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Publisher: Elsevier   (Total: 3042 journals)

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Showing 1 - 200 of 3042 Journals sorted alphabetically
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 19, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 16, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 81, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 23, 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: 328, 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: 205, 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: 22, 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: 4, 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: 3)
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: 124, 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: 9, 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: 25, 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: 25, 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: 40, 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: 45, 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: 12)
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: 20, 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: 24)
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: 34, 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: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
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: 22)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 4)
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: 21, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 13)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, 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: 19, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 58)
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: 2, SJR: 0.1, h-index: 2)
Advances in Space Research     Full-text available via subscription   (Followers: 339, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
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: 29, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 15)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 43, 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: 308, 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: 5, 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: 422, 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: 30, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 38, 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: 50, 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: 5, 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: 10, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 6)
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: 8, 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: 46, 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: 47, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 44, 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: 15, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 30, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 24, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 32, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 44, 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: 179, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 54, 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: 23, 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: 33, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, 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: 53, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 5)
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: 160, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 8, 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: 153, 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  [3042 journals]
  • Understanding peroral absorption: regulatory aspects and contemporary
           approaches to tackling solubility and permeability hurdles

    • Authors: Prachi B. Shekhawat; Varsha B. Pokharkar
      Pages: 260 - 280
      Abstract: Publication date: May 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 3
      Author(s): Prachi B. Shekhawat, Varsha B. 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: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2016.09.005
       
  • Nanotechnology-based strategies for treatment of ocular disease

    • Authors: Yuhua Weng; Juan Liu; Shubin Jin; Weisheng Guo; Xingjie Liang; Zhongbo Hu
      Pages: 281 - 291
      Abstract: Publication date: May 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 3
      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.
      Graphical abstract image

      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2016.09.001
       
  • Establishment of a new acute-on-chronic liver failure model

    • Authors: Fangfang Li; Luyang Miao; Hua Sun; Yuyang Zhang; Xiuqi Bao; Dan Zhang
      Pages: 326 - 333
      Abstract: Publication date: May 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 3
      Author(s): Fangfang Li, Luyang Miao, Hua Sun, Yuyang Zhang, Xiuqi Bao, Dan Zhang
      To establish an animal model of acute-on-chronic liver failure (ACLF) that would replicate the pathological process of ACLF in humans, rats were administered porcine serum (PS) for 11 weeks. Liver fibrosis was determined by pathological and biochemical assessments. The animals then were injected with d-galactosamine (d-gal) and lipopolysaccharide (LPS). The survival times of animals with cirrhosis and ACLF were determined over 48h. Other animals were killed at 0, 4, 8 and 12h after administration of d-gal/LPS. Liver injury was assessed by histopathological analysis and biochemical indices, and apoptosis was detected by Western blot and TUNEL analysis. After PS administration for 11 weeks the serum levels of hyaluronic acid and N-procollagen type III peptide increased significantly, and serious fibrosis and cirrhosis was observed at weeks 10 and 11. Cirrhotic rats were injected with d-gal/LPS to induced ACLF; the rate of mortality over 48h was 80%. ALT and AST levels increased markedly at 4h, but decreased significantly at 8 and 12h post-treatment. The total bilirubin, direct bilirubin, and total bile acids levels increased markedly at 8 and 12h. Clotting times, TNF-α and IL-6 levels increased significantly, except for 12h post-treatment. Apoptosis, inflammation and necrosis were elevated as determined by hematoxylin-eosin staining and TUNEL assays. BCL-2 levels decreased significantly, While BAX levels increased significantly. Cytochrome c expression peaked at 8h post-d-gal/LPS treatment. In conclusion, an ACLF model induced by PS and d-gal/LPS was established and the underlying mechanisms of ACLF development were explored.
      Graphical abstract image

      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2016.09.003
       
  • 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
      Pages: 347 - 352
      Abstract: Publication date: May 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 3
      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.
      Graphical abstract image

