Study on the potential active components and molecular mechanism of Xiao Huoluo Pills in the treatment of cartilage degeneration of knee osteoarthritis based on bioinformatics analysis and molecular docking technology

Chen, Weijian; Lin, Tianye; He, Qi; Yang, Peng; Zhang, Gangyu; Huang, Fayi; Wang, Zihao; Peng, Hao; Li, Baolin; Du, Liqing; Wang, Haibin

doi:10.1186/s13018-021-02552-w

Cited by 18 publications

(10 citation statements)

References 57 publications

(53 reference statements)

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“…This active biomolecule could be related to six targets, namely, NCOA2, PGR, PTGS1, PTGS2, RXRA, and NR3C2. These primary target genes are linked to signaling pathways involved in cartilage degeneration in knee OA, including the PI3K-Akt signaling pathway and the TNF-α signaling pathway [ 100 ].…”

Section: Anti-osteoarthritis Effectsmentioning

confidence: 99%

Health Benefits and Pharmacological Properties of Stigmasterol

et al. 2022

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Stigmasterol is an unsaturated phytosterol belonging to the class of tetracyclic triterpenes. It is one of the most common plant sterols, found in a variety of natural sources, including vegetable fats or oils from many plants. Currently, stigmasterol has been examined via in vitro and in vivo assays and molecular docking for its various biological activities on different metabolic disorders. The findings indicate potent pharmacological effects such as anticancer, anti-osteoarthritis, anti-inflammatory, anti-diabetic, immunomodulatory, antiparasitic, antifungal, antibacterial, antioxidant, and neuroprotective properties. Indeed, stigmasterol from plants and algae is a promising molecule in the development of drugs for cancer therapy by triggering intracellular signaling pathways in numerous cancers. It acts on the Akt/mTOR and JAK/STAT pathways in ovarian and gastric cancers. In addition, stigmasterol markedly disrupted angiogenesis in human cholangiocarcinoma by tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor receptor-2 (VEGFR-2) signaling down-regulation. The association of stigmasterol and sorafenib promoted caspase-3 activity and down-regulated levels of the anti-apoptotic protein Bcl-2 in breast cancer. Antioxidant activities ensuring lipid peroxidation and DNA damage lowering conferred to stigmasterol chemoprotective activities in skin cancer. Reactive oxygen species (ROS) regulation also contributes to the neuroprotective effects of stigmasterol, as well as dopamine depletion and acetylcholinesterase inhibition. The anti-inflammatory properties of phytosterols involve the production of anti-inflammatory cytokines, the decrease in inflammatory mediator release, and the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Stigmasterol exerts anti-diabetic effects by reducing fasting glucose, serum insulin levels, and oral glucose tolerance. Other findings showed the antiparasitic activities of this molecule against certain strains of parasites such as Trypanosoma congolense (in vivo) and on promastigotes and amastigotes of the Leishmania major (in vitro). Some stigmasterol-rich plants were able to inhibit Candida albicans, virusei, and tropicalis at low doses. Accordingly, this review outlines key insights into the pharmacological abilities of stigmasterol and the specific mechanisms of action underlying some of these effects. Additionally, further investigation regarding pharmacodynamics, pharmacokinetics, and toxicology is recommended.

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Section: Anti-osteoarthritis Effectsmentioning

confidence: 99%

Health Benefits and Pharmacological Properties of Stigmasterol

et al. 2022

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“…Then, molecular docking between proteins and molecular compounds was performed using the default setting. The binding forces between the small molecules and proteins were analyzed using the docking fraction ( 19 ).…”

Section: Methodsmentioning

confidence: 99%

Simiao Wan and its ingredients alleviate type 2 diabetes mellitus via IRS1/AKT2/FOXO1/GLUT2 signaling

Xia

Xu²,

et al. 2023

Front. Nutr.

