression in the brain of
           male rats during ejaculation

    • Authors: Xijun Qin; Xiaojun Ma; Dongping Tu; Zuliang Luo; Jie Huang; Changming Mo
      Abstract: Publication date: Available online 14 March 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xijun Qin, Xiaojun Ma, Dongping Tu, Zuliang Luo, Jie Huang, Changming Mo
      The 5-HT1A receptor agonist 8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT) promotes ejaculation of male rats, whereas dapoxetine delays this process. However, the gene expression profile of the brain at ejaculation following administrationof these two compounds has not been fully elucidated. In the present study, a transcriptomic BodyMap was generated by conducting mRNA-Seq on brain samples of male Sprague–Dawley rats. The study included four groups: pre-copulatory control (CK) group, ejaculation (EJ) group, 0.5mg/kg 8-OH-DPAT-ejaculation group (DPAT), and 60mg/kg dapoxetine-ejaculation (DAP) group. The resulting analysis generated an average of approximately 47 million sequence reads. Significant differences in the gene expression profiles of the aforementioned groups were observed in the EJ (257 genes), DPAT (349 genes) and the DAP (207 genes) compared with the control rats. The results indicate that the expression of Drd1 and Slc6a3 was significantly different after treatment with 8-OH-DPAT, whereas the expression of Drd4 was significantly different after treatment with dapoxetine. Other genes, such as Wnt9b, Cdkn1a and Fosb, exhibited significant differences in expression after the two treatments and are related to bladder cancer, renal cell carcinoma and sexual addiction. The present study reveals the basic pattern of gene expression that was activated at ejaculation in the presence of 8-OH-DPAT or dapoxetine, providing preliminary gene expression information during rat ejaculation.
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      PubDate: 2017-03-17T16:42:06Z
      DOI: 10.1016/j.apsb.2016.11.004
       
  • Application of CRISPR/Cas9 in plant biology

    • Authors: Xuan Liu; Surui Wu; Jiao Xu; Chun Sui; Jianhe Wei
      Abstract: Publication date: Available online 11 March 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xuan Liu, Surui Wu, Jiao Xu, Chun Sui, Jianhe Wei
      The CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system was first identified in bacteria and archaea and can degrade exogenous substrates. It was developed as a gene editing technology in 2013. Over the subsequent years, it has received extensive attention owing to its easy manipulation, high efficiency, and wide application in gene mutation and transcriptional regulation in mammals and plants. The process of CRISPR/Cas is optimized constantly and its application has also expanded dramatically. Therefore, CRISPR/Cas is considered a revolutionary technology in plant biology. Here, we introduce the mechanism of the type II CRISPR/Cas called CRISPR/Cas9, update its recent advances in various applications in plants, and discuss its future prospects to provide an argument for its use in the study of medicinal plants.
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      PubDate: 2017-03-17T16:42:06Z
      DOI: 10.1016/j.apsb.2017.01.002
       
  • Inhibition of protein kinases by anticancer DNA intercalator,
           4-butylaminopyrimido[4′,5′:4,5]thieno(2,3-b)quinoline

    • Authors: HeggoduG. Rohit Kumar; Chethan S. Kumar; Hulihalli N. Kiran Kumar; Gopal M. Advi Rao
      Abstract: Publication date: Available online 7 March 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): HeggoduG. Rohit Kumar, Chethan S. Kumar, Hulihalli N. Kiran Kumar, Gopal M. Advi Rao
      Targeting protein kinases (PKs) has been a promising strategy in treating cancer, as PKs are key regulators of cell survival and proliferation. Here in this study, we studied the ability of pyrimido[4′,5′:4,5]thieno(2,3-b)quinolines (PTQ) to inhibit different PKs by performing computational docking and in vitro screening. Docking studies revealed that 4-butylaminopyrimido[4′,5′:4,5]thieno(2,3-b)quinoline (BPTQ) has a higher order of interaction with the kinase receptors than other PTQ derivatives. In vitro screening confirms that BPTQ inhibits VEGFR1 and CHK2, with the IC50 values of 0.54 and 1.70µmol/L, respectively. Further, cytotoxicity of BPTQ was measured by trypan blue assay. Treatment with BPTQ decreased the proliferation of HL-60 cells with an IC50 value of 12µmol/L and induces apoptosis, as explicated by the fall in the mitochondrial membrane potential, annexin V labeling and increased expression of caspase-3. Taken together, these data suggest that BPTQ possess ability to inhibit PKs and to induce cell death in human promyelocytic leukemia cells.
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      PubDate: 2017-03-09T15:32:45Z
      DOI: 10.1016/j.apsb.2017.01.001
       
  • Editor profile: Luqi Huang and Wei Gao

    • Abstract: Publication date: March 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 2


      PubDate: 2017-03-09T15:32:45Z
       
  • Editorial

    • Abstract: Publication date: March 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 2