      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2016.11.003
       
  • 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.
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      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.
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      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.
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      PubDate: 2017-03-09T15:32:45Z
      DOI: 10.1016/j.apsb.2016.08.004
       
  • Isocartormin, a novel quinochalcone C-glycoside from Carthamus tinctorius

    • Authors: Feng Li; Zhisheng He; Yang Ye
      Abstract: Publication date: Available online 21 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Feng Li, Zhisheng He, Yang Ye
      A new semi-quinonechalcone C-glycoside isocartormin along with cartormin and safflomin C were isolated from the water extract of Carthamus tinctorius L. The structure of isocartormin was determined by extensive analysis of HR-MS, 1D- and 2D NMR data, and by comparison with those of cartormin reported previously by our group. Isocartormin was identified as a diastereoisomer of cartormin with a reverse configuration at C-18.
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      PubDate: 2017-06-22T16:57:59Z
      DOI: 10.1016/j.apsb.2017.04.005
       
  • Chinese herbal medicine compound Yi-Zhi-Hao pellet inhibits replication of
           influenza virus infection through activation of heme oxygenase-1

    • Authors: Jinqiu Yin; Linlin Ma; Huiqiang Wang; Haiyan Yan; Jin Hu; Wen Jiang; Yuhuan Li
      Abstract: Publication date: Available online 20 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jinqiu Yin, Linlin Ma, Huiqiang Wang, Haiyan Yan, Jin Hu, Wen Jiang, Yuhuan Li
      As a leading cause of respiratory disease, influenza A virus (IAV) presents a pandemic threat in annual seasonal outbreaks. Given the limitation of existing anti-influenza therapies, there remains to be a requirement for new drugs. Compound Yi-Zhi-Hao pellet (CYZH) is a famous traditional Chinese medicine (TCM) used in the clinic, whose formula has been recorded in Complication of National Standard for Traditional Chinese Medicine to treat common cold. In this study, we found that CYZH exhibited a broad-spectrum anti-influenza activity and inhibited the expression of viral RNA and proteins in vitro. Mechanistically, CYZH had no inhibitory activities against viral protein hemagglutinin and IAV RNA-dependent RNA polymerase. Instead, it induced activation of erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB), which subsequently upregulated heme oxygenase-1 (HO-1) expression. Also, CYZH protected cells from oxidative damage induced by reactive oxygen series. In conclusions, CYZH inhibits IAV replication in vitro, at least partly by activating expression of the Nrf2/HO-1 pathway.
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      PubDate: 2017-06-22T16:57:59Z
      DOI: 10.1016/j.apsb.2017.05.006
       
  • The potential of natural products for targeting PPARα

    • Authors: Daniela Rigano; Carmina Sirignano; Orazio Taglialatela-Scafati
      Abstract: Publication date: Available online 16 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Daniela Rigano, Carmina Sirignano, Orazio Taglialatela-Scafati
      Peroxisome proliferator activated receptors (PPARs) α, -γ and -β/δ are ligand-activated transcription factors and members of the superfamily of nuclear hormone receptor. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, e.g. fenofibrate and gemfibrozil) and diabetes (thiazolidinediones, e.g. rosiglitazone and pioglitazone) are ligands for the various PPAR isoforms. More precisely, antidiabetic thiazolidinediones act on PPARγ, while PPARα is the main molecular target of antidyslipidemic fibrates. Over the past few years, our understanding of the mechanism underlying the PPAR modulation of gene expression has greatly increased. This review presents a survey on terrestrial and marine natural products modulating the PPARα system with the objective of highlighting how the incredible chemodiversity of natural products can provide innovative leads for this “hot” target.
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      PubDate: 2017-06-17T16:32:29Z
      DOI: 10.1016/j.apsb.2017.05.005
       
