Zanthoxylum alatum fruits: process optimization for tambulin-rich valuable phyto-compounds, antifungal action coupled with molecular modeling analysis

Extraction of phytochemicals (EZA) from Zanthoxylum alatum fruits was optimized using ultrasound-assisted (UAE) and microwave-assisted extraction (MAE) by response surface methodology (RSM). Intensive optimum conditions of UAE were ultrasonic frequency 30 KHz, solvent 10.41 mL/g, and extraction time 17.26 min to produce 358.24 mg EZA/g. MAE gave yield of 396.30 mg EZA/g at the microwave power 832.37 W, solvent-to-solute ratio of 59.78, and irradiation time 81.43s. Better extraction yield in MAE and UAE over conventional solid–liquid extraction (CSLE) was also proven through microstructural analysis. Further, extraction efficiency was assessed by extraction rate kinetic, explaining the role of second-order extraction models on mass transfer of phytochemicals, owing to UAE multi-factorial influences. Energy consumption and carbon emission pattern showed significant lower impact for UAE and MAE over CSLE. Characterizations of EZA displayed twenty-nine bioactive phytochemicals belong to alkaloids, lignans, and flavonoids in UPLC-QToF-ESI-MS/MS. Additionally, FT-IR spectra demonstrated the presence of major functional groups, corresponding to lignans and isoquinoline alkaloids. EZA comprising of abundant tambulin exhibited strong antifungal action against virulent Aspergillus flavus 2838 (EC 50 57.2 μg/mL) and A. flavus 6347 (EC 50 60.9 μg/mL). Fungal ergosterol inhibition (96.85%) was observed with 75.0 μg/mL concentration of EZA. Further, molecular docking and dynamics simulations revealed significant stable interactions with tambulin and sterol 14- α -demethylase complex using four conventional H-bonds, two π–sulfur bonds, one π–π bond, and three π–alkyl bonds.