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BackgroundType 2 diabetes mellitus (T2DM) is a metabolic disease. Simiao Wan (SMW) is a commonly used clinical drug for hyperuricemia treatment. SMW has been confirmed to improve insulin resistance and is expected to be a novel hypoglycemic agent. However, the hypoglycemic bioactive ingredients and mechanisms of action of SMW are unclear.ObjectiveTo explore the hypoglycemic effects and reveal the mechanisms of SMW and bioactive ingredients (SMW-BI).Study design and methodsThe hypoglycemic effects of SMW and SMW-BI were verified in a mouse model of T2DM induced by streptozotocin (STZ) and a high-fat and high-sugar diet (HFSD). Network pharmacology was used to predict the mechanisms of SMW and SMW-BI. Histological analysis and real-time quantitative polymerase chain reaction (RT-qPCR) verified network pharmacology results. RT-qPCR results were further verified by immunofluorescence (IFC) and molecular docking. The correlation between proteins and biochemical indicators was analyzed by Spearman’s correlation.ResultsChlorogenic acid, phellodendrine, magnoflorine, jateorhizine, palmatine, berberine, and atractydin were identified as SMW-BI. After 8 weeks of treatment, SMW and SMW-BI decreased the levels of fasting blood glucose (FBG), total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-C), increased the level of high-density lipoprotein cholesterol (HDL-C), alleviated weight loss, and increased serum insulin levels in T2DM mice. In addition, SMW and SMW-BI improved hepatocyte morphology in T2DM mice, decreased the number of adipocytes, and increased liver glycogen. Network pharmacological analysis indicated that SMW and SMW-BI may exert hypoglycemic by regulating insulin receptor substrate 1 (IRS1)/RAC-beta serine/threonine-protein kinase (AKT2)/forkhead box protein O1 (FOXO1)/glucose transporter type 2 (GLUT2) signaling. Moreover, correlation analysis showed that SMW and SMW-BI were associated with activation of IRS1, AKT2, and GLUT2, and inhibiting FOXO1. RT-qPCR revealed that SMW and SMW-BI could increase levels of IRS1, AKT2, and GLUT2 in the livers of T2DM mice and lower the level of FOXO1. Furthermore, immunofluorescence analysis showed that FOXO1 expression in the livers of T2DM mice decreased after oral administration of SMW and SMW-BI. Furthermore, molecular docking showed that SMW-BI could bind directly to IRS1 and AKT2.ConclusionSMW and SMW-BI are potential hypoglycemic drugs that alleviate T2DM by regulating IRS1/AKT2/FOXO1 signaling. Our study provides a research idea for screening the bioactive ingredients in traditional Chinese medicine (TCM).

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“…LibDockScore ≥90 indicates that the ligand and receptor affinity is strong, and the ligand binding is easier ( Chen peng et al, 2021 ). The smaller the docking bond energy is, the more stable the complex of the ligand and protein is ( Chen Weijian et al, 2021 ). The result with the highest score for molecular docking will be presented as the final conformation, from which the interaction energy after docking can be calculated.…”

Section: Methodsmentioning

confidence: 99%

Investigative on the Molecular Mechanism of Licorice Flavonoids Anti-Melanoma by Network Pharmacology, 3D/2D-QSAR, Molecular Docking, and Molecular Dynamics Simulation

Jiang

et al. 2022

Front. Chem.

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Licorice flavonoids (LCFs) are natural flavonoids isolated from Glycyrrhiza which are known to have anti-melanoma activities in vitro. However, the molecular mechanism of LCF anti-melanoma has not been fully understood. In this study, network pharmacology, 3D/2D-QSAR, molecular docking, and molecular dynamics (MD) simulation were used to explore the molecular mechanism of LCF anti-melanoma. First of all, we screened the key active components and targets of LCF anti-melanoma by network pharmacology. Then, the logIC50 values of the top 20 compounds were predicted by the 2D-QSAR pharmacophore model, and seven highly active compounds were screened successfully. An optimal 3D-QSAR pharmacophore model for predicting the activity of LCF compounds was established by the HipHop method. The effectiveness of the 3D-QSAR pharmacophore was verified by a training set of compounds with known activity, and the possible decisive therapeutic effect of the potency group was inferred. Finally, molecular docking and MD simulation were used to verify the effective pharmacophore. In conclusion, this study established the structure–activity relationship of LCF and provided theoretical guidance for the research of LCF anti-melanoma.

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Study on the potential active components and molecular mechanism of Xiao Huoluo Pills in the treatment of cartilage degeneration of knee osteoarthritis based on bioinformatics analysis and molecular docking technology

Cited by 18 publications

References 57 publications

Health Benefits and Pharmacological Properties of Stigmasterol

Health Benefits and Pharmacological Properties of Stigmasterol

Simiao Wan and its ingredients alleviate type 2 diabetes mellitus via IRS1/AKT2/FOXO1/GLUT2 signaling

Investigative on the Molecular Mechanism of Licorice Flavonoids Anti-Melanoma by Network Pharmacology, 3D/2D-QSAR, Molecular Docking, and Molecular Dynamics Simulation

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