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Elucidating pharmacological mechanisms of natural medicines by biclustering analysis of the gene expression profile: a case study on curcumin and Si-Wu-Tang.

Quan Y, Li B, Sun YM, Zhang HY - Int J Mol Sci (2014)

Bottom Line: The biological functions of gene modules provide preliminary insights into pharmacological mechanisms of both natural medicines.Accordingly, we predicted a series of pharmacological effects for curcumin and Si-Wu-Tang by the indications of cMap-covered drugs.Most predictions were supported by experimental observations, suggesting the potential use of this method in natural medicine dissection.

View Article: PubMed Central - PubMed

Affiliation: Agricultural Bioinformatics Key Laboratory of Hubei Province, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China. qyuan@webmail.hzau.edu.cn.

ABSTRACT
Natural medicines have attracted wide attention in recent years. It is of great significance to clarify the pharmacological mechanisms of natural medicines. In prior studies, we established a method for elucidating pharmacological mechanisms of natural products contained in connectivity map (cMap), in terms of module profiles of gene expression in chemical treatments. In this study, we explore whether this methodology is applicable to dissecting the pharmacological mechanisms of natural medicines beyond the agents contained in cMap. First, the gene expression profiles of curcumin (a typical isolated natural medicine) and Si-Wu-Tang (a classic traditional Chinese medicine formula) treatments were merged with those of cMap-derived 1309 agents, respectively. Then, a biclustering analysis was performed using FABIA method to identify gene modules. The biological functions of gene modules provide preliminary insights into pharmacological mechanisms of both natural medicines. The module profile can be characterized by a binary vector, which allowed us to compare the expression profiles of natural medicines with those of cMap-derived agents. Accordingly, we predicted a series of pharmacological effects for curcumin and Si-Wu-Tang by the indications of cMap-covered drugs. Most predictions were supported by experimental observations, suggesting the potential use of this method in natural medicine dissection.

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The enriched GO function of module 27 of cMap-Si-Wu-Tang dataset, with p-values adjusted by False Discovery Rate calculation using Benjamini-Hochberg method [24].
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ijms-16-00510-f001: The enriched GO function of module 27 of cMap-Si-Wu-Tang dataset, with p-values adjusted by False Discovery Rate calculation using Benjamini-Hochberg method [24].

Mentions: The biological functions were enriched for each module by the records in GO and KEGG pathways (DAVID) [17]. For the cMap-curcumin dataset, 49 modules have enriched GO functions, with 47 having significant KEGG functions (Table S3). For the cMap-Si-Wu-Tang dataset, 53 modules have enriched GO functions, with 51 having significant KEGG functions (Table S4). For both datasets, GO functions and KEGG pathway annotations match well with each other, illustrating the functional consistence of the modules. Thus, we can get some preliminary insights into the medicinal effects of curcumin and Si-Wu-Tang according to the module functions. For instance, module 27 of Si-Wu-Tang dataset is tightly associated with oxidative reduction according to the GO and KEGG (Figure 1 and Figure 2). This module contains the antioxidant genes controlled by nuclear factor (erythroid-derived 2)-like 2 (Nrf2), such as GPX2, FTH1, GCLM, GCLC, NQO1, HMOX1, GSR and PRDX1 [18]. It is well known that the Nrf2-mediated Keap1-Nrf2-ARE pathway is the most important cellular defense pathway against oxidative stress in human body [19]. Therefore, module 27 can be defined as an antioxidant module. Indeed, some known antioxidants, such as ascorbic acid, ebselen, tanespimycin, 1,4-chrysenequinone, menadione, tetroquinone [9], are included in this module. Because Si-Wu-Tang is also involved in this module, it can be inferred that Si-Wu-Tang has antioxidant function, well consistent with the experimental observation [4].


Elucidating pharmacological mechanisms of natural medicines by biclustering analysis of the gene expression profile: a case study on curcumin and Si-Wu-Tang.

Quan Y, Li B, Sun YM, Zhang HY - Int J Mol Sci (2014)

The enriched GO function of module 27 of cMap-Si-Wu-Tang dataset, with p-values adjusted by False Discovery Rate calculation using Benjamini-Hochberg method [24].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307259&req=5

ijms-16-00510-f001: The enriched GO function of module 27 of cMap-Si-Wu-Tang dataset, with p-values adjusted by False Discovery Rate calculation using Benjamini-Hochberg method [24].
Mentions: The biological functions were enriched for each module by the records in GO and KEGG pathways (DAVID) [17]. For the cMap-curcumin dataset, 49 modules have enriched GO functions, with 47 having significant KEGG functions (Table S3). For the cMap-Si-Wu-Tang dataset, 53 modules have enriched GO functions, with 51 having significant KEGG functions (Table S4). For both datasets, GO functions and KEGG pathway annotations match well with each other, illustrating the functional consistence of the modules. Thus, we can get some preliminary insights into the medicinal effects of curcumin and Si-Wu-Tang according to the module functions. For instance, module 27 of Si-Wu-Tang dataset is tightly associated with oxidative reduction according to the GO and KEGG (Figure 1 and Figure 2). This module contains the antioxidant genes controlled by nuclear factor (erythroid-derived 2)-like 2 (Nrf2), such as GPX2, FTH1, GCLM, GCLC, NQO1, HMOX1, GSR and PRDX1 [18]. It is well known that the Nrf2-mediated Keap1-Nrf2-ARE pathway is the most important cellular defense pathway against oxidative stress in human body [19]. Therefore, module 27 can be defined as an antioxidant module. Indeed, some known antioxidants, such as ascorbic acid, ebselen, tanespimycin, 1,4-chrysenequinone, menadione, tetroquinone [9], are included in this module. Because Si-Wu-Tang is also involved in this module, it can be inferred that Si-Wu-Tang has antioxidant function, well consistent with the experimental observation [4].

Bottom Line: The biological functions of gene modules provide preliminary insights into pharmacological mechanisms of both natural medicines.Accordingly, we predicted a series of pharmacological effects for curcumin and Si-Wu-Tang by the indications of cMap-covered drugs.Most predictions were supported by experimental observations, suggesting the potential use of this method in natural medicine dissection.

View Article: PubMed Central - PubMed

Affiliation: Agricultural Bioinformatics Key Laboratory of Hubei Province, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China. qyuan@webmail.hzau.edu.cn.

ABSTRACT
Natural medicines have attracted wide attention in recent years. It is of great significance to clarify the pharmacological mechanisms of natural medicines. In prior studies, we established a method for elucidating pharmacological mechanisms of natural products contained in connectivity map (cMap), in terms of module profiles of gene expression in chemical treatments. In this study, we explore whether this methodology is applicable to dissecting the pharmacological mechanisms of natural medicines beyond the agents contained in cMap. First, the gene expression profiles of curcumin (a typical isolated natural medicine) and Si-Wu-Tang (a classic traditional Chinese medicine formula) treatments were merged with those of cMap-derived 1309 agents, respectively. Then, a biclustering analysis was performed using FABIA method to identify gene modules. The biological functions of gene modules provide preliminary insights into pharmacological mechanisms of both natural medicines. The module profile can be characterized by a binary vector, which allowed us to compare the expression profiles of natural medicines with those of cMap-derived agents. Accordingly, we predicted a series of pharmacological effects for curcumin and Si-Wu-Tang by the indications of cMap-covered drugs. Most predictions were supported by experimental observations, suggesting the potential use of this method in natural medicine dissection.

Show MeSH