Metformin ameliorates the age‐related changes of d‐galactose administration in ovariectomized mice

Metformin (Met) has been shown to have pleiotropic effects such as neuroprotective, antioxidant, and anti‐inflammatory properties making that a potential candidate for the treatment of central nervous system (CNS) disorders. This study was designed to investigate the possible effect of Met on the d ‐galactose (d ‐gal)‐induced aging in ovariectomized mice. The female mice underwent bilateral ovariectomy. d ‐gal was administered orally at a dose of 500 mg/kg, and Met was administrated orally at doses of 1 and 10 mg/kg for 6 weeks. Anxiety‐like behavior was evaluated by the elevated plus‐maze. Physical power was assessed by vertical grid holding test and forced swimming capacity test. The brains were assessed for the level of superoxide dismutase (SOD) and brain‐derived neurotrophic factor (BDNF). Ovariectomy caused anxiety and declined the physical power as well as BDNF and SOD levels. d ‐gal administration in ovariectomized mice exacerbated these deleterious effects. Met hampered the anxiety‐like behavior and strengthened the physical power of d ‐gal‐treated ovariectomized mice. Met also increased the SOD and BDNF levels in the brains of d ‐gal‐treated ovariectomized animals. Based on the obtained results, we suggest Met administration as a novel therapeutic approach for the treatment of age‐related conditions in the absence of female sex hormones.     

腹腔镜与开腹卵巢囊肿切除术对患者应激反应的影响

目的：研究腹腔镜卵巢囊肿切除术与开腹卵巢囊肿切除术对患者应激反应的影响。方法：选择2007年12月—2009月2月因卵巢囊肿行腹腔镜手术者25例（腹腔镜组）和行开腹手术者21例（开腹组）。两组患者在手术前24 h及手术后24 h,48 h,72 h采集外周静脉血,分别测定血糖（BG）、皮质醇、C反应蛋白（CRP）和白细胞介素-6（IL-6）。结果：两组患者术前24 h的BG、皮质醇、CRP及IL-6水平相比较,差异无统计学意义（P〉0.05）。术后开腹组的BG、皮质醇、CRP及IL-6水平均高于腹腔镜组（P〈0.05）。结论：腹腔镜手术对机体应激反应小。     

组蛋白去乙酰化酶在卵巢切除小鼠骨髓间充质干细胞中的表达

背景：骨髓间充质干细胞的多向分化能力在骨代谢疾病中发挥重要作用,受激素、细胞因子等多种因素调节。目前骨髓间充质干细胞骨向分化的表观遗传学调控机制尚不明确,组蛋白去乙酰化酶与骨质疏松的关系尚需进一步探讨。 目的：建立雌激素缺乏骨质疏松小鼠的实验动物模型,检测骨髓间充质干细胞组蛋白去乙酰化酶1,3,4 mRNA表达水平,探索卵巢切除小鼠骨组织形成障碍的表观遗传学机制。 方法：昆明种小鼠30只随机等分为模型组和假手术组。小鼠适应性喂养7 d后,模型组小鼠切除双侧卵巢,造成雌激素缺乏骨质疏松实验动物模型,假手术组小鼠仅切除等量脂肪组织。 结果与结论：模型组小鼠股骨骨小梁稀疏或断裂,骨小梁宽度变窄,骨小梁间距变宽,骨小梁占视野面积降低。与假手术组相比,模型组小鼠骨髓间充质干细胞中组蛋白去乙酰化酶3 mRNA表达水平显著降低,组蛋白去乙酰化酶1,4表达水平变化差异无显著性意义。提示雌激素缺乏导致骨髓间充质干细胞去乙酰化状态改变可能是骨形成障碍的重要原因之一。     

Effects of diphenyl diselenide on lipid profile and hepatic oxidative stress parameters in ovariectomized female rats

Objectives Ovarian hormone decline after menopause is linked to many pathophysiological reactions. Female rats submitted to ovariectomy are employed as a model of post‐menopausal condition. This study investigated the effects of diphenyl diselenide (PhSe)₂ on body weight gain, intra‐abdominal fat deposition, plasma lipid profile and hepatic oxidative stress in ovariectomized rats. Methods Female adult Wistar rats were ovariectomized (OVX rats) or sham‐operated and divided into four groups: (i) sham‐operated, (ii) (PhSe)₂, (iii) OVX and (iv) OVX + (PhSe)₂. (PhSe)₂ (5 mg/kg; 5 ml/kg, p.o.) was administered once a day for 30 days to groups (ii) and (iv). After that, rats were anaesthetized for blood sample gathering and submitted to euthanasia. Key findings (PhSe)₂ (5 mg/kg) was effective in preventing the rise in body weight gain and intra‐abdominal fat deposition induced in OVX rats. Although (PhSe)₂ was not effective in avoiding the increase in plasma total cholesterol and non‐HDL levels induced in OVX rats, (PhSe)₂ reduced plasma triglycerides and augmented HDL levels in OVX rats. (PhSe)₂ also increased hepatic ascorbic acid levels, reduced glutathione content, glutathione S‐transferase activity and restored catalase activity in liver of OVX rats. Conclusions These findings suggest that (PhSe)₂ could be a promising alternative to minimize menopause related symptoms.     

