Biosensor-Based Active Ingredients Recognition System for Screening STAT3 Ligands from Medical Herbs

Area of Science:

• Biochemistry
• Biosensing Technology
• Drug Discovery

Background:

• Signal transducer and activator of transcription 3 (STAT3) is a key regulator in cellular processes, and its dysregulation is implicated in various diseases.
• Identifying specific STAT3 ligands from complex natural product mixtures is challenging due to potential interference from inactive compounds.

Purpose of the Study:

• To develop and validate a surface plasmon resonance (SPR) biosensor-based active ingredients recognition system (SPR-AIRS) for screening STAT3 ligands.
• To identify novel STAT3-targeting compounds from medicinal herbs using the developed SPR-AIRS.

Main Methods:

• Development and validation of the SPR-AIRS, assessing chip specificity, linearity, limit of detection (LOD), saturability, and robustness.
• Screening of medicinal herb extracts using SPR-AIRS to identify potential STAT3 ligands.
• Verification of compound-STAT3 interactions using SPR assays and molecular docking.
• Functional validation of identified compounds using apoptosis and luciferase reporter assays, and Western blotting to assess STAT3 phosphorylation inhibition.

Main Results:

• The SPR-AIRS demonstrated high specificity, linearity, and robustness for screening STAT3 ligands from complex mixtures.
• Nine candidate compounds were identified from medicinal herbs.
• Neobaicalein and polydatin were confirmed as effective STAT3 ligands, inhibiting STAT3 phosphorylation.
• This study represents the first report of neobaicalein and polydatin as STAT3 ligands.

Conclusions:

• The SPR-AIRS is a sensitive and effective platform for discovering active compounds from complex matrices.
• The findings highlight the potential of neobaicalein and polydatin as therapeutic agents targeting STAT3-mediated pathways.