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Epimedium‐Derived Phytoestrogen Flavonoids Exert Beneficial Effect on Preventing Bone Loss in Late Postmenopausal Women: A 24‐Month Randomized, Double‐Blind and Placebo‐Controlled Trial

Published on Apr 9, 2007in Journal of Bone and Mineral Research 6.31
· DOI :10.1359/jbmr.070405
Ge Zhang31
Estimated H-index: 31
(Shanghai University),
Ling Qin52
Estimated H-index: 52
(The Chinese University of Hong Kong),
Yinyu Shi4
Estimated H-index: 4
(Shanghai University)
Abstract
Epimedium brevicornum maxim, a nonleguminous medicinal plant, has been found to be rich in phytoestrogen flavonoids. Results from a 24-month randomized double-blind placebo-controlled clinical trial showed that Epimedium-derived phytoestrogen flavonoids were able to exert beneficial effects on preventing bone loss in late postmenopausal women, without resulting in a detectable hyperplasia effect on the endometrium. Introduction: We performed a 24-mo randomized double-blind placebo-controlled clinical trial for evaluating the effect of the Epimedium-derived phytoestrogen flavonoids (EPFs) on BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness in postmenopausal women. Materials and Methods: One hundred healthy late postmenopausal women, with a natural menopausal history within 10 ∼18 yr and with a BMD T-score at the lumbar spine between −2 and −2.5 SD, were randomized into EPF treatment group (n = 50; a daily dose of 60 mg Icariin, 15 mg Daidzein, and 3 mg Genistein) or placebo control group (n = 50). All participants received 300 mg element calcium daily. BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness were measured at baseline and 12 and 24 mo after intervention. Results: Eighty-five participants completed the trial. The patterns of BMD changes were significantly different between the EPF treatment group and placebo control group by repeated-measures ANOVA (p = 0.045 for interaction between time and group at femoral neck; p = 0.006 for interaction between time and group at lumbar spine). BMD was found with a decreased tendency in the placebo control group at 12 (femoral neck: −1.4%, p = 0.104; lumbar spine: −1.7%, p = 0.019) and 24 mo (femoral neck: −1.8%, p = 0.048; lumbar spine: −2.4%, p = 0.002), whereas EPF treatment maintained BMD at 12 (femoral neck: 1.1%, p = 0.285; lumbar spine:1.0%, p = 0.158) and 24 mo (femoral neck: 1.6%, p = 0.148; lumbar spine: 1.3%, p = 0.091). The difference in lumbar spine between the two groups was significant at both 12 (p = 0.044) and 24 mo (p = 0.006), whereas the difference in the femoral neck was marginal at 12 mo (p = 0.061) and significant at 24 mo (p = 0.008). Levels of bone biochemical markers did not change in the placebo control group. In contrast, EPF intervention significantly decreased levels of deoxypyrdinoline at 12 (−43%, p = 0.000) and 24 mo (−39%, p = 0.000), except for osteocalcin at 12 (5.6%, p = 0.530) and 24 mo (10.7%, p = 0.267). A significant difference in deoxypyrdinoline between the two groups was found at both 12 (p = 0.000) and 24 mo (p = 0.001). Furthermore, neither serum estradiol nor endometrial thickness was found to be changed in either groups during the clinical trial. Conclusions: EPFs exert a beneficial effect on preventing bone loss in late postmenopausal women without resulting in a detectable hyperplasia effect on the endometrium.
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  • Citations (143)
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References60
Newest
Published on Aug 1, 2006in Journal of Nutritional Biochemistry 4.41
Hui-Ying Huang1
Estimated H-index: 1
(Taipei Medical University),
Hsiao-Ping Yang1
Estimated H-index: 1
(Taipei Medical University Hospital)
+ 3 AuthorsShih Yi Huang22
Estimated H-index: 22
(Taipei Medical University)
Abstract It is believed that soy isoflavone has much potential effectiveness on the postmenopausal status; however, the optimal dose for preventing postmenopausal bone loss still remains unclear. This open-labeled, self-controlled pilot study was undertaken to determine the effect of 1-year supplementation of different high dosages of soy isoflavone in postmenopausal Taiwanese women. Forty-three women aged 45–67 years were enrolled and randomly assigned into a control (C), 100 mg/day isoflavone ...
36 Citations Source Cite
Published on Jun 1, 2006in Bone 4.46
Ge Zhang31
Estimated H-index: 31
(The Chinese University of Hong Kong),
Ling Qin52
Estimated H-index: 52
(The Chinese University of Hong Kong)
+ 4 AuthorsKwong-Sak Leung38
Estimated H-index: 38
(The Chinese University of Hong Kong)
Aim: Factorial design was used to test our hypothesis whether a group of flavonoids (FE) derived from herbal Epimedium Brevicornum Maxim exerted its preventive effects on estrogen-deficiency-induced osteoporosis mainly through an enhancement in intestinal calcium absorption. Materials and methods: Forty-five 12-month-old female Wistar rats were used and randomly assigned into sham-operated group and four ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX group), OVX with FE (FE group), OVX ...
