Current Computer - Aided Drug Design - Online First
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Mechanisms Underlying the Attenuating Effects of Bugantang on Liver Fibrosis Based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation
Authors: Taojing Zhang, Jia Chang, Zengle Zheng, Guobi Chen, Yiping Wu, Jinxiang Xiang and Jing ChenAvailable online: 02 December 2024More LessBackgroundLiver fibrosis, a chronic liver disease, threatens people's health, increases the burden of healthcare, and currently lacks effective treatment measures. Bugantang (BGT) is a traditional Chinese herbal prescription from Jin Kui Yi with promising potential for treating liver fibrosis. Despite this potential, the efficacy and mechanism for treating liver fibrosis remain unclear.
ObjectiveTo primarily prove the efficacy, predict the active components of BGT, and explore the mechanism of BGT on liver fibrosis.
MethodsThe liver condition of CCL4-induced mice was examined using hematoxylin and eosin staining. The targets and active compounds of BGT were sourced from HERB and TCMSP databases, while the targets related to liver fibrosis were acquired from DisGeNET, Gene Expression Omnibus, and GeneCards databases. The core targets were identified, and the network of protein-protein interactions was established. KEGG and GO analyses were performed on DAVID. Molecular docking and molecular dynamics simulations assessed the active components’ interactions with potential targets.
ResultsA total of 215 targets and 152 active compounds were identified for BGT. The network analysis identified kaempferol, quercetin, 2-(2,4-dihydroxyphenyl)-7-hydroxy-4H-chromen-4-one, sitosterol, naringenin, adenosine, plo, and beta-sitosterol as potential key compounds, and AKT1, MMP9, SRC, TNF, ESR1, NF-κB, and PPARG as potential key targets. KEGG and GO analyses revealed that the therapeutic effect of BGT on liver fibrosis may be associated with the PI3K-AKT and MAPK signaling pathways, as well as cell apoptosis, protein phosphorylation, and inflammation. Molecular docking demonstrated high-affinity binding of the identified targets to the active compounds. Additionally, molecular dynamics simulation further confirmed that the bindings of AKT1-beta-sitosterol and MMP9-quercetin exhibited good stability.
ConclusionsThe potential of BGT in alleviating liver fibrosis may be attributed to a combination of various active compounds, targets, and pathways. These results could support the use of BGT in treating liver fibrosis and facilitate the development of new drug candidates for this condition.
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Study on the Mechanism of Alpinia officinarum Hance in the Improvement of Insulin Resistance through Network Pharmacology, Molecular Docking and in vitro Experimental Verification
Authors: Mingyan Zhou, Xiuxia Lian, Xuguang Zhang, Jian Xu and Junqing ZhangAvailable online: 01 November 2024More LessBackgroundResearch has elucidated that the pathophysiological underpinnings of non-alcoholic fatty liver disease and type 2 diabetes mellitus are intrinsically linked to insulin resistance (IR). However, there are currently no pharmacotherapies specifically approved for combating IR. Although Alpinia officinarum Hance (A. officinarum) can ameliorate diabetes, the detailed molecular mechanism through which it influences IR has not been fully clarified.
AimsTo predict the active components of A. officinarum and determine the mechanism by which A. officinarum affects IR.
MethodsThe active compounds and molecular mechanism underlying the improvement of IR by A. officinarum were predicted via network pharmacology and molecular docking. To further substantiate these predictions, an in vitro model of IR was induced in HepG2 cells using high glucose concentrations. Cytotoxicity and oxidative stress levels were evaluated using Cell Counting Kit-8, reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) assay kits. The putative molecular mechanisms were corroborated through Western blot and RT-PCR analyses.
ResultsFourteen principal active components in A. officinarum, 133 potential anti-IR gene targets, and the top five targets with degree values were ALB, AKT1, TNF, IL6, and VEGFA. A. officinarum was posited to exert its pharmacological effects on IR through mechanisms involving lipid and atherosclerosis, the AGE-RAGE signaling pathway in diabetic complications, the PI3K-AKT signaling pathway, fluid shear stress, and atherosclerosis. Intriguingly, network pharmacology analysis highlighted (4E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (A14) as the most active compound. Molecular docking studies further confirmed that A14 has a strong binding affinity for the main targets of PI3K, AKT, and Nrf2. The experiments demonstrated that A14 significantly diminished the ROS and MDA levels while augmenting the SOD activity. Moreover, A14 was found to elevate the protein expression of PI3K, AKT, Nrf2, and HO-1, and increase the mRNA levels of these targets as well as NQO1.
ConclusionA. officinarum could play a therapeutic role in IR through multiple components, targets, and pathways. The most active component of A. officinarum responsible for combating IR is A14, which has the ability to regulate oxidative stress in IR-HepG2 cells by activating the PI3K/AKT/Nrf2 pathway. These findings suggest a potential pharmacological intervention strategy for the treatment of IR.
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