Systems Biology Approach to Berberine Metabolomics and Toxicity: An In Silico Investigation of Bioactive Pathways and...

Area of Science:

• Pharmacology and Toxicology
• Computational Chemistry
• Natural Product Chemistry

Background:

• Berberine, a plant-derived isoquinoline alkaloid, exhibits promising antimicrobial, anti-inflammatory, and anticancer properties.
• Comprehensive evaluation of berberine's metabolic profile and toxicity is crucial for its safe therapeutic use.

Purpose of the Study:

• To conduct an integrated analysis of berberine's ADME profiling, in silico toxicity, and in vivo evaluation.
• To identify berberine metabolites and predict their toxicological impact using computational and experimental methods.

Main Methods:

• Integrative approach including ADME profiling, in silico toxicity prediction, in vivo evaluation, quantum description, SAR analysis, network pharmacology, protein target prediction, and molecular docking.
• Metabolomics profiling using an augmented computational pipeline.
• Interactome prediction and molecular docking studies.

Main Results:

• Identified four potential berberine metabolites: BTMR1030, BTMR0052, BTMR1070, and BTMR1071.
• BTMR0052 was identified as the most detrimental metabolite with the highest toxicity score.
• Berberine and its metabolites showed potential interactions with various protein targets, including hydrolases, cytochrome P450, kinases, and GPCRs.

Conclusions:

• The study provides mechanistic insights into berberine's toxicity.
• Identified BTMR0052 as a key toxic metabolite.
• Highlighted potential structural modifications for improved therapeutic applications of berberine.