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

Shaik M Fayaz,Krishnamurthy G Rajanikant,Valsala S Suvanish Kumar,Muzamil Ahmad

doi:10.1371/journal.pone.0112911

Shaik M Fayaz, Krishnamurthy G Rajanikant + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0112911

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Journal: PloS one	Publication Date: Nov 14, 2014
Citations: 73	License type: CC BY 4.0

Affiliation: National Institute of Technology Calicut

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.

Highlights

Diabetes mellitus is a major chronic metabolic disorder and an extremely serious condition from both clinical and public health standpoints
A good or ideal formulation would contain active compounds that target multiple proteins as well as the proteins that are involved in multiple pathways related to diabetes
Network analysis revealed important information like 1) the anti-diabetic plants that contain many active compounds, 2) the active compounds that are present in most of the anti-diabetic plants, 3) the active compounds that target most of the proteins, 4) proteins that are targeted by most of the active compounds, 5) proteins that are involved in multiple pathways, 6) pathways that involve most of the proteins, 7) proteins that are involved in different diabetes-related complications and 8) the proteins that are involved in various other diseases

Summary

Introduction

Diabetes mellitus is a major chronic metabolic disorder and an extremely serious condition from both clinical and public health standpoints. 5% of the world’s population is affected by diabetes. According to the World Health Organisation (WHO) projections, the diabetic population is likely to increase to 300 million or more by the year 2025 [1]. Diabetes imperils public health through various complications such as retinopathy, neuropathy, nephropathy, ischemic heart disease, stroke and peripheral vascular disease [3]. Even though the insulin therapy and oral hypoglycemic agents are the first line of treatment for the disease, they show side effects and fail to significantly alter the course of diabetic complications. Due to these reasons, there is a growing interest in herbal medicines [4]

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