  • Mitochondrial uncoupler triclosan induces vasorelaxation of rat arteries

    • Authors: Xiyue Zhang; Xinzi Zhang; Yanqiu Zhang; Mingyu Liu; Jing Jin; Jie Yan; Xin Shen; Nan Hu; Deli Dong
      Abstract: Publication date: Available online 16 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xiyue Zhang, Xinzi Zhang, Yanqiu Zhang, Mingyu Liu, Jing Jin, Jie Yan, Xin Shen, Nan Hu, Deli Dong
      Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca2+]i, mitochondrial reactive oxygen species (mitoROS), and mitochondrial membrane potential of smooth muscle cells (A10 cells) were measured using laser scanning confocal microscopy. Triclosan treatment relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction, and pre-treatment with triclosan inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, triclosan also relaxed PE- and KPSS-induced constriction. Triclosan induces vasorelaxation without involving KATP channel activation in smooth muscle cells of arteries. Triclosan treatment increased cytosolic [Ca2+]i, mitochondrial ROS production and depolarized mitochondrial membrane potential in A10 cells. In conclusion, triclosan induces mitochondrial uncoupling in vascular smooth muscle cells and relaxes the constricted rat mesenteric arteries and aorta of rats. The present results suggest that triclosan would indicate vasodilation effect if absorbed excessively in vivo.
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      PubDate: 2017-06-17T16:32:29Z
      DOI: 10.1016/j.apsb.2017.06.001
       
  • Arylamine N-acetyltransferase 2 genotype-dependent N-acetylation of
           isoniazid in cryopreserved human hepatocytes

    • Authors: Mark A. Doll; Raúl A. Salazar-González; Srineil Bodduluri; David W. Hein
      Abstract: Publication date: Available online 7 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Mark A. Doll, Raúl A. Salazar-González, Srineil Bodduluri, David W. Hein
      Cryopreserved human hepatocytes were used to investigate the role of arylamine N-acetyltransferase 2 (NAT2; EC 2.3.1.5) polymorphism on the N-acetylation of isoniazid (INH). NAT2 genotype was determined by Taqman allelic discrimination assay and INH N-acetylation was measured by high performance liquid chromatography. INH N-acetylation rates in vitro exhibited a robust and highly significant (P 0.005) NAT2 phenotype-dependent metabolism. N-acetylation rates in situ were INH concentration- and time-dependent. Following incubation for 24h with 12.5 or 100 µmol/L INH, acetyl-INH concentrations varied significantly (P = 0.0023 and P = 0.0002) across cryopreserved human hepatocytes samples from rapid, intermediate, and slow acetylators, respectively. The clear association between NAT2 genotype and phenotype supports use of NAT2 genotype to guide INH dosing strategies in the treatment and prevention of tuberculosis.
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      PubDate: 2017-06-12T15:43:53Z
      DOI: 10.1016/j.apsb.2017.05.003
       
  • Identification and characterization of loop7 motif and its role in
           regulating biological function of human APOBEC3G through molecular
           modeling and biological assay

    • Authors: Congjie Zhai; Ling Ma; Zhixin Zhang; Jiwei Ding; Jing Wang; Yongxin Zhang; Xiaoyu Li; Fei Guo; Liyan Yu; Jinming Zhou; Shan Cen
      Abstract: Publication date: Available online 2 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Congjie Zhai, Ling Ma, Zhixin Zhang, Jiwei Ding, Jing Wang, Yongxin Zhang, Xiaoyu Li, Fei Guo, Liyan Yu, Jinming Zhou, Shan Cen
      Human APOBEC3G (hA3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor (Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the hA3G–Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the hA3G–Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation. Furthermore, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, hA3G--Vif interaction, Vif-mediated hA3G degradation as well as subcellular localization of hA3G. This work highlights a multiple-task interface formed by loop7 motif, which regulates biological function of hA3G, thus providing the feasibility of the strategy of blocking Vif-mediated A3G degradation by targeting the putative site around loop7.
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      PubDate: 2017-06-03T04:02:25Z
      DOI: 10.1016/j.apsb.2017.05.002
       
