• Vikram Khedgikar, Naseer Ahmad, Priyanka Kushwaha, Jyoti Gautam, Geet K Nagar, Divya Singh, Prabodh K Trivedi, Prabhat R Mishra, Neelam S Sangwan, and Ritu Trivedi.
• Division of Endocrinology, Central Drug Research Institute, Council of Scientific and Industrial Research-CDRI, Lucknow, India; Jawaharlal Nehru University, New Delhi, India.
• Nutrition. 2015 Jan 1;31(1):205-13.

ObjectiveBone protective effects of withaferin A (WFA) from leaves of Withania somnifera (L.) were evaluated in preventive model of Balb/c mice with 17 β-estradiol (E2) and alendronate (ALD).MethodsAdult female Balb/c mice, 7 to 9 wk, were bilaterally ovariectomized (OVx) to mimic the state of E2 deficiency. Immediately after surgery mice were administrated WFA at doses of 1, 5, 10 mg/kg/d while other two OVx groups received ALD or E2 for 2 mo. Sham and OVx groups with vehicle and no treatment served as controls.ResultsWFA administration increased new bone formation, as well as improving microarchitecture and biomechanical strength of the bones. It prevented bone loss by reducing expression of osteoclastic genes tartrate resistant acid phosphatase (TRAP) and receptor activator of nuclear factor κ B (RANK). Increase in bone turnover marker, osteocalcin (OCN) and inflammatory cytokine tumor necrosis factor-alpha (TNF-α) because of ovariectomy were reduced with WFA treatment, with effects comparable to E2 administration. Histomorphometric analysis of uterus shows that WFA was not fraught with estrogenic or antiestrogenic effects. At cellular level, WFA promoted differentiation of bone marrow cells (BMCs) and increased mineralization by inducing expression of osteogenic genes. WFA has bone protective potential as its treatment prevents bone loss that is comparable to ALD and E2.ConclusionsIt is surmised that WFA in preclinical setting is effective in preserving bone loss by both inhibition of resorption and stimulation of new bone formation before onset of osteoporosis with no uterine hyperplasia.Copyright © 2015 Elsevier Inc. All rights reserved.

48 keywords...

hide…