Effects of oestradiol and raloxifene on the induction and effector phases of experimental postmenopausal arthritis and secondary osteoporosis

Oestradiol and the selective oestrogen receptor modulator (SERM) raloxifene have been shown to ameliorate collagen-induced arthritis (CIA) in rats and in mice. One aim was to investigate if raloxifene exerts its anti-arthritic and anti-osteoporotic effects during the induction or effector phase of arthritis. A second aim was to analyse if raloxifene activates the oestrogen response element (ERE) to produce its immune-modulator effects. CIA or collagen-antibody-induced arthritis (CAIA) was induced in ovariectomized DBA/1-mice. CIA was used for evaluation of treatment during the induction, and CAIA for the effector phase of arthritis and osteoporosis development. Raloxifene, oestradiol or vehicle was administered 5 days/week. The clinical disease was evaluated continuously. Bone marrow density (BMD) was analysed with peripheral quantitative computer tomography, paws were collected for histological examination, and sera were analysed for markers of bone and cartilage turnover and proinflammatory cytokines. Transgenic luciferase (Luc)-ERE mice were immunized with collagen (CII), and after 10 days injected once with raloxifene, oestradiol or vehicle before termination. Spleens were analysed for luciferase activity to measure ERE activation. Treatment with oestradiol or raloxifene during the induction phase of CIA failed to affect arthritis. Raloxifene did not hamper disease activity in CAIA, whereas oestradiol delayed the onset and ameliorated the severity. Both raloxifene and oestradiol preserved BMD in CAIA. CII-immunization increased the oestradiol-induced ERE activation in spleen, and raloxifene activated the ERE at about 25% the intensity of oestradiol. Further experiments are needed to elucidate the exact mechanisms behind this finding.     

Decrease in particle‐induced osteolysis in ovariectomized mice

Postmenopausal osteoporosis is a common disorder that results from increased osteoclastic activity caused by estrogen deficiency. Whether postmenopausal bone remodeling can alter the response to particulate debris is unknown. The purpose of this study was to evaluate the bone response to polyethylene particles in an ovariectomized murine model. Polyethylene particles were implanted onto the calvaria of seven control mice and seven ovariectomized (OVX) mice, as compared with calvaria from sham‐operated and OVX mice. Calvaria were harvested after 14 days. Skulls were analyzed with a high‐resolution micro‐CT and by histomorphometry after staining with Stevenel blue and picrofuschine, and for tartrate‐specific alkaline phosphatase. As assessed by micro‐CT, particle implantation induced a significant decrease in bone thickness in control mice, while bone thickness remained stable in OVX mice. In particle‐implanted animals, the osteoclast number was 2.84 ± 0.3 in control mice and 1.74 ± 0.22 in OVX mice. Mean bone loss was ?12% ± 1.9% in control mice and ?4.7% ± 1.7% in OVX animals. The reduction of osteolytic response suggests that ovariectomy may have a protective role against particle‐induced bone resorption. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:178–183, 2010     

双侧卵巢切除对围绝经期妇女骨密度及身体成分的影响

目的探讨双侧卵巢切除术对围绝经期妇女骨密度、身体成分及性激素的影响。方法选择2009年1月1日—2009年12月31日期间在上海交通大学附属第六人民医院妇产科行双侧卵巢切除术的围绝经期患者33例（卵巢切除组）,以同期更年期门诊自然绝经妇女35例为对照组,采用美国GE-Lunar-Prodigy双能X线骨密度检测仪和化学发光法检测两组妇女在闭经6和12个月时的骨密度、脂肪含量、肌肉含量及性激素。结果两组妇女在闭经后6和12个月时,骨密度、脂肪含量、肌肉含量比较差异均无统计学意义（P〉0.05）。在闭经6个月时,卵巢切除组的雌二醇（E2）水平明显低于对照组[（14.79±22.17）U/Lvs（32.74±31.02U/L）]（P〈0.05）;闭经后12个月时,卵巢切除组的E2和卵泡刺激素（FSH）水平与对照组比较差异均有统计学意义[E2：（8.09±4.38）U/Lvs（25.92±3.53）U/L;FSH：（64.88±18.39）U/Lvs（40.69±31.63）U/L]（P〈0.05）。结论围绝经期双侧卵巢切除后12个月内主要表现为E2和FSH改变,而E2水平的降低对骨密度、脂肪含量以及肌肉含量的影响并未显现。     

Combined treatment with a traditional Chinese medicine, Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) and alendronate improves bone microstructure in ovariectomized rats

Ethnopharmacological relevance

Hachimi-jio-gan is one of the most common recipes in traditional Chinese, Japanese and Korean medicines and has been used for preventing and treating various diseases associated with aging, including osteoporosis.

