doi:10.1038/nindia.2015.90 Published online 9 July 2015
Two plants products with potential to treat bone loss in women after menopause and heal fractures quickly are under test in India for use as nutraceuticals.
Both substances have been isolated by India's Council of Scientific and Industrial Research (CSIR) lab Central Drug Research Institute (CDRI), Lucknow, and their technology transferred to industry for further development and clinical testing. One of the natural extracts is from the leaves of Dalbergia sissoo or the Indian rosewood tree (locally known as shisham), and the second from Ulmus wallichiana or the Himalayan elm that grows in the Indian Himalayas, besides Nepal and Afghanistan.
Both could offer an alternative strategy to treat bone loss during osteoporosis – a ‘porous bone’ condition when bones lose proteins and minerals, especially calcium, excessively. The condition is common in women after menopause when their ovaries stop producing the hormone estrogen that protects against bone loss.
Currently the only available agent to treat fractures is a fragment of human parathyroid hormone (PTH), an ‘anabolic’ substance that in a constructive process helps cells build simple substances into more complex substances, in this case, bone tissue. But PTH is costly, and has serious potential side-effects such as bone cancer. Also, it needs to be given daily as an injection, and can be given to a patient only once in a life time, for a maximum period of two years.
One of CDRI’s potential bone-promoting compounds is a leaf extract from the Dalbergia sissoo, whose leaves showed efficacy against osteoporosis in animal tests. On screening the compounds present in the leaf extracts, CDRI scientists identified a novel compound responsible for bone restoration.
The scientists next tested the novel compound’s ability to restore bone formation in fractures and found that fracture healing was reduced from 21 days to seven days, CDRI scientist Ritu Trivedi said. CDRI has transferred the technology to Pharmanza, a company based in the western Indian state of Gujarat for clinical trials. If successful, CDRI hopes to market the compound as a nutraceutical, she added.
The CDRI team had previously found1 that an extract of Dalbergia sissoo made from leaves and pods has anti-resorptive (blocking bone cell loss) and bone-forming effects.They attributed the positive effects on bone formation to active molecules present in the extract of Dalbergia sissoo, especially a novel isoflavonoid ‘CAFG’ (Caviunin 7-O-[β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside], which is present in higher amounts in the extracts.
Mice whose ovaries were removed, and were hence estrogen-deficient, were given CAFG at 1 mg/kg/day dose in (human dose ∼0.081 mg/kg) which led to enhanced bone formation, reduced bone resorption and bone turnover. Owing to CAFG's inherent properties for bone, it could be positioned as a potential drug, food supplement, for postmenopausal osteoporosis and fracture repair, their report said.
CDRