| Summary: | Several studies have explored the biological activities of <i>Citrus aurantium</i> flowers, fruits, and seeds, but the bioactivity of <i>C. aurantium</i> leaves, which are treated as waste, remains unclear. Thus, this study developed a pilot-scale ultrasonic-assisted extraction process using the Box–Behnken design (BBD) for the optimized extraction of active compounds from <i>C. aurantium</i> leaves, and their antityrosinase, antioxidant, antiaging, and antimicrobial activities were evaluated. Under optimal conditions in a 150× scaleup configuration (a 30 L ultrasonic machine) of a pilot plant, the total phenolic content was 69.09 mg gallic acid equivalent/g dry weight, which was slightly lower (3.17%) than the theoretical value. The half maximal inhibitory concentration of <i>C. aurantium</i> leaf extract (CALE) for 2,2-diphenyl-1-picrylhydrazyl–scavenging, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)–scavenging, antityrosinase, anticollagenase, antielastase and anti-matrix metalloprotein-1 activities were 123.5, 58.5, 181.3, 196.4, 216.3, and 326.4 mg/L, respectively. Moreover, the minimal inhibitory concentrations for bacteria and fungi were 150–350 and 500 mg/L, respectively. In total, 17 active compounds were detected in CALE—with linalool, linalyl acetate, limonene, and α-terpineol having the highest concentrations. Finally, the overall transdermal absorption and permeation efficiency of CALE was 95.9%. In conclusion, our CALE demonstrated potential whitening, antioxidant, antiaging, and antimicrobial activities; it was also nontoxic and easily absorbed into the skin as well as inexpensive to produce. Therefore, it has potential applications in various industries.
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