ABSTRACT
OBJECTIVE@#To explore the molecular-level mechanism on the hematopoiesis effect of Angelicae sinensis Radix (ASR) with systems-based interactome analysis.@*METHODS@#This systems-based interactome analysis was designed to enforce the workflow of "ASR (herb)→compound→target protein→internal protein actions→ending regulated protein for hematopoiesis". This workflow was deployed with restrictions on regulated proteins expresses in bone marrow and anemia disease and futher validated with experiments.@*RESULTS@#The hematopoiesis mechanism of ASR might be accomplished through regulating pathways of cell proliferation towards hemopoiesis with cross-talking agents of spleen tyrosine kinase (SYK), Janus kinase 2 (JAK2), and interleukin-2-inducible T-cell kinase (ITK). The hematopoietic function of ASR was also validated by colony-forming assay performed on mice bone marrow cells. As a result, SYK, JAK2 and ITK were activated.@*CONCLUSION@#This study provides a new approach to systematically study and predict the therapeutic mechanism for ASR based on interactome analysis towards biological process with experimental validations.
ABSTRACT
Triptolide (TP) is a kind of epoxy diterpene lactone compound extracted from xylem of Tripterygium wilfordii (TWHF). It is one of the main active components of TWHF, with anti-inflammatory, immunomodulatory and anti-tumor activities and pharmacological effect. It can be used in the treatment of rheumatoid arthritis and such cancers as leukemia, breast cancer, pancreatic cancer and lung cancer. In recent years, TP has been gradually applied in clinic and basic research, with a certain curative effect. But it also has certain side effect on digestive system, urinary system, reproductive system, circulatory system and immune system, including liver dysfunction, reduced fertility, chest tightness, heart palpitations, bradycardia, atrioventricular block, arrhythmia, kidney dysfunction, lymphoid organ atrophy, lymphoid tissue necrosis of lymphocytes, and reduction in the number of cells, impaired immune function. These toxic and side effect have greatly restricted the clinical application of TP. In the meantime, the researches and development related to preparations of TP have also been restricted, which has aroused wide attention from clinicians and researchers. To improve the therapeutic effect of TP and reduce the toxicity of TP in the process of application, domestic and foreign researchers have made a lot of studies and attempts, such as changing the chemical structure of TP to improve its solubility, developing drug delivery system to reduce its toxicity and using combination therapy with traditional Chinese herbal medicines to increase efficiency and reduce toxicity. In this paper, the toxic dose and mechanism of TP, TP's derivatives, drug loading system, compatibility and attenuation were integrated to provide ideas for further researches on toxicity and attenuation of TP.
ABSTRACT
To explore the pharmacological mechanism of glycyrrhizin with series methods of systems pharmacology, main diseases related to glycyrrhizin were obtained by text mining tool; and the target proteins of glycyrrhizin were obtained via the database of Polysearch and PubChem. Then, the target proteins interaction network of glycyrrhizin was built using the software called Cytoscape. Next, the protein groups related to glycyrrhizin were analyzed by using Gene Ontology (GO) tool, and the action pathway of its target proteins was analyzed by using enrichment method. Text mining results showed that the related diseases of glycyrrhizin included chronic hepatitis C, chronic hepatitis, hepatitis, HIV virus, liver cancer and so on. Gene ontology analysis indicated that glycyrrhizin played a role mainly through modification of proteins and chromatin. The signaling pathway enrichment results showed that the main action proteins of glycyrrhizin were related to MAPK signaling pathway, toll-like receptor signaling pathway, neurotrophic factor signaling pathway, cancer and apoptosis pathways. So we can conclude that glycyrrhizin may exert its biological functions primarily by regulating multiple pathways such as MAPK signaling pathway and Toll-like receptors signaling pathway. The pharmacological action of a drug can be rapidly and comprehensively analyzed by the ways of systems pharmacology.