ABSTRACT
The crosstalk between signaling and metabolic pathways has been known to play key roles in human diseases and plant biological processes. The integration of signaling and metabolic pathways can provide an essential reference framework for crosstalk analysis. However, current databases use distinct structures to present signaling and metabolic pathways, which leads to the chaos in the integrated networks. Moreover, for the metabolic pathways, the metabolic enzymes and the reactions are disconnected by the current widely accepted layout of edges and nodes, which hinders the topological analysis of the integrated networks. Here, we propose a novel "meta-pathway" structure, which uses the uniformed structure to display the signaling and metabolic pathways, and resolves the difficulty in linking the metabolic enzymes to the reactions topologically. We compiled a comprehensive collection of global integrative networks (GINs) by merging the meta-pathways of 7077 species. We demonstrated the assembly of the signaling and metabolic pathways using the GINs of four species-human, mouse, Arabidopsis, and rice. Almost all of the nodes were assembled into one major network for each of the four species, which provided opportunities for robust crosstalk and topological analysis, and knowledge graph construction. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-022-00078-1.
ABSTRACT
Shenling Baizhusan is a traditional Chinese medicine compound prescription formulated on the basis of Si Junzitang （Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Glycyrrhizae Radix et Rhizoma）. It has excellent functions of replenishing Qi， invigorating spleen， draining dampness， and checking diarrhea， and is one of the classical prescriptions of ''reinforcing earth to generate metal''. This prescription is primarily used in clinical practice to treat malnutrition in children， chronic diarrhea， gastrointestinal dysfunction， and other disorders. In addition， it has a good effect on gastrointestinal adverse reactions associated with radiotherapy and chemotherapy. With the booming of molecular biology， researchers have revealed the role of Shenling Baizhusan in the treatment of diseases， especially the mechanism of regulating different signaling pathways. We retrieved 26 relevant papers （4 written in English and 22 in Chinese） published in recent 5 years from 6 databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， PubMed， Cochrance Library， and Excerpta Medica Database （Embase）. On the basis of these papers， we summarized the mechanisms of Shenling Baizhusan in disease treatment. In the animal model of inflammatory bowel disease， Shenling Baizhusan can protect gastrointestinal mucosa by regulating the activation of nuclear factor kappa-B （NF-κB）， mitogen-activated protein kinase （MAPK）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， and myosin light chain kinase-myosin light chain （MLCK-MLC） signaling pathways. In the animal model of non-alcoholic fatty liver disease， Shenling Baizhusan regulates the activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and Kelch-like ECH-associating protein 1/NF-E2-related factor 2/advanced glycation end-products （KEAP1/NRF2/AREs） signaling pathway， thus alleviating the lipid metabolism disorder induced by high-fat diet and reducing liver lipid accumulation and inflammatory response. In the animal model of lung cancer with bone metastasis， Shenling Baizhusan regulates the activation of PI3K/Akt/mTOR signaling pathway， thus playing an analgesic role. By summarizing the mechanisms of Shenling Baizhusan in treatment of different disease models from signaling pathways， we aim to provide clues for the in-depth study of this prescription.
