6-shogaol, a neuroactive compound of ginger (jahe gajah) induced neuritogenic activity via NGF responsive pathways in PC-12 cells

BMC Complementary and Alternative Medicine

Research Article

Guan Serm Lee¹  Sok Lai Hong¹  Vikineswary Sabaratnam¹  Syntyche Ling Sing Seow¹  Sri Nurestri Abd Malek¹ 

[1]Mushroom Research Centre, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia

[2]Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia

关键词: 6-Shogaol;    Ginger;    Nerve growth factor;    Neuritogenesis;    PC-12 cells;    NGF mimics;    TrkA;    MEK/ERK1/2;    PI3K/AKT;    Neurodegenerative disease;   

DOI  :  10.1186/s12906-017-1837-6

 received in 2016-03-14, accepted in 2017-06-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundGinger is a popular spice and food preservative. The rhizomes of the common ginger have been used as traditional medicine to treat various ailments. 6-Shogaol, a pungent compound isolated from the rhizomes of jahe gajah (Zingiber officinale var officinale) has shown numerous pharmacological activities, including neuroprotective and anti-neuroinflammatory activities. The aim of this study was to investigate the potential of 6-shogaol to mimic the neuritogenic activity of nerve growth factor (NGF) in rat pheochromocytoma (PC-12) cells.MethodsThe cytotoxic effect of 6-shogaol was determined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The neuritogenic activity was assessed by neurite outgrowth stimulation assay while the concentration of extracellular NGF in cell culture supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). Involvement of cellular signaling pathways, mitogen-activated protein kinase kinase/extracellular signal-regulated kinase1/2 (MEK/ERK1/2) and phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) in 6-shogaol-stimulated neuritogenesis were examined by using specific pharmacological inhibitors.Results6-Shogaol (500 ng/ml) induced neuritogenesis that was comparable to NGF (50 ng/ml) and was not cytotoxic towards PC-12 cells. 6-Shogaol induced low level of NGF biosynthesis in PC-12 cells, showing that 6-shogaol stimulated neuritogenesis possibly by inducing NGF biosynthesis, and also acting as a substitute for NGF (NGF mimic) in PC-12 cells. The inhibitors of Trk receptor (K252a), MEK/ERK1/2 (U0126 and PD98059) and PI3K/AKT (LY294002) attenuated the neuritogenic activity of both NGF and 6-shogaol, respectively.ConclusionsThe present findings demonstrated that 6-shogaol induced neuritogenic activity in PC-12 cells via the activation MEK/ERK1/2 and PI3K/AKT signaling pathways. This study suggests that 6-shogaol could act as an NGF mimic, which may be beneficial for preventive and therapeutic uses in neurodegenerative diseases.

【 授权许可】

CC BY   
© The Author(s). 2017