Tanuphol Nutchaninad, Girard Corine, Temkitthawon Prapapan, Suphrom Nungruthai, Nuengchamnong Nitra, Saesong Tongchai, Insumrong Kamonlak, Wadeng Abdulaziz, Khangkhachit Wiyada, Zedet Andy, Intayot Ratchadaree, Jungsuttiwong Siriporn, Plubrukarn Anuchit, Senejoux Francois, Ingkaninan Kornkanok
Center of Excellence for Natural Health Product Innovation and Center of Excellence for Innovation in Chemistry, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
Université Marie et Louis Pasteur, EFS, INSERM RIGHT (UMR1098), F-25000 Besançon, France.
Molecules. 2025 Jul 8;30(14):2895. doi: 10.3390/molecules30142895.
The inhibition of steroid 5-alpha reductase (S5AR), a key mechanism for managing dihydrotestosterone-dependent conditions, has been demonstrated in teak ( 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.
柚木（柚木属）叶提取物已被证明具有抑制类固醇5-α还原酶（S5AR）的作用，这是治疗双氢睾酮依赖性疾病的关键机制。我们最近的临床研究证实，一种含有柚木叶提取物的生发配方对雄激素性脱发男性有效。然而，不同地区的柚木叶样本中S5AR抑制活性存在显著差异，这凸显了对原材料进行质量控制的必要性。本研究采用代谢组学方法，研究叶龄、采收期和地理来源对化学成分和S5AR抑制活性的影响，并鉴定活性S5AR抑制剂。地理来源是化学特征和S5AR抑制活性变化的主要决定因素。通过正交偏最小二乘法分析，鉴定出6种二萜类S5AR抑制剂，其中4种化合物首次被报道为S5AR抑制剂：犀角酸、7-氧代-8-拉丹-15-酸、8-羟基-拉丹-13-烯-15-酸和一种新型二萜7-羟基-拉丹-8,13-二烯-15-酸。这些发现凸显了代谢组学作为发现生物活性化合物和优化原材料选择的强大工具的潜力。通过优先选择经过验证的地理来源，可以实现一致的生物活性，支持柚木叶在治疗S5AR相关疾病方面的治疗潜力。
