Antiosteoporotic activity of Er-Xian Decoction, a traditional Chinese herbal formula, in ovariectomized rats

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Abstract

The antiosteoporotic effect of a herbal formula, Er-Xian Decoction (EXD), in ovariectomized (OVX) rats model of osteoporosis was investigated. The rats were divided into Sham and OVX groups. The OVX rats were further sub-divided into four groups administered orally with water, nylestriol (1 mg/kg, weekly) or EXD (300, 600 mg/kg, daily) for 12 weeks. In OVX rats, the increases of body weight, serum BGP and ALP were significantly decreased by EXD treatment. In OVX rats, atrophy of uterus and descent of BMD were suppressed by treatment with EXD and nylestriol. In addition, EXD completely corrected the decreased concentration of calcium, phosphorus, and estradiol in serum observed in OVX rats. EXD also significantly increased biomechanical strength comparable to the Sham group. This was also confirmed by histological results that showed its protective action. The findings assessed on the basis of biochemical, bone mineral density, biomechanical, and histopathological parameters strongly suggested that EXD had a definite antiosteoporotic effect, which is similar to estrogen.

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.

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