The purpose of this study was to examine whether hesperidin inhibits bone loss in ovariectomized mice (OVX), an animal model of postmenopausal osteoporosis. Forty 8-wk-old female ddY mice were assigned to five groups: a sham-operated group fed the control diet (AIN-93G), an OVX group fed the control diet, an OVX+HesA group fed the control diet containing 0.5 g/100 g hesperidin, and an OVX+HesB group fed the control diet containing 0.7 g/100 g alpha-glucosylhesperidin and an OVX+17beta-estradiol (E(2)) group fed the control diet and administered 0.03 micro g E(2)/d with a mini-osmotic pump. After 4 wk, the mice were killed and blood, femoral, uterine and liver were sampled immediately. Hesperidin administration did not affect the uterine weight. In OVX mice, the bone mineral density of the femur was lower than in the sham group (P < 0.05) and this bone loss was significantly prevented by dietary hesperidin or alpha-glucosylhesperidin. The Ca, P and Zn concentrations in the femur were significantly higher in the hesperidin-fed and E(2) groups than in the OVX group. Histomorphometric analyses showed that the trabecular bone volume and trabecular thickness in the femoral distal metaphysis were markedly decreased (P < 0.05) by OVX, and alpha-glucosylhesperidin significantly prevented this bone loss. Furthermore, hesperidin decreased the osteoclast number of the femoral metaphysis in OVX mice, as did E(2). Serum and hepatic lipids were lower in mice that consumed the hesperidin-containing diets (P < 0.05) than in the OVX group fed the control diet. These results suggest a possible role for citrus flavonoids in the prevention of lifestyle-related diseases because of their beneficial effects on bone and lipids.

Genistein, an isoflavone abundantly present in soybeans, has structural similarity to estrogen, suggesting that genistein may act as a phytoestrogen. To examine the possible role of genistein in hemopoiesis and bone metabolism, female mice were either sham-operated or ovariectomized (OVX), and selected OVX mice were administered genistein for 2-4 weeks (0.1-0.7 mg/day) or 17beta-estradiol (E2; 0.01-0.1 microg/day) s.c., using a miniosmotic pump (Alza Corp., Palo Alto, CA). In OVX mice, uterine weight declined but was completely restored by E2 administration. In contrast, genistein did not demonstrate a reversal of the OVX-induced uterine atrophy. The number of bone marrow cells markedly increased, 2-4 weeks after OVX, and most of these were B220-weakly positive pre-B cells. The increased B-lymphopoiesis was completely restored, not only by E2 but also by genistein administration. In OVX mice, the trabecular bone volume of the femoral distal metaphysis, measured by microcomputed tomography scanning and dual-energy x-ray absorptiometry, was markedly reduced; and genistein restored this, as did E2. These results indicate that genistein exhibits estrogenic action in bone and bone marrow, to regulate B-lymphopoiesis and prevent bone loss, without exhibiting estrogenic action in the uterus. Phytoestrogens may be useful for preventing bone loss caused by estrogen deficiency in females.

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Puerariae radix (PR), the root of Pueraria labata (Willd.) Ohwi, a wild creeper leguminous plant, is one of the earliest and most important crude herbs used in Chinese medicine for various medicinal purposes. PR contains a high amount of isoflavonoids such as daidzein and genistein, which are known to prevent bone loss induced by estrogen deficiency. We have demonstrated that soybean isoflavones prevent bone loss in an osteoporotic animal model. To examine the possible role of PR in bone metabolism, female mice were ovariectomized (OVX), and some OVX mice were fed a diet containing low, middle, and high doses (5%, 10%, and 20% of diet, respectively) of PR for 4 weeks. In OVX mice, the uterine weight declined, and intake of PR at any dose did not affect uterine weight. The total femoral bone mineral density (BMD) was significantly reduced by OVX, and the decrease in BMD caused by OVX was significantly inhibited by intake of the diet with the low dose of PR and completely prevented by the middle dose of PR. Histological analysis of the femoral metaphysis showed that intake of the diet with the middle dose of PR completely prevented decrease in trabecular bone volume (BV/TV) and trabecular thickness (Tb.Th) and restored the increase in trabecular separation (Tb.Sp) in OVX mice. In contrast, intake of the diet with the high dose of PR further increased BV/TV and Tb.Th and decreased Tb.Sp in OVX mice compared with that in the sham-operated mice. These results suggest that PR may represent a potential alternative medicine for hormone replacement therapy (HRT) in the prevention of osteoporosis in postmenopausal women.

Retinoids are known to be of special importance for normal bone growth and development. Recently, we reported that retinoids not only induced osteoblast differentiation, but also inhibited osteoclast formation in vitro. In this study, we examined the osteogenic effects of geranylgeranoic acid (GGA), a chemically synthe-

Interleukin (IL)-8 has been implicated in a wide range of diseases. The polymorphism of IL-8 gene, which may affect the production level of the cytokine, may be associated with cancer cachexia. To test this hypothesis, we investigated the potential influence of the polymorphisms of the IL-8 gene, -251 A/T and +781 C/T, on susceptibility to cachexia from patients with gastric cancer in a Chinese population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A significantly increased frequency of +781 T allele was noted in patients with cachexia (OR = 1.765, 95% CI: 1.192-2.615, P = 0.004). The +781 TT genotypes were observed to be associated with a significantly increased risk of cachexia (OR = 2.156, 95% CI: 1.056-4.400, P = 0.033), and the difference was enhanced beyond the level of statistical significance when logistic regression was applied (OR = 3.500, 95% CI: 1.406-8.710, P = 0.007). Haplotype analysis revealed that A(251)T(781) haplotype (defined by SNPs at positions -251 and +781) was associated with a significantly increased risk of cachexia as compared with the T(251)C(781) haplotype (OR = 1.69; 95% CI: 1.08-2.62; P = 0.022). These results suggest that the genetic polymorphisms of proinflammatory cytokine IL-8 may contribute to the pathogenesis of cachexia in gastric cancer patients.

Background. Interleukin (IL)-8 has been implicated in the development of cancer cachexia. The polymorphism of IL-8 gene, which may affect the production level of IL-8, may be associated with cancer cachexia. Methods. The serum IL-8 level in our study was examined by radioimmunoassay. We also analyzed single nucleotide polymorphisms (SNPs) −251 A/T and +781 C/T of IL-8 gene, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. The serum levels of IL-8 were significantly elevated in patients with low-third gastric cancer compared with controls, and were further up-regulated in patients with cachexia than those without (Z = −3.134, P = .002). A significantly increased frequency of +781 T allele was noted in patients with cachexia (OR = 2.247, 95% CI: 1.351–3.737, P = .002). The +781 TT genotype was observed to be associated with a significantly increased risk of cachexia (OR = 3.167, 95% CI: 1.265–7.929, P = .011), and with odds ratio of 3.033 (95% CI: 1.065–8.639, P = .038) for cachexia after adjusting for potential confounding factors. Meanwhile, haplotype analysis indicated a borderline positive association between T251T781 haplotype and cachexia as compared with the T251C781 haplotype (OR = 4.92, 95% CI: 1.00–24.28;, P = .053). Conclusions. IL-8 appears to be associated with cachexia from patients with low-third gastric cancer.