  • Insects: an underrepresented resource for the discovery of biologically
           active natural products

    • Authors: Lauren Seabrooks; Longqin Hu
      Abstract: Publication date: Available online 30 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Lauren Seabrooks, Longqin Hu
      Nature has been the source of life-changing and -saving medications for centuries. Aspirin, penicillin and morphine are prime examples of Nature׳s gifts to medicine. These discoveries catalyzed the field of natural product drug discovery which has mostly focused on plants. However, insects have more than twice the number of species and entomotherapy has been in practice for as long as and often in conjunction with medicinal plants and is an important alternative to modern medicine in many parts of the world. Herein, an overview of current traditional medicinal applications of insects and characterization of isolated biologically active molecules starting from approximately 2010 is presented. Insect natural products reviewed were isolated from ants, bees, wasps, beetles, cockroaches, termites, flies, true bugs, moths and more. Biological activities of these natural products from insects include antimicrobial, antifungal, antiviral, anticancer, antioxidant, anti-inflammatory and immunomodulatory effects.
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      PubDate: 2017-06-03T04:02:25Z
      DOI: 10.1016/j.apsb.2017.05.001
       
  • Approaches to establish Q-markers for the quality standards of traditional
           Chinese medicines

    • Authors: Wenzhi Yang; Yibei Zhang; Wanying Wu; Luqi Huang; Dean Guo; Changxiao Liu
      Abstract: Publication date: Available online 23 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Wenzhi Yang, Yibei Zhang, Wanying Wu, Luqi Huang, Dean Guo, Changxiao Liu
      Traditional Chinese medicine (TCM) has played a pivotal role in maintaining the health of Chinese people and is now gaining increasing acceptance around the global scope. However, TCM is confronting more and more concerns with respect to its quality. The intrinsic “multicomponent and multitarget” feature of TCM necessitates the establishment of a unique quality and bioactivity evaluation system, which is different from that of the Western medicine. However, TCM is investigated essentially as “herbal medicine” or “natural product”, and the pharmacopoeia quality monographs are actually chemical-markers-based, which can ensure the consistency only in the assigned chemical markers, but, to some extent, have deviated from the basic TCM theory. A concept of “quality marker” (Q-marker), following the “property-effect-component” theory, is proposed. The establishment of Q-marker integrates multidisciplinary technologies like natural products chemistry, analytical chemistry, bionics, chemometrics, pharmacology, systems biology, and pharmacodynamics, etc. Q-marker-based fingerprint and multicomponent determination conduce to the construction of more scientific quality control system of TCM. This review delineates the background, definition, and properties of Q-marker, and the associated technologies applied for its establishment. Strategies and approaches for establishing Q-marker-based TCM quality control system are presented and highlighted with a few TCM examples.
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      PubDate: 2017-05-29T02:35:50Z
      DOI: 10.1016/j.apsb.2017.04.012
       
  • Crystal structures, absolute configurations and molecular docking studies
           of naftopidil enantiomers as α1D-adrenoceptor antagonists

    • Authors: Wei Xu; Junjun Huang; Renwang Jiang; Mu Yuan
      Abstract: Publication date: Available online 16 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Wei Xu, Junjun Huang, Renwang Jiang, Mu Yuan
      Chiral drug naftopidil (NAF), a specific α 1D-adrenoceptor (AR) antagonist for the treatment of benign prostatic hyperplasia, was used in racemic form for several decades. Our recent work declared that NAF enantiomers showed the same antagonistic effects on the α 1D-AR, but the binding mechanism of these two stereochemical NAF isomers to the α 1D receptor remained unclear. Herein, we reported the crystallographic structures of optically pure NAF stereoisomers for the first time and unambiguously determined their absolute configurations. The crystal data of R and S enantiomers matched satisfactorily the pharmacophore model for α 1D-selective antagonists. Based on the constructed α 1D homology model, molecular docking studies shed light on the molecular mechanism of NAF enantiomers binding to α 1D-AR. The results indicated that NAF enantiomers exhibited the very similar binding poses and occupied the same binding pocket.
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      PubDate: 2017-05-18T16:23:15Z
      DOI: 10.1016/j.apsb.2017.04.011
       
