Phytochemical Profiling of the Halophyte Artemisia fukudo Makino and Its In Vitro Effects on Androgen‐Related Pathways Associated With Benign Prostatic Hyperplasia and Alopecia

Artemisia fukudo Makino is a biennial halophyte from the Asteraceae family, known for its tolerance to high-salinity soils. Based on the excellent activity of A. fukudo extract in regulating the 5α-reductase type 2 (5αR2) enzyme, this study aimed to investigate the phytochemical properties and pharmaceutical potential of A. fukudo for treating benign prostatic hyperplasia (BPH) and alopecia. Eight compounds including sesquiterpenes (1-4), coumarin (5), and flavonoids (6-8) were isolated from 90% MeOH fraction of A. fukudo, and their structures were determined using NMR and MS experiments. Among the isolated compounds, compounds 5-7 were detected in HPLC-DAD, and contents of compounds 5-8 were successfully quantified using ESI-MS. It was found that 90% MeOH fraction of A. fukudo contained scopoletin (5), jaceosidin (6), eupatilin (7), and jaceidin (8) at the concentration of 1.44, 35.71, 6.44, and 11.19 mg/g, respectively. Compound 8 effectively inhibited the expressions of BPH-related proteins, AR, PCNA, PSA, and 5αR2 in LNCaP and RWPE-1 cells. Meanwhile, compound 7 exhibited potent activity in regulating Wnt/β-catenin signaling and induced the expression of VEGF and IGF-1 in HaCaT and HUVECs. These findings suggest that A. fukudo and its bioactive constituents represent novel natural substances for treatment or improvement of BPH and alopecia.