Aim of the study

The present study was performed to examine the combined effects of a traditional Chinese medicine, Hachimi-jio-gan (HJG) and antiresorptive agent, alendronate (ALN) on ovariectomy-induced bone loss in rats.

Materials and methods

Six-month-old female Sprague-Dawley rats were underwent ovariectomy (OVX) or sham operation. Eight weeks later, the OVX rats were treated either with HJG or ALN alone or in combination of both. The skeletal response was evaluated using micro-computed tomography (micro-CT), image analysis software, and biochemical markers.

Results

This study demonstrated that treatment with HJG or ALN alone increased trabecular bone volume and bone mineral density (BMD), and partially improved bone microstructure of the proximal tibia and vertebra in OVX rats. Treatment with ALN to OVX rats resulted in significant reduction in both bone resorption and bone formation. Treatment with HJG to OVX rats inhibited bone resorption, with no marked effects on bone formation. Combined treatment of HJG and ALN significantly improved trabecular bone mass and bone microstructure, compared with either agent alone.

Conclusions

We conclude that the combined treatment with HJG and ALN has beneficial effects on trabecular bone mass, improving the structural properties of both tibia and vertebra in OVX rats.     

Effects of alpinumisoflavone and abyssinone V-4'-methyl ether derived from Erythrina lysistemon (Fabaceae) on the genital tract of ovariectomized female Wistar rat

Erythrina lysistemon is an African medicinal plant used as a palliative for problems in women. The crude extract of this plant was shown to exhibit estrogenic effects on the female rat reproductive tract and on cell cuture. Using classic chromatographic methods, two compounds have been isolated as major constituents of this extract: alpinumisoflavone (1) and abyssinone V‐4′‐methyl ether (2). To determine whether both compounds are actives principles accounting for E. lysistemon effects, we applied the classic 3‐day uterotrophic assay. We also carried out a ligand binding assay to determine whether the observed effects are estrogen receptor (ER) mediated. This study showed that whereas compound 1 displayed a fourfold preference for ERα, compound 2 bound ERα and ERβ with a same affinity. The in vivo study showed that compound 1 increased the uterine wet weight by 182.23% (p < 0.01) and 71.79% (p < 0.05) at doses of 0.1 and 1 mg/kg BW/day respectively. The uterine epithelium thickened dose‐dependently. Vaginal epithelial height also increased by 369.97 and 226.76% respectively (p < 0.01). Compound 2 acted only on the vagina and increased vaginal epithelial height by 244.56% (p < 0.01) at 1 mg/kg BW/day. These results suggest that compounds 1 and 2 are endowed with estrogenic properties accounting, at least in part, for E. lysistemon effects. Copyright © 2011 John Wiley & Sons, Ltd.     

Antidiabetic effects of fermented soybean products on type 2 diabetes

Historically, the incidence of type 2 diabetes has been lower in Asian populations compared with those in Western countries. One possible reason for the lower incidence among Asians is that they consume fermented soybean products, which are unique to the traditional Asian diet. Some have hypothesized that dietary phytoestrogens and soy peptides in fermented soybean foods consumed in traditional Asian diets may help prevent and slow the progression of type 2 diabetes. This review evaluates the existing evidence from animal studies and clinical and epidemiologic investigations on fermented soybeans in the prevention and treatment of type 2 diabetes. Nutritional studies performed in animals and intervention studies with humans suggest that the ingestion of soy protein with isoflavones improves glucose control and reduces insulin resistance. Korean fermented soybean products such as doenjang, kochujang, and chungkookjang contain alterations in the structures and content of isoflavonoids and small bioactive peptides, which are produced during fermentation. Several studies revealed improvements in insulin resistance and insulin secretion with the consumption of these fermented products. Therefore, fermented soybean products may help prevent or attenuate the progression of type 2 diabetes. Although the lack of human intervention trials does not permit definitive conclusions, the evidence does suggest that fermented soy products may be better for preventing or delaying the progression of type 2 diabetes compared with nonfermented soybeans.