An Integrated Pharmacokinetic Study of an Acanthopanax senticosus Extract Preparation by Combination of Virtual Screening, Systems Pharmacology, and Multi-Component Pharmacokinetics in Rats

Shi, Peiying; Xie, Yunjiao; Xie, Rongfang; Lin, Zuan; Yao, Hong; Wu, Shuang

doi:10.3389/fphar.2020.01295

Cited by 13 publications

(15 citation statements)

References 47 publications

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“…Furthermore, the collection of targets genes and proteins abovementioned for Tan IIA is without doubt a good dataset to in depth predict the potential effects and underlying mechanisms of the active ingredient on diseases by bioinformatics analysis. To explore the possible relationship of targets abovementioned for Tan IIA, the potential protein interaction (PPI) network was contructed according to our previous report (Xie R. et al, 2020) by input the reported targets into the online STRING webserver (https://string-db.org). As a result, 65 nodes and 191 edges were generated in the PPI network afer hiding disconnected nodes.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, Nrf2 is associated with decreased oxidative stress. Investigations illustrated that the transcriptions, expressions, and activities of AMPK and Nrf2 were inhibited by Tan IIA, which significantly reduced survival, migration and invasion in MG63 osteosarcoma (Xie Z. et al, 2020). The functional assay showed that Tan IIA inhibited AMPK pathway and resulted in S-phase kinase associated protein 2 (Skp2) inactivation.…”

Section: Endoplasmic Reticulum Stress and Energy Supplymentioning

confidence: 99%

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Recent Research Progress (2015–2021) and Perspectives on the Pharmacological Effects and Mechanisms of Tanshinone IIA

Zhong

Lin

et al. 2021

Front. Pharmacol.

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Tanshinone IIA (Tan IIA) is an important characteristic component and active ingredient in Salvia miltiorrhiza, and its various aspects of research are constantly being updated to explore its potential application. In this paper, we review the recent progress on pharmacological activities and the therapeutic mechanisms of Tan IIA according to literature during the years 2015–2021. Tan IIA shows multiple pharmacological effects, including anticarcinogenic, cardiovascular, nervous, respiratory, urinary, digestive, and motor systems activities. Tan IIA modulates multi-targets referring to Nrf2, AMPK, GSK-3β, EGFR, CD36, HO-1, NOX4, Beclin-1, TLR4, TNF-α, STAT3, Caspase-3, and bcl-2 proteins and multi-pathways including NF-κB, SIRT1/PGC1α, MAPK, SREBP-2/Pcsk9, Wnt, PI3K/Akt/mTOR pathways, TGF-β/Smad and Hippo/YAP pathways, etc., which directly or indirectly influence disease course. Further, with the reported targets, the potential effects and possible mechanisms of Tan IIA against diseases were predicted by bioinformatic analysis. This paper provides new insights into the therapeutic effects and mechanisms of Tan IIA against diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Endoplasmic Reticulum Stress and Energy Supplymentioning

confidence: 99%

Recent Research Progress (2015–2021) and Perspectives on the Pharmacological Effects and Mechanisms of Tanshinone IIA

Zhong

Lin

et al. 2021

Front. Pharmacol.

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“…To further explore the molecular mechanisms of Mibefradil's anti-tumor effects in TNBC cells, we firstly predicted the targets of Mibefradil by network pharmacology analysis using PharmMapper and SwissTargetPrediction reverse docking database. As a result, a total of 185 potential human target genes of Mibefradil were predicted [36,37] (Table S2). Next, the protein-protein interaction (PPI) network of the potential target genes of Mibefradil were achieved using String database, and the compoundtargets network of Mibefradil was constructed and visualized by Cytoscape ( Figure 4A).…”

Section: Aurka Was Identified As the Key Target Of Mibefradil In Tnbcmentioning

confidence: 99%

Mibefradil inhibits the proliferation of triple-negative breast cancer by targeting AURKA to regulate apoptosis signal pathway

