Suzuki Aoi, Matsuura Daisuke, Kanatani Hirotoshi, Yano Shingo, Tsunakawa Mitsuo, Matsuyama Shigeru, Shigemori Hideyuki
Graduate School of Life and Environmental Sciences, University of Tsukuba.
Products Development Department, BATHCLIN CORPORATION.
Biol Pharm Bull. 2017;40(10):1784-1788. doi: 10.1248/bpb.b17-00205.
Neurotrophins play an important role in the control of the hair growth cycle. Therefore, neurotrophin receptor antagonists have therapeutic potential for the treatment of hair growth disorders. In this study, we investigated the inhibitory effect of Panax ginseng, a medicinal plant commonly used to treat alopecia, on the binding of neurotrophins to their receptors. In addition, we isolated and characterized the bioactive compounds of P. ginseng extracts. P. ginseng hexane extracts strongly inhibited brain-derived neurotrophic factor (BDNF)-TrkB and β-nerve growth factor (β-NGF)-p75 neurotrophin receptor (p75NTR) binding. Furthermore, we identified the following 6 polyacetylene compounds as the bioactive components in P. ginseng hexane extract: panaxynol (1), panaxydol (2), panaxydol chlorohydrin (3), 1,8-heptadecadiene-4,6-diyne-3,10-diol (4), panaxytriol (5), and dihydropanaxacol (6). In particular, compounds 4, 5, and 6 significantly inhibited BDNF-TrkB binding in a dose-dependent manner. To identify the structural component mediating the inhibitory effect, we investigated the effects of the hydroxyl moiety in these compounds. We found that the inhibitory effect of panaxytriol (5) was strong, whereas the inhibitory effect of Ac-panaxytriol (7) was relatively weak. Our findings suggest that P. ginseng-derived polyacetylenes with a hydroxyl moiety might provide therapeutic benefits to patients with hair growth disorders such as alopecia by inhibiting the binding of neurotrophins to their receptors. Although saponins have been proposed to be the primary mediators of the effects of P. ginseng on hair growth, this study revealed that polyacetylene compounds exert similar effects.
神经营养因子在调控毛发生长周期中发挥着重要作用。因此，神经营养因子受体拮抗剂在治疗毛发疾病方面具有治疗潜力。在本研究中，我们调查了常用于治疗脱发的药用植物人参对神经营养因子与其受体结合的抑制作用。此外，我们分离并鉴定了人参提取物中的生物活性化合物。人参己烷提取物强烈抑制脑源性神经营养因子（BDNF）-TrkB和β-神经生长因子（β-NGF）-p75神经营养因子受体（p75NTR）的结合。此外，我们鉴定出以下6种聚乙炔化合物为人参己烷提取物中的生物活性成分：人参炔醇（1）、人参二醇（2）、人参二醇氯醇（3）、1,8-十七碳二烯-4,6-二炔-3,10-二醇（4）、人参三醇（5）和二氢人参醇（6）。特别是，化合物4、5和6以剂量依赖性方式显著抑制BDNF-TrkB结合。为了确定介导抑制作用的结构成分，我们研究了这些化合物中羟基部分的作用。我们发现人参三醇（5）的抑制作用很强，而乙酰基人参三醇（7）的抑制作用相对较弱。我们的研究结果表明，具有羟基部分的人参衍生聚乙炔可能通过抑制神经营养因子与其受体的结合，为脱发等毛发疾病患者提供治疗益处。尽管有人提出皂苷是人参与毛发生长相关作用的主要介导物，但本研究表明聚乙炔化合物也发挥着类似作用。
