Kushwaha Priyanka, Khedgikar Vikram, Ahmad Naseer, Karvande Anirudha, Gautam Jyoti, Kumar Padam, Maurya Rakesh, Trivedi Ritu
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; AcSIR, Academy of CSIR, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Eur J Pharmacol. 2016 Oct 5;788:65-74. doi: 10.1016/j.ejphar.2016.06.003. Epub 2016 Jun 15.
Dalbergia sissoo Roxb. is a well known medicinal plant of India, enriched with various flavonoids used for treating multiple diseases. Earlier, we have shown that extract of Dalbergia sissoo Roxb. leaves mitigate ovariectomy induced bone loss and pure compounds (neoflavonoids) isolated from it, promote osteoblastogenesis in primary calvarial osteoblasts cells in vitro. Here, we hypothesize that dalsissooal (DSL), a novel neoflavonoid isolated from the heartwood of Dalbergia sissoo Roxb. is an important constituent of the extract that imparts bone forming effects. Treatment with DSL enhanced trabecular bone micro-architecture parameters, biomechanical strength, increased bone formation rate and mineral apposition rate in OVx mice comparable to 17β-estradiol. It increased bone formation by enhancing osteoblast gene expression and reduced bone turnover by decreasing osteoclastic gene expressions. Interestingly, we observed that DSL has no uterine estrogenic effects. At cellular levels, DSL promoted differentiation of bone marrow cells as well as calvaria osteoblast cells towards osteoblast lineage by enhancing differentiation and mineralizing ability to form mineralizing nodules via stimulating BMP-2 and RunX-2 expressions. Overall, our data suggest that oral supplementation of a novel neoflavonoid dalsissooal isolated from heartwood of Dalbergia sissoo Roxb. exhibited bone anabolic action by improving structural property of bone, promoting new bone formation and reducing bone turnover rate in post-menopausal model for osteoporosis with no uterine hyperplasia.
印度黄檀是印度一种著名的药用植物，富含多种用于治疗多种疾病的黄酮类化合物。此前，我们已经表明，印度黄檀叶提取物可减轻去卵巢诱导的骨质流失，并且从其中分离出的纯化合物（新黄酮类化合物）可促进原代颅骨成骨细胞的成骨作用。在此，我们假设，从印度黄檀心材中分离出的一种新型新黄酮类化合物——达西索醇（DSL）是该提取物中具有成骨作用的重要成分。与17β-雌二醇相当，用DSL处理可增强去卵巢小鼠的小梁骨微结构参数、生物力学强度，提高骨形成率和矿化沉积率。它通过增强成骨细胞基因表达来增加骨形成，并通过降低破骨细胞基因表达来减少骨转换。有趣的是，我们观察到DSL没有子宫雌激素作用。在细胞水平上，DSL通过刺激骨形态发生蛋白-2（BMP-2）和RunX-2的表达，增强分化和矿化能力以形成矿化结节，从而促进骨髓细胞以及颅骨成骨细胞向成骨谱系分化。总体而言，我们的数据表明，口服补充从印度黄檀心材中分离出的新型新黄酮类化合物达西索醇，在绝经后骨质疏松模型中通过改善骨结构特性、促进新骨形成和降低骨转换率，表现出骨合成代谢作用，且不会导致子宫增生。
