Zholos Alexander V, Moroz Olesia F, Storozhuk Maksim V
A.A. Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, 4 Bogomoletz Street, Kiev 01024, Ukraine.
Taras Shevchenko National University of Kyiv, Educational and Scientific Centre "Institute of Biology and Medicine", 2 Academician Glushkov Avenue, Kiev 03022, Ukraine.
Curr Mol Pharmacol. 2019;12(1):12-26. doi: 10.2174/1874467211666181012150847.
Millions of people worldwide are suffering from Alzheimer's disease (AD), and there are only symptomatic treatments available for this disease. Thus, there is a great need to identify drugs capable of arresting or reversing AD. Constituents of the spice turmeric, in particular, curcuminoids, seem to be very promising, as evident from in vitro experiments and tests using animal models of AD. However, most of the clinical trials did not reveal any beneficial effects of curcuminoids in the treatment of AD. These controversies, including conflicting results of clinical trials, are thought to be related to bioavailability of curcuminoids, which is low unless it is enhanced by developing a special formulation. However, there is growing evidence suggesting that other reasons may be of even greater importance, but these avenues are less explored.
Review relevant literature, and analyze potential reasons for the controversial results.
Recent in vitro and preclinical studies; clinical trials (without a limiting period) were searched in PubMed and Google Scholar.
While recent in vitro and preclinical studies confirm the therapeutic potential of curcuminoids in the treatment of AD and cognitive dysfunctions, results of corresponding clinical trials remain rather controversial.
The controversial results obtained in the clinical trials may be in part due to particularities of the curcuminoid formulations other than bioavailability. Namely, it seems likely that the various formulations differ in terms of their minor turmeric constituent(s). We hypothesize that these distinctions may be of key importance for efficacy of the particular formulation in clinical trials. A testable approach addressing this hypothesis is suggested.
全球数以百万计的人患有阿尔茨海默病（AD），而针对这种疾病目前只有对症治疗方法。因此，迫切需要找到能够阻止或逆转AD的药物。姜黄这种香料的成分，尤其是姜黄素类化合物，从体外实验和AD动物模型试验来看似乎很有前景。然而，大多数临床试验并未显示姜黄素类化合物在AD治疗中有任何有益效果。这些争议，包括临床试验结果相互矛盾，被认为与姜黄素类化合物的生物利用度有关，其生物利用度较低，除非通过开发特殊制剂来提高。然而，越来越多的证据表明其他原因可能更为重要，但这些方面较少被探索。
回顾相关文献，分析产生争议结果的潜在原因。
在PubMed和谷歌学术中检索近期的体外研究和临床前研究；不限定时间范围的临床试验。
虽然近期的体外研究和临床前研究证实了姜黄素类化合物在治疗AD和认知功能障碍方面的治疗潜力，但相应的临床试验结果仍颇具争议。
临床试验中获得的有争议结果可能部分归因于姜黄素类化合物制剂的特殊性而非生物利用度。也就是说，各种制剂的姜黄次要成分似乎有所不同。我们推测这些差异可能对特定制剂在临床试验中的疗效至关重要。本文提出了一种针对该假设的可测试方法。