      PubDate: 2017-03-09T15:32:45Z
       
  • Arterial relaxation is coupled to inhibition of mitochondrial fission in
           arterial smooth muscle cells: comparison of vasorelaxant effects of
           verapamil and phentolamine

    • Authors: Jing Jin; Xin Shen; Yu Tai; Shanliang Li; Mingyu Liu; Changlin Zhen; Xiuchen Xuan; Xiyue Zhang; Nan Hu; Xinzi Zhang; Deli Dong
      Abstract: Publication date: Available online 3 March 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jing Jin, Xin Shen, Yu Tai, Shanliang Li, Mingyu Liu, Changlin Zhen, Xiuchen Xuan, Xiyue Zhang, Nan Hu, Xinzi Zhang, Deli Dong
      Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine (PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K+ (KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PE- but not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE- and KPSS-induced aorta constriction. Transmission electron microscopy (TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells, and verapamil prevented both PE- and KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells (A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.
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      PubDate: 2017-03-04T13:41:31Z
      DOI: 10.1016/j.apsb.2016.12.009
       
  • Dissecting the role of AMP-activated protein kinase in human diseases

    • Authors: Jin Li; Liping Zhong; Fengzhong Wang; Haibo Zhu
      Abstract: Publication date: Available online 3 March 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jin Li, Liping Zhong, Fengzhong Wang, Haibo Zhu
      AMP-activated protein kinase (AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes. Accompanying the application of genetic methods and a plethora of AMPK agonists, rapid progress has identified AMPK as an attractive therapeutic target for several human diseases, such as cancer, type 2 diabetes, atherosclerosis, myocardial ischemia/reperfusion injury and neurodegenerative disease. The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere. In the present review, we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered. Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.
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      PubDate: 2017-03-04T13:41:31Z
      DOI: 10.1016/j.apsb.2016.12.003
       
  • Scanometry as microplate reader for high throughput method based on DPPH
           dry reagent for antioxidant assay

    • Authors: Mochammad Amrun Hidayat; Aulia Fitri; Bambang Kuswandi
      Abstract: Publication date: Available online 28 February 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Mochammad Amrun Hidayat, Aulia Fitri, Bambang Kuswandi
      The stable chromogenic radical 1,1′-diphenyl-2-picrylhydrazyl (DPPH) solution was immobilized on the microwell plate as dry reagent to construct a simple antioxidant sensor. Then, a regular flatbed scanner was used as microplate reader to obtain analytical parameters for antioxidant assay using one-shot optical sensors as scanometry technique. Variables affecting the acquisition of the images were optimized and the analytical parameters are obtained from an area of the sensing zone inside microwell using the average luminosity of the sensing zone captured as the mean of red, green, and blue (RGB) value using ImageJ® program. By using this RGB value as sensor response, it is possible to determine antioxidant capacity in the range 1–25ppm as gallic acid equivalent (GAE) with the response time of 9min. The reproducibility of sensor was good (RSD<1%) with recovery at 93%–96%. The antioxidant sensor was applied to the plant extracts, such as sappan wood and Turmeric Rhizome. The results are good when compared to the same procedure using a UV/Vis spectrophotometer.
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      PubDate: 2017-03-04T13:41:31Z
      DOI: 10.1016/j.apsb.2017.02.001
       
  • Self-microemulsifying drug delivery system for improving the
           bioavailability of huperzine A by lymphatic uptake

    • Authors: Fang Li; Rongfeng Hu; Bin Wang; Yun Gui; Gang Cheng; Song Gao; Lei Ye; Jihui Tang
      Abstract: Publication date: Available online 28 February 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Fang Li, Rongfeng Hu, Bin Wang, Yun Gui, Gang Cheng, Song Gao, Lei Ye, Jihui Tang
      Huperzine A (Hup-A) is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration–time curve (AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (P<0.01). The absorption rate constant (K a) and the apparent permeability coefficient (P app) for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values of K a and P app of Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration (C max) of the blocking model were significantly lower than those of the control model (P<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.
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      PubDate: 2017-03-04T13:41:31Z
      DOI: 10.1016/j.apsb.2017.02.002
       
  • Structural analysis of recombinant human ubiquitin-conjugating enzyme
           UbcH5c

    • Authors: Fangshu Wu; Junsheng Zhu; Honglin Li; Lili Zhu
      Abstract: Publication date: Available online 28 February 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Fangshu Wu, Junsheng Zhu, Honglin Li, Lili Zhu
      UbcH5c belongs to the ubiquitin-conjugating enzyme family and plays an important role in catalyzing ubiquitination during TNF-α--triggered NF-κB activation. Therefore, UbcH5c is a potent therapeutic target for the treatment of inflammatory and autoimmune diseases induced by aberrant activation of NF-κB. In this study, we established a stable expression system for recombinant UbcH5c and solved the crystal structure of UbcH5c belonging to space group P22121 with one molecule in the asymmetric unit. This study provides the basis for further study of UbcH5c including the design of UbcH5c inhibitors.
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      PubDate: 2017-03-04T13:41:31Z
      DOI: 10.1016/j.apsb.2016.12.008
       