Han

Liu³

et al. 2021

Preprint

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Background: Triple negative breast cancer (TNBC) is a tumor characterized by high recurrence and mortality, but without effective targeted therapy. It is urgent to explore new treatment strategy to improve the efficacy of TNBC therapy. Methods: Transcriptomic profiling datasets of TNBC were used for screening TNBC specific gene sets. Drug prediction was performed in Connectivity map (CMap) database. Molecular docking method was used for analyzing drug targets. In vitro and in vivo models of TNBC were constructed to examine the drug efficacy. Results: We screened out Mibefradil, a T-type Ca2+ channel blocker, might be a potential therapeutic drug for TNBC by transcriptomics and bioinformatics analysis, and verified that Mibefradil could inhibit the proliferation of TNBC cells by inducing apoptosis and cell cycle arrest. Furthermore, by network pharmacology and molecular docking analysis, AURKA was predicted as the most possible drug target of Mibefradil. Finally, it was proved that Mibefradil treatment could induce apoptosis by decreasing protein expression and phosphorylation level of AURKA in vitro and in vivo. Conclusions: Mibefradil played anti-cancer role in TNBC cells by targeting to AURKA to induce cell cycle and apoptosis. Our results repurposed Mibefradil as a potential targeted drug of TNBC and provided a fundamental research for a novel strategy TNBC treatment.

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“…These components are the main active components in the leaves of Acanthopanax sessiliflorus , and the structure is shown in Figure 1. Previous studies have shown that Acanthopanax senticosus works well in cardiovascular diseases such as coronary artery disease, angina pectoris, [16] cerebral infarction, and cerebral hemorrhage [17] . However, Acanthopanax sessiliflorus , especially leaves, have been less studied in cardiovascular disease.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have shown that Acanthopanax senticosus works well in cardiovascular diseases such as coronary artery disease, angina pectoris, [16] cerebral infarction, and cerebral hemorrhage. [17] However, Acanthopanax sessiliflorus, especially leaves, have been less studied in cardiovascular disease. In this study, aconitine was used to establish a myocardial injury model to investigate the potential protective effect of 3,4-seco-lupane triterpenoids on cardiomyocytes and their regulatory mechanisms in the leaves of Acanthopanax sessiliflorus.…”

Section: Introductionmentioning

confidence: 99%

Potential Myocardial Protection of 3,4‐seco‐Lupane Triterpenoids from Acanthopanax sessiliflorus Leaves

Wang

Chen

Liu

et al. 2020

Chemistry & Biodiversity

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A rich of 3,4-seco-lupane triterpenoids including chiisanoside (CSS), divaroside (DVS), sessiloside-A1 (SSA) and chiisanogenin (CSG) were isolated from the ethanol extract of the leaves of Acanthopanax sessiliflorus. On the basis of previous studies, this article focused on four important components of 3,4-seco-lupane triterpenoids in Acanthopanax sessiliflorus leaves and explored their protective effects against aconitine-induced cardiomyocyte injury and their molecular mechanisms. The results showed that pretreatment with 3,4-seco-lupane triterpenoids could effectively increase cell viability, reduce CK-MB and LDH activities, reduce ROS production, maintain calcium concentration balance, and inhibit apoptosis, with divaroside having the best effect. In addition, Western blot results showed that divaroside down-regulated Cleaved caspase-3 and Bax and up-regulated Bcl-2 expression through activating the PI3 K/AKT pathway. However, the LY294002 inhibitor reversed this situation. This suggests that 3,4-seco-lupane triterpenoids may be a new hotspot for potential myocardial protective drugs research.

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An Integrated Pharmacokinetic Study of an Acanthopanax senticosus Extract Preparation by Combination of Virtual Screening, Systems Pharmacology, and Multi-Component Pharmacokinetics in Rats

Abstract: mechanisms of ASEP against cardiovascular diseases, and provided useful insights for future integrated PK study on anti-cardiovascular diseases TCM injections.

Cited by 13 publications

References 47 publications

Recent Research Progress (2015–2021) and Perspectives on the Pharmacological Effects and Mechanisms of Tanshinone IIA

Recent Research Progress (2015–2021) and Perspectives on the Pharmacological Effects and Mechanisms of Tanshinone IIA

Mibefradil inhibits the proliferation of triple-negative breast cancer by targeting AURKA to regulate apoptosis signal pathway

Potential Myocardial Protection of 3,4‐seco‐Lupane Triterpenoids from Acanthopanax sessiliflorus Leaves

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