Deciphering the therapeutic mechanisms of Xiao-Ke-An in treatment of type 2 diabetes in mice by a Fangjiomics approach

Abstract

Aim: Xiao-Ke-An (XKA) is a traditional Chinese medicine (TCM) formula for the treatment of type 2 diabetes (T2D), and the effective ingredients and their targets as well as the mechanisms of XKA remain to be elucidated. In this study we investigated the therapeutic mechanisms of XKA in the treatment of T2D in mice using a Fangjiomics approach. Methods: KKAy mice feeding on a high-fat diet were used as models of T2D, and were orally treated with XKA (0.75 or 1.5 g·kg -1 ·d -1 ) for 32 d. Microarray mRNA expression data were obtained from the livers of the mice. Differentially expressed genes (DEGs) were identified by reverse rate analysis and ANOVA analysis. The compounds in XKA were identified by LC-MS analysis or collected from TCM databases. The relationships between the compounds and targets were established by combining the DEGs with information derived from mining literature or herb target databases. Relevant pathways were identified through a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using WebGestalt. Results: The compound-target-pathway network based on compounds identified by LC-MS analysis (NCA) included 20 constituent compounds, 46 targets and 36 T2D-related pathways, whereas the compound-target-pathway network based on compounds collected from databases (NCD) consisted of 40 compounds, 68 targets and 21 pathways. In the treatment of T2D, XKA might act mainly by improving carbohydrate and lipid metabolism, as well as ameliorating insulin resistance, inflammation and diabetic vascular complications. Conclusion: The network-based approach reveals complex therapeutic mechanisms of XKA in the treatment of T2D in mice that involve numerous compounds, targets, and signaling pathways.

Chinese herbal drugs for the treatment of diabetic retinopathy

“…Besides, catalpol induces antioxidant effects by upregulating the activity of SOD. Catalpol can also downregulate inflammation by suppressing the expressions of various cytokines . Scrophuloside B, another iridoid glycoside obtained from S. ningpoensis , is reported to be a more effective anti‐inflammatory constituent as compared to catalpol.…”

Network Pharmacology and Traditional Chinese Medicine: Development of Anti-Diabetic Therapies

“…Zhang, et al [29] presented a-self-developed TCM network pharmacology platform to decipher the network regulation mechanism of qing-luo-yin and to identify active ingredients as well as to guide further experiments. Yang, et al [30] used 1743 Differentially Expressed Genes (DEGs), identified after treating a T2DM mice model with Xiao-Ke-An (XKA), to establish a T2D-specific compound-target-pathway network. Based on the network, they deciphered XKA therapeutic mechanisms mainly by improving carbohydrate and lipid metabolism.…”

Combining Chemical Profiling and Network Analysis to Investigate the Pharmacology of Complex Prescriptions in Traditional Chinese Medicine

“…However, the complicated chemical composition also brings great difficulties to the pharmacological investigations of TCM prescriptions. Network pharmacology, which was first proposed by Hopkins2, offers an ideal paradigm to deal with multi-target combination drugs and has recently been successfully adopted to investigate the formulae in TCM34567. The core of the scheme is the construction and analysis of the pharmacological network, which is normally composed of the nodes of active ingredients, the nodes of candidate protein targets, the nodes of intermediate proteins transferring protein-protein interactions (PPI) and the connections (i.e., edges) between them.…”

“…For example, in the work of Yang et al . on Xiao-Ke-An, 40 chemicals were found from relevant databases while only 20 compounds were identified experimentally5. Moreover, the compounds identified in vitro may not be able to enter the plasma, and thus could not really explain the mechanisms of these TCM formulae.…”