Deciphering the underlying mechanisms of Diesun Miaofang in traumatic injury from a systems pharmacology perspective

Abstract

Diesun Miaofang (DSMF) is a traditional herbal formula, which has been reported to activate blood, remove stasis, promote qi circulation and relieve pain. DSMF holds a great promise for the treatment of traumatic injury in an integrative and holistic manner. However, its underlying mechanisms remain to be elucidated. In the present study, a systems pharmacology model, which integrated cluster ligands, human intestinal absorption and aqueous solution prediction, chemical space mapping, molecular docking and network pharmacology techniques were used. The compounds from DSMF were diverse in the clusters and chemical space. The majority of the compounds exhibited drug-like properties. A total of 59 compounds were identified to interact with 16 potential targets. In the herb-compound-target network, the majority of compounds acted on only one target; however, a small number of compounds acted on a large number of targets, up to a maximum of 12. The comparison of key topological properties in compound-target networks associated with the above efficacy intuitively demonstrated that potential active compounds possessed diverse functions. These results successfully explained the polypharmcological mechanism underlying the efficiency of DSMF for the treatment of traumatic injury as well as provided insight into potential novel therapeutic strategies for traumatic injury from herbal medicine.

Herb-target interaction network analysis helps to disclose molecular mechanism of traditional Chinese medicine

“…Many studies have been reported to elucidate the molecular mechanism of TCM formulae in systematic view23456789. Compound-target networks were constructed and analyzed in these studies, and the effectiveness of TCM formulae was evaluated at compound level.…”

“…Systematic docking and drug-target network analysis is widely applied in these studies23456789, however, the therapeutic effectiveness of TCM formulae is still ascribed to a few number of interactions between individual compounds and key target proteins. As TCMs are prescribed as herbs, compounds from one herb should be considered as a whole and mode of action at herb-level should be noticed.…”

Computational methods and applications for quantitative systems pharmacology

“…Data mining, target prediction, network analysis [144] Sinomenium acutum Pathway, network and function analyses, data mining [145] Anti-Thrombosis Drug from TCMs Data mining, molecular docking, in silico screening [146] Qi-enriching herbs and blood-tonifying herbs ADME prediction, target fishing and network analysis [147] Baihe Dihuang Tang ADME/T calculation, target prediction, network analysis [148] Bufei Jianpi formula Systems pharmacology modeling based on absorption filtering, network targeting and systems analyses [132,149] Bushenhuoxue formula Target screening, molecular docking, network analysis, literature mining [150] Bushen-Yizhi prescription ADME/T filter analysis, target prediction, network analysis [151] Danlu Capsules Oral bioavailability and drug-likeness evaluation, gene enrichment analysis [152] Danggui-shaoyao-san Oral bioavailability screening, drug-likeness assessment, target identification and network analysis [153] Diesun Miaofang Cluster ligands, human intestinal absorption and aqueous solution prediction, chemical space mapping, molecular docking and network pharmacology techniques [154] Dragon's blood tablets Chemical analysis, prediction of ADME, and network analysis [155] Ge-Gen-Qin-Lian decoction Target profile clustering, network target analysis [156] Liu-Wei-Di-Huang pill Chemical and therapeutic properties, network analysis [157] Ma-huang decoction Pharmacokinetic analysis, drug targeting, and drug-target-disease network analysis [158] Mahuang Fuzi Xixin decoction Drug-likeness evaluation, oral bioavailability prediction, multiple drug target prediction, and network analysis [159] MaZiRenWan UPLC-QTOF-MS/MS identification, hierarchical clustering analysis, in vitro experiment verification, network analysis [160] NiaoDuQing granules ADME modelling and target prediction, topology analysis, pathway enrichment analysis, rat test [161] Qigui Tongfeng tablet Molecular similarity analysis, network analysis [162] Radix Curcumae formula Chemical predictors based on chemical structure and chemogenomics data linking compounds, pharmacological information, a system biology functional data analysis and network reconstruction method [163] Reduning injection ADME filtering, network targeting, pathways integrating, target selection, reverse drug targeting and network analysis [164][165]…”

Integrating System Biology Tools to Decipher the Mechanisms of Action of Herbal Medicine

“…Results showed similar (parallel) profile distribution between key topological properties of compound-target network associated with activating blood and removing stasis mechanism with compoundtarget network promoting qi circulation and relieving pain mechanism; for instances ferulic acid showed strong interaction with catechol-O-methyl transferase, phenylethanolamine N-methyltransferase, phenyl-ethanolamine, phosphodiesterase 5A in homeostasis & blood circulation and with factor-IXa in anti-inflammation. 22 A third application of systems pharmacology integrated pharmacokinetic parameters, target fishing and network analysis to demonstrate the extend compounds-target interactions support clinical effects of Tianshu formula in treating migraine. Results showed that Rhizoma chuanxiong modulates PTGS2, ESR1, NOS2, HTR1B & NOS3 targets acting on the vascular and nervous systems and secondary to the inflammation and pain-related pathways while the adjuvant Gastrodia elata acts on ABAT, HTR1D, ALOX15 & KCND3 to alleviate migraine symptoms, such as vomiting, vertigo and gastrointestinal disorders.…”