Interpreting the Pharmacological Mechanisms of Sho-saiko-to on Thyroid Carcinoma through Combining Network Pharmacology and Experimental Evaluation

Wang, Kun; Qian, Ruijie; Li, Hongyan; Wang, Chenyang; Ding, Ying; Gao, Zairong

doi:10.1021/acsomega.1c07335

Cited by 7 publications

(4 citation statements)

References 50 publications

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“…Confirming the primary mechanism by which Chrysin addresses breast cancer through quantitative animal experiments can be a formidable challenge. Network pharmacology emerges as an invaluable tool for predicting the mechanisms, toxicity, and metabolic characteristics of traditional Chinese medicines ( 24 ). Consequently, we embarked on a network pharmacological analysis to unveil the workings of Chrysin in the context of breast cancer.…”

Section: Resultsmentioning

confidence: 99%

Enhancing breast cancer treatment: mesoporous dopamine nanoparticles in synergy with chrysin for photothermal therapy

Zhu,

Zhang,

Lan

et al. 2024

Front. Oncol.

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IntroductionBreast cancer is one of the most prevalent cancers, primarily affecting women. Among its subtypes, estrogen receptor-positive (ER+) breast cancer is particularly common. Inhibiting estrogen's effects is crucial for treating ER+ breast cancer, but current therapies often have significant side effects and limitations. Chrysin, a natural flavonoid, has shown potential in reducing estrogen receptor expression, but its poor water solubility hampers clinical application. This study explores the use of mesoporous dopamine nanoparticles (mPDA) to enhance the delivery and efficacy of Chrysin, combined with photothermal therapy (PTT), for breast cancer treatment.MethodsChrysin-loaded mPDA nanoparticles (Chrysin@mPDA) were synthesized and characterized for their morphology, drug-loading efficiency, stability, and photothermal properties. Network pharmacology was used to predict Chrysin's mechanisms in breast cancer, which were validated through gene expression analysis in cell experiments. The therapeutic efficacy of Chrysin@mPDA with and without PTT was evaluated in a mouse model of breast cancer, with tumor volume and weight measured. Immunohistochemical analysis was conducted to assess estrogen receptor expression and immune cell infiltration in tumor tissues.ResultsChrysin@mPDA nanoparticles demonstrated a high drug-loading capacity and excellent stability. Photothermal studies confirmed the nanoparticles' ability to generate heat upon laser exposure, significantly enhancing Chrysin release in acidic conditions with laser irradiation. Network pharmacology identified key target genes affected by Chrysin, including ESR1, BRCA1, CTNNB1, and BAX, which were validated through qPCR. In vivo, the combination of Chrysin@mPDA and PTT significantly reduced tumor volume and weight, decreased estrogen receptor-positive cells, and increased infiltration of CD3+CD4+ and CD3+CD8+ T cells in tumor tissues.DiscussionThe study highlights the potential of Chrysin-loaded mPDA nanoparticles combined with PTT as an effective strategy for breast cancer treatment. This approach addresses the limitations of Chrysin's solubility and enhances its therapeutic efficacy through synergistic mechanisms. The dual action of Chrysin in modulating gene expression and PTT in inducing localized hyperthermia and immune response suggests a promising avenue for improved breast cancer prognosis and reduced recurrence.

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Section: Resultsmentioning

confidence: 99%

Enhancing breast cancer treatment: mesoporous dopamine nanoparticles in synergy with chrysin for photothermal therapy

Zhu,

Zhang,

Lan

et al. 2024

Front. Oncol.

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“…The therapeutic mechanism of natural drugs on diseases is extraordinarily complex, with various pathways and targets together being the main feature. Network pharmacology is a form of bioinformatics method, by which we can predict effective drug targets, understand the relationship between drugs and diseases, and explore the mechanism of drugs [ 23 ]. Therefore, we aimed to assess the possibility of TPL against MI and determined the related mechanisms by network pharmacology to guide the design of the follow-up TPL-related experiments.…”

Section: Resultsmentioning

confidence: 99%

Triptolide with hepatotoxicity and nephrotoxicity used in local delivery treatment of myocardial infarction by thermosensitive hydrogel

