Effects of Huanglian-Jie-Du-Tang and Its Modified Formula on the Modulation of Amyloid-beta Precursor Protein Processing in Alzheimer's Disease Models
Publication in refereed journal

香港中文大學研究人員

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摘要Huanglian-Jie-Du-Tang (HLJDT) is a famous traditional Chinese herbal formula that has been widely used clinically to treat cerebral ischemia. Recently, we found that berberine, a major alkaloid compound in HLJDT, reduced amyloid-beta (A beta) accumulation in an Alzheimer's disease (AD) mouse model. In this study, we compared the effects of HLJDT, four single component herbs of HLJDT (Rhizoma coptidis (RC), Radix scutellariae (RS), Cortex phellodendri (CP) and Fructus gardenia (FG)) and the modified formula of HLJDT (HLJDT-M, which is free of RS) on the regulatory processing of amyloid-beta precursor protein (APP) in an in vitro model of AD. Here we show that treatment with HLJDT-M and its components RC, CP, and the main compound berberine on N2a mouse neuroblastoma cells stably expressing human APP with the Swedish mutation (N2a-SwedAPP) significantly decreased the levels of full-length APP, phosphorylated APP at threonine 668, C-terminal fragments of APP, soluble APP (sAPP)-alpha and sAPP beta-Swedish and reduced the generation of A beta peptide in the cell lysates of N2a-SwedAPP. HLJDT-M showed more significant APP- and A beta-reducing effects than berberine, RC or CP treatment alone. In contrast, HLJDT, its component RS and the main active compound of RS, baicalein, strongly increased the levels of all the metabolic products of APP in the cell lysates. The extract from FG, however, did not influence APP modulation. Interestingly, regular treatment of TgCRND8 APP transgenic mice with baicalein exacerbated the amyloid plaque burden, APP metabolism and A beta production. Taken together, these data provide convincing evidence that HLJDT and baicalein treatment can increase the amyloidogenic metabolism of APP which is at least partly responsible for the baicalein-mediated A beta plaque increase in the brains of TgCRND8 mice. On the other hand, HLJDT-M significantly decreased all the APP metabolic products including A beta. Further study of HLJDT-M for therapeutic use in treating AD is warranted.
著者Durairajan SSK, Huang YY, Yuen PY, Chen LL, Kwok KY, Liu LF, Song JX, Han QB, Xue L, Chung SK, Huang JD, Baum L, Senapati S, Li M
期刊名稱PLoS ONE
出版年份2014
月份3
日期26
卷號9
期次3
出版社PUBLIC LIBRARY SCIENCE
國際標準期刊號1932-6203
語言英式英語
Web of Science 學科類別Multidisciplinary Sciences; MULTIDISCIPLINARY SCIENCES; Science & Technology - Other Topics

上次更新時間 2020-25-11 於 01:54