Identifying the active ingredients from natural herbal medicines and demonstrating their potential mechanisms are key points in the traditional Chinese medicine (TCM) field. In recent years, increasing studies have focused on the effects and mechanisms of Chinese herbal formulas. Basic studies on these formulas further coincide with the theory and practical use of TCM according to the clinical experiences for thousands of years. Single compounds have specific molecular structures; therefore, their methodologies in effect and mechanism studies are similar in both Western and Eastern medicines, making them more acceptable by researchers worldwide. On the contrary, the multicomponent, multitarget, and multipathway structures of Chinese formulas make it challenging to explore their mechanisms accurately where the routine method used in Western medicine studies would be inapplicable, which is the main reason for the unacceptance of Chinese herbal formulas by researchers worldwide and presents a huge obstacle to the modernization of TCM. With the rapid progress in basic TCM studies, scientific and technological innovations have achieved a breakthrough in TCM. Omic technology, a series of research methods based on high-throughput analysis and detection techniques in modern biological research system such as genomics, transcriptomics, proteomics, and metabolomics, evaluates thousands of targets and pathways rather than focusing on a single target or pathway and could screen the global changes in genes, proteins, metabolites, and other factors involved in the process of biological signaling transduction [1]. This is in agreement with the “holism” theory in TCM, which explains the overall mechanisms of Chinese herbal formulas comprehensively. In this study, we introduced the conventionally used omic technologies and their applications in research of mechanism studies of Chinese herbal formulas.

1. Traditional Medicine Research
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doi: 10.12032/TMR20200920199
Traditional Chinese Medicine
Omics technology: an important tool in mechanism studies of Chinese
herbal formulas
Huan-Tian Cui1
, Lu Yang2
, Yu-Ting Li2
, Hong-Wu Wang3*
1
Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong
University, Qingdao 250100, China; 2
Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617,
China; 3
College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
*Corresponding to: Hong-Wu Wang. College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese
Medicine, No.10 Poyanghu Road, Jinghai District, Tianjin 301617, China. E-mail: whw2009@tjutcm.edu.cn.
Competing interests:
The authors declare no conflicts of interest.
Abbreviations:
TCM, traditional Chinese medicine; GO, Gene Oncology; KEGG, Kyoto Encyclopedia of Genes and Genomes;
AMI, acute myocardial infarction; MicroRNA, miRNA; QSYQ, the Chinese patent medicine Qi-Shen-Yi-Qi;
XFZY, the classic ancient prescription Xue-Fu-Zhu-Yu decoction.
Citation:
Cui HT, Yang L, Li YT, Wang HW. Omics technology: an important tool in mechanism studies of Chinese herbal
formulas. Tradit Med Res. 2021; 6(1): 2. doi: 10.12032/TMR20200920199.
Executive editor: Yu-Pinging Shi.
Submitted: 11 June 2020, Accepted: 12 September 2020, Online: 13 October 2020.
© 2021 By Authors. Published by TMR Publishing Group Limited. This is an open access article under the CC-BY
license (http://creativecommons.org/licenses/BY/4.0/).

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Background
Identifying the active ingredients from natural herbal
medicines and demonstrating their potential
mechanisms are key points in the traditional Chinese
medicine (TCM) field. In recent years, increasing
studies have focused on the effects and mechanisms of
Chinese herbal formulas. Basic studies on these
formulas further coincide with the theory and practical
use of TCM according to the clinical experiences for
thousands of years. Single compounds have specific
molecular structures; therefore, their methodologies in
effect and mechanism studies are similar in both
Western and Eastern medicines, making them more
acceptable by researchers worldwide. On the contrary,
the multicomponent, multitarget, and multipathway
structures of Chinese formulas make it challenging to
explore their mechanisms accurately where the routine
method used in Western medicine studies would be
inapplicable, which is the main reason for the
unacceptance of Chinese herbal formulas by
researchers worldwide and presents a huge obstacle to
the modernization of TCM. With the rapid progress in
basic TCM studies, scientific and technological
innovations have achieved a breakthrough in TCM.
Omic technology, a series of research methods based
on high-throughput analysis and detection techniques
in modern biological research system such as
genomics, transcriptomics, proteomics, and
metabolomics, evaluates thousands of targets and
pathways rather than focusing on a single target or
pathway and could screen the global changes in genes,
proteins, metabolites, and other factors involved in the
process of biological signaling transduction [1]. This is
in agreement with the “holism” theory in TCM, which
explains the overall mechanisms of Chinese herbal
formulas comprehensively. In this study, we introduced
the conventionally used omic technologies and their
applications in research of mechanism studies of
Chinese herbal formulas.
Genomics and transcriptomics techniques
Genomics and transcriptomics techniques, including
gene microarray and high-throughput sequencing, are
concerned with all gene transcription and its regulation
on the cell level [2]. Genomics is the first developed
omics technique and could screen the whole genic
changes before and after drug intervention, whereas
transcriptomics is more likely to focus on total RNAs
after transcription. The amount of data generated in
transcriptomics is less than that in genomics, making it
easier to be analyzed [3]. Currently, transcriptomics is
widely used in the identification of differentially
expressed genes with or without TCM treatment in
vivo and in vitro. High-throughput sequencing is a
powerful tool for analyzing high-throughput gene
expression spectrum. Key genes are obtained by
analyzing the interactions of differentially expressed
genes and major pathways affected by drug
intervention could be identified using Gene Oncology
(GO) and Kyoto Encyclopedia of Genes and Genomes
(KEGG) analyses [4]. Wang et al. used
high-throughput sequencing to screen the multifaceted
therapeutic effects of the Chinese patent medicine
Qi-Shen-Yi-Qi (QSYQ, the approved number by China
FDA: YBZ04332003) on acute myocardial infarction
(AMI). Generally, after QSYQ treatment, 2,733
differentially expressed genes, including 1,344
upregulated and 1,389 downregulated genes, were
identified in the AMI model in rats. Further KEGG
analysis and experimental validation suggested that
arachidonic acid LOX pathway, nitric oxide production,
and fatty acid oxidation could be the potential
mechanisms of QSYQ on AMI [5].
Gene microarray evaluates the epigenetic
modulation in cells and organs. Epigenetics techniques
are focused on the alterations in the function of genes
that do not involve changes in the DNA sequence [6].
In addition to the changes of DNA and RNA sequences,
several regulatory approaches have been discovered to
regulate turning genes “on” and “off” in tissues and
cells, such as DNA methylation, histone modification,
miRNA, lncRNA, and circRNA. DNA methylation has
been widely studied to regulate the transcription of
target genes. Abnormalities in DNA methylation are
associated with coronary heart disease and the Chinese
patent medicine Yang-Xin-Tong-Mai formula (the
approved number by China FDA: Z12020589) could
affect the methylation of the ZEB2 gene to treat it [7].
MicroRNA (miRNA) is a small single-stranded
RNA molecule that has been involved in many
physiological and pathological processes. Active
ingredients in Chinese herbal formulas have extensive
regulatory effects on miRNA, and studying miRNA
has opened a new field for the exploration of TCM
mechanisms [8]. Moreover, the roles of lncRNAs and
circRNAs in health and diseases have also been widely
investigated in recent years [9]. Modulating lncRNAs
and circRNAs is a new research approach to defining
the epigenetic regulatory mechanisms and targets of
Chinese herbal formula. Dai et al. studied the
mechanisms of QSYQ dripping pills on ischemic heart
disease using miRNA chip. The results revealed that
QSYQ could promote the angiogenesis in ischemic
cardiac microvascular endothelial cells by regulating
the expression of miR-223-3p and RPS6KB1/HIF-1α
signaling pathway [10].
Proteomics technique
The proteomics technique assesses the types, levels,
modifications, interactions, functions, and structures of
proteins in cells, tissues, body fluids, and other
samples. It provides high flux, high sensitivity, high