  • Regulation of drug metabolism and toxicity by multiple factors of
           genetics, epigenetics, lncRNAs, gut microbiota, and diseases: A meeting
           report of the 21st International Symposium on Microsomes and Drug
           Oxidations (MDO)

    • Authors: Ai-Ming Yu; Magnus Ingelman-Sundberg; Nathan J. Cherrington; Lauren M. Aleksunes; Ulrich M. Zanger; Wen Xie; Hyunyoung Jeong; Edward M. Morgan; Peter J. Turnbaugh; Curtis D. Klaassen; Aadra P. Bhatt; Matthew R. Redinbo; Pengying Hao; David J. Waxman; Li Wang; Xiao-bo Zhong
      Abstract: Publication date: Available online 1 February 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Ai-Ming Yu, Magnus Ingelman-Sundberg, Nathan J. Cherrington, Lauren M. Aleksunes, Ulrich M. Zanger, Wen Xie, Hyunyoung Jeong, Edward M. Morgan, Peter J. Turnbaugh, Curtis D. Klaassen, Aadra P. Bhatt, Matthew R. Redinbo, Pengying Hao, David J. Waxman, Li Wang, Xiao-bo Zhong
      Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21st International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2–6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.
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      PubDate: 2017-02-05T12:00:32Z
      DOI: 10.1016/j.apsb.2016.12.006
       
  • Anemone medicinal plants: ethnopharmacology, phytochemistry and biology

    • Authors: Da-Cheng Hao; Xiaojie Gu; Peigen Xiao
      Abstract: Publication date: Available online 28 January 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Da-Cheng Hao, Xiaojie Gu, Peigen Xiao
      The Ranunculaceae genus Anemone (order Ranunculales), comprising more than 150 species, mostly herbs, has long been used in folk medicine and worldwide ethnomedicine. Various medicinal compounds have been found in Anemone plants, especially triterpenoid saponins, some of which have shown anti-cancer activities. Some Anemone compounds and extracts display immunomodulatory, anti-inflammatory, antioxidant, and antimicrobial activities. More than 50 species have ethnopharmacological uses, which provide clues for modern drug discovery. Anemone compounds exert anticancer and other bioactivities via multiple pathways. However, a comprehensive review of the Anemone medicinal resources is lacking. We here summarize the ethnomedical knowledge and recent progress on the chemical and pharmacological diversity of Anemone medicinal plants, as well as the emerging molecular mechanisms and functions of these medicinal compounds. The phylogenetic relationships of Anemone species were reconstructed based on nuclear ITS and chloroplast markers. The molecular phylogeny is largely congruent with the morphology-based classification. Commonly used medicinal herbs are distributed in each subgenus and section, and chemical and biological studies of more unexplored taxa are warranted. Gene expression profiling and relevant “omics” platforms could reveal differential effects of phytometabolites. Genomics, transcriptomics, proteomics, and metabolomics should be highlighted in deciphering novel therapeutic mechanisms and utilities of Anemone phytometabolites.
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      PubDate: 2017-01-29T11:31:30Z
      DOI: 10.1016/j.apsb.2016.12.001
       
  • Flavanols from the Camellia sinensis var. assamica and their hypoglycemic
           and hypolipidemic activities

    • Authors: Xin Wang; Quan Liu; Hongbo Zhu; Hongqing Wang; Jie Kang; Zhufang Shen; Ruoyun Chen
      Abstract: Publication date: Available online 24 January 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xin Wang, Quan Liu, Hongbo Zhu, Hongqing Wang, Jie Kang, Zhufang Shen, Ruoyun Chen
      α-Glucosidase and lipase inhibitors play important roles in the treatment of hyperglycaemia and dyslipidemia. † These authors make equal contributions to this work. To identify novel naturally occurring inhibitors, a bioactivity-guided phytochemical research was performed on the pu-erh tea. One new flavanol, named (–)-epicatechin-3-O-(Z)-coumarate (1), and 16 known analogs (2 17) were isolated from the aqueous extract of the pu-erh tea. Their structures were determined by spectroscopic and chemical methods. Furthermore, the water extract of pu-erh tea and its fractions exhibited inhibitory activities against α-glucosidases and lipases in vitro; compound 15 showed moderate inhibitory effect against sucrase with an IC50 value of 32.5μmol/L and significant inhibitory effect against maltase with an IC50 value of 1.3μmol/L. Compounds 8, 10, 11 and 15 displayed moderate activity against a lipase with IC50 values of 16.0, 13.6, 19.8, and 13.3μmol/L, respectively.
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      PubDate: 2017-01-29T11:31:30Z
      DOI: 10.1016/j.apsb.2016.12.007
       
