PART 2 DNA Microarray-Based Screening And Characterization Of Traditional Chinese Medicine
Mar 03, 2022
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4. Applications of DNA Microarray Assays for Traditional Chinese Medicine
Modernization of TCM has been discussed in association with several key issues, such as the material basis of TCM formulas, the quality evaluation system and evaluation of the efficiency and safety of TCM formulas; key technological tools in systems biology, such as those in genomics, interactomics, metabolomics, phenomics, and proteomics, could also be used to understand the chamomile of TCM, an integrated world of the external TCM system and the internal human body [2]. TCMs, such as Beimu (Fritillaria spp.), Chishao (Paeonia spp.), Chuanxiong (Ligusticum chuanxiong), Chuipencao (Sedum sarmentosum), Danggui (Angelica sinensis), Danshen (Salvia miltiorrhiza), Dongchongxiacao (Cordyceps sinensis), Ezhu/YYujin (rhizome and radix of Curcuma), Guanghuoxiang (Pogostemon cablin), Huangqi (Astragalus spp.), Jinyinhua (Lonicera japonica), Juhua (Chrysanthemum morifolium), Lingzhi (Ganoderma spp.), Sanqi (Panax notoginseng), Wuweizi (Schisandra chinensis), and Yingyanghuo (Epimedium spp.), were analyzed by biophysical techniques such as capillary electrophoresis, gas chromatography, HPLC, mass spectrometry (MS), thin-layer chromatography (TLC), ultra-performance liquid chromatography (UPLC), and ultraviolet/near-infrared spectrometry, by molecular biological techniques such as genomic PCR and RT-PCR, or by immunological assays such as enzyme-linked immunosorbent assay (ELISA) for screening and/or quality control of effective components, which include alkaloids, cyanophoric glycosides, ergosterol, essential oils, flavonoids, iridoid glycosides, lignans, paeoniflorin, phenolic acids, saponins, steroids, sugars/polysaccharides, and triterpenoids [5].
Chinese medicinal plants were analyzed by DNA-based technologies, such as those detecting amplified fragment length polymorphism (AFLP), cleaved amplified polymorphic sequence (CAPS), inter-simple sequence repeat (ISSR), random amplified polymorphic DNA (RAPD), restriction fragment length polymorphism (RFLP), and simple sequence repeat (SSR), and those by amplification refractory mutation system (ARMS), DNA amplification fingerprinting (DAF), hybridization, microarray assay and sequencing [8], or by assays at the cell/tissue/animal levels, such as gene knockout and cell membrane chromatography and transgenics [187].
The literature surveyed for transcriptomics using DMA in the study of 297 frequently used medicinal herbs in China showed that most of the studies focused on finding their biological effects [10]. However, there are cases where DMA was applied to screen effective components and for quality control of https://www.xjcistanche.com/cistanche-health-products/cistanche-tubulosa-benefits.html. In this section, we discuss how DMA has been used for quality control of TCM.
Additional applications of effective chemicals in TCM analyzed by DMA include patent filing, drug discovery, and clinical trials. An effective chemical identified and characterized by these applications can be patented as a new chemical, or otherwise as a known chemical with a new application.
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4.1. DNA Microarray Assays for Quality Control of Traditional Chinese Medicine
DMA has been used to detect and evaluate various activities of pure chemicals and mixtures of chemicals [13,188]. When DMA was applied for the study of TCM, gene sets specific to herbs were selected. For example, a set of 55 genes were screened by DMA in order to understand the effect of the Qingfei Xiaoyan Wan formula on asthma by the regulation of gene/protein networks [80]. A set of 92 genes was found to be differentially regulated by Toki-shakuyaku-san, a formula effective for circulation problems [89]. A set of nine marker genes was initially screened by DMA and subsequently confirmed by RT-PCR to assess the batch-to-batch consistency of the biological effects of ISF-1, a formula used for the management of post-stroke disorders [6].
