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DNA Microarray-Based Screening and Characterization of Traditional Chinese Medicine

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DNA Microarray-Based Screening and Characterization of Traditional Chinese Medicine Review DNA Microarray‐Based Screening and Characterization of Traditional Chinese Medicine Ryoiti Kiyama Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1‐1‐ 1 Higashi, Tsukuba 305‐8566, Ibaraki, Japan; [email protected]; Tel.: +81‐29‐861‐6189 Academic Editor: Christophe A. Marquette Received: 16 December 2016; Accepted: 23 January 2017; Published: 30 January 2017 Abstract: The application of DNA microarray assay (DMA) has entered a new era owing to recent innovations in omics technologies. This review summarizes recent applications of DMA‐based gene expression profiling by focusing on the screening and characterization of traditional Chinese medicine. First, herbs, mushrooms, and dietary plants analyzed by DMA along with their effective components and their biological/physiological effects are summarized and discussed by examining their comprehensive list and a list of representative effective chemicals. Second, the mechanisms of action of traditional Chinese medicine are summarized by examining the genes and pathways responsible for the action, the cell functions involved in the action, and the activities found by DMA (silent estrogens). Third, applications of DMA for traditional Chinese medicine are discussed by examining reported examples and new protocols for its use in quality control. Further innovations in the signaling pathway‐based evaluation of beneficial effects and the assessment of potential risks of traditional Chinese medicine are expected, just as are observed in other closely related fields, such as the therapeutic, environmental, nutritional, and pharmacological fields. Keywords: DNA microarray; traditional Chinese medicine; signaling pathway; estrogen; food chemicals 1. Introduction Herbal medicine is an important part of the medical practices in traditional Chinese medicine (TCM), and consists of a variety of plant species [1,2]. While the effectiveness of herbal medicine has sometimes been considered doubtful [3,4], this could be due in part to the difficulty of controlling the quality of herbs and the amounts of their effective components. Thus, various methods have been used to confirm their efficacy and identify the effective components [5]. Modern technologies, such as high‐performance liquid chromatography (HPLC) and quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), have been continually developed and utilized to replace conventional technologies for the comprehensive and cost‐effective quality control of herbal medicine [6]. Although recent progress in the human and other genome projects and the development of a variety of omics technologies—such as genomics and transcriptomics—have contributed to the identification and utilization of effective components and quality control/authentication of medicinal plants [7–11], we are still searching for the best strategy for the maximum utilization of herbal medicine. This review focuses on DNA microarray‐based gene expression profiling, a key technology in transcriptomics, and shows how researchers used this technology for the screening and characterization of TCM. In particular, cross‐examination of the data on TCMs, and their constituent herbs, mushrooms, and dietary plants, has become quite important to evaluate the knowledge accumulated and to assess the advantages/disadvantages of TCM and its effective applications. TCM includes practices such as acupuncture, moxibustion, Chinese herbal medicine, tui na, dietary therapy, tai chi, and qi gong, which is rooted in the ancient philosophy of Taoism and is more Microarrays 2017, 6, 4; doi: 10.3390/microarrays6010004 www.mdpi.com/journal/microarrays Microarrays 2017, 6, 4 2 of 27 than 2500 years old [12]. The original TCM has been further developed and modified to adapt it to people of various nationalities and genetic backgrounds (giving rise to different types of health problems, dietary and nutritional customs/practices, and ways of thinking and beliefs about medicine), based on variations in the types of herbs and their ingredients in countries such as Japan and Korea, where Kampo and traditional Korean medicine (TKM), respectively, were developed. Therefore, herbal medicine includes a number of plant species and ways of processing them. Furthermore, herbal medicine is often used with other constituents such as mushrooms and dietary plants, and thus their extracts and effective chemicals are also discussed here. DNA microarrays are a type of biotechnological device used to detect alterations in genomic DNA and mRNA and to monitor genes and their expressions associated with various functions; thus, they have been widely used in basic research and industrial research/development (reviewed by Kiyama & Zhu [13]). DNA microarray assay (DMA) has been used to screen and characterize useful materials among mixtures of chemicals and extracts of natural resources including plants. DMA has advantages and disadvantages compared with other technologies. It has been used as a diagnostic device, such as for the genotyping of drug‐metabolizing genes and predicting the metastatic risk of breast cancer, which is attributable to its unique characteristic of providing sufficient complexity to differentiate the variations needed for diagnosis and the reliability needed to predict genotypes/gene expression profiles accurately. 