  • Molecular cloning and functional identification of a cDNA encoding
           4-hydroxy-3-methylbut-2-enyl diphosphate reductase from Tripterygium
           wilfordii

    • Authors: Qiqing Cheng; Yuru Tong; Zihao Wang; Ping Su; Wei Gao; Luqi Huang
      Abstract: Publication date: Available online 22 January 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Qiqing Cheng, Yuru Tong, Zihao Wang, Ping Su, Wei Gao, Luqi Huang
      The 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR) is the last step key enzyme of the methylerythritol phosphate (MEP) pathway, synthesizing isopentenyl diphosphate and its allyl isomer dimethylallyl diphosphate, which is important for regulation of isoprenoid biosynthesis. Here the full-length cDNA of HDR, designated TwHDR (GenBank Accession No. KJ933412.1), was isolated from Tripterygium wilfordii for the first time. TwHDR has an open reading frame (ORF) of 1386bp encoding 461 amino acids. TwHDR exhibits high homology with HDRs of other plants, with an N-terminal conserved domain and three conserved cysteine residues. TwHDR cDNA was cloned into an expression vector and transformed into an Escherichia coli hdr mutant. Since loss-of-function E.coli hdr mutant is lethal, the result showed that transformation of TwHDR cDNA rescued the E.coli hdr mutant. This complementation assay suggests that the TwHDR cDNA encodes a functional HDR enzyme. The expression of TwHDR was induced by methyl-jasmonate (MJ) in T. wilfordii suspension cells. The expression of TwHDR reached the highest level after 1h of MJ treatment. These results indicate that we have identified a functional TwHDR enzyme, which may play a pivotal role in the biosynthesis of diterpenoid triptolide in T. wilfordii.
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      PubDate: 2017-01-29T11:31:30Z
      DOI: 10.1016/j.apsb.2016.12.002
       
  • Editor Profile: Guest Editor of Special Issue on Targets and Anticancer
           Drug Research

    • Authors: Liwu
      Abstract: Publication date: January 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 1
      Author(s): Liwu Fu


      PubDate: 2017-01-22T11:15:03Z
       
  • Editorial for targets and anticancer drug research

    • Authors: Liwu
      Abstract: Publication date: January 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 1
      Author(s): Liwu Fu


      PubDate: 2017-01-22T11:15:03Z
       
  • Identification and differentiation of major components in three different
           “Sheng-ma” crude drug species by UPLC/Q-TOF-MS

    • Authors: Mengxue Fan; Kunming Qin; Fei Ding; Yuting Huang; Xiaoli Wang; Baochang Cai
      Abstract: Publication date: Available online 7 January 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Mengxue Fan, Kunming Qin, Fei Ding, Yuting Huang, Xiaoli Wang, Baochang Cai
      Rhizoma Cimicifugae (Sheng ma) is a Ranunculaceae herb belonging to a composite family and well known in China. has been widely used in traditional Chinese medicine. The Pharmacopoeia of the People׳s Republic of China contains three varieties (Cimicifuga dahurica (Turcz.), Cimicifuga foetida L. and Cimicifuga heracleifolia Kom.) which have been used clinically as “Sheng-ma”. However, the chemical constituents of three components of “Sheng-ma” have never been documented. In this study, a rapid method for the analysis of the main components of “Sheng-ma” was developed using ultra-high performance liquid chromatography with quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS). The present study reveals the major common and distinct chemical constituents of C. dahurica, C. foetida and C. heracleifolia and also reports principal component and statistical analyses of these results. The components were identified by comparing the retention time, accurate mass, mass spectrometric fragmentation characteristic ions and matching empirical molecular formula with that of the published compounds. A total of 32 common components and 8 markers for different “Sheng-ma” components were identified. These findings provide an important basis for the further study and clinical utilities of the three “Sheng-ma” varieties.
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      PubDate: 2017-01-14T10:44:17Z
      DOI: 10.1016/j.apsb.2016.11.002
       
  • Simultaneous determination of 14 active constituents of Shengjiang Xiexin
           decoction using ultrafast liquid chromatography coupled with electrospray
           ionization tandem mass spectrometry

