Preventive effects of withaferin A isolated from the leaves of an Indian medicinal plant Withania somnifera (L.): Comparisons with 17-β-estradiol and alendronate

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2015, Vol.31 (1), p.205-213
• Main Authors: Khedgikar, Vikram, M.Sc, Ahmad, Naseer, M.Sc, Kushwaha, Priyanka, M.Sc, Gautam, Jyoti, M.Sc, Nagar, Geet K., B.Sc, Singh, Divya, Ph.D, Trivedi, Prabodh K., Ph.D, Mishra, Prabhat R., Ph.D, Sangwan, Neelam S., Ph.D, Trivedi, Ritu, Ph.D
• Format: Article
• Language: English
• Subjects: Acid Phosphatase - genetics; Acid Phosphatase - metabolism; Alendronate - pharmacology; Animals; Antiresorptive; Biomarkers - blood; Bone and Bones - drug effects; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Estradiol - pharmacology; Female; Gastroenterology and Hepatology; Isoenzymes - genetics; Isoenzymes - metabolism; Mice; Mice, Inbred BALB C; Microcomputed tomography; Osteocalcin - blood; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteogenic; Osteoporosis - prevention & control; Ovariectomy; Plant Leaves - chemistry; Plants, Medicinal - chemistry; Premenopausal; Receptor Activator of Nuclear Factor-kappa B - genetics; Receptor Activator of Nuclear Factor-kappa B - metabolism; Tartrate-Resistant Acid Phosphatase; Trabecular microarchitecture; Tumor Necrosis Factor-alpha - blood; Withania - chemistry; Withanolides - pharmacology
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2014.05.010

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.