A novel systems pharmacology model for herbal medicine injection: a case using reduning injection

NiaoDuQing (NDQ) granules, a traditional Chinese medicine, has been clinically used in China for over fourteen years to treat chronic kidney disease (CKD). To elucidate the mechanisms underlying the therapeutic benefits of NDQ, we designed an approach incorporating chemoinformatics, bioinformatics, network biology methods, and cellular and molecular biology experiments. A total of 182 active compounds were identified in NDQ granules, and 397 putative targets associated with different diseases were derived through ADME modelling and target prediction tools. Protein-protein interaction networks of CKD-related and putative NDQ targets were constructed, and 219 candidate targets were identified based on topological features. Pathway enrichment analysis showed that the candidate targets were mostly related to the TGF-β, the p38MAPK, and the erythropoietin (EPO) receptor signaling pathways, which are known contributors to renal fibrosis and/or renal anemia. A rat model of CKD was established to validate the drug-target mechanisms predicted by the systems pharmacology analysis. Experimental results confirmed that NDQ granules exerted therapeutic effects on CKD and its comorbidities, including renal anemia, mainly by modulating the TGF-β and EPO signaling pathways. Thus, the pharmacological actions of NDQ on CKD symptoms correlated well with in silico predictions.

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“…Active compounds were selected by setting OB ≥ 30%, DL ≥ 0.18, Caco-2 ≥ -0.4, and HL ≥ 4 as the threshold [ 57 ].…”

Section: Methodsmentioning

confidence: 99%

NiaoDuQing granules relieve chronic kidney disease symptoms by decreasing renal fibrosis and anemia

Wang

Jia

et al. 2017

Oncotarget

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“…A new in silico model has been developed to predict half-life (preDHL) of drugs with good overall accuracy of internal validation (85.21%) and external validation (86.05%) by using the C-partial least square (C-PLS) algorithm31. In our present paper, the compounds with the half-life value ≥4 hours were selected by the preDHL model since a medication generally has a 4 hour half-life to reach a consistent level in the body.…”

Section: Methodsmentioning

confidence: 99%

Systems pharmacology exploration of botanic drug pairs reveals the mechanism for treating different diseases

Zhou

Wang

et al. 2016

Sci Rep

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Multi-herb therapy has been widely used in Traditional Chinese medicine and tailored to meet the specific needs of each individual. However, the potential molecular or systems mechanisms of them to treat various diseases have not been fully elucidated. To address this question, a systems pharmacology approach, integrating pharmacokinetics, pharmacology and systems biology, is used to comprehensively identify the drug-target and drug-disease networks, exemplified by three representative Radix Salviae Miltiorrhizae herb pairs for treating various diseases (coronary heart disease, dysmenorrheal and nephrotic syndrome). First, the compounds evaluation and the multiple targeting technology screen the active ingredients and identify the specific targets for each herb of three pairs. Second, the herb feature mapping reveals the differences in chemistry and pharmacological synergy between pairs. Third, the constructed compound-target-disease network explains the mechanisms of treatment for various diseases from a systematic level. Finally, experimental verification is taken to confirm our strategy. Our work provides an integrated strategy for revealing the mechanism of synergistic herb pairs, and also a rational way for developing novel drug combinations for treatments of complex diseases.

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“…It refers to the time taken to reduce the blood concentration of the compound into the body by half. The rate of elimination of the drug in the body is often used to calculate the administration time, guide rational application of the drug, and to determine a dosage regimen [20,21] . We used HL > 3 h as the cutoff for potentially active ingredients.…”

Section: Adme Screening Of the Ygl Capsulementioning

confidence: 99%

Network pharmacology-based study on the mechanism of Yiganling capsule in hepatitis B treatment

Lü

Zhou

et al. 2020

BMC Complement Med Ther

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Background: Yiganling (YGL) capsule is a traditional Chinese medicine preparation consisting of eight herbs that has been clinically proven to have a favorable treatment effect on Hepatitis B (HB). However, due to its multiple targets and multi-pharmacological effects, the mechanisms of YGL capsule in the treatment of HB are unknown. Methods: First, the chemical constituents of YGL capsules were obtained from the Chinese medicine database, and YGL capsules were constructed. Second, active compounds were screened by the ADME model. The target fishing model was used to screen the corresponding targets of active compounds and to construct a compounds and compound targets network. Using human disease databases and literature mining, we systematically identified genes associated with HB, constructed disease-specific protein-protein interaction networks, and performed clustering and enrichment analyses of these networks. These networks were then merged to obtain a compounddisease target network, and cluster and enrichment analyses were performed on the compound-disease target network to acquire a compounds-disease targets-mechanism network and a clustering network. Results: We successfully built eight pharmacological network diagrams, including four primary networks and other network maps. The four dominating network maps included a HB disease-associated protein-protein interaction network, a YGL capsule compounds-target network, a YGL capsule ingredient target-HB disease target network, and a YGL-HB disease mechanism network. Other networks included a pathway of HB disease targets, the HB disease protein-protein interaction cluster analysis network, and the YGL-HB target clustering network. Conclusion: This study successfully forecasted, illuminated, and confirmed the synergistic effects of HB disease molecules and discovered the potential of HB relevant targets, clusters, and target-related biological processes and signaling pathways. Our research not only provides theoretical support for the molecular and pharmacological mechanisms of YGL capsule in HB treatment, but also provides new research methods for the study of the other traditional Chinese medicinal compounds.

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A novel systems pharmacology model for herbal medicine injection: a case using reduning injection

Cited by 60 publications

References 75 publications

NiaoDuQing granules relieve chronic kidney disease symptoms by decreasing renal fibrosis and anemia

NiaoDuQing granules relieve chronic kidney disease symptoms by decreasing renal fibrosis and anemia

Systems pharmacology exploration of botanic drug pairs reveals the mechanism for treating different diseases

Network pharmacology-based study on the mechanism of Yiganling capsule in hepatitis B treatment

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