title: HGSD attenuates neuronal apoptosis through enhancing neuronal autophagy in the brain of diabetic mice: The role of AMP-activated protein kinase.
abstract: OBJECTIVE
  Berberine (BBR) holds promising effect for neuronal injury in diabetes because its anti-apoptotic activity and our laboratory developed the Huang-Gui Solid Dispersion (HGSD) to improve oral bioavailability of BBR. However, anti-apoptotic effect and the mechanism of HGSD in the brain of diabetic mice are not clear. We hypothesized that the AMPK/mTOR signaling pathway could exert a protective role in high glucose induced cellular apoptotic death via inducing autophagy and HGSD could inhibit apoptosis by activating AMPK/mTOR pathway.
  
  
  METHODS
  In vivo, we established C57/BL6 mice diabetic model by STZ and detected apoptosis, autophagy and AMPK/mTOR to explore the effect of HGSD. In vitro, we established high glucose-induced apoptotic death model, treating cells with 3-MA, compound C and AICAR to explore the anti-apoptotic mechanism of BBR.
  
  
  RESULTS
  HGSD significantly inhibited cell apoptosis, enhanced cell autophagy and activated the AMPK/mTOR pathway in the hippocampi of diabetic C57/BL6 mice, and the function of BBR is not obvious at the same dosage. Moreover, BBR significantly attenuated apoptotic death, enhanced autophagy and activated the AMPK/mTOR pathway in high glucose-treated SH-SY5Y cells. Pretreated cells with 3-MA, an inhibitor of autophagy, abolished BBR-inhibited apoptosis. Pretreated cells with Compound C, an AMPK inhibitor, blocked BBR-inhibited apoptotic and BBR-induced cell autophagy. AICAR, an AMPK activator, strengthened the function of BBR.
  
  
  CONCLUSIONS
  HGSD protected against neurotoxicity induced by high glucose through activating autophagy and eventually inhibiting neuronal apoptosis, which was activated by the AMPK/mTOR signaling pathway.
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Yingshi
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yao
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China. Electronic address: zhouweichen@yahoo.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal; D005947:Glucose; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose
keywords: AMPK/m TOR pathway; Autophagy; Diabetes; Huang-gui solid dispersion; Neuronal apoptosis