Vikram Khedgikar1, Naseer Ahmad2, Priyanka Kushwaha3, Jyoti Gautam1, Geet K Nagar2, Divya Singh2, Prabodh K Trivedi4, Prabhat R Mishra5, Neelam S Sangwan6, Ritu Trivedi7. 1. Division of Endocrinology, Central Drug Research Institute, Council of Scientific and Industrial Research-CDRI, Lucknow, India; Jawaharlal Nehru University, New Delhi, India. 2. Division of Endocrinology, Central Drug Research Institute, Council of Scientific and Industrial Research-CDRI, Lucknow, India. 3. Division of Endocrinology, Central Drug Research Institute, Council of Scientific and Industrial Research-CDRI, Lucknow, India; Academy of Scientific and Innovation Research, New Delhi, India. 4. Plant Gene Expression Laboratory, Council of Scientific and Industrial Research-National Botanic Research Institute, Lucknow, India. 5. Division of Pharmaceutics Central Drug Research Institute, Council of Scientific and Industrial Research-CDRI, Lucknow, India. 6. Council of Scientific and Industrial Research-Central Institute of Medicinal and Aromatic Plants, Lucknow, India. 7. Division of Endocrinology, Central Drug Research Institute, Council of Scientific and Industrial Research-CDRI, Lucknow, India. Electronic address: Ritu_trivedi@cdri.res.in.
Abstract
OBJECTIVE: Bone 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). METHODS: Adult 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. RESULTS: WFA 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. CONCLUSIONS: It 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.
OBJECTIVE: Bone 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). METHODS: Adult 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. RESULTS:WFA 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. CONCLUSIONS: It 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.