Gallic, Aconitic, and Crocetin Acids as Potential TNF Modulators: An Integrated Study Combining Molecular Docking,...

Area of Science:

• Biochemistry
• Immunology
• Pharmacology

Background:

• Organic acids are vital metabolites influencing human health.
• Tumor Necrosis Factor (TNF) is a key mediator of inflammation and an important therapeutic target.

Purpose of the Study:

• To evaluate organic acids as potential modulators of Tumor Necrosis Factor (TNF).
• To investigate the anti-inflammatory properties of gallic, aconitic, and crocetin acids targeting TNF.

Main Methods:

• In silico molecular docking and molecular dynamics (MD) simulations were employed.
• ADMET profiling assessed pharmacokinetic properties.
• In vivo mouse leukocyte models evaluated TNF gene expression.

Main Results:

• Crocetin exhibited the highest predicted TNF binding affinity, while gallic acid showed the most stable complex.
• ADMET analysis indicated potential pharmacokinetic limitations like low permeability.
• In vivo studies revealed gallic and aconitic acids inhibited TNF, whereas crocetin stimulated it.

Conclusions:

• Organic acids demonstrate complex interactions with TNF, acting as either inhibitors or stimulators.
• Gallic and aconitic acids show potential as TNF inhibitors for anti-inflammatory applications.
• Further research is needed to overcome pharmacokinetic challenges and develop these compounds for TNF-mediated diseases.