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| Identification of a potential drug for the treatment of post-menopausal osteoporosis and fracture healing from our group has recently led to the development of new medication for bone health. We have standardized a fraction from Dalbergia sissoo or Sheesham as an osteogenic agent that has rapid fracture healing efficacyand will also be valuable in primary osteoporosis. In this standardized extract have identified a novel isoflavonoidCaviunin 7-O-[b-Dapiofuranosyl-(1-6)-b-D-glucopyranoside] abbreviated as CAFG that is present in the highest percentage.CAFG administration in rodents improved trabecular microarchitecture of the long bones and increased strength at the vertebral and femur sites. CAFG is also an effective accelerant for chondrogenesis and has stimulatory effect on the repair of cortical bone as observed after drill-hole injury at tissue and cellular level. Signal transduction inhibitors in osteoblast demonstrated involvement of p-38 mitogen-activated protein kinase pathway that is stimulated by BMP2 to initiate Wnt/b-catenin to be involved in this process. Overall, CAFG inhibits phosphorylation of GSK3-β and subsequent nuclear accumulation of b-catenin.These osteogenic effects were confirmedby abrogation observed by Dkk1, Wnt-receptor blocker and FH535, inhibitor of TCF-complex by reduction in β-catenin levels. This technology has been transferred to Pharmanza Pvt. Ltd.and is now in market, PAN India by the name of REUNION. |
1. Khedgikar V, Kushwaha P, Ahmad N, Gautam J, Kumar P, Maurya R, Trivedi R (2017). Ethanolic extract of Dalbergia sissoo promotes rapid regeneration of cortical bone in drill-hole defect model of rat.Biomedicine & Pharmacotherapy. 86: 16-22
2. Choudhary D, Kushwaha P, Gautam J, Kumar P, Verma A, Kumar A, Maurya SW, Siddiqui IR, Mishra PR, Maurya R, Trivedi R (2016). Fast and long acting neoflavonoidsdalbergin isolated from Dalbergia sissoo heartwood is osteoprotective in ovariectomized model of osteoporosis: Osteoprotective effect of Dalbergin. Biomedicine & Pharmacotherapy 83, 942-957
3. Kushwaha P, Khedgikar V, Ahmad N, Karvande A,Gautam J, Kumar P, Maurya R, Trivedi R(2016) A neoflavonoiddalsissooal isolated from heartwood of Dalbergia sissoo Roxb. has bone forming effects in mice model for osteoporosis. Journal European Journal of Pharmacology. 788: 65-74.
4. Gautam J, Kumar P, Kushwaha P, Khedgikar V, Choudhary D, Singh D, Maurya R, Trivedi R (2015). Neoflavonoiddalbergiphenol from heartwood of Dalbergia sissoo acts as bone savior in an estrogen withdrawal model for osteoporosis.Menopause 22: 1246-55.
5. Kumar P, Kushwaha P, Khedgikar V, Gautam J, Choudhary D, Singh D, Trivedi R, Maurya R (2015). Neoflavonoids as potential osteogenic agents from Dalbergia sissoo heartwoodBioorganic & Medicinal Chemistry Letters 24:12, 2664-2668.
6. Dixit P, Chillara R, Khedgikar V, Gautam J, Kushwaha P, Kumar A, Singh D, Trivedi R,Maurya R (2012) Constituents of Dalbergia sissoo Roxb. leaves with osteogenic activity Bioorg Med Chem Lett. 22:890-7.
7. Khedgikar V, Gautam J, Kushwaha P, Kumar A, Nagar GK, Dixit P, Chillara R, Voruganti S, Singh SP, Uddin W, Jain GK, Singh D, Maurya R, Chattopadhyay N, Trivedi R (2012) A standardized phytopreparation from an Indian medicinal plant (Dalbergia sissoo) has antiresorptive and bone-forming effects on a postmenopausal osteoporosis model of rat Menopause 19:1336-46.
8. Kushwaha P, Khedgikar V, Gautam J, Dixit P, Chillara R, Verma A, Thakur R, Mishra DP, Singh D, Maurya R, Chattopadhyay N, Mishra PR, Trivedi R (2014). A novel therapeutic approach with Caviunin-based isoflavonoid that en routes bone marrow cells to bone formation via BMP2/Wnt-b-catenin signalingCell Death and Disease 5:9, e1422.
9. Karvande A, Khedgikar V, Kushwaha P, Ahmad N, Kothari P, Verma A Kumar P, Nagar GK, Mishra PR, Maurya R, Trivedi R (2017)Heartwood extract from dalbergia sissoo promotes fracture healing and its application in ovariectomy‐induced osteoporotic rats Journal of Pharmacy and Pharmacology 69 :10, 1381-1397