    • Authors: Gang Peng; Huanyu Guan; Xiaoming Wang; Yue Shi
      Abstract: Publication date: Available online 30 December 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Gang Peng, Huanyu Guan, Xiaoming Wang, Yue Shi
      An effective herbal medicinal prescription of Shengjiang Xiexin decoction (SXD) was used in treating the inflammatory bowel disease in clinic. In this study, an ultrafast liquid chromatographytandem mass spectrometry (UFLCMS/MS) method was developed to separate and to simultaneously determine 14 major active ingredients in SXD. Chromatographic separation was successfully accomplished on an Acquity BEH C18 (100mm×2.1mm, 1.7μm) column using gradient elution with 0.1% (v/v) formic acid water (A) and 0.1% (v/v) formic acid in methanol (B). Negative and positive electrospray ionization tandem mass spectrometry was used to detect the 14 analytes using its selective reaction monitoring (SRM) mode. A good linear regression relationship for each analyte was obtained over the range from 3.88ng/mL to 4080ng/mL. The precision was evaluated by intra- and inter-day assays with a relative standard deviation (RSD) of less than 6.25%. The recovery measured at three concentration levels varied from 98.72% to 103.47%. The overall limits of quantification (LOQ) ranged from 2.05ng/mL to 4.72ng/mL. The method was successfully implemented in the qualitative and quantitative analyses of the 14 chemical constituents in SXD. The results showed that the developed UFLCMS/MS method was linear and accurate. The method could be used reliably as a quality control method for SXD.
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      PubDate: 2017-01-06T10:12:59Z
      DOI: 10.1016/j.apsb.2016.11.006
       
  • A novel class of apical sodium--dependent bile salt transporter
           inhibitors:
           1-(2,4-bifluorophenyl)-7-dialkylamino-1,8-naphthyridine-3-carboxamides

    • Authors: Hongtao Liu; Guoxun Pang; Jinfeng Ren; Yue Zhao; Juxian Wang
      Abstract: Publication date: Available online 23 December 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Hongtao Liu, Guoxun Pang, Jinfeng Ren, Yue Zhao, Juxian Wang
      The apical sodium--dependent bile acid transporter (ASBT) is the main transporter to promote re-absorption of bile acids from the intestinal tract into the enterohepatic circulation. Inhibition of ASBT could increase the excretion of bile acids, thus increasing bile acid synthesis and consequently cholesterol consumption. Therefore, ASBT is an attractive target for developing new cholesterol-lowering drugs. In this report, a series of 1-(2,4-bifluorophenyl)-7-dialkylamino-1,8-naphthyridine-3-carboxamides were designed as inhibitors of ASBT. Most of them demonstrated potency against ASBT transport of bile acids. In particular, compound 4a 1 was found to have the best activity, resulting in 80.1% inhibition of ASBT at 10μmol/L.
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      PubDate: 2016-12-29T08:42:46Z
      DOI: 10.1016/j.apsb.2016.11.005
       
  • Inhalable oridonin-loaded poly(lactic-co-glycolic)acid large porous
           microparticles for in situ treatment of primary non-small cell lung cancer
           

    • Authors: Lifei Zhu; Miao Li; Xiaoyan Liu; Lina Du; Yiguang Jin
      Abstract: Publication date: Available online 22 December 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Lifei Zhu, Miao Li, Xiaoyan Liu, Lina Du, Yiguang Jin
      Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic-co-glycolic)acid (PLGA) large porous microparticle (LPMP) for in situ treatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of ~10µm, the aerodynamic diameter of the spheres was only 2.72µm, leading to highly efficient lung deposition. In vitro studies showed that most of oridonin was released after 1h, whereas the alveolar macrophage uptake of LPMPs occurred after 8h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPs via airway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGA LPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations for in situ treatment of lung cancer.
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      PubDate: 2016-12-29T08:42:46Z
      DOI: 10.1016/j.apsb.2016.09.006
       
  • Targeting calcium signaling in cancer therapy

    • Authors: Chaochu Cui; Robert Merritt; Liwu Fu; Zui Pan
      Abstract: Publication date: Available online 13 December 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Chaochu Cui, Robert Merritt, Liwu Fu, Zui Pan
      The intracellular calcium ions (Ca2+) act as second messenger to regulate gene transcription, cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca2+ homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis, progression and metastasis. Targeting derailed Ca2+ signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca2+ channels, transporters and Ca2+-ATPases, which have been reported to be altered in human cancer patients. It discusses the current research effort toward evaluation of the blockers, inhibitors or regulators for Ca2+ channels/transporters or Ca2+-ATPase pumps as anti-cancer drugs. This review is also aimed to stimulate interest in, and support for research into the understanding of cellular mechanisms underlying the regulation of Ca2+ signaling in different cancer cells, and to search for novel therapies to cure these malignancies by targeting Ca2+ channels or transporters.
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      PubDate: 2016-12-20T07:44:43Z
      DOI: 10.1016/j.apsb.2016.11.001
       
  • Nonlinear relationship between enteric-coated mycophenolate sodium dose
           and mycophenolic acid exposure in Han kidney transplantation recipients

