Optimized Ultrasound-Assisted Extraction Enhances the Recovery of Anti-Collagenase Phytochemicals from Mitragyna speciosa Korth. Leaves.

Mitragyna speciosa Korth. (Kratom) is a plant native to Southeast Asia, traditionally used for its stimulant and analgesic properties. Beyond mitragynine, the principal alkaloid dominating M. speciosa research, this study explored the cosmeceutical and nutraceutical potential of its phenolic and flavonoid constituents. Kratom leaf extract (MLE) was obtained via ultrasound-assisted extraction optimized by Central Composite Design, yielding high polyphenol content and antioxidant capacity. The optimized MLE showed measurable collagenase inhibition (IC50 = 92.63 ± 7.81 µg/mL) while maintaining fibroblast viability (>80%). UHPLC-ESI-QTOF-MS/MS tentatively identified chlorogenic acid, rutin, and kaempferol 3-glucosyl-(1→6)-galactoside (K3G). Chlorogenic acid and rutin were quantified by HPLC at 31.37 ± 2.41 and 18.76 ± 1.66 µg/mg extract, respectively, while K3G remained linked to an unidentified peak. Mitragynine was also quantified at an appreciable level (59.38 ± 0.21 µg/mg extract), indicating that removal of the alkaloid fraction is required before application. Molecular docking identified chlorogenic acid as the strongest predicted collagenase binder (-12.82 kcal/mol), though chlorogenic acid and rutin together could not fully account for the extract's activity, suggesting possible contributions from K3G and other unidentified compounds. These findings provide preliminary evidence for the cosmeceutical potential of kratom leaf extract, pending control of its alkaloid content.