93 Citations Source Cite
Published on May 1, 2006in Phytochemistry 3.19
Zuzana Mackova4
Estimated H-index: 4
(Institute of Chemical Technology in Prague),
R. Koblovská6
Estimated H-index: 6
(Institute of Chemical Technology in Prague),
Oldrich Lapcik5
Estimated H-index: 5
(Institute of Chemical Technology in Prague)
Abstract Common emphasis of the fact that isoflavonoids are characteristic metabolites of leguminous plants sometimes leads to overlooking that the presence of isoflavonoids has been reported in several dozen other families. The spectrum of isoflavonoid producing taxa includes the representatives of four classes of multicellular plants, namely the Bryopsida, the Pinopsida, the Magnoliopsida and the Liliopsida. A review, recently published by Reynaud et al. [Reynaud, J., Guilet D., Terreux R., Lu...
37 Citations Source Cite
Published on May 1, 2006in International Journal of Oncology 3.33
Vera Cappelletti18
Estimated H-index: 18
,
Patrizia Miodini17
Estimated H-index: 17
+ 1 AuthorsMaria Grazia Daidone52
Estimated H-index: 52
High consumption of phytoestrogen-rich food correlates with reduced incidence of breast cancer. However, the effect of phytoestrogens on growth of pre-existing breast tumors presents concerns when planning the use of phytoestrogens as chemoprevention strategy. Genistein, the active phytoestrogen in soy, displays weak estrogenic activity mediated by estrogen receptor (ER) with a preferential binding for the ER-B species. However, no information is at present available on the interaction between p...
33 Citations Source Cite
Published on Feb 20, 2006in Journal of Bone and Mineral Research 6.31
Jian Wu39
Estimated H-index: 39
,
Jun Oka19
Estimated H-index: 19
+ 8 AuthorsKazuhiko Yamada17
Estimated H-index: 17
The combined intervention of isoflavone intake and walking exercise over 1 year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and Ward's triangle regions. Introduction: The additive effects of isoflavones and exercise on bone and lipid metabolism have been shown in estrogen-deficient animals. In this study, we determined the effects of isoflavone intake, walking exercise, and their interaction on bone, fat mass, and lipid meta...
91 Citations Source Cite
Published on Jan 1, 2006in Endocrine Journal 1.91
Takeshi Usui25
Estimated H-index: 25
Interest in the physiologic and pharmacologic role of bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the classes of compounds known as the phytoestrogens, which embody several groups of non-steroidal estrogens, including isoflavones and lignans that are widely distributed within nature. The impact of dietary phytoestrogens on normal biologic processes was first recognized in sheep. Observations of shee...
169 Citations Source Cite
Published on Dec 1, 2005in Die Pharmazie
Chen Km3
Estimated H-index: 3
,
Ge Bf3
Estimated H-index: 3
+ 3 AuthorsWang Y3
Estimated H-index: 3
The herb Epimedium has long been used in Traditional Chinese Medicine to treat bone fracture and prevent osteoporosis. Researchers believe that the flavonoids contained in the herb are the effective component for this activity. However, no single flavonoid has been studied for its effect on bone-related cells. In the present study, icariin, one of the major flavonoids of the herb, supplemented the primary culture medium of rat bone marrow stromal cells (rMSCs) at 0.1 μM, 1 μM and 10 μM respectiv...
67 Citations
Xiao Qiangbing1
Estimated H-index: 1
(Huazhong University of Science and Technology),
Chen Anmin4
Estimated H-index: 4
(Huazhong University of Science and Technology),
Guo Fengjin1
Estimated H-index: 1
(Huazhong University of Science and Technology)
To study the effects of Icariin on expression of osteopontin (OPN) mRNA and type I collagen in rat osteoblastsin vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvaria of new-born new-born fetal Sprague-Dawley (SD) rats by means of modified sequential collagenase digestion and incubated in MEM medium and the cell morphology was observed under inverted phase contrast microscope, OB was identified by alkaline phosphatase (ALP) staining. Different con...
22 Citations Source Cite
Published on Nov 1, 2005in Journal of Nutrition 4.40
Pierangela Totta11
Estimated H-index: 11
,
Filippo Acconcia29
Estimated H-index: 29
+ 4 AuthorsMaria Marino38
Estimated H-index: 38
Daidzein (D), a soy isoflavone, is almost completely metabolized in the gut and liver. This biotransformation converts D to more water-soluble products and may affect its biological activity. The ability of daidzein metabolites to modulate 17/3-estradiol (E2)-sensitive gene transcription, cell growth, and a proapoptotic cascade was determined in human cancer cells devoid of any estrogen receptor (ER) and rendered E2 sensitive after transfection with ER/3. The data show that D and some but not al...