  • Anti-diabetic effects and mechanisms of action of a Chinese herbal
           medicine preparation JQ-R in vitro and in diabetic KKAy mice

    • Authors: Quan Liu; Shuainan Liu; Lihui Gao; Sujuan Sun; Yi Huan; Caina Li; Yue Wang; Nan Guo; Zhufang Shen
      Abstract: Publication date: Available online 16 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Quan Liu, Shuainan Liu, Lihui Gao, Sujuan Sun, Yi Huan, Caina Li, Yue Wang, Nan Guo, Zhufang Shen
      Refined-JQ (JQ-R) is a mixture of refined extracts from Coptis chinensis (Ranunculaceae), Astragalus membranaceus (Leguminosae) and Lonicera japonica (Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KKAy mice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KKAy mice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF-κB p65), inhibitor of NF-κB (IκB α), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KKAy mice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.
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      PubDate: 2017-05-18T16:23:15Z
      DOI: 10.1016/j.apsb.2017.04.010
       
  • Schisandra sphenanthera extract (Wuzhi Tablet) protects against
           chronic-binge and acute alcohol-induced liver injury by regulating the
           NRF2-ARE pathway in mice

    • Authors: Xuezhen Zeng; Xi Li; Chenshu Xu; Fulin Jiang; Yufei Mo; Xiaomei Fan; Yaoting Li; Yiming Jiang; Dongshun Li; Min Huang; Huichang Bi
      Abstract: Publication date: Available online 11 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xuezhen Zeng, Xi Li, Chenshu Xu, Fulin Jiang, Yufei Mo, Xiaomei Fan, Yaoting Li, Yiming Jiang, Dongshun Li, Min Huang, Huichang Bi
      Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.
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      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2017.04.002
       
  • Potassium 2-(l-hydroxypentyl)-benzoate attenuates neuroinflammatory
           responses and upregulates heme oxygenase-1 in systemic
           lipopolysaccharide-induced inflammation in mice

    • Authors: Chunyang Zhao; Weizhen Hou; Hui Lei; Longjian Huang; Shan Wang; Dandan Cui; Changhong Xing; Xiaoliang Wang; Ying Peng
      Abstract: Publication date: Available online 9 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Chunyang Zhao, Weizhen Hou, Hui Lei, Longjian Huang, Shan Wang, Dandan Cui, Changhong Xing, Xiaoliang Wang, Ying Peng
      A neuroinflammatory response is commonly involved in the progression of many neurodegenerative diseases. Potassium 2-(1-hydroxypentyl)-benzoate (PHPB), a novel neuroprotective compound, has shown promising effects in the treatment of ischemic stroke and Alzheimer׳s disease (AD). In the present study, the anti-inflammatory effects of PHPB were investigated in the plasma and brain of C57BL/6 mice administered a single intraperitoneal (i.p.) injection of lipopolysaccharide (LPS). Levels of iNOS and the cytokines TNFα, IL-1β and IL-10 were elevated in plasma, cerebral cortex and hippocampus after LPS injection and the number of microglia and astrocytes in cortex and hippocampus were increased. LPS also upregulated the expression of heme oxygenase-1 (HO-1) in the cortex and hippocampus. PHPB reduced the levels of iNOS and cytokines in the plasma and brain, decreased the number of microglia and astrocytes and further enhanced the upregulation of HO-1. In addition, PHPB inhibited the LPS-induced phosphorylation of ERK, P38 and JNK. These results suggest that PHPB is a potential candidate in the treatment of neurodegenerative diseases through inhibiting neuroinflammation.
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      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2017.04.007
       
  • In vivo retention of poloxamer-based in situ hydrogels for vaginal
           application in mouse and rat models

