PMID- 28924549 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2211-3835 (Print) IS - 2211-3843 (Electronic) IS - 2211-3835 (Linking) VI - 7 IP - 5 DP - 2017 Sep TI - Potassium 2-(1-hydroxypentyl)-benzoate attenuates neuronal apoptosis in neuron-astrocyte co-culture system through neurotrophy and neuroinflammation pathway. PG - 554-563 LID - 10.1016/j.apsb.2017.06.006 [doi] AB - Potassium 2-(1-hydroxypentyl)-benzoate (d,l-PHPB), a new drug candidate for ischemic stroke at the phase II clinic trial, has been shown to protect neurons by inhibiting oxidative injury and reducing neuron apoptosis in previous studies. But the mechanisms of d,l-PHPB remain to be studied. In this study, a neuron-astrocytes co-culture system was used to elucidate the roles of astrocytes in neuroprotection of d,l-PHPB under oxygen-glucose deprivation/reoxygenation (OGD/R) condition. Our data showed that d,l-PHPB reduced neuronal apoptosis in mono-culture system and this effect was enhanced in neuron-astrocyte co-culture system under the OGD/R condition. Meanwhile, d,l-PHPB obviously increased the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which were mainly secreted from astrocytes, in the co-culture system after OGD/R. The PI3K/AKT and ERK signaling pathways as well as the p-TRKA/B receptors were involved in the process. In addition, the levels of TNF-alpha and IL-1beta secreted from astrocytes after OGD/R were markedly reduced after d,l-PHPB treatment, which was mainly due to the suppression of phosphorylated p38. In conclusion, the present study demonstrates that the neuroprotective effects of d,l-PHPB were improved by astrocytes, mainly mediated by increasing the release of BDNF/NGF and attenuating inflammatory cytokines. FAU - Liu, Dongmei AU - Liu D AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Zhang, Man AU - Zhang M AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Rong, Xianfang AU - Rong X AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Li, Jiang AU - Li J AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Wang, Xiaoliang AU - Wang X AD - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. LA - eng PT - Journal Article DEP - 20170715 PL - Netherlands TA - Acta Pharm Sin B JT - Acta pharmaceutica Sinica. B JID - 101600560 PMC - PMC5595293 OTO - NOTNLM OT - Astrocytes OT - Neuro--astrocyte co-culture OT - Neuron apoptosis OT - Oxygen-glucose deprivation OT - d,l-PHPB EDAT- 2017/09/20 06:00 MHDA- 2017/09/20 06:01 PMCR- 2017/07/15 CRDT- 2017/09/20 06:00 PHST- 2017/05/14 00:00 [received] PHST- 2017/06/11 00:00 [revised] PHST- 2017/06/12 00:00 [accepted] PHST- 2017/09/20 06:00 [entrez] PHST- 2017/09/20 06:00 [pubmed] PHST- 2017/09/20 06:01 [medline] PHST- 2017/07/15 00:00 [pmc-release] AID - S2211-3835(17)30200-9 [pii] AID - 10.1016/j.apsb.2017.06.006 [doi] PST - ppublish SO - Acta Pharm Sin B. 2017 Sep;7(5):554-563. doi: 10.1016/j.apsb.2017.06.006. Epub 2017 Jul 15.