(+)-Erythro-Δ8′-7S,8R-dihydroxy-3,3′,5′-trimethoxy-8-O-4′-neolignan, an Anti-Acne Component in Degreasing Myristica fragrans Houtt

Abstract

Acne is a common skin condition observed in adolescents. Nutmeg (Myristica fragrans Houtt) (MF) is a well-known traditional Chinese medicine; its major toxic components, safrole and myristicin, are rich in essential oils. Essential oils of MF (MFO) were extracted by hydrodistillation; the residue was extracted using 50% methanol (MFE-M). The minimum inhibitory concentration (MIC) of MFE-M against Cutibacterium acnes and Staphylococcus aureus was 0.64 mg. Four compounds were obtained from MFE-M: myristicin (1), (+)-erythro-Δ^8′-7S,8R- dihydroxy-3,3,5′-trimethoxy-8-O-4′-neolignan (2), (+)-erythro-Δ^8’-7-hydroxy-3,4,3’,5’-tetramethoxy 8-O-4-neolignan (3), and erythro-Δ^8′-7-acetoxy-3,4,3′,5′-tetramethoxy-8-O-4′-neolignan (4). Compound 2 exerted the strongest antimicrobial activity, with MICs of 6.25 and 3.12 μg/mL against C. acnes and S. aureus, respectively. Moreover, 2 inhibited NO, PGE₂, iNOS, and COX-2 levels in RAW 264.7 cells induced by LPS or heat-killed C. acnes; NO production at 50% inhibitory concentrations (IC₅₀) was 11.07 and 11.53 μg/mL, respectively. Myristicin and safrole content was higher in MFO than in MFE-M. MFO and MFE-M caused no skin irritation after a single topical application in Wistar rats. MFE-M, with low safrole and myristicin content, did not cause skin irritation and exhibited an anti-acne effect; moreover, 2 was identified as the active substance. Therefore, MFE-M could be employed to develop anti-acne compounds for use in cosmetics.