58 Citations Source Cite
Published on Sep 1, 2005in Osteoporosis International 3.86
Warren T. K. Lee19
Estimated H-index: 19
(The Chinese University of Hong Kong),
Catherine S. K. Cheung9
Estimated H-index: 9
+ 5 AuthorsJack C. Y. Cheng50
Estimated H-index: 50
(The Chinese University of Hong Kong)
Generalized low bone mass has been well documented in patients with adolescent idiopathic scoliosis (AIS). However, studies linking calcium-intake (CA), weight-bearing physical-activity (PA) and bone mass of AIS are lacking. We aimed to study the relationship between CA, PA and bone mass in AIS girls and compared to those of healthy non-AIS controls during the peripubertal period. Newly diagnosed AIS girls (n=596) aged 11–16 years with Cobb angle ≥10° were recruited to compare with age-matched h...
63 Citations Source Cite
Cited By143
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Published on Feb 14, 2019in Scientific Reports 4.12
Yuxin Zheng6
Estimated H-index: 6
(Shanghai University),
Xuezong Wang5
Estimated H-index: 5
(Shanghai University)
+ 24 AuthorsYongfang Zhao5
Estimated H-index: 5
Falls in late postmenopausal women with osteopenia usually cause fractures with severe consequences. This 36-month randomized, double-blind and placebo-controlled trial with a 10-year observational follow-up study aimed to investigate the long-term effect of herbal formula Bushen Yijing Fang (BSYJF) on fall risk in the late postmenopausal women with osteopenia. 140 late postmenopausal women (Femoral neck T-score, −2.5~−2 SD) were recruited and randomized to orally receive calcium carbonate 300 m...
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John F. Rebhun3
Estimated H-index: 3
,
Qin Du + 8 AuthorsMinjie Li
Abstract Objective To investigate the development of a minimal traditional Chinese medicine (TCM) formula using selected TCM ingredients and evaluating their biological activity with bone-specific in vitro tests. Finally, determining if the minimal formula can maintain bone mineral density (BMD) in a low bone mass (LBM)/osteoporosis (OP) model system. Methods and results Sixteen different TCM plant extracts were tested for estrogenic, osteogenic and osteoclastic activities. Despite robust activa...
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Published on Jul 1, 2019in Journal of Ethnopharmacology 3.12
Wenxiao Wu (Peking Union Medical College), Ting Wang + 6 AuthorsBo Li1
Estimated H-index: 1
(Peking Union Medical College)
Abstract Ethnopharmacological relevance Xian-Ling-Gu-Bao (XLGB) Fufang is an herbal formula that has been used in clinical settings to treat osteoporosis, osteoarthritis, aseptic bone necrosis, and climacteric syndrome. Despite its uses, XLGB treatment has been linked to potential liver injury. To date, there is a lack of clear demonstration of such toxicity in animal models. Aim of the study As animal models fail to reproduce the XLGB hepatotoxicity reported in humans, because human hepatocytes...
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Published on Apr 26, 2019in Royal Society Open Science 2.50
Chang Fu Zhao (Jilin University), Zhen Hua Li (Changchun University)+ 3 AuthorsYang Wang (Jilin University)
Icariin, the main effective component extracted from epimedium, has been shown to stimulate osteogenic differentiation and bone formation and to increase synthesis of the cartilage extracellular matrix. However, there has been little study on the effects of icariin on osteoarthritis. In this study, we loaded icariin onto poly(lactic-co-glycolic acid) (PLGA) electrospinning. The aim of this study was to explore a composite scaffold and to inhibit the progression of osteoarthritis. Our main experi...
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Published on Apr 4, 2019in Stem Cells International 3.99
Aofei Yang1
Estimated H-index: 1
(Hubei University of Chinese Medicine),
Chaochao Yu1
Estimated H-index: 1
(Hubei University of Chinese Medicine)
+ 3 AuthorsChengjian He1
Estimated H-index: 1
Osteoporosis, femoral head necrosis, and congenital bone defects are orthopedic disorders characterized by reduced bone generation and insufficient bone mass. Bone regenerative therapy primarily relies on the bone marrow mesenchymal stem cells (BMSCs) and their ability to differentiate osteogenically. Icariin (ICA) is the active ingredient of Herba epimedii, a common herb used in traditional Chinese medicine (TCM) formulations, and can effectively enhance BMSC proliferation and osteogenesis. How...
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Published on Mar 19, 2019in Frontiers in Pharmacology 3.83
Cristina Angeloni1
Estimated H-index: 1
(University of Camerino),
Maria Cristina Barbalace3
Estimated H-index: 3
(University of Bologna),
Silvana Hrelia24
Estimated H-index: 24
(University of Bologna)
Alzheimer’s disease (AD) is a neurodegenerative disorder affecting more than 35 million people worldwide. As the prevalence of AD is dramatically rising, there is an earnest need for the identification of effective therapies. Available drug treatments only target the symptoms and do not halt the progression of this disorder; thus, the use of natural compounds has been proposed as an alternative intervention strategy. Icariin, a prenylated flavonoid, has several therapeutic effects, including ost...
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