    • Authors: Jun Zhang; Mengmeng Jia; Lihua Zuo; Na Li; Yonggang Luo; Zhi Sun; Xiaojian Zhang; Zhenfeng Zhu
      Abstract: Publication date: Available online 10 December 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jun Zhang, Mengmeng Jia, Lihua Zuo, Na Li, Yonggang Luo, Zhi Sun, Xiaojian Zhang, Zhenfeng Zhu
      The aim of the research was to investigate the pharmacokinetics (PK) of enteric-coated mycophenolate sodium (EC-MPS) by quantification of the active metabolite of mycophenolic acid (MPA) after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from 0 to 12h after EC-MPS administration. MPA plasma concentrations were measured by UPLCUV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to 900mg, C max and AUC012h did not increase with dose escalation. The AUC012h, C max, C 0 and T max for the 540 720 and 900mg doses were not significantly different, respectively (P >0.05). AUC012h and C max were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC012h, C max and C 0 were considerable. Nonlinear PK relationships were found from the doses of 540–900mg of EC-MPS.
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      PubDate: 2016-12-13T06:51:45Z
      DOI: 10.1016/j.apsb.2016.11.003
       
  • Structure of the 40S ribosomal subunit of Plasmodium falciparum by
           homology and de novo modeling

    • Authors: HarrisonNdung׳u Mwangi; Peter Wagacha; Peterson Mathenge; Fredrick Sijenyi; Francis Mulaa
      Abstract: Publication date: Available online 7 December 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): HarrisonNdung׳u Mwangi, Peter Wagacha, Peterson Mathenge, Fredrick Sijenyi, Francis Mulaa
      Generation of three dimensional structures of macromolecules using in silico structural modeling technologies such as homology and de novo modeling has improved dramatically and increased the speed by which tertiary structures of organisms can be generated. This is especially the case if a homologous crystal structure is already available. High-resolution structures can be rapidly created using only their sequence information as input, a process that has the potential to increase the speed of scientific discovery. In this study, homology modeling and structure prediction tools such as RNA123 and SWISS–MODEL were used to generate the 40S ribosomal subunit from Plasmodium falciparum. This structure was modeled using the published crystal structure from Tetrahymena thermophila, a homologous eukaryote. In the absence of the Plasmodium falciparum 40S ribosomal crystal structure, the model accurately depicts a global topology, secondary and tertiary connections, and gives an overall root mean square deviation (RMSD) value of 3.9Å relative to the template׳s crystal structure. Deviations are somewhat larger in areas with no homology between the templates. These results demonstrate that this approach has the power to identify motifs of interest in RNA and identify potential drug targets for macromolecules whose crystal structures are unknown. The results also show the utility of RNA homology modeling software for structure determination and lay the groundwork for applying this approach to larger and more complex eukaryotic ribosomes and other RNA-protein complexes. Structures generated from this study can be used in in silico screening experiments and lead to the determination of structures for targets/hit complexes.
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      PubDate: 2016-12-13T06:51:45Z
      DOI: 10.1016/j.apsb.2016.10.003
       
  • Regulation of multidrug resistance by microRNAs in anti-cancer therapy

    • Authors: Xin An; Cesar Sarmiento; Tao Tan; Hua Zhu
      Abstract: Publication date: Available online 3 December 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xin An, Cesar Sarmiento, Tao Tan, Hua Zhu
      Multidrug resistance (MDR) remains a major clinical obstacle to successful cancer treatment. Although diverse mechanisms of MDR have been well elucidated, such as dysregulation of drugs transporters, defects of apoptosis and autophagy machinery, alterations of drug metabolism and drug targets, disrupti on of redox homeostasis, the exact mechanisms of MDR in a specific cancer patient and the cross-talk among these different mechanisms and how they are regulated are poorly understood. MicroRNAs (miRNAs) are a new class of small noncoding RNAs that could control the global activity of the cell by post-transcriptionally regulating a large variety of target genes and proteins expression. Accumulating evidence shows that miRNAs play a key regulatory role in MDR through modulating various drug resistant mechanisms mentioned above, thereby holding much promise for developing novel and more effective individualized therapies for cancer treatment. This review summarizes the various MDR mechanisms and mainly focuses on the role of miRNAs in regulating MDR in cancer treatment.

      PubDate: 2016-12-06T06:26:24Z
      DOI: 10.1016/j.apsb.2016.09.002
       
  • The modification of natural products for medical use

    • Authors: Zongru Guo
      Abstract: Publication date: Available online 25 November 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Zongru Guo
      Drug innovation is characterized by painstaking molecular-level syntheses and modifications as the basic components of research and development. Similarly, natural products are chemically tailored and modified based upon their structural and biological properties. To some extent, the modification of natural products is quite different from de novo structure-based drug discovery. This review describes the general strategies and principles for the modification of natural products to drugs, as illustrated by several successful medicines that originated from natural products.
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      PubDate: 2016-11-29T05:42:54Z
      DOI: 10.1016/j.apsb.2016.06.003
       