    • Authors: Yu Liu; Fujin Yang; Linglin Feng; Long Yang; Lingyun Chen; Gang Wei; Weiyue Lu
      Abstract: Publication date: Available online 9 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yu Liu, Fujin Yang, Linglin Feng, Long Yang, Lingyun Chen, Gang Wei, Weiyue Lu
      The purpose of this study is to evaluate the in vivo retention capabilities of poloxamer-based in situ hydrogels for vaginal application with nonoxinol-9 as the model drug. Two in situ hydrogel formulations, which contained 18% poloxamer 407 plus 1% poloxamer 188 (GEL1, relative hydrophobic) or 6% poloxamer 188 (GEL2, relative hydrophilic), were compared with respect to the rheological properties, in vitro hydrogel erosion and drug release. The vaginal retention capabilities of these hydrogel formulations were further determined in two small animal models, including drug quantitation of vaginal rinsing fluid in mice and isotope tracing with 99mTc in rats. The two formulations exhibited similar phase transition temperatures ranging from 27 to 32°C. Increasing the content of poloxamer 188 resulted in higher rheological moduli under body temperature, but slightly accelerated hydrogel erosion and drug release. When compared in vivo, GEL1 was eliminated significantly slower in rat vagina than GEL2, while the vaginal retention of these two hydrogel formulations behaved similarly in mice. In conclusion, increases in the hydrophilic content of formulations led to faster hydrogel erosion, drug release and intravaginal elimination. Rats appear to be a better animal model than mice to evaluate the in situ hydrogel for vaginal application.
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      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2017.03.003
       
  • Syringaresinol-4-O-β-D-glucoside alters lipid and glucose metabolism in
           HepG2 cells and C2C12 myotubes

    • Authors: Shuai Wang; Chongming Wu; Xin Li; Yue Zhou; Quanyang Zhang; Fuchao Ma; Jianhe Wei; Xiaopo Zhang; Peng Guo
      Abstract: Publication date: Available online 9 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Shuai Wang, Chongming Wu, Xin Li, Yue Zhou, Quanyang Zhang, Fuchao Ma, Jianhe Wei, Xiaopo Zhang, Peng Guo
      Syringaresinol-4-O-β-D-glucoside (SSG), a furofuran-type lignan, was found to modulate lipid and glucose metabolism through an activity screen of lipid accumulation and glucose consumption, and was therefore considered as a promising candidate for the prevention and treatment of metabolic disorder, especially in lipid and glucose metabolic homeostasis. In this study, the effects of SSG on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were further investigated. Treatment with SSG significantly inhibited lipid accumulation by oil red O staining and reduced the intracellular contents of total lipid, cholesterol and triglyceride in HepG2 cells. No effect was observed on cell viability in the MTT assay at concentrations of 0.1–10 μmol/L. SSG also increased glucose consumption by HepG2 cells and glucose uptake by C2C12 myotubes. Furthermore, real-time quantitative PCR revealed that the beneficial effects were associated with the down-regulation of sterol regulatory element-binding proteins-1c, -2 (SREBP-1c, -2), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC) and hydroxyl methylglutaryl CoA reductase (HMGR), and up-regulation of peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ). SSG also significantly elevated transcription activity of PPARγ tested by luciferase assay. These results suggest that SSG is an effective regulator of lipogenesis and glucose consumption and might be a candidate for further research in the prevention and treatment of lipid and glucose metabolic diseases.
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      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2017.04.008
       
