Fast and long acting neoflavonoids dalbergin isolated from Dalbergia sissoo heartwood is osteoprotective in ovariectomized model of osteoporosis: Osteoprotective effect of Dalbergin

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• 作者：Dharmendra Choudhary ; MSc^a ; ¹ ; Priyanka Kushwaha ; MSc^a ; Jyoti Gautam ; MSc^a ; Padam Kumar ; MSc^b ; Ashwani Verma ; MSc^c ; Avinash Kumar ; PhD^a ; Saransh Wales Maurya ; MSc^d ; Ibadur Rahman Siddiqui ; PhD^d ; Prabhat Ranjan Mishra ; PhD^c ; Rakesh Maurya ; PhD^b ; Ritu Trivedi ; PhD^a ; ^{ritu_trivedi@cdri.res.in" class="auth_mail" title="E-mail the corresponding author} ; ^{ritu_pgi@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：DBN ; dalbergin ; E2 ; estrogen(17 β-estradiol) ; BMC&rsquo ; s ; bone marrow cells ; OVx ; ovariectomized ; BV/TV ; trabecular bone volume ; Tb.N ; trabecular number ; Tb.Sp ; trabecular separation ; Tb.Pf ; trabecular pattern factor ; SMI ; structure model index
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：83
• 期：Complete
• 页码：942-957
• 全文大小：9032 K

文摘

This study aims to evaluate the skeletal effects of dalbergin (DBN), isolated from Dalbergia sissoo heartwood, in ovariectomized (OVx) BALB/c mice, a postmenopausal osteoporosis model of bone loss.

Methods

Adult BALB/c mice were used and randomly assigned in to six groups with 6 animals (n = 6) in each group: sham (surgery operated without ovariectomy) with vehicle, ovariectomy with vehicle, ovariectomy (OVx) with estradiol (E2 5.0 μg kg⁻1 day⁻¹), or ovariectomy with dalbergin at three different doses of DBN (1.0, 5.0 and10 mg kg⁻¹ day⁻¹). Daily oral administration of the vehicle, estradiol, or DBN was started 8 weeks post-surgery and continued for 8 weeks. At the end of experiment, mice were sacrificed and assessed for trabecular bone structure of tibia, lumbar vertebra (L5) and alterations in biochemical and uterine parameters, pharmacokinetic profile and gene expression were monitored for each group.

Results

Treatment with DBN prevented trabecular bone loss in cancellous bone in the tibial metaphysis and lumbar vertebra region of the ovariectomized mice. Micro-CT data showed that mice treated with DBN at 1.0 mg kg⁻¹ day⁻¹ exhibited improved bone micro-architecture that was sustained with decreased expression of bone resorption markers like TRAP and RANK and caused an increase in osteogenic markers like RUNX2, BMP2 and OPG/RANKL ratio compared with OVx + vehicle treated mice. Moreover, DBN treatment induced no uterine estrogenicity and significantly lowered the osteocalcin amount in serum when compared with OVx + V group. DBN reached its maximum concentration (C_max) 238.49 ± 21.37 ng ml⁻¹ in serum as early as 1 h of administration. Overall, DBN (1.0 mg kg⁻¹ day⁻¹) treatment exhibited similar bone conserving effect against bone-loss as estradiol treatment.

Conclusion

Daily oral administration of DBN for 8 weeks showed significant anabolic effects on bone micro-architectural parameters along with down regulation of bone resorptive markers without compromising safety at uterine level. Therefore, our study provides basis for DBN as a therapeutic candidate against postmenopausal osteoporosis.