  • Nanotechnology-based strategies for treatment of ocular disease

    • Authors: Yuhua Weng; Juan Liu; Shubin Jin; Weisheng Guo; Xingjie Liang; Zhongbo Hu
      Abstract: Publication date: Available online 18 November 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yuhua Weng, Juan Liu, Shubin Jin, Weisheng Guo, Xingjie Liang, Zhongbo Hu
      Ocular diseases include various anterior and posterior segment diseases. Due to the unique anatomy and physiology of the eye, efficient ocular drug delivery is a great challenge to researchers and pharmacologists. Although there are conventional noninvasive and invasive treatments, such as eye drops, injections and implants, the current treatments either suffer from low bioavailability or severe adverse ocular effects. Alternatively, the emerging nanoscience and nanotechnology are playing an important role in the development of novel strategies for ocular disease therapy. Various active molecules have been designed to associate with nanocarriers to overcome ocular barriers and intimately interact with specific ocular tissues. In this review, we highlight the recent attempts of nanotechnology-based systems for imaging and treating ocular diseases, such as corneal d iseases, glaucoma, retina diseases, and choroid diseases. Although additional work remains, the progress described herein may pave the way to new, highly effective and important ocular nanomedicines.
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      PubDate: 2016-11-21T14:33:07Z
      DOI: 10.1016/j.apsb.2016.09.001
       
  • Synthesis, characterization and pharmacological evaluation of pyrazolyl
           urea derivatives as potential anti-inflammatory agents

    • Authors: Kanagasabai Somakala; Mohammad Amir
      Abstract: Publication date: Available online 10 November 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Kanagasabai Somakala, Mohammad Amir
      p38α mitogen activated protein kinase (MAPK) inhibitors provide a novel approach for the treatment of inflammatory disorders. A series of fifteen pyrazolyl urea derivatives (3a o) were synthesized and evaluated for their p38α MAPK inhibition and antioxidant potential. Compounds 3a e, 3g and 3h showed low micromolar range potency (IC50 values ranging from 0.037 ± 1.56 to 0.069 ± 0.07µmol/L) compared to the standard inhibitor SB 203580 (IC50 = 0.043 ± 3.62µmol/L) when evaluated for p38α MAPK inhibition by an immunosorbent-based assay. Antioxidant activity was measured by a 2,2′-diphenyl-1-picryl hydrazyl radical (DPPH) free radical scavenging method and one of the compounds, 3c, showed better percentage antioxidant activity (75.06%) compared to butylated hydroxy anisole (71.53%) at 1mmol/L concentration. Compounds 3a e, 3g and 3h showed promising in vivo anti-inflammatory activity (ranging from 62.25% to 80.93%) in comparison to diclofenac sodium (81.62%). The ulcerogenic liability and lipid peroxidation activity of these compounds were observed to be less in comparison to diclofenac sodium. These compounds also potently inhibited the lipopolysaccharide (LPS)-induced TNF-α release in mice (ID50 of 3a c = 19.98, 11.32 and 9.67mg/kg, respectively). Among the screened compounds, derivative 3c was found to be the most potent and its binding mode within the p38α MAPK is also reported.
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      PubDate: 2016-11-14T12:13:54Z
      DOI: 10.1016/j.apsb.2016.08.006
       
  • Analysis of Cordyceps by multi-column liquid chromatography

    • Authors: Zhengming Qian; Shaoping Li
      Abstract: Publication date: Available online 9 November 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Zhengming Qian, Shaoping Li
      Cordyceps is a famous traditional Chinese medicine (TCM) that has been used in China for hundreds of years. In the present study a multi-column liquid chromatography (MC-LC) system was developed for the qualitative analysis of macromolecules and micromolecules in Cordyceps. The MC-LC system includes a size exclusion pre-column, a size exclusion column (SEC) and a reversed phase column (RP) which were controlled by column-switching valves. The sample was separated by the size exclusion pre-column into two fractions (macromolecules and micromolecules). These fractions were further separated on SEC and RP columns, respectively. A diode array detector (DAD) and a mass spectrometer (MS) were used to detect the components. This MC-LC method was utilized for analysis of Cordyceps samples. Two macromolecular peaks and 15 micromolecular peaks were found in Cordyceps, and 11 of the micromolecular peaks were identified as adenosine-5′-monophosphate (AMP), phenylalanine, uridine, hypoxanthine, inosine, guanine, guanosine, deoxyadenosine-5′-monophosphate (dAMP), adenosine, adenine and cordycepin (or its isomer). This method is useful for quality control of Cordyceps.
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      PubDate: 2016-11-14T12:13:54Z
      DOI: 10.1016/j.apsb.2016.10.002
       
  • Aromatic compounds from an aqueous extract of “ban lan gen” and their
           antiviral activities

