title: Daucosterol protects neurons against oxygen-glucose deprivation/reperfusion-mediated injury by activating IGF1 signaling pathway.
abstract: We previously reported that daucosterol (a sterolin) up-regulates the expression of insulin-like growth factor I (IGF1)(1) protein in neural stem cells. In this study, we investigated the effects of daucosterol on the survival of cultured cortical neurons after neurons were subjected to oxygen and glucose deprivation and simulated reperfusion (OGD/R)(2), and determined the corresponding molecular mechanism. The results showed that post-treatment of daucosterol significantly reduced neuronal loss, as well as apoptotic rate and caspase-3 activity, displaying the neuroprotective activity. We also found that daucosterol increased the expression level of IGF1 protein, diminished the down-regulation of p-AKT(3) and p-GSK-3β(4), thus activating the AKT(5) signal pathway. Additionally, it diminished the down-regulation of the anti-apoptotic proteins Mcl-1(6) and Bcl-2(7), and decreased the expression level of the pro-apoptotic protein Bax(8), thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol was inhibited in the presence of picropodophyllin (PPP)(9), the inhibitor of insulin-like growth factor I receptors (IGF1R)(10). Our study provided information about daucosterol as an efficient and inexpensive neuroprotectants, to which the IGF1-like activity of daucosterol contributes. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment.
authors: Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210038, China; Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors: Li-hua
authors: LH
authors: Jiang
authors: Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210038, China.
authors: Xiao-lin
authors: XL
authors: Yuan
authors: Department of Pharmacogonosy, Nanjing University of Chinese Medicine, Nanjing 210038, China.
authors: Nian-yun
authors: NY
authors: Yang
authors: Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210038, China.
authors: Li
authors: L
authors: Ren
authors: Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210038, China.
authors: Feng-ming
authors: FM
authors: Zhao
authors: Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210038, China.
authors: Ban-xin
authors: BX
authors: Luo
authors: School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210038, China.
authors: Yao-yao
authors: YY
authors: Bian
authors: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing University of Chinese Medicine, Nanjing 210038, China.
authors: Jian-ya
authors: JY
authors: Xu
authors: School of Medicine, Jinan University, Guangzhou 510632, China.
authors: Da-xiang
authors: DX
authors: Lu
authors: School of Medicine, Jinan University, Guangzhou 510632, China.
authors: Yuan-yuan
authors: YY
authors: Zheng
authors: School of Medicine, Jinan University, Guangzhou 510632, China.
authors: Chuan-juan
authors: CJ
authors: Zhang
authors: School of Basic Medical Science,Guangzhou University of Chinese Medicine, Guangzhou 510006,China.
authors: Yuan-ming
authors: YM
authors: Diao
authors: Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210038, China.
authors: Bao-mei
authors: BM
authors: Xia
authors: Laboratory of Integrative Biomedicine of Brain Diseases, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210038, China; Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: chengang@njucm.edu.cn.
authors: Gang
authors: G
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000166:cytology; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis; D000071679:Glycogen Synthase Kinase 3 beta; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D012855:Sitosterols / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C494828:Bax protein, rat; C579093:Mcl1 protein, rat; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017451:Receptors, Somatomedin; D012855:Sitosterols; D051028:bcl-2-Associated X Protein; C548904:insulin-like growth factor-1, rat; C415032:picropodophyllin; D007334:Insulin-Like Growth Factor I; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3; D005947:Glucose; D011034:Podophyllotoxin; D010100:Oxygen; C011015:lyoniside
keywords: Daucosterol; IGF1; Ischemic stroke; Neuron; Oxygen and glucose deprivation and simulated reperfusion