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Finding needles in a haystack: application of network analysis and target enrichment studies for the identification of potential anti-diabetic phytochemicals.

Fayaz SM, Suvanish Kumar VS, Rajanikant KG - PLoS ONE (2014)

Bottom Line: Herbal medicines have been proven to be effective anti-diabetic agents compared to synthetic drugs in terms of side effects.This study also involves a focused and constructive strategy for preparing new effective anti-diabetic formulations.Therefore, the successive use of network analysis combined with target enrichment studies would accelerate the discovery of potential anti-diabetic phytochemicals.

View Article: PubMed Central - PubMed

Affiliation: School of Biotechnology, National Institute of Technology Calicut, Calicut 673601, India.

ABSTRACT
Diabetes mellitus is a debilitating metabolic disorder and remains a significant threat to public health. Herbal medicines have been proven to be effective anti-diabetic agents compared to synthetic drugs in terms of side effects. However, the complexity in their chemical constituents and mechanism of action, hinder the effort to discover novel anti-diabetic drugs. Hence, understanding the biological and chemical basis of pharmacological action of phytochemicals is essential for the discovery of potential anti-diabetic drugs. Identifying important active compounds, their protein targets and the pathways involved in diabetes would serve this purpose. In this context, the present study was aimed at exploring the mechanism of action of anti-diabetic plants phytochemicals through network and chemical-based approaches. This study also involves a focused and constructive strategy for preparing new effective anti-diabetic formulations. Further, a protocol for target enrichment was proposed, to identify novel protein targets for important active compounds. Therefore, the successive use of network analysis combined with target enrichment studies would accelerate the discovery of potential anti-diabetic phytochemicals.

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Compounds (with their pharmacophoric features) that target aldose reductase.(A) Apigenin, (B) Astragalin, (C) Ellagic acid, (D) Gallic acid, (E) Gallocatechin, (F) Kaempferol, (G) Luteolin, (H) Perilloside A, (I) Quercetin and (J) Rosmarinic acid. These compounds show similar pharmacophoric features.
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pone-0112911-g008: Compounds (with their pharmacophoric features) that target aldose reductase.(A) Apigenin, (B) Astragalin, (C) Ellagic acid, (D) Gallic acid, (E) Gallocatechin, (F) Kaempferol, (G) Luteolin, (H) Perilloside A, (I) Quercetin and (J) Rosmarinic acid. These compounds show similar pharmacophoric features.

Mentions: In this study, the pharmacophore analysis showed that the compounds that have similar pharmacophoric features bind to the same target. For example, the active compounds that bind to their respective protein targets like aldose reductase, DNA polymerase, DNA polymerase β and alpha glucosidase have similar pharmacophoric features (Figures 8–11). All the compounds that bind to aldose reductase share similar pharmacophoric features (Figure 8). It can be seen that the benzene rings on the left harbours pharmacophoric features that are common to all of them. The compounds that target DNA polymerase also share similar pharmacophoric features (Figure 9). They contain an aromatic benzene ring to which an H-bond acceptor and a donor group are attached. Similarly, all the compounds of DNA polymerase β share similar pharmacophoric features (Figure 10). On their left side, they contain an H-bond acceptor and a donor group. The compounds of alpha glucosidase do not have similar structures. However, they share few common pharmacophoric features, due to which, all of them might be binding to alpha glucosidase (Figure 11).


Finding needles in a haystack: application of network analysis and target enrichment studies for the identification of potential anti-diabetic phytochemicals.

Fayaz SM, Suvanish Kumar VS, Rajanikant KG - PLoS ONE (2014)

Compounds (with their pharmacophoric features) that target aldose reductase.(A) Apigenin, (B) Astragalin, (C) Ellagic acid, (D) Gallic acid, (E) Gallocatechin, (F) Kaempferol, (G) Luteolin, (H) Perilloside A, (I) Quercetin and (J) Rosmarinic acid. These compounds show similar pharmacophoric features.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232558&req=5

pone-0112911-g008: Compounds (with their pharmacophoric features) that target aldose reductase.(A) Apigenin, (B) Astragalin, (C) Ellagic acid, (D) Gallic acid, (E) Gallocatechin, (F) Kaempferol, (G) Luteolin, (H) Perilloside A, (I) Quercetin and (J) Rosmarinic acid. These compounds show similar pharmacophoric features.
Mentions: In this study, the pharmacophore analysis showed that the compounds that have similar pharmacophoric features bind to the same target. For example, the active compounds that bind to their respective protein targets like aldose reductase, DNA polymerase, DNA polymerase β and alpha glucosidase have similar pharmacophoric features (Figures 8–11). All the compounds that bind to aldose reductase share similar pharmacophoric features (Figure 8). It can be seen that the benzene rings on the left harbours pharmacophoric features that are common to all of them. The compounds that target DNA polymerase also share similar pharmacophoric features (Figure 9). They contain an aromatic benzene ring to which an H-bond acceptor and a donor group are attached. Similarly, all the compounds of DNA polymerase β share similar pharmacophoric features (Figure 10). On their left side, they contain an H-bond acceptor and a donor group. The compounds of alpha glucosidase do not have similar structures. However, they share few common pharmacophoric features, due to which, all of them might be binding to alpha glucosidase (Figure 11).

Bottom Line: Herbal medicines have been proven to be effective anti-diabetic agents compared to synthetic drugs in terms of side effects.This study also involves a focused and constructive strategy for preparing new effective anti-diabetic formulations.Therefore, the successive use of network analysis combined with target enrichment studies would accelerate the discovery of potential anti-diabetic phytochemicals.

View Article: PubMed Central - PubMed

Affiliation: School of Biotechnology, National Institute of Technology Calicut, Calicut 673601, India.

ABSTRACT
Diabetes mellitus is a debilitating metabolic disorder and remains a significant threat to public health. Herbal medicines have been proven to be effective anti-diabetic agents compared to synthetic drugs in terms of side effects. However, the complexity in their chemical constituents and mechanism of action, hinder the effort to discover novel anti-diabetic drugs. Hence, understanding the biological and chemical basis of pharmacological action of phytochemicals is essential for the discovery of potential anti-diabetic drugs. Identifying important active compounds, their protein targets and the pathways involved in diabetes would serve this purpose. In this context, the present study was aimed at exploring the mechanism of action of anti-diabetic plants phytochemicals through network and chemical-based approaches. This study also involves a focused and constructive strategy for preparing new effective anti-diabetic formulations. Further, a protocol for target enrichment was proposed, to identify novel protein targets for important active compounds. Therefore, the successive use of network analysis combined with target enrichment studies would accelerate the discovery of potential anti-diabetic phytochemicals.

Show MeSH
Related in: MedlinePlus