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A standardized phytopreparation from an Indian medicinal plant (Dalbergia sissoo) has antiresorptive and bone-forming effects on a postmenopausal osteoporosis model of rat

Khedgikar, Vikram MSc1; Gautam, Jyoti MSc1; Kushwaha, Priyanka MSc1; Kumar, Avinash MSc1; Nagar, Geet K. BSc1; Dixit, Preety MSc2; Chillara, Raju MSc2; Voruganti, Swathi MSc3; Singh, Sheelendra P. MSc3; Uddin, Wahaj MSc3; Jain, Girish K. PhD3; Singh, Divya PhD1; Maurya, Rakesh PhD2; Chattopadhyay, Naibedya PhD1; Trivedi, Ritu PhD1

Menopause:
doi: 10.1097/GME.0b013e318256b6ae
Original Articles
Abstract

Objective: The aim of this study was to evaluate the skeletal effects of an extract made from the leaves and pods of Dalbergia sissoo (butanol-soluble standardized fraction [BSSF]) on ovariectomized rats, a model for postmenopausal osteopenia.

Methods: Adult Sprague-Dawley rats were ovariectomized and administered BSSF (50 and 100 mg/kg per day) or 17β-estradiol orally for 12 weeks. The sham-operated group and the ovariectomy + vehicle group served as controls. Bone microarchitecture, bone turnover markers (serum osteocalcin and C-telopeptide fragment of collagen type I), biomechanical strength, new bone formation (based on mineral apposition rate and bone formation rate), and skeletal expressions of osteogenic and resorptive gene markers were studied. Uterine histomorphometry was used to assess estrogenicity. Bioactive marker compounds in BSSF were analyzed by high-performance liquid chromatography. One-way analysis of variance was used to test the significance of effects.

Results: In comparison with ovariectomized rats treated with vehicle, BSSF treatment in ovariectomized rats resulted in an improved trabecular microarchitecture of the long bones, increased biomechanical strength parameters of the vertebra and femur, decreased bone turnover markers (osteocalcin and type I collagen) and expression of skeletal osteoclastogenic genes, and increased new bone formation and expression of osteogenic genes in the femur. Overall, the osteoprotective effects of BSSF were comparable to those of 17β-estradiol. BSSF did not exhibit uterine estrogenicity. Analysis of marker compounds revealed the presence of osteogenic methoxyisoflavones, including caviunin 7-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside] (a novel compound), biochanin A, and pratensin.

Conclusions: Oral doses of BSSF in the preclinical setting are effective in preventing estrogen deficiency–induced bone loss by dual action: inhibition of bone resorption and stimulation of new bone formation.

Author Information

From the Divisions of 1Endocrinology, 2Medicinal and Process Chemistry, and 3Pharmacokinetics and Metabolism, Council of Scientific and Industrial Research-Central Drug Research Institute, Chattar Manzil Palace, Lucknow, India.

Received February 6, 2012; revised and accepted March 21, 2012.

Funding/support: This study was supported by generous funding from the Ministry of Health and Family Welfare (grant-in-aid), Government of India.

Financial disclosure/conflicts of interest: None reported.

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Address correspondence to: Ritu Trivedi, PhD, Division of Endocrinology, Council of Scientific and Industrial Research-Central Drug Research Institute, Chattar Manzil Palace, PO Box 173, Lucknow 226001, India. E-mail: ritu_trivedi@cdri.res.in

©2012The North American Menopause Society