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Abstract

Introduction

Inflammatory disorders profoundly affect quality of life, with existing treatments often limited by resistance, adverse effects, and administration challenges. , highly esteemed for its potent anti-inflammatory efficacy, harbors andrographolide, a pharmacologically active compound whose clinical utilization is impeded by its limited aqueous solubility and reduced oral bioavailability.

Methods

To address these limitations, we synthesized a mixture of andrographolide sulfonated derivatives to improve solubility. The major derivatives were isolated and analyzed qualitatively by NMR and UHPLC-Q/TOF-MS. Their anti-inflammatory effects were evaluated using a zebrafish inflammation model, and the most active derivatives were further analyzed through network pharmacological analysis to uncover the underlying anti-inflammatory mechanisms.

Results

The synthesis of andrographolide sulfonate derivatives enhanced andrographolide’s solubility. Structural characterization of the seven predominant derivatives was performed. Testing in a zebrafish model revealed that andrographolide and three sulfonated derivatives substantially reduced inflammation. Network pharmacology analysis identified significant connections in the “active compounds-inflammation targets-pathways-therapeutic effects” network, highlighting important biological processes and six key molecular targets (PRKCA, PRKCB, MAPK14, IL6, CASP3, and CDK4) associated with the anti-inflammatory actions of these derivatives.

Discussion

This integrative chemical–bioinformatic workflow significantly enhances the solubility of andrographolide while preserving its anti-inflammatory potency and identifying six key inflammatory targets. It therefore provides a transferable blueprint for optimising hydrophobic natural products and accelerating anti-inflammatory drug discovery.

Conclusion

Overall, this study not only improves the solubility and maintains the anti-inflammatory efficacy of andrographolide through sulfonation but also elucidates the underlying potential mechanisms of action of its sulfonated derivative mixture.

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2025-06-19
2025-09-04

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From Synthesis and Structural Characterization to Anti-inflammatory Activity Evaluation and Network Pharmacology Analysis: Revealing the Potential Anti-inflammatory Mechanisms of Andrographolide Sulfonated Derivative Mixture
Bentham Science Publishers ; https://doi.org/10.2174/0115734110333071250613041616
/content/journals/cac/10.2174/0115734110333071250613041616
/content/journals/cac/10.2174/0115734110333071250613041616
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  • Article Type:     Research Article
Keywords: network pharmacology ; solubility ; zebrafish inflammation model ; Andrographolide ; synthesis ; anti-inflammation

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