Antiosteoporotic activity of Er-Xian Decoction, a traditional Chinese herbal formula, in ovariectomized rats
Introduction
Osteoporosis is a chronic, progressive disease of the skeleton characterized by bone fragility due to a reduction in bone mass and possibly alteration in bone architecture which leads to a propensity to fracture with minimum trauma (Kelly, 1996). Osteoporosis, which is associated with ovarian hormone deficiency following menopause, is by far the most common cause of age related bone loss (Albright et al., 1941). Menopause brings about elevated bone turnover, an imbalance between bone formation and bone resorption (Riggs and Melton, 1986). Therefore, postmenopausal osteoporosis has become a major problem with significant morbidity and mortality (Cummings et al., 1990).
At present, oestrogen, bisphosphonates, calcitonin, calcium products, ipriflavone (Wronsky et al., 1993) and anabolic steroids are clinically used as effective medications. However, each one of them is associated with numerous side effects (Canalis et al., 1998, Gorman and Park, 2002). Traditional Chinese medicines have been reevaluated by clinicians for the prevention and treatment of postmenopausal osteoporosis, since these medicines have fewer side effects and are more suitable for long-term use compared with chemically synthesized medicines.
After extensive survey, we found that Chinese women treated with traditional oriental medicines have had a low morbidity of fracture in climacteric and senescent periods. As part of our continuing screening of biologically active antiosteoporotic agents using ovariectomized rat models from the medicinal resources, Er-Xian Decoction (EXD) was investigated.
EXD, the herbal formula comprised of Epimedium sagittatum (Sieb. et Zucc) Maxim. (Berberidaceae, whole herb), Curculigo orchioides Gaertn. (Hypoxidaceae, rhizome), Morinda officinalis How (Rubiaceae, root), Angelica sinensis (Oliv.) Diels (Umbelliferae, root), Phellodendron chinense Schneid. (Rutaceae, bark) and Anemarrhena asphodeloides Bunge (Anthericaceae, rhizome), has long been used for the treatment of osteoporotic disorders (Wang et al., 1998), perimenopausal syndrome (Liu et al., 2005), and aging diseases (Shen et al., 1995) in elderly patents. EXD has been used widely for the clinical treatment of postmenopausal osteoporosis for several decades. The formula and its medicinal properties have been described in classic works like Practical Pharmacology of Traditional Chinese Medical Formulas (Zhou, 1989). Many studies have demonstrated that EXD can stimulate the secretion of T of the Leydig cell, P of Luteal cell and E2 of granulose cell (Liu et al., 2005). Pharmacological studies have showed that EXD can markedly increase adrenocorticotropic hormone (ATCH) level in kidney-yang deficiency rats through up-regulating the expression ATCH mRNA (Zheng et al., 2003). EXD and its separated prescription are capable of increasing the amount of gonadotrop in-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the anterior pituitary and concentration of testosterone (T) in blood, and decreasing concentration of LH in blood (Fang et al., 1997). In addition, EXD can retard the aging of spermatid sperm and increase the amount of succinate dehydrogenase in the middle-section of spermatozoal tail (Fang et al., 1993). It also possesses prominent effects on reducing the product of free radicals by means of regulating and enhancing the gene expression levels of antioxidant enzymes (Shen et al., 1995). In clinical studies, EXD has been reported to offer relief from various types of pain associated with osteoporosis (Wang et al., 1998).However, the pharmacological properties and biochemical activities of EXD on the osteoporosis associated with estrogen deficiency have not been reported. In order to clarify the effects of EXD on osteoporosis in postmenopausal changes, an animal model was developed using OVX in female rats to deplete ovarian hormones. The primary aim of the study was to evaluate the effects of EXD in preventing osteoporosis and ameliorating bone loss, in ovariectomized rats.
Section snippets
Plant materials
The six plant materials of EXD were obtained from Shanghai Changhai Hospital and identified by Prof. H.C. Zheng of the Department of Pharmacognosy, School of Pharmacy of the Second Military Medical University, Shanghai. Their voucher specimens (030512) are available in the herbarium of this Department.
Preparation of EXD
One thousand and five hundred grams of the six medicinal mixed materials (250 g each material) was extracted by decocting the mixed herbs with 10× (v/w) distilled water at 100 °C for 2 h. After
Effect of EXD on body weight
Body weight of the OVX model rats was significantly higher than that of Sham-operation rats (Fig. 1). After 12 weeks, body weight of the Sham and OVX model rats were 286 ± 13 g (mean ± S.D., n = 10) and 358 ± 14 g (n = 10), respectively (Table 1). Increase in body weight of EXD groups was almost the same as that of nylestriol group (in 11–12 weeks) (Fig. 1). Body weight of EXD groups was significantly lower than that of OVX model rats after treatment.
Effect of EXD on uterine weight
As shown in Table 1, uterine weight of the Sham and OVX
Discussion and conclusion
In traditional Chinese medicine, there are many outstanding herbal formulas that have potential efficacy of preventing and curing osteoporosis; however, not much research has been carried out in their mechanisms of action. EXD is a “kidney-tonifying” traditional Chinese formula. According to traditional Chinese medicine theory, “kidney” controls bone and osteoporosis is due to kidney deficiency. Therefore, it is believed that the “kidney-tonifying” action of traditional Chinese medicine is
Acknowledgement
This work was supported by the National Natural Science Foundation of China, no. 90209043.
References (31)
- et al.
Immunostimulatory effect of methanol extract of Curculigo orchioides on immunosuppressed mice
Journal of Ethnopharmacology
(2006) - et al.
The effects of recombinant human interleukin-1β on cellular proliferation and the production of prostaglandin E2, plasminogen activator, osteocalcin and alkaline phosphatase by osteoblast-like cells derived from human bone
Biochemical and Biophysical Research Communication
(1990) - et al.
Comparative effects of droloxifene, tamoxifen, and estrogen on bone, serum cholesterol, and uterine histology in the ovariectomized rat model
Bone
(1997) - et al.
Osteoblastic proliferative activity of Epimedium brevicornum Maxim.
Phytomedicine
(2005) - et al.
The mechanical strength of bone in different rat models of experimental osteoporosis
Bone
(1994) - et al.
Basic mechanical measurements of bone: a tutorial
Bone
(1993) - et al.
Effect of Angelica sinensis on the proliferation of human bone cells
Clinica Chimica Acta
(2002) - et al.
Postmenopausal osteoporosis: its clinical features
Journal of the American Medical Association
(1941) - et al.
Dietary soybean prevents bone loss in an ovariectomized rat model of osteoporosis
The Journal of Nutrition
(1996) - et al.
Growth factors and the regulation on bone remodeling
Journal of Clinical Investigation
(1998)
The future of hip fractures in the United States: number, costs and potential effects of postmenopausal estrogen
Clinical Orthopedics
Bone strength: the bottom line
Calcified Tissue International
Effect of erxian decoction and its partial constituents on the hypothalamic–pituitary–gonadal axis in aged rats
Geriatrics and Health care
Effect of “two fairy” decoction and its separated prescription on ultrastructure and SDH of spermatid and sperm in old rats’ testis
Reproduction and Contraception
Advances in the study on the treatment of osteoporosis with Herba epimedii and its compound prescriptions
China Journal of Chinese Materia Medica
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