Wang

Zhu

et al. 2023

J Nanobiotechnol

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Myocardial infarction (MI) resulting from coronary artery occlusion is the leading global cause of cardiovascular disability and mortality. Anti-inflammatory treatment plays an important role in MI treatment. Triptolide (TPL), as a Chinese medicine monomer, has a variety of biological functions, including anti-inflammatory, anti-tumor, and immunoregulation. However, it has been proved that TPL is poorly water soluble, and has clear hepatotoxicity and nephrotoxicity, which seriously limits its clinical application. Herein, we designed a long-acting hydrogel platform (TPL@PLGA@F127) for MI treatment by intramyocardial injection. First, we found that the inflammatory response and immune regulation might be the main mechanisms of TPL against MI by network pharmacology. Subsequently, we prepared the hydrogel platform (TPL@PLGA@F127) and tested its effects and toxicity on normal organs in the early stage of MI (3 days after MI-operation). The results showed that TPL@PLGA@F127 could not only promote “repair” macrophages polarization (to M2 macrophage) by day 3 after MI, but also has a long-lasting anti-inflammatory effect in the later stage of MI (28 days after MI-operation). Additionally, we proved that TPL@PLGA@F127 could attenuate the toxicity of TPL by releasing it more slowly and stably. Finally, we observed the long-term effects of TPL@PLGA@F127 on MI and found that it could improve cardiac function, depress the myocardial fibrosis and protect the cardiomyocytes. In summary, this study indicated that TPL@PLGA@F127 could not only enhance the therapeutic effects of TPL on MI, but also attenuate the hepatotoxicity and nephrotoxicity, which established a strong foundation for the clinical application of TPL for MI.

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“…In traditional Chinese medicine, because the therapeutic mechanism of natural drugs is extremely complex, compounds composed of natural drugs are often used to treat patients through network interactions [ 34 ]. The most important mechanism of BBR in the treatment of MI is difficult to confirm by quantitative analysis in animal experiments.…”

Section: Resultsmentioning

confidence: 99%

Berberin sustained-release nanoparticles were enriched in infarcted rat myocardium and resolved inflammation

et al. 2023

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Inflammatory regulation induced by macrophage polarization is essential for cardiac repair after myocardial infarction (MI). Berberin (BBR) is an isoquinoline tetrasystemic alkaloid extracted from plants. This study analyzes the most likely mechanism of BBR in MI treatment determined via network pharmacology, showing that BBR acts mainly through inflammatory responses. Because platelets (PLTs) can be enriched in the infarcted myocardium, PLT membrane-coated polylactic-co-glycolic acid (PLGA) nanoparticles (BBR@PLGA@PLT NPs) are used, which show enrichment in the infarcted myocardium to deliver BBR sustainably. Compared with PLGA nanoparticles, BBR@PLGA@PLT NPs are more enriched in the infarcted myocardium and exhibit less uptake in the liver. On day three after MI, BBR@PLGA@PLT NPs administration significantly increases the number of repaired macrophages and decreases the number of inflammatory macrophages and apoptotic cells in infarcted rat myocardium. On the 28th day after MI, the BBR@PLGA@PLT group exhibits a protective effect on cardiac function, reduced cardiac collagen deposition, improved scar tissue stiffness, and an excellent angiogenesis effect. In addition, BBR@PLGA@PLT group has no significant impact on major organs either histologically or enzymologically. In summary, the therapeutic effect of BBR@PLGA@PLT NPs on MI is presented in detail from the perspective of the resolution of inflammation, and a new solution for MI treatment is proposed. Graphical Abstract

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Interpreting the Pharmacological Mechanisms of Sho-saiko-to on Thyroid Carcinoma through Combining Network Pharmacology and Experimental Evaluation

Cited by 7 publications

References 50 publications

Enhancing breast cancer treatment: mesoporous dopamine nanoparticles in synergy with chrysin for photothermal therapy

Enhancing breast cancer treatment: mesoporous dopamine nanoparticles in synergy with chrysin for photothermal therapy

Triptolide with hepatotoxicity and nephrotoxicity used in local delivery treatment of myocardial infarction by thermosensitive hydrogel

Berberin sustained-release nanoparticles were enriched in infarcted rat myocardium and resolved inflammation

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