Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China; Hubei Tujia Institute of Medicine, China Three Gorges University, Yichang 443002, China.
Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China.
Fitoterapia. 2014 Jun;95:93-101. doi: 10.1016/j.fitote.2014.03.007. Epub 2014 Mar 15.
Hispolon was the main antitumor active ingredient in Phellinus sensu lato species. In order to confirm the dual regulating estrogenic ingredient and obtain more effective natural estrogen replacement drugs, hispolon was separated from Phellinus lonicerinus (Bond.) Bond. et sing. Hispolon exhibited significant anti-proliferative effect against estrogen-sensitive ER (+) MCF-7 cells in the absence of estrogen, and exhibits antagonistic effects on 17β-estradiol (E2)-induced MCF-7 cell proliferation when E2 and the different concentrations of hispolon were treated simultaneously. Hispolon also inhibited the proliferation of estrogen-negative ER (-) MDA-MB-231 cells at the concentration of 5.00×10(-5) M. The yeast two-hybrid experiments showed that hispolon had strong and non-selective effects on the estrogen receptor (ER) α and ERβ at a concentration of 1.00×10(-6) M. The ERβ-binding ability of hispolon was larger than ERα in the concentration range of 1.00×10(-9) M and 1.00×10(-7) M. Hispolon could increase the body weight coefficient, serum E2 and progesterone contents in immature female mice at dose of 9.10×10(-6) mol/kg, and increase coefficient of thymus and spleen in mice. The Gscores of hispolon-ERα and hispolon-ERβ docked complexes were -7.93 kcal/mol and -7.79 kcal/mol in docking simulations. Hispolon presented dual regulating estrogenic activities, which showed estrogenic agonist activity at low concentration or lack of endogenous estrogen, and the estrogenic antagonistic effect was stimulated at high concentrations or too much endogenous estrogen. Hispolon could be used for treating the estrogen deficiency-related disease with the benefit of non-toxic to normal cells, good antitumor effects and estrogenic activity.
松苓酮是假芝属（Phellinus sensu lato）物种中的主要抗肿瘤活性成分。为了确认具有双重调节雌激素作用的成分，并获得更有效的天然雌激素替代药物，本研究从松生薄孔菌（Bond.）中分离出松苓酮。松苓酮在缺乏雌激素的情况下对雌激素敏感的 ER（+）MCF-7 细胞表现出显著的抗增殖作用，并且当同时用 E2 和不同浓度的松苓酮处理时，对 17β-雌二醇（E2）诱导的 MCF-7 细胞增殖表现出拮抗作用。松苓酮在 5.00×10（-5）M 浓度下也抑制了雌激素阴性的 ER（-）MDA-MB-231 细胞的增殖。酵母双杂交实验表明，松苓酮在 1.00×10（-6）M 浓度下对雌激素受体（ER）α和 ERβ具有强且非选择性的作用。在 1.00×10（-9）M 和 1.00×10（-7）M 的浓度范围内，松苓酮与 ERβ 的结合能力大于 ERα。松苓酮在 9.10×10（-6）mol/kg 剂量下可增加未成年雌性小鼠的体重系数、血清 E2 和孕酮含量，并增加小鼠的胸腺和脾脏系数。在对接模拟中，松苓酮-ERα 和松苓酮-ERβ 对接复合物的 G 分数分别为-7.93 kcal/mol 和-7.79 kcal/mol。松苓酮具有双重调节雌激素活性，在低浓度或缺乏内源性雌激素时表现出雌激素激动剂活性，在高浓度或过多内源性雌激素时表现出雌激素拮抗作用。松苓酮可用于治疗雌激素缺乏相关疾病，具有对正常细胞无毒、良好的抗肿瘤作用和雌激素活性的优点。