2. Herbal Medicine, Effective Chemicals, and Their Effects 2.1. Herbs, Mushrooms, and Dietary Plants Analyzed by DNA Microarray Assays A number of herbs, mushrooms, and dietary plants, including those used as TCM in China, Korea (TKM), and Japan (Kampo), have been analyzed by DMA (Table 1). Table 1. Herbs, traditional medicines, mushrooms, and dietary plants analyzed by DNA microarray assay (DMA). Extract or Material Pathway or Function Source Reference (Assay a) Examined Examined/Identified Herb Einbond et al., 2012 [14] Actaea racemosa (Black cohosh) Extract Anti‐carcinogenesis (A, C, T) Angelica sinensis (Dong quai) Extract Wound healing Zhao et al., 2012 [15] (C, T) Anoectochilus formosanus (an orchid) Extract Anti‐carcinogenesis Yang et al., 2004 [16] (C, T) Astragalus propinquus, Rehmannia Wnt Zhang et al., 2011 [17] (C, Radix extract glutinosa signaling/Angiogenesis P, T) Kiela et al., 2005 [18] (A, C, Boswellia serrata (Salai) Extract Anti‐inflammation R, T) Chelidonium majus (Greater El‐Readi et al., 2013 [19] Extract (Alkaloids) Anti‐carcinogenesis celandine) (C, T) Chrysanthemum lavandulifolium Extract Antibiotic Kim et al., 2013 [20] (T) (Mum) Shimoda et al., 2009 [21] Cistanche tubulosa Root extract Anti‐atherosclerosis (A, T) Cheng et al., 2008 [22] (C, Coptis chinensis (Chinese goldthread) Rhizome extract p53 signaling T) Iizuka et al., 2003 [23] (C, Coptis japonica (Goldthread) Rhizome extract Anti‐carcinogenesis T) Kang et al., 2005 [24] (C, P, Coptis japonica (Goldthread) Rhizome extract IFβ/TNF‐α/Apoptosis T) Kim et al., 2013 [25] (A, C, Curcuma longa (Turmeric) Extract Anti‐inflammation T) Honda et al., 2006 [26] (A, Curcuma longa (Turmeric) Essential oil Anti‐diabetic effect T) Dioscorea villosa (Wild yam), Mazzio et al., 2014 [27] (C, Lithospermum canescens (Alkanet Extract Anti‐mitotic effect T) root), Microarrays 2017, 6, 4 3 of 27 Trillium erectum (Beth root) Echinacea purpurea (Purple Wang et al., 2006 [28] (C, Extract Immune response coneflower) T) Echinacea purpurea (Purple Wang et al., 2008 [29] (C, Extract Immune response coneflower) P, T) Metabolism/Stress Equisetum arvense (Field horsetail) Extract Cook et al., 2013 [30] (C, T) response Maas et al., 2011 [31] (C, P, Eupatorium perfoliatum (Boneset) Extract Anti‐inflammation T) Hedyotis diffusa Extract Anti‐carcinogenesis Kuo et al., 2015 [32] (C, T) Hypericum perforatum (St. John’s Wong et al., 2004 [33] (A, Extract Antidepressant wort) T) Hypericum perforatum (St. John’s Neurological McCue & Phang, 2008 [34] Extract wort) disease/Angiogenesis (A, P, T) Levisticum officinale (Lovage) Essential oil Cell proliferation Sertel et al., 2011 [35] (C, T) MAPK/NO/Anti‐ Sohn et al., 2009 [36] (C, P, Nelumbo nucifera (Lotus) Seed extract inflammation T) Nelumbo nucifera (Lotus) Seed extract Neuroprotection Lee et al., 2010 [37] (A, T) Paeonia lactiflora (Chinese peony) Root extract Apoptosis Lee et al., 2002 [38] (C, T) Paeonia suffruticosa (Moutan) Extract Anti‐inflammation Yun et al., 2012 [39] (C, T) Panax quinquefolius (American Extract Anti‐carcinogenesis Luo et al., 2008 [40] (C, T) ginseng) Piper methysticum (Kava) Extract Hepatotoxicity Guo et al., 2010 [41] (A, T) Piper methysticum (Kava) Extract Hepatotoxicity Guo et al., 2009 [42] (A, T) Fong et al., 2011 [43] (C, P, Salvia miltiorrhiza, Pueraria lobata Root extract MAPK/Insulin signaling T) Scrophularia ningpoensis (Chinese Shen et al., 2012 [44] (C, P, Extract MAPK/NF‐κB/Apoptosis figwort) T) Scutellaria barbata (Barbed skullcap) Extract Anti‐carcinogenesis Yin et al., 2004 [45] (C, T) Stander et al., 2007 [46] (C, Sutherlandia frutescens (Cancer bush) Extract Apoptosis T) Mukherjee et al., 2009 [47] Tabebuia avellandae (Pink Lapacho) Extract Apoptosis (C, T) Zhang et al., 2012 [48] (A, Tripterygium wilfordii (Leigongteng) Extract PPAR/Hepatotoxicity T) Vitex rotundifolia (Beach vitex) Extract MAPK/Anti‐inflammation Sohn et al., 2009 [49] (C, T) Mushroom Agaricus bisporus (Common Adams et al., 2008 [50] (C, Extract Anti‐carcinogenesis mushroom) T) Ellertsen et al., 2006 [51] Agaricus blazei (Himematsutake) Extract Immune response (P, T) Grinde et al., 2006 [52] (C, Agaricus blazei Extract
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