| Summary: | Research targeting natural cosmeceuticals is now increasing due to the safety and/or limited side effects of natural products that are highly valued in cosmetology. Within a research program exploring botanical sources for valuable skincare antioxidant components, the current study investigated the phytochemical content and the biological potential of <i>Faucaria tuberculosa</i>. Phytochemical investigation of <i>F. tuberculosa</i> extract resulted in purification and characterization of six phytoconstituents, including a new one. The structure of the new constituent was elucidated as (-) catechin-(2→1′,4→2′)-phloroglucinol (<b>4</b>). The structural identity of all isolated compounds were confirmed on the basis of extensive physical and spectral (1D, 2D-NMR and HRESIMS) investigations. The ethanolic extract exhibits a rich content of total phenolics (TPC) and total flavonoids (TFC), estimated as 32 ± 0.034 mg GAE/g and 43 ± 0.004 mg RE/g, respectively. In addition, the antioxidant (ABTS and FRAP), antihyaluronidase and antityrosinase activities of all purified phytoconstituents were evaluated. The results noted (-) catechin-(2→1′,4→2′) phloroglucinol (<b>4</b>) and phloroglucinol (<b>1</b>) for their remarkable antioxidant activity, while isorhamnetin 3-<i>O</i>-rutinoside (<b>3</b>) and 3,5-dihydroxyphenyl <i>β</i>-D-glucopyranoside (<b>2</b>) achieved the most potent inhibitory activity against tyrosinase (IC<sub>50</sub> 22.09 ± 0.7 µM and 29.96 ± 0.44 µM, respectively) and hyaluronidase enzymes (IC<sub>50</sub> 49.30 ± 1.57 µM and 62.58 ± 0.92, respectively) that remarkably exceeds the activity of the standard drugs kojic acid (IC<sub>50</sub> = 65.21 ± 0.47 µM) and luteolin, (IC<sub>50</sub> = 116.16 ± 1.69 µM), respectively. A molecular docking study of the two active compounds (<b>3</b> and <b>2</b>) highlighted their high potential to bind to the active sites of the two enzymes involved in the study.
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