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      Antiosteoporotic activity of phytoestrogen-rich fraction separated from ethanol extract of aerial parts of Cissus quadrangularis in ovariectomized rats

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          Abstract

          Objective:

          Cissus quadrangularis L. ( C. quadrangularis L.) (Vitaceae) has been reported in Ayurveda for its antiosteoporotic activity. The study separated the phytoestrogen-rich fraction (IND-HE) from aerial parts of C. quadrangularis L. and evaluated its effect on osteoporosis caused by ovariectomy in rats.

          Materials and Methods:

          IND-HE was separated from the ethanol extract of C. quadrangularis. Ovariectomized female Wistar rats were divided into four groups ( n = 6). Group 1: Control (distilled water), Group II: IND-HE (75 mg/kg p.o.), Group III: IND-HE (100 mg/kg p.o.) were treated once daily for 8 weeks and Group IV: standard estradiol group, received estrogen (1 mg/kg, s.c. bi-weekly). The effects on body weight were determined. DEXA (Dual energy-emission X-ray absorptimatory analysis) of whole body bone and femur was carried out. Blood was removed and analyzed for biochemical parameters. After sacrificing the animals, biomechanical study of right tibia and histopathology of pelvic bone was carried out.

          Results:

          IND-HE showed presence of phytoestrogen-rich fraction. IND-HE (75 and 100 mg/ kg) and estrogen treatment showed statistically significant increase in bone thickness, bone density and bone hardness. IND-HE (75 and 100 mg/kg) and estrogen treatment significantly increased serum estradiol. IND-HE (100 mg/kg) ( P<0.05) and estrogen treatment increased serum vitamin D3 and serum calcium compared to control. Alkaline phosphatase was significantly reduced by IND-HE (100 mg/kg p.o.) and estrogen treatment. Histopathology and DEXA results indicated that IND-HE (75 and 100 mg/kg) prevented bone loss.

          Discussion and Conclusion:

          These findings confirm that phytoestrogen-rich fraction (IND- HE) possess good antiosteoporotic activity.

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          Most cited references34

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          Estrogen deficiency and bone loss: an inflammatory tale.

          Estrogen plays a fundamental role in skeletal growth and bone homeostasis in both men and women. Although remarkable progress has been made in our understanding of how estrogen deficiency causes bone loss, the mechanisms involved have proven to be complex and multifaceted. Although estrogen is established to have direct effects on bone cells, recent animal studies have identified additional unexpected regulatory effects of estrogen centered at the level of the adaptive immune response. Furthermore, a potential role for reactive oxygen species has now been identified in both humans and animals. One major challenge is the integration of a multitude of redundant pathways and cytokines, each apparently capable of playing a relevant role, into a comprehensive model of postmenopausal osteoporosis. This Review presents our current understanding of the process of estrogen deficiency-mediated bone destruction and explores some recent findings and hypotheses to explain estrogen action in bone. Due to the inherent difficulties associated with human investigation, many of the lessons learned have been in animal models. Consequently, many of these principles await further validation in humans.
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            The ovariectomized rat model of postmenopausal bone loss.

            Dike Kalu (1991)
            An animal model of postmenopausal bone loss can be defined as a living animal in which spontaneous or induced bone loss due to ovarian hormone deficiency can be studied, and in which the characteristics of the bone loss and its sequalae resemble those found in postmenopausal women in one or more respects. Although in comparison to humans, the skeletal mass of rats remains stable for a protracted period during their lifespan, rats can be ovariectomized to make them sex-hormone deficient, and to stimulate the accelerated loss of bone that occurs in women following menopause. Ovariectomy induced bone loss in the rat and postmenopausal bone loss share many similar characteristics. These include: increased rate of bone turnover with resorption exceeding formation; and initial rapid phase of bone loss followed by a much slower phase; greater loss of cancellous than cortical bone; decreased intestinal absorption of calcium; some protection against bone loss by obesity; and similar skeletal response to therapy with estrogen, tamoxifen, bisphosphonates, parathyroid hormone, calcitonin and exercise. These wide-ranging similarities are strong evidence that the ovariectomized rat bone loss model is suitable for studying problems that are relevant to postmenopausal bone loss.
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              Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial.

              Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive. To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women. Randomized, double-blind, placebo-controlled trial. 3 university medical centers in Italy. 389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions. After a 4-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo (n = 191) or 54 mg of genistein (n = 198) daily for 24 months. Both the genistein and placebo tablets contained calcium and vitamin D. The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase and insulin-like growth factor I, urinary excretion of pyridinoline and deoxypyridinoline, and endometrial thickness. Data on adverse events were also collected. At 24 months, BMD had increased in genistein recipients and decreased in placebo recipients at the anteroposterior lumbar spine (change, 0.049 g/cm2 [95% CI, 0.035 to 0.059] vs. -0.053 g/cm2 [CI, -0.058 to -0.035]; difference, 0.10 g/cm2 [CI, 0.08 to 0.12]; P < 0.001) and the femoral neck (change, 0.035 g/cm2 [CI, 0.025 to 0.042] vs. -0.037 g/cm2 [CI, -0.044 to -0.027]; difference, 0.062 g/cm2 [CI, 0.049 to 0.073]; P < 0.001). Genistein statistically significantly decreased urinary excretion of pyridinoline and deoxypyridinoline, increased levels of bone-specific alkaline phosphatase and insulin-like growth factor I, and did not change endometrial thickness compared with placebo. More genistein recipients than placebo recipients experienced gastrointestinal side effects (19% vs. 8%; P = 0.002) and discontinued the study. The study did not measure fractures and had limited power to evaluate adverse effects. Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women. ClinicalTrials.gov registration number: NCT00355953.
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                Author and article information

                Journal
                Indian J Pharmacol
                Indian J Pharmacol
                IJPharm
                Indian Journal of Pharmacology
                Medknow Publications & Media Pvt Ltd (India )
                0253-7613
                1998-3751
                May-Jun 2012
                : 44
                : 3
                : 345-350
                Affiliations
                [1]Department of Pharmacology, STES's Sinhgad Institute of Pharmacy, Narhe, Pune, Maharashtra, India
                [1 ]Indus Biotech Private Limited, Kondhwa, Pune, Maharashtra, India
                [2 ]Department of Pharmacology, BVP's Poona College of Pharmacy, Erandwane, Pune, Maharashtra, India
                Author notes
                Correspondence to: E-mail: sbodhind@ 123456rediffmail.com
                Article
                IJPharm-44-345
                10.4103/0253-7613.96310
                3371457
                22701244
                91da4075-be80-4868-b0e1-5bbafa321331
                Copyright: © Indian Journal of Pharmacology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 04 May 2011
                : 03 January 2012
                : 28 February 2012
                Categories
                Research Article

                Pharmacology & Pharmaceutical medicine
                phytoestrogen-rich fraction,ovariectomized rats,antiosteoporosis,estrogenic activity,serum alcium

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