Abstract
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.
Highlights
Ginger is a popular spice and food preservative
Consistent with the reports by Liao et al (2012) [47] and John et al (2013) [48], the present study showed the ability of 6-shogaol to independently induce neuritogenesis which was comparable to the nerve growth factor (NGF) in cells rat pheochromocytoma cells (PC-12) cells
The present findings demonstrated that 6-shogaol-induced neuritogenesis in PC12 cells was significantly attenuated by the addition of U0126, PD98059, and LY294002 inhibitors, Fig. 7 Hypothetical mechanisms of NGF and 6-shogaol neuritogenesis in PC-12 cells
Summary
Ginger is a popular spice and food preservative. The rhizomes of the common ginger have been used as traditional medicine to treat various ailments. Members of the Zingiberaceae family have attracted enormous interest among researchers due to their popularity as spices and food preservatives, and their use in traditional medicine. One of the most well-known members of the Zingiberaceae family is the common ginger, Zingiber officinale Roscoe var. Originally from South-East Asia, was introduced to many parts of the world and has been cultivated for the past thousands of years for use as spices and traditional remedies [4, 5]. The rhizomes of the common ginger have been used for a wide array of ailments conditions such as colds, nauseas, headaches, hypertension, dementia, indigestion, vomiting, fever, gastrointestinal discomfort, constipation, arthritis, and rheumatism as early as 2500 years ago [5,6,7,8]
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