Xin-Yin Cai1, Zi-Jia Zhang2, Jing-Lin Xiong1, Meng Yang1, Zheng-Tao Wang1. 1. The MOE Key Laboratory for Standardization of Chinese Medicines, The Shanghai Key Laboratory for Compound Chinese medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China. 2. The MOE Key Laboratory for Standardization of Chinese Medicines, The Shanghai Key Laboratory for Compound Chinese medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China. Electronic address: zijiazhang66@163.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Psoraleae (FP), dry mature fruits of Cullen corylifolium (L.) Medik., has been used clinically to treat kidney yang deficiency-induced impotence, asthma and cold pain in waist and knee caused by kidney deficiency. A study of the source of the significant kidney-enhancing effect of FP revealed that it may be due to its strong estrogen-like activity. AIM OF THE STUDY: This study aimed to investigate the estrogen-like activity of the FP extract and 13 bioactive compounds in it, as well as the mechanisms underlying their estrogen-like and anti-osteoporosis activities. MATERIALS AND METHODS: The estrogen-like activities of the 75% ethanol-only FP extract, and 75% ethanol plus petroleum ether, ethyl acetate, n-butanol or water FP extracts were each measured using Cell Counting Kit-8 (CCK-8) and luciferase reporter gene assays. The compounds were identified by high-performance liquid chromatography analysis. The activation of estrogen receptor signaling by the compounds was compared with that by estradiol (E2) using the molecular docking software MOE-Dock 2008.10. The activation of the ER-Wnt-β-catenin signaling pathway was investigated using an alkaline phosphatase (ALP) assay, qPCR analysis and Western blot analysis. RESULTS: The results revealed that the 75% ethanol plus ethyl acetate extract showed the highest estrogen-like activity among the four 75% ethanol extract fractions (further extracted with petroleum ether, ethyl acetate, n-butanol or water). Some compounds in FP showed strong estrogenic effect and anti-osteoporosis activity, and activated the Wnt-β-catenin pathway. The isoflavone compound was the most active. CONCLUSIONS: This study demonstrated that FP has a strong estrogen-like activity and some of its component compounds have anti-osteoporosis activity by activating the ER-Wnt-β-catenin signaling pathway. Our detections provide a new insight into the mechanisms underlying the estrogen-like and anti-osteoporosis activities of FP, as well as a better understanding of structure effects.
ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Psoraleae (FP), dry mature fruits of Cullen corylifolium (L.) Medik., has been used clinically to treat kidney yang deficiency-induced impotence, asthma and cold pain in waist and knee caused by kidney deficiency. A study of the source of the significant kidney-enhancing effect of FP revealed that it may be due to its strong estrogen-like activity. AIM OF THE STUDY: This study aimed to investigate the estrogen-like activity of the FP extract and 13 bioactive compounds in it, as well as the mechanisms underlying their estrogen-like and anti-osteoporosis activities. MATERIALS AND METHODS: The estrogen-like activities of the 75% ethanol-only FP extract, and 75% ethanol plus petroleum ether, ethyl acetate, n-butanol or water FP extracts were each measured using Cell Counting Kit-8 (CCK-8) and luciferase reporter gene assays. The compounds were identified by high-performance liquid chromatography analysis. The activation of estrogen receptor signaling by the compounds was compared with that by estradiol (E2) using the molecular docking software MOE-Dock 2008.10. The activation of the ER-Wnt-β-catenin signaling pathway was investigated using an alkaline phosphatase (ALP) assay, qPCR analysis and Western blot analysis. RESULTS: The results revealed that the 75% ethanol plus ethyl acetate extract showed the highest estrogen-like activity among the four 75% ethanol extract fractions (further extracted with petroleum ether, ethyl acetate, n-butanol or water). Some compounds in FP showed strong estrogenic effect and anti-osteoporosis activity, and activated the Wnt-β-catenin pathway. The isoflavone compound was the most active. CONCLUSIONS: This study demonstrated that FP has a strong estrogen-like activity and some of its component compounds have anti-osteoporosis activity by activating the ER-Wnt-β-catenin signaling pathway. Our detections provide a new insight into the mechanisms underlying the estrogen-like and anti-osteoporosis activities of FP, as well as a better understanding of structure effects.