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linear range, and high accuracy. Furthermore,
proteomics is able to detect changes in protein levels
between physiological or pathological conditions and
identify the dysregulated proteins before and after
TCM treatment [11]. Compared with the
transcriptomics, proteomics could explain the
biological function and process in more detail [12].
According to proteomic studies of the classic ancient
prescription Xue-Fu-Zhu-Yu (XFZY) decoction on
traumatic brain injury, 17 differentially expressed
proteins were identified as the potential therapeutic
targets of XFZY. Bioinformatics analysis showed that
XFZY could ameliorate traumatic brain injury by
regulating the platelet activity and PI3K-Akt signaling
pathways [13].
Metabolomics
Metabolomics is a new technique developed after
transcriptomics and proteomics; it applies advanced
detection techniques, analytical methods, and
statistical algorithms to quantitatively and qualitatively
analyze overall metabolites in organisms or cells [14].
The metabolites are low-molecular-weight
biomolecules and could act as signal molecules, energy
sources, and metabolic vectors in various biological
processes [15]. The levels in metabolome could be
influenced by the synergistic effects of genome,
transcriptome, and proteome and directly reflect the
current metabolic state of organs or cells. Therefore,
the metabolome is also known as the molecular
phenotype of a specific cell or organ [6]. The database
of metabolome is more simple and easier to be
understood than those of the transcriptome and
proteome. Additionally, small changes in gene and
protein expressions can be amplified at the metabolite
levels, making this technique more systematic,
intuitive, and sensitive. Untargeted metabolomic
analysis revealed that the experienced prescription
Bu-Zang-Tong-Luo formula could alleviate diabetic
vascular dysfunction by modulating lipid, glutamine,
and tryptophan metabolic pathways [7].
Gut microbiota
The homeostasis of gut microbiota is closely
associated with several biological processes
physiologically and pathologically [16]. Gut
microbiota intervention, such as dietary therapy,
probiotics, and fecal transplantation, has provided new
insights into the treatment of diseases. As most of the
Chinese herbal formulas are administered orally to
patients and several ingredients have demonstrated low
bioavailability, modulating gut microbiota is
increasingly becoming an important approach to
uncover the mechanisms of Chinese herbal formulas
[17]. 16S rRNA sequencing and metagenomics could
analyze the changes of diversity in gut microbiota and
screen the dysregulated gut microbiota before and after
drug intervention [18]. The classic ancient prescription
Tong-Xie-Yao formula could relieve irritable bowel
syndrome and regulate 5-HT levels by affecting the
abundance of Akkermansia and Clostridium sensu
stricto 1 in the gut [19].
Conclusion
Omics technology could be very helpful in revealing
the efficacy of TCM systematically. Transcriptomics
recognizes the transcription conditions and rules of the
whole genome; proteomics analyzes the general
functions of proteins encoded by target genes;
metabolomics provides metabolic information, which
could have resulted from transcriptome and proteome.
16S rRNA sequencing and metagenomics focus on the
changes in microbiota diversity and abundance,
whereas miRNA, lncRNA, and circRNA microarrays
reveal the changing factors based on epigenetic levels
(Figure 1) [20].
Figure 1 Experimental process of omics techniques in mechanism studies of Chinese herbal formulas

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