  • 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors

    • Authors: Hasnah Osman; Nor Hashima Idris; Ezatul Ezleen Kamarulzaman; Habibah A. Wahab; Mohd. Zaheen Hassan
      Abstract: Publication date: Available online 4 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Hasnah Osman, Nor Hashima Idris, Ezatul Ezleen Kamarulzaman, Habibah A. Wahab, Mohd. Zaheen Hassan
      Dengue is a severe mosquito-borne viral infection causing half a million deaths annually. Dengue virus NS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones analogues 4a 4j were synthesized and screened in silico against DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through an in vitro DENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-bis(arylidene)-4-piperidones (4e and 4j) emerged as promising lead molecules for novel protease inhibitors with an IC50 of 15.22 and 16.23µmol/L, respectively, compared to the standard, panduratin A, having IC50 of 57.28µmol/L.
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      PubDate: 2017-05-08T14:43:45Z
      DOI: 10.1016/j.apsb.2017.04.009
       
  • Steroids hydroxylation catalyzed by the monooxygenase mutant 139-3 from
           Bacillus megaterium BM3

    • Authors: Xing Liu; Jian-Qiang Kong
      Abstract: Publication date: Available online 4 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xing Liu, Jian-Qiang Kong
      The search of new substrates with pharmaceutical and industrial potential for biocatalysts including cytochrome P450 enzymes is always challenging. Cytochrome P450 BM3 mutant 139-3, a versatile biocatalyst, exhibited hydroxylation activities towards fatty acids and alkanes. However, there were limited reports about its hydroxylation activity towards steroids. Herein, an Escherichia coli–based whole-cell extract containing the recombinant 139-3 protein was used as the biocatalyst to screen 13 steroids. Results revealed that 139-3 was able to specifically hydroxylate androstenedione (1) at 1α-position, generating a hydroxylated steroid 1α-OH-androstenedione (1a). To investigate whether C-1α hydroxylation catalyzed by BM3 mutant 139-3 could be industrially used, an optimization of catalyzing conditions was performed. Accordingly, the BM3 mutant 139-3 enzyme was observed to display maximum activity at 37°C, under pH 7.0 for 4h, with 37% transformation rate. Moreover, four 139-3 variants were generated by random mutagenesis with the aim of improving its activity and expanding substrate scope. Surprisingly, these mutants, sharing a common mutated site R379S, lost their activities towards androstenedione (1). These data clearly indicated that arginine residue located at site 379 played key role in the hydroxylation activities of 139-3. Overall, these new findings broadened the substrate scope of 139-3 enzyme, thereby expanding its potential applications as a biocatalyst on steroids hydroxylation in pharmaceutical industry.
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      PubDate: 2017-05-08T14:43:45Z
      DOI: 10.1016/j.apsb.2017.04.006
       
  • Amino-functionalized poloxamer 407 with both mucoadhesive and
           thermosensitive properties: preparation, characterization and application
           in a vaginal drug delivery system

    • Authors: Liqian Ci; Zhigang Huang; Yu Liu; Zhepeng Liu; Gang Wei; Weiyue Lu
      Abstract: Publication date: Available online 3 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Liqian Ci, Zhigang Huang, Yu Liu, Zhepeng Liu, Gang Wei, Weiyue Lu
      Lack of mucoadhesive properties is the major drawback to poloxamer 407 (F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an amino-functionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407 (F127-NH2) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol (AG) as model drug, AG-loaded F127-NH2-based in situ hydrogels (NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin was revealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.
      Graphical abstract image

      PubDate: 2017-05-08T14:43:45Z
      DOI: 10.1016/j.apsb.2017.03.002
       
  • Nine compounds from the root bark of Lycium chinense and their
           anti-inflammatory activitieslammatory activitiesretain-->

    • Authors: Yanan Yang; Yawen An; Wei Wang; Ning Du; Jinghua Zhang; Ziming Feng; Jianshuang Jiang; Peicheng Zhang
      Abstract: Publication date: Available online 3 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yanan Yang, Yawen An, Wei Wang, Ning Du, Jinghua Zhang, Ziming Feng, Jianshuang Jiang, Peicheng Zhang
      Two new compounds, named lyciumlignan D (1) and lyciumphenyl propanoid A (2), along with seven known compounds, were isolated from the root bark of Lycium chinense. Their structures were elucidated using spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR, CD), as well as by comparison with those of the literature. Compounds 3 9 were isolated from this genus for the first time. In the in vitro assay, compounds 3, 6, and 7 exhibited stronger anti-inflammatory effects than the positive control curcumin at a concentration of 10μmol/L.
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      PubDate: 2017-05-03T14:06:15Z
      DOI: 10.1016/j.apsb.2017.04.004
       
