Ginsenoside compound K promotes β‑amyloid peptide clearance in primary astrocytes via autophagy enhancement

Guo,Jinhui; Chang,Li; Zhang,Xin; Pei,Sujuan; Yu,Meishuang; Gao,Jianlian

doi:10.3892/etm.2014.1885

Ginsenoside compound K promotes β‑amyloid peptide clearance in primary astrocytes via autophagy enhancement

Authors:
- Jinhui Guo
- Li Chang
- Xin Zhang
- Sujuan Pei
- Meishuang Yu
- Jianlian Gao
View Affiliations

Affiliations: Department of Pharmaceutics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
Published online on: August 6, 2014 https://doi.org/10.3892/etm.2014.1885
Pages: 1271-1274

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the effect of ginsenoside compound K on β‑amyloid (Aβ) peptide clearance in primary astrocytes. Aβ degradation in primary astrocytes was determined using an intracellular Aβ clearance assay. Aggregated LC3 in astrocyte cells, which is a marker for the level of autophagy, was detected using laser scanning confocal microscope. The effect of compound K on the mammalian target of rapamycin (mTOR)/autophagy pathway was determined using western blot analysis, and an enzyme‑linked immunosorbent assay was used for Aβ detection. The results demonstrated that compound K promoted the clearance of Aβ and enhanced autophagy in primary astrocytes. In addition, it was found that phosphorylation of mTOR was inhibited by compound K, which may have contributed to the enhanced autophagy. In conclusion, compound K promotes Aβ clearance by enhancing autophagy via the mTOR signaling pathway in primary astrocytes.

View Figures

View References

1	Brookmeyer R, Johnson E, Ziegler-Graham K and Arrighi HM: Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement. 3:186–191. 2007.
2	Younkin SG: The role of A beta 42 in Alzheimer’s disease. J Physiol Paris. 92:289–292. 1998.
3	Ohno M, Sametsky EA, Younkin LH, et al: BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer’s disease. Neuron. 41:27–33. 2004.PubMed/NCBI
4	Jarvis CI, Goncalves MB, Clarke E, et al: Retinoic acid receptor-α signalling antagonizes both intracellular and extracellular amyloid-β production and prevents neuronal cell death caused by amyloid-β. Eur J Neurosci. 32:1246–1255. 2010.
5	Bachmeier C, Beaulieu-Abdelahad D, Mullan M and Paris D: Selective dihydropyiridine compounds facilitate the clearance of β-amyloid across the blood-brain barrier. Eur J Pharmacol. 659:124–129. 2011.PubMed/NCBI
6	Kennelly SP, Abdullah L, Paris D, et al: Demonstration of safety in Alzheimer’s patients for intervention with an anti-hypertensive drug Nilvadipine: results from a 6-week open label study. Int J Geriatr Psychiatry. 26:1038–1045. 2011.
7	Klionsky DJ and Emr SD: Autophagy as a regulated pathway of cellular degradation. Science. 290:1717–1721. 2000. View Article : Google Scholar : PubMed/NCBI
8	Zhu Z, Yan J, Jiang W, et al: Arctigenin effectively ameliorates memory impairment in Alzheimer’s disease model mice targeting both β-amyloid production and clearance. J Neurosci. 33:13138–13149. 2013.PubMed/NCBI
9	Spilman P, Podlutskaya N, Hart MJ, et al: Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer’s disease. PLoS One. 5:e99792010.PubMed/NCBI
10	Cho CW, Kim YC, Kang JH, et al: Characteristic study on the chemical components of Korean curved ginseng products. J Ginseng Res. 37:349–354. 2013. View Article : Google Scholar : PubMed/NCBI
11	Seo SK, Hong Y, Yun BH, et al: Antioxidative effects of Korean red ginseng in postmenopausal women: A double-blind randomized controlled trial. J Ethnopharmacol. 154:753–757. 2014. View Article : Google Scholar : PubMed/NCBI
12	Zhang X, Wang J, Xing Y, et al: Effects of ginsenoside Rg1 or 17β-estradiol on a cognitively impaired, ovariectomized rat model of Alzheimer’s disease. Neuroscience. 220:191–200. 2012.
13	Wakabayashi C, Murakami K, Hasegawa H, Murata J and Saiki I: An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem Biophys Res Commun. 246:725–730. 1998. View Article : Google Scholar : PubMed/NCBI
14	Cramer PE, Cirrito JR, Wesson DW, et al: ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models. Science. 335:1503–1506. 2012. View Article : Google Scholar : PubMed/NCBI
15	Mizushima N: The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol. 22:132–139. 2010. View Article : Google Scholar : PubMed/NCBI
16	Hara T, Nakamura K, Matsui M, et al: Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 441:885–889. 2006. View Article : Google Scholar : PubMed/NCBI
17	Nixon RA: The role of autophagy in neurodegenerative disease. Nat Med. 19:983–997. 2013. View Article : Google Scholar : PubMed/NCBI
18	Vingtdeux V, Chandakkar P, Zhao H, et al: Novel synthetic small-molecule activators of AMPK as enhancers of autophagy and amyloid-β peptide degradation. FASEB J. 25:219–231. 2011.PubMed/NCBI
19	Steele JW and Gandy S: Latrepirdine (Dimebon^®), a potential Alzheimer therapeutic, regulates autophagy and neuropathology in an Alzheimer mouse model. Autophagy. 9:617–618. 2013.
20	Gao C, Liu Y, Jiang Y, Ding J and Li L: Geniposide ameliorates learning memory deficits, reduces tau phosphorylation and decreases apoptosis via GSK3β pathway in streptozotocin-induced alzheimer rat model. Brain Pathol. 24:261–269. 2014.PubMed/NCBI