A neoflavonoid dalsissooal isolated from heartwood of Dalbergia sissoo Roxb. has bone forming effects in mice model for osteoporosis.
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.
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; AcSIR, Academy of CSIR, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Priyanka
P
Kushwaha
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Vikram
V
Khedgikar
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Naseer
N
Ahmad
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Anirudha
A
Karvande
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Jyoti
J
Gautam
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Padam
P
Kumar
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Rakesh
R
Maurya
Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India. Electronic address: ritu_trivedi@cdri.res.in.
Ritu
R
Trivedi
D000171:Acrolein / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D000071556:Cancellous Bone / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects; D035782:Dalbergia / Q000737:chemistry*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000172:deficiency; D005260:Female; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010052:Ovariectomy; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D004967:Estrogens; D005419:Flavonoids; D010636:Phenols; C000615598:dalsissooal; D015675:Osteocalcin; D000171:Acrolein
17β-estradiol; Bmp-2/runx-2 pathway; Bone mechanical strength; Micro-ct; Neoflavonoid; Post-menopausal osteoporosis