  • T cell--associated immunoregulation and antiviral effect of oxymatrine in
           hydrodynamic injection HBV mouse model

    • Authors: Xiuxiu Sang; Ruilin Wang; Yanzhong Han; Cong'en Zhang; Honghui Shen; Zhirui Yang; Yin Xiong; Huimin Liu; Shijing Liu; Ruisheng Li; Ruichuang Yang; Jiabo Wang; Xuejun Wang; Zhaofang Bai; Xiaohe Xiao
      Abstract: Publication date: Available online 2 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xiuxiu Sang, Ruilin Wang, Yanzhong Han, Cong'en Zhang, Honghui Shen, Zhirui Yang, Yin Xiong, Huimin Liu, Shijing Liu, Ruisheng Li, Ruichuang Yang, Jiabo Wang, Xuejun Wang, Zhaofang Bai, Xiaohe Xiao
      Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV) in vitro, limited research has been done with this drug in vivo. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution. OMT (2.2, 6.7 and 20mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20mg/kg inhibited HBV replication, and it was more efficient than entecavir (ETV) in the elimination of serum HBsAg and intrahepatic HBcAg. In addition, OMT accelerated the production of interferon-γ (IFN-γ) in a dose-dependent manner in CD4+ T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.
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      PubDate: 2017-05-03T14:06:15Z
      DOI: 10.1016/j.apsb.2017.02.005
       
  • Indole alkaloid sulfonic acids from an aqueous extract of Isatis
           indigotica roots and their antiviral activity

    • Authors: Lingjie Meng; Qinglan Guo; Yufeng Liu; Minghua Chen; Yuhuan Li; Jiandong Jiang; Jiangong Shi
      Abstract: Publication date: Available online 29 April 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Lingjie Meng, Qinglan Guo, Yufeng Liu, Minghua Chen, Yuhuan Li, Jiandong Jiang, Jiangong Shi
      Six new indole alkaloid sulfonic acids (1–6), together with two analogues (7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their structures including the absolute configurations were determined by spectroscopic data analysis, combined with enzyme hydrolysis and comparison of experimental circular dichroism and calculated electronic circular dichroism spectra. In the preliminary assay, compounds 2 and 4 showed antiviral activity against Coxsackie virus B3 and influenza virus A/Hanfang/359/95 (H3N2), respectively.
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      PubDate: 2017-05-03T14:06:15Z
      DOI: 10.1016/j.apsb.2017.04.003
       
  • Establishment and characterization of arsenic trioxide resistant KB/ATO
           cells

    • Authors: Yun-Kai Zhang; Chunling Dai; Chun-gang Yuan; Hsiang-Chun Wu; Zhijie Xiao; Zi-Ning Lei; Dong-Hua Yang; X. Chris Le; Liwu Fu; Zhe-Sheng Chen
      Abstract: Publication date: Available online 28 April 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yun-Kai Zhang, Chunling Dai, Chun-gang Yuan, Hsiang-Chun Wu, Zhijie Xiao, Zi-Ning Lei, Dong-Hua Yang, X. Chris Le, Liwu Fu, Zhe-Sheng Chen
      Arsenic trioxide (ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein (BCRP) inhibitor, or multidrug resistance protein 1 (MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells. In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy.
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      PubDate: 2017-05-03T14:06:15Z
      DOI: 10.1016/j.apsb.2017.04.001
       
  • 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
       
  • 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
       
  • 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
       
  • 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.
      Graphical abstract image

      PubDate: 2017-01-06T10:12:59Z
      DOI: 10.1016/j.apsb.2016.11.006
       
 
 
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