Network Pharmacology, Molecular Docking Analysis and Molecular Dynamics Simulation of Scutellaria baicalensis in the Treatment of Liver Fibrosis.

BACKGROUND: Traditional Chinese medicine Scutellaria Baicalensis (SB), one of the clinical firstline heat-clearing drugs, has obvious symptomatic advantages for hepatic fibrosis with dampness-heat stasis as its syndrome. We aim to predict and validate the potential mechanism of Scutellaria baicalensis active ingredients against liver fibrosis more scientifically and effectively. METHODS: The underlying mechanism of Scutellaria baicalensis in inhibiting hepatic fibrosis was studied by applying network pharmacology, molecular docking and molecular dynamics simulation. Expression levels of markers in activated Hepatic Stellate Cells (HSC) after administration of three Scutellaria baicalensis extracts were determined by Western blot and Real-time PCR, respectively, in order to verify the anti-fibrosis effect of the active ingredients Results: There are 164 common targets of drugs and diseases screened and 115 signaling pathways obtained, which were mainly associated with protein phosphorylation, senescence and negative regulation of the apoptotic process. Western blot and Real-time PCR showed that Scutellaria baicalensis extracts could reduce the expression of HSC activation markers, and Oroxylin A had the strongest inhibitory effect on it. Molecular docking results showed that Oroxylin A had high binding activity to target proteins. Molecular dynamics simulation demonstrates promising stability of the Oroxylin A-AKT1 complex over the simulated MD time of 200 ns. CONCLUSION: Scutellaria baicalensis active ingredients may inhibit HSC proliferation, reduce the generation of pro-inflammatory factors and block the anti-inflammatory effect of inflammatory signal transduction by inducing HSC apoptosis and senescence, thus achieving the effect of anti-fibrosis.

Tumor-self-targeted "thermoferroptosis-sensitization" magnetic nanodroplets for multimodal imaging-guided tumor-specific therapy.

Ferroptosis-based nanomedicine has drawn increasing attention in antitumor therapy because of the advantages of this unconventional mode of apoptosis, but the difficulties of delivery to the tumor site and surface-to-core penetration after arrival seriously hinder further clinical transformation and application. Herein, we propose an unprecedented strategy of injecting magnetic nanodroplets (MNDs) to solve these two longstanding problems. MNDs are nanocarriers that can carry multifunctional drugs and imaging materials. MNDs can effectively accumulate in the tumor site by active tumor targeting (multifunctional drugs) and passive tumor targeting (enhanced permeability and retention effect), allowing diffusion of the MNDs from the surface to the core through mild-temperature magnetic fluid hyperthermia (MHT) under multimodal imaging guidance. Finally, the ferroptosis pathway is activated deep within the tumor site through the drug release. This approach was inspired by the ability of mild-temperature MHT to allow MNDs to quickly pass through the blood vessel-tumor barrier and deeply penetrate the tumor tissue from the surface to the core to amplify the antitumor efficacy of ferroptosis. This strategy is termed as "thermoferroptosis sensitization". Importantly, this behavior can be performed under the guidance of multimodal imaging, making the design of MNDs for cancer therapy safer and more reasonable.