Dataset Information

Systems Pharmacological Approach to the Effect of Bulsu-san Promoting Parturition.

ABSTRACT: Bulsu-san (BSS) has been commonly used in oriental medicine for pregnant women in East Asia. The purpose of this research was to elucidate the effect of BSS on ease of parturition using a systems-level in silico analytic approach. Research results show that BSS is highly connected to the parturition related pathways, biological processes, and organs. There were numerous interactions between most compounds of BSS and multiple target genes, and this was confirmed using herb-compound-target network, target-pathway network, and gene ontology analysis. Furthermore, the mRNA expression of relevant target genes of BSS was elevated significantly in related organ tissues, such as those of the uterus, placenta, fetus, hypothalamus, and pituitary gland. This study used a network analytical approach to demonstrate that Bulsu-san (BSS) is closely related to the parturition related pathways, biological processes, and organs. It is meaningful that this systems-level network analysis result strengthens the basis of clinical applications of BSS on ease of parturition.

SUBMITTER: Suh SY

PROVIDER: S-EPMC5682096 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Systems Pharmacological Approach to the Effect of <i>Bulsu-san</i> Promoting Parturition.

Suh Su Yeon SY An Won G WG

Evidence-based complementary and alternative medicine : eCAM 20171029

<i>Bulsu-san</i> (BSS) has been commonly used in oriental medicine for pregnant women in East Asia. The purpose of this research was to elucidate the effect of BSS on ease of parturition using a systems-level in silico analytic approach. Research results show that BSS is highly connected to the parturition related pathways, biological processes, and organs. There were numerous interactions between most compounds of BSS and multiple target genes, and this was confirmed using herb-compound-target ...[more]

PMID: 29234425

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Project description:BackgroundAlzheimer's disease (AD) is the most common cause of dementia in the elderly, characterized by a progressive and irreversible loss of memory and cognitive abilities. Currently, the prevention and treatment of AD still remains a huge challenge. As a traditional Chinese medicine (TCM) prescription, Danggui-Shaoyao-san decoction (DSS) has been demonstrated to be effective for alleviating AD symptoms in animal experiments and clinical applications. However, due to the complex components and biological actions, its underlying molecular mechanism and effective substances are not yet fully elucidated.MethodsIn this study, we firstly systematically reviewed and summarized the molecular effects of DSS against AD based on current literatures of in vivo studies. Furthermore, an integrated systems pharmacology framework was proposed to explore the novel anti-AD mechanisms of DSS and identify the main active components. We further developed a network-based predictive model for identifying the active anti-AD components of DSS by mapping the high-quality AD disease genes into the global drug-target network.ResultsWe constructed a global drug-target network of DSS consisting 937 unique compounds and 490 targets by incorporating experimental and computationally predicted drug-target interactions (DTIs). Multi-level systems pharmacology analyses revealed that DSS may regulate multiple biological pathways related to AD pathogenesis, such as the oxidative stress and inflammatory reaction processes. We further conducted a network-based statistical model, drug-likeness analysis, human intestinal absorption (HIA) and blood-brain barrier (BBB) penetration prediction to uncover the key ani-AD ingredients in DSS. Finally, we highlighted 9 key ingredients and validated their synergistic role against AD through a subnetwork.ConclusionOverall, this study proposed an integrative systems pharmacology approach to disclose the therapeutic mechanisms of DSS against AD, which also provides novel in silico paradigm for investigating the effective substances of complex TCM prescription.

Project description:In ungulates, parturition is correlated with a reduction in movement rate. With advances in movement-based technologies comes an opportunity to develop new techniques to assess reproduction in wild ungulates that are less invasive and reduce biases. DeMars et al. (2013, Ecology and Evolution 3:4149-4160) proposed two promising new methods (individual- and population-based; the DeMars model) that use GPS inter-fix step length of adult female caribou (Rangifer tarandus caribou) to infer parturition and neonate survival. Our objective was to apply the DeMars model to caribou populations that may violate model assumptions for retrospective analysis of parturition and calf survival. We extended the use of the DeMars model after assigning parturition and calf mortality status by examining herd-wide distributions of parturition date, calf mortality date, and survival. We used the DeMars model to estimate parturition and calf mortality events and compared them with the known parturition and calf mortality events from collared adult females (n = 19). We also used the DeMars model to estimate parturition and calf mortality events for collared female caribou with unknown parturition and calf mortality events (n = 43) and instead derived herd-wide estimates of calf survival as well as distributions of parturition and calf mortality dates and compared them to herd-wide estimates generated from calves fitted with VHF collars (n = 134). For our data, the individual-based method was effective at predicting calf mortality, but was not effective at predicting parturition. The population-based method was more effective at predicting parturition but was not effective at predicting calf mortality. At the herd-level, the predicted distributions of parturition date from both methods differed from each other and from the distribution derived from the parturition dates of VHF-collared calves (log-ranked test: χ2 = 40.5, df = 2, p < 0.01). The predicted distributions of calf mortality dates from both methods were similar to the observed distribution derived from VHF-collared calves. Both methods underestimated herd-wide calf survival based on VHF-collared calves, however, a combination of the individual- and population-based methods produced herd-wide survival estimates similar to estimates generated from collared calves. The limitations we experienced when applying the DeMars model could result from the shortcomings in our data violating model assumptions. However despite the differences in our caribou systems, with proper validation techniques the framework in the DeMars model is sufficient to make inferences on parturition and calf mortality.

Dataset Information

Systems Pharmacological Approach to the Effect of Bulsu-san Promoting Parturition.

Publications

Systems Pharmacological Approach to the Effect of <i>Bulsu-san</i> Promoting Parturition.

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