Effects of Huanglian-Jie-Du-Tang and its modified formula on the modulation of amyloid-β precursor protein processing in Alzheimer's disease models.
Effects of Huanglian-Jie-Du-Tang and its modified formula on the modulation of amyloid-β precursor protein processing in Alzheimer's disease models.
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DOI：
10.1371/journal.pone.0092954
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Durairajan SS;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
黄连解毒汤是临床上广泛应用的治疗脑缺血的著名中药方剂。最近，我们发现黄连解毒汤中的主要生物碱化合物小檗碱可减少阿尔茨海默病（AD）小鼠模型中β淀粉样蛋白（Aβ）的积累。本研究比较了黄连解毒汤、黄连解毒汤单味药（黄连、黄芩、黄柏、栀子）及不含黄芩的黄连解毒汤改良方（黄连解毒汤-M）对体外AD模型中淀粉样β前体蛋白（APP）调节加工的影响。在这里，我们表明HLJDT-M及其组分RC、CP和主要化合物小檗碱对稳定表达具有瑞典突变的人APP的N2 a小鼠神经母细胞瘤细胞的处理，（N2 a-SwedAPP）显著降低了全长APP、在苏氨酸668处磷酸化的APP、APP的C末端片段、可溶性APP（sAPP）-α和sAPPβ-Swedish，并减少N2 a-SwedAPP细胞裂解物中Aβ肽的产生。HLJT-M对APP和Aβ的降低作用比单独使用小檗碱、RC或CP更显著。与此相反，HLJDT，其组分RS和RS的主要活性化合物黄芩素，强烈增加细胞裂解物中APP的所有代谢产物的水平。然而，FG的提取物不影响APP调制。有趣的是，用黄芩素定期治疗TgCRND 8 APP转基因小鼠加重了淀粉样斑块负荷、APP代谢和Aβ产生。总之，这些数据提供了令人信服的证据，表明HLJDT和黄芩素治疗可增加APP的淀粉样蛋白代谢，这至少部分导致TgCRND 8小鼠脑中黄芩素介导的Aβ斑块增加。另一方面，HLJDT-M可显著降低所有APP代谢产物，包括Aβ。HLJDT-M治疗AD的进一步研究是必要的。
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-β (Aβ) 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-β 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)-α and sAPPβ-Swedish and reduced the generation of Aβ peptide in the cell lysates of N2a-SwedAPP. HLJDT-M showed more significant APP- and Aβ- 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 Aβ 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 Aβ plaque increase in the brains of TgCRND8 mice. On the other hand, HLJDT-M significantly decreased all the APP metabolic products including Aβ. Further study of HLJDT-M for therapeutic use in treating AD is warranted.
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DOI：
10.1083/jcb.200301115
发表时间：
2003-10-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lee MS;Kao SC;Lemere CA;Xia W;Tseng HC;Zhou Y;Neve R;Ahlijanian MK;Tsai LH
通讯作者：
Tsai LH
影响因子：
3.2
作者：
Okamoto H;Chino A;Hirasaki Y;Ueda K;Iyo M;Namiki T
通讯作者：
Namiki T
影响因子：
5.3
作者：
Lazarov, O;Morfini, GA;Sisodia, SS
通讯作者：
Sisodia, SS
影响因子：
4.2
作者：
Durairajan, Siva Sundara Kumar;Liu, Liang-Feng;Li, Min
通讯作者：
Li, Min
加速溶剂萃取结合光电二极管阵列超高效液相色谱分析和串联质谱检测分析黄连中的生物碱
影响因子：
6.2
作者：
Chen, Junhui;Wang, Fenymei;Yang, Huanghao
通讯作者：
Yang, Huanghao