Once gene sets have been selected, they can be used for screening and/or quality control of the herbs. For example, DMA was used to screen TCM species with inhibitory effects on Cytochrome P450 (CYP450) intended to treat HIV infection [189]. High-throughput DMA was applied to screen for anti-mitotic effects (independent of toxicity) on the proliferation of MDA-MB-231 cells from 897 aqueous extracts of commonly used natural products, and less than 1.34% of the extracts tested showed growth inhibitory properties at a concentration of less than 0.0183 mg/mL [27]. The DMA based on the yeast transcriptome was used for quality control of the extracts of Equisetum arvense [30].
Specific activity was examined to evaluate the quality of materials in food and supplements. For example, estrogenic activity was examined by DMA using a customized DNA microarray containing 172 estrogen-responsive genes in order to evaluate food materials, such as phytoestrogens [127] and ginsenosides [148], and for the extracts of plants and mushrooms, such as soybeans [127], Glycyrrhiza glabra [150], and Agaricus blazei [138]. The estrogen-responsive genes were further classified into six functional groups (enzymes, signaling, proliferation, transcription, transport, and others) and some showed preferences for specific groups [183].
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4.2. Protocols of DNA Microarray Assays for Quality Control
Schemes of new DMA-based protocols for quality control of herbal extracts are summarized in Figure 2. A simplified protocol is based on gene expression profiles of different sources of herbal extracts (A1 to A5), which are compared with that of a standard (S) by correlation coefficients (R-values) based on linear regression (Figure 2A). Deviations (such as in A3, Figure 2A) can be detected by comparing R-values. While gene sets for expression profiling can be used without selection (Figure 2A), the genes having specific cell functions could be used to improve the level of quality control (Figure 2B, C), where the gene sets (G1 to G3) can be selected arbitrarily, such as those showing stable (G1), less stable (G2) or unstable (G3) reproducibility when various lots (A1 and A2) of the herbal extracts are compared with a standard (Figure 2B). Alternatively, gene sets can be selected according to gene functions (Figure 2C), where profiling can be performed with functionally grouped genes (F1 to F3) to give a protocol of efficacy-based quality control of herbal extracts. The advantages of using these protocols are that: (1) cell function-based gene ex procession profiling is good for efficacy-based quality control; (2 ) gene sets can be selected.
4. Conclusions and Perspectives
Owing to the progress of new biotechnological tools, new approaches have been developed, including systems biology, signal transduction study, and RNA-sequencing-based whole genome/exome analysis, which provide us with massive amounts of omics data. However, we still do not know how to use these tools effectively. For example, we now know a number of chemicals showing estrogenic activity and the number is steadily increasing because they affect cells, tissues, and organs through complex and novel pathways of cell signaling, such as intracellular signal transduction, signal crosstalk/bypassing, and intercellular networks of autocrine/paracrine signaling [185,186]. This complex status would be the same as in the study and the application of TCM because, since the estrogenic activity is one of the most important activities of effective components in herbs and has been shown to affect the human body, the findings of estrogen would be true for more complex statuses, which include other hormones and growth factors. Chemicals having other hormonal and growth-factor activities could show such complexities, and thus new approaches are needed to understand the effects of chemicals. Other than the pharmacological use of chemicals, DMA-based gene expression profiling and pathway-based testing of chemicals have been developed for the diagnosis of diseases and risk assessment of endocrine disruptors, where the development of new types of diagnostic tool is in progress, such as the in vitro diagnostic multivariate index assay (IVDMIA), and toxicity pathway-based risk management protocols, such as those proposed by the U.S. National Research Council [190]. Thus, a pathway-based evaluation of beneficial effects and the assessment of potential risks by means of omics technologies are needed for the study and development of TCM.
Acknowledgments: This research was supported partly by a Knowledge Cluster Initiative program and a Grant-in-aid for Basic Areas from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, a grant from Kyushu Sangyo University for promoting the development and application of new fluorescent dyes, and by the Guideline Program for Medical Device Development from the Ministry of Economy, Trade, and Industry of Japan.
Conflicts of Interest: The author declares no conflict of interest.
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