    • Authors: Yufeng Liu; Minghua Chen; Qinglan Guo; Yuhuan Li; Jiandong Jiang; Jiangong Shi
      Abstract: Publication date: Available online 8 November 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yufeng Liu, Minghua Chen, Qinglan Guo, Yuhuan Li, Jiandong Jiang, Jiangong Shi
      A pair of new diphenyl glycerol ether enantiomers (−)-1 and (+)-1 and two new methyl benzamidobenzoates 2 and 3, named (−)-(R)- and (+)-(S)-isatindigotrioic acid [(−)-1 and (+)-1] and isatindigoticamides A (2) and B (3), respectively, were isolated from an aqueous decoction of the roots of Isatis indigotica (ban lan gen). Their structures were elucidated by spectroscopic data analysis including 2D NMR experiments. The absolute configurations of (−)-1 and (+)-1 were assigned based on the CD exciton chirality method. Compounds 2 and 3 exhibited antiviral activities against HSV-1 with IC50 values of 4.87 and 25.87μmol/L, respectively. Compound 2 was also found active against Coxsackie virus B3 and LPS-induced NO production.
      Graphical abstract image

      PubDate: 2016-11-14T12:13:54Z
      DOI: 10.1016/j.apsb.2016.09.004
       
  • Understanding peroral absorption: Regulatory aspects and contemporary
           approaches to tackling solubility and permeability hurdles

    • Authors: Prachi Shekhawat; Varsha Pokharkar
      Abstract: Publication date: Available online 2 November 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Prachi Shekhawat, Varsha Pokharkar
      Oral drug absorption is a process influenced by the physicochemical and biopharmaceutical properties of the drug and its inter-relationship with the gastrointestinal tract. Drug solubility, dissolution and permeability across intestinal barrier are the key parameters controlling absorption. This review provides an overview of the factors that affect drug absorption and the classification of a drug on the basis of solubility and permeability. The biopharmaceutical classification system (BCS) was introduced in early 90׳s and is a regulatory tool used to predict bioavailability problems associated with a new entity, thereby helping in the development of a drug product. Strategies to combat solubility and permeability issues are also discussed.
      Graphical abstract image

      PubDate: 2016-11-08T10:30:32Z
      DOI: 10.1016/j.apsb.2016.09.005
       
  • New sensor technologies in quality evaluation of Chinese materia medica:
           2010–2015

    • Authors: Xiaosu Miao; Qingyu Cui; Honghui Wu; Yanjiang Qiao; Yanfei Zheng; Zhisheng Wu
      Abstract: Publication date: Available online 2 November 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xiaosu Miao, Qingyu Cui, Honghui Wu, Yanjiang Qiao, Yanfei Zheng, Zhisheng Wu
      New sensor technologies play an important role in quality evaluation of Chinese materia medica (CMM) and include near-infrared spectroscopy, chemical imaging, electronic nose and electronic tongue. This review on quality evaluation of CMM and the application of the new sensors in this assessment is based on studies from 2010 to 2015, with prospects and opportunities for future research.
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      PubDate: 2016-11-08T10:30:32Z
      DOI: 10.1016/j.apsb.2016.10.001
       
  • How to unleash mitochondrial apoptotic blockades to kill cancers?

    • Authors: Jing Deng
      Abstract: Publication date: Available online 21 September 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jing Deng
      Apoptosis, especially the intrinsic mitochondrial cell death pathway, is regulated by the BCL-2 family of proteins. Defects in apoptotic machinery are one of the main mechanisms that cells employ to evade cell death and become cancerous. Targeting the apoptotic defects, either by direct inhibition of BCL-2 family proteins or through modulation of regulatory pathways, can restore cell sensitivity to cell death. This review will focus on the aspects of BCL-2 family proteins, their interactions with kinase pathways, and how novel targeted agents can help overcome the apoptotic blockades. Furthermore, functional assays, such as BH3 profiling, may help in predicting responses to chemotherapies and aid in the selection of combination therapies by determining the mitochondrial threshold for initiating cell death.
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      PubDate: 2016-09-22T17:09:50Z
      DOI: 10.1016/j.apsb.2016.08.005
       
  • The Ikaros family of zinc-finger proteins

    • Authors: Yingzhi Fan; Duo Lu
      Abstract: Publication date: Available online 24 June 2016
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yingzhi Fan, Duo Lu
      Ikaros represents a zinc-finger protein family important for lymphocyte development and certain other physiological processes. The number of family members is large, with alternative splicing producing various additional isoforms from each of the five homologous genes in the family. The functional forms of Ikaros proteins could be even more diverse due to protein–protein interactions readily established between family members. Emerging evidence suggests that targeting Ikaros proteins is feasible and effective in therapeutic applications, although the exact roles of Ikaros proteins remain elusive within the intricate regulatory networks in which they are involved. In this review we collect existing knowledge as to the functions, regulatory pathways, and molecular mechanisms of this family of proteins in an attempt to gain a better understanding through the comparison of activities and interactions among family members.

      PubDate: 2016-06-27T07:14:17Z
      DOI: 10.1016/j.apsb.2016.06.002
       
 
 
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