The leaf extract of Tectona grandis L.f. has shown potential as a 5α-reductase inhibitor, with two bioactive markers, namely (+)-eperua-8,13-dien-15-oic acid (1) and (+)-eperua-7,13-dien-15-oic acid (2), used for extract standardization. The purpose of this research was to investigate the in vitro skin penetration behavior of 1 and 2 in T. grandis leaf ethanolic extract solution and ready-to-use extract in propylene glycol (PG), and secondly, to determine their physicochemical properties, including partition coefficients and solubility. The appropriate vehicle for the in vitro skin penetration study was evaluated using the shake-flask method. The in vitro skin penetration study was conducted using the Franz diffusion cell model, and the amounts of the two active compounds in the extracts were analyzed using the HPLC method. Compounds 1 and 2 showed poor solubility in distilled water, whereas their solubility in HEPES buffer with 2% w/v of Tween 20 was significantly greater. The partition coefficient (log P_o/w) value for 1 was 5.77 ± 0.07, and for 2, it was 5.66 ± 0.02, indicating that both compounds are hydrophobic. After 24 h of an in vitro skin penetration study, 1 in both extracts showed significantly higher cumulative amounts (%) compared to 2. These findings suggest that 1 is more hydrophobic and readily penetrates the stratum corneum. When a PG enhancer was added, high cumulative amount trends of 1 and 2 in the ethanolic extract and extract in PG in the receiver compartment were detected after 24 h. These studies provide important insights that will guide the further development of products with T. grandis extracts for treating hair loss.

The inhibition of steroid 5-alpha reductase (S5AR), a key mechanism for managing dihydrotestosterone-dependent conditions, has been demonstrated in teak (Tectona grandis L.f.) leaf extracts. Our recent clinical study confirmed the effectiveness of a hair growth formulation containing teak leaf extract in males with androgenic alopecia. However, significant variability in S5AR inhibitory activity among teak leaf samples from different regions underscores the need for quality control of raw materials. This study applied a metabolomics approach to investigate the influence of leaf age, harvesting period, and geographic origin on chemical composition and S5AR inhibitory activity, as well as to identify active S5AR inhibitors. Geographic origin emerged as the primary determinant of variations in chemical profiles and S5AR inhibitory activity. Using orthogonal partial least squares analysis, six diterpenoid S5AR inhibitors were identified, including four compounds reported for the first time as S5AR inhibitors: rhinocerotinoic acid, 7-oxo-8-labden-15-oic acid, 8-hydroxy-labd-13-en-15-oic acid, and a novel diterpene, 7-hydroxy-labd-8,13-dien-15-oic acid. These findings highlight the potential of metabolomics as a powerful tool for discovering bioactive compounds and optimizing raw material selection. By prioritizing proven geographic sources, consistent bioactivity can be achieved, supporting the therapeutic potential of teak leaves in managing S5AR-related conditions.