An Integrative Pharmacology-Based Strategy to Uncover the Mechanism of Xiong-Pi-Fang in Treating Coronary Heart Disease with Depression

Zhang, Lihong; Yu, Zhang; Zhu, Min; Pei, Li-min; Deng, Fangjun; Chen, Jinhong; Zhang, Shaoqiang; Cong, Zidong; Du, Wei; Xiao, Xuefeng

doi:10.3389/fphar.2021.590602

Cited by 4 publications

(4 citation statements)

References 88 publications

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“…To verify the prediction of network pharmacology, serum pharmacology is commonly combined to explore the specific mechanisms of TCM by applying drug-containing serum in vitro. Pieces of literature combined network pharmacology with serum pharmacology have been successfully reported [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Mechanism Investigation of Wuwei Shexiang Pills on Gouty Arthritis via Network Pharmacology, Molecule Docking, and Pharmacological Verification

Lang

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Gout is a common crystal-related arthritis caused by the deposition of monosodium urates (MSU). Tibetan medicine Wuwei Shexiang Pills (WSP) has been demonstrated to exhibit anti-inflammatory, antihyperuricemia, and antigout activities. However, the underlying mechanism is unknown. Objectives. To explore the mechanisms of Wuwei Shexiang Pills on gouty arthritis via network pharmacology, molecule docking, and pharmacological verification. Methods. The ingredients and targets of WSP were obtained by searching and screening in BATMAN-TCM and SwissADME. The targets involving the gout were acquired from public databases. The shared targets were put onto STRING to construct a PPI network. Furthermore, Metascape was applied for the GO and KEGG enrichment analysis to predict the biological processes and signaling pathways. And molecular docking was performed to validate the binding association between the key ingredients and the relative proteins of TNF signaling. Based on the serum pharmacology, the predicted antigout mechanism of WSP was validated in MSU-induced THP-1 macrophages. The levels of inflammatory cytokines and mRNA were measured by ELISA and qRT-PCR, respectively, and MAPK, NF-κB, and NLRP3 signaling-associated proteins were determined by western blot and immunofluorescence staining. Results. 48 bioactive ingredients and 165 common targets were found in WSP. The data showed that 5-Cis-Cyclopentadecen-1-One, 5-Cis-Cyclotetradecen-1-One, (−)-isoshyobunone, etc. were potential active ingredients. TNF signaling, HIF-1 signaling, and Jak-STAT signaling were predicted to be the potential pathways against gout. The molecule docking analysis found that most ingredients had a high affinity for p65, NLRP3, IL-1β, TNF-α, and p38. The data from in vitro experiment showed that WSP suppressed the production and gene expression of inflammatory cytokines. Furthermore, WSP could inhibit the activation of MAPK, NF-κB, and NLRP3 signaling pathways. Conclusion. Our finding suggested that the antigout effect of WSP could be achieved by inhibiting MAPK, NF-κB, and NLRP3 signaling pathways. WSP might be a candidate drug for gouty treatment.

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Section: Introductionmentioning

confidence: 99%

Mechanism Investigation of Wuwei Shexiang Pills on Gouty Arthritis via Network Pharmacology, Molecule Docking, and Pharmacological Verification

Lang

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Notably, network pharmacology analysis highlighted 5 targets, namely AKT1, GAPDH, MAPK3, TP53 and EGFR. Among them, AKT1 was highly related to depression 47 associated with disturbances of sleep, cancer 48 and hypnosis. 49 AKT1 encodes a serine/threonine kinase and is involved in lithium signaling, which has been considered a vulnerable gene for bipolar disorder previously.…”

Section: Discussionmentioning

confidence: 99%

Discovery of Biomarkers and Potential Mechanisms of Agarwood Incense Smoke Intervention by Untargeted Metabolomics and Network Pharmacology

Dong¹,

Du²,

X³

et al. 2022

DDDT

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Background Agarwood, as a traditional Chinese medicine, has great potential value for the treatment of tranquilization. However, its potential mechanisms and biomarkers are still unclear. Methods In this study, ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS)-based metabonomics was adopted to discover the potential biomarkers in mice after agarwood incense smoke (AIS) intervention. Furthermore, the chemical components in agarwood were identified based on UHPLC-Q-Exactive Orbitrap-MS. The global view of potential compound-target-pathway (C-T-B) network was constructed through network pharmacology to understand the potentially material basis of biomarkers. Results Metabolic profiling indicated that the metabolic changed significantly in mice serum after AIS intervention. A total of 18 potential biomarkers closely related to insomnia and emotional disease were identified, mainly involving in tryptophan metabolism, arginine and proline metabolism, cysteine and methionine metabolism and steroid hormone biosynthesis pathways. A total of 138 components in agarwood were identified based on UHPLC-Q-Exactive Orbitrap-MS. The results showed that mainly compounds such as flidersia type 2-(2-phenylethyl) chromones (FTPECs) and sesquiterpenes exerted good docking abilities with key target proteins, which were involved in multiple diseases including depression and hypnosis. Conclusion In conclusion, this study enhanced current understanding of the change of metabolic markers after AIS intervention. Meanwhile, it also confirmed the feasibility of combining metabolomics and network pharmacology to identify active components and elucidate the material basis of biomarkers and mechanisms.

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“…In total, 12 SD rats were randomly divided into blank and experimental groups. The experimental group was administered the Menispermi Rhizoma extract by gavage at a 2.5 g/kg dose once a day for three consecutive days ( Zhang et al, 2021 ). The blank group was given the same amount of 0.5% CMC-Na aqueous solution according to the same protocol.…”

Section: Methodsmentioning

confidence: 99%

Integrated Serum Pharmacochemistry and Network Pharmacology Approach to Explore the Effective Components and Potential Mechanisms of Menispermi Rhizoma Against Myocardial Ischemia

Wei

Zhang

et al. 2022

Front. Chem.

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Background: Myocardial ischemia (MI) is a leading cause of death worldwide. Menispermi Rhizoma is a traditional Chinese medicine that exerts a variety of beneficial pharmacological activities in many diseases, including MI.Purpose: Serum pharmacochemistry and network pharmacology were used to explore the material basis and mechanism of action of Menispermi Rhizoma against MI.Methods: The absorbed components of Menispermi Rhizoma in rat plasma were analyzed by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). The key components, targets, pathways, and interrelated information were obtained by network pharmacology. The potential effective components of Menispermi Rhizoma against MI were screened by methyl-thiazolyl-tetrazolium (MTT) assay, and the cardioprotective effect and mechanism of active components were verified by Western blotting and molecular docking.Results: In total, 25 absorbed components of Menispermi Rhizoma in plasma were identified. Network pharmacology revealed 81 major targets of Menispermi Rhizoma against MI, mainly involving the regulation of the PI3K/AKT and MAPK pathways. In vitro validation of H9c2 cells revealed that acutumine, daurisoline, dauricoside, and 6-O-demethylmenisporphine are the main bioactive components of Menispermi Rhizoma. The levels of lactate dehydrogenase, creatine kinase, and malondialdehyde (MDA) were significantly decreased by four alkaloids, whereas the activities of superoxide dismutase (SOD) and glutathione (GSH) were significantly increased. Four alkaloids effectively protected H9c2 cells against OGD-induced apoptosis by Hoechst/PI staining and flow cytometry assay. Western blotting results showed that the four alkaloids upregulated the expression ratio of Bcl-2/Bax and downregulated the expression levels of Cyt-C and cleaved caspase 3, which further supported the anti-cardiomyocyte apoptosis and antioxidative stress effect of Menispermi Rhizoma. Molecular docking confirmed that the four compounds were capable of binding to AKT1, MAPK1, EGFR, CASP3, and MAPK8 proteins, suggesting the protective effect of Menispermi Rhizoma on MI via PI3K/AKT, MAPK, and apoptosis pathways.Conclusion: Menispermi Rhizoma exerted cardioprotective effects through the effect characteristics: multiple-ingredient, multi-target, and multi-pathway. This research provided a reference for further mechanistic research on wider applications of Menispermi Rhizoma for MI treatment.

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An Integrative Pharmacology-Based Strategy to Uncover the Mechanism of Xiong-Pi-Fang in Treating Coronary Heart Disease with Depression

Cited by 4 publications

References 88 publications

Mechanism Investigation of Wuwei Shexiang Pills on Gouty Arthritis via Network Pharmacology, Molecule Docking, and Pharmacological Verification

Mechanism Investigation of Wuwei Shexiang Pills on Gouty Arthritis via Network Pharmacology, Molecule Docking, and Pharmacological Verification

Discovery of Biomarkers and Potential Mechanisms of Agarwood Incense Smoke Intervention by Untargeted Metabolomics and Network Pharmacology

Integrated Serum Pharmacochemistry and Network Pharmacology Approach to Explore the Effective Components and Potential Mechanisms of Menispermi Rhizoma Against Myocardial Ischemia

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