Abstract

Xiao Ke Yin Shui (XKYS) formula is a traditional Chinese medicine formula treating type 2 diabetes mellitus (T2DM). XKYS formula consists of four herbs, i.e., Coptidis rhizoma, Liriopes radix, bitter melon, and Cassiae semen. Herein, the chemical profiles of four herb extracts were investigated, and further analysis of the underlying mechanism of XKYS formula treating T2DM was performed using network pharmacology. The main components were selected for our network-based research. Targets of XKYS formula were mainly collected from two databases, SwissTargetPrediction and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the text-mining method was also implemented. T2DM relating genes and therapeutic targets were collected from five databases. Subsequently, STRING and Cytoscape were employed for the analysis of protein-protein interaction (PPI) networks. Functional annotation and pathway analysis were conducted to investigate the functions and relating pathways of target genes. The content of 12 compounds in the herb extracts was determined. With the analysis of PPI networks, a total of 76 genes were found to be important nodes and could be defined as the main target genes regulated by XKYS formula in the treatment of T2DM and its complications. Components in XKYS formula mainly regulate proteins including protein kinase B (Akt), phosphatidylinositol 3-kinase (PI3K), insulin receptor substrate (IRS), and tumor necrosis factor (TNF). XKYS formula exerts therapeutic effects in a synergetic manner and exhibits antidiabetic effect mainly via reducing insulin resistance. These findings could be guidelines in the further investigation of this formula.

Highlights

  • Diabetes mellitus (DM) is recognized as a complex metabolic disorder, and type 2 diabetes mellitus (T2DM) is the most common type of diabetes [1]

  • Such therapies may be promising in glycemic control but could cause side-effects like hypoglycemia or gastrointestinal dysfunction [2]. us, more and more people have turned their attention to herbal medicine or diet-based therapies, seeking for safer and more cost-effective complementary medicine for T2DM [3,4,5,6]

  • Screening of Main Components from Four Herb Extracts and Construction of protein-protein interaction (PPI) Networks. e screening of 19 components (Table 2) in Xiao Ke Yin Shui (XKYS) had led to the acquisition of 216 targets, while 602 genes relating to the pathophysiology of T2DM were collected (Supplementary Materials, Tables S1 and S2)

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Summary

Introduction

Diabetes mellitus (DM) is recognized as a complex metabolic disorder, and type 2 diabetes mellitus (T2DM) is the most common type of diabetes [1]. Different kinds of therapies are applied in the treatment of diabetes, including insulin and other oral medications. Such therapies may be promising in glycemic control but could cause side-effects like hypoglycemia or gastrointestinal dysfunction [2]. XKYS formula contains four herbs, namely, Coptidis rhizoma (dried rhizomes of Coptis chinensis Franch.), Liriopes radix (the dried tuberous roots of Liriope spicata ( unb.) Lour. T. Ma), bitter melon (the immature fresh fruits of Momordica charantia L.), and Cassiae semen (the dried seeds of Cassia obtusifolia L.). Ma), bitter melon (the immature fresh fruits of Momordica charantia L.), and Cassiae semen (the dried seeds of Cassia obtusifolia L.) All these herbs are widely used in clinical practice treating diabetes [7]

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