LC-HRMS-Based Phytochemical Profiling and Computational Evaluation of Butea monosperma Against IGF2R

The present study aimed to comprehensively evaluate the phytochemical composition and therapeutic potential of Butea monosperma through experimental and computational approaches. Hydroalcoholic extraction yielded a stable, dark brownish extract with a 10.5% yield, near-neutral pH, low moisture content, and acceptable ash values, confirming purity and stability. Microbial evaluation demonstrated absence of pathogenic organisms, validating its safety for therapeutic applications. Preliminary phytochemical screening revealed abundant flavonoids and phenolics, along with moderate levels of tannins, glycosides, anthraquinones, and saponins, supporting its pharmacological relevance. LC-HRMS profiling identified five major bioactive constituents—quercetin, rutin, kaempferol-3-O-rutinoside, apigenin-7-O-glucoside, and soyasaponin I—compounds well-known for antioxidant, anti-inflammatory, cardioprotective, and anticancer properties. Molecular docking studies targeting Insulin-like Growth Factor Receptor Type-2 (IGF2R) revealed rutin (−9.3 kcal/mol) and quercetin (−8.2 kcal/mol) exhibited superior binding affinities compared to the NL-2V5O (Native Ligand) (−6.6 kcal/mol), forming stable hydrogen bonding, hydrophobic, and electrostatic interactions. Apigenin-7-O-glucoside and kaempferol-3-O-rutinoside showed moderate binding, while soyasaponin I displayed binding comparable to the NL-2V5O. ADMET predictions provided insight into pharmacokinetic and toxicity profiles. Quercetin demonstrated the most balanced drug-likeness, with favorable absorption and bioavailability, though limited by high plasma protein binding and metabolic interactions. Rutin and kaempferol-3-O-rutinoside showed restricted intestinal absorption, whereas soyasaponin I exhibited strong bioavailability but raised toxicity concerns. Apigenin-7-O-glucoside showed moderate promise with minimal rule violations. In conclusion, B. monosperma is a flavonoid-rich medicinal plant with significant therapeutic potential. Quercetin emerged as the most promising lead compound, warranting further in vivo validation and formulation strategies to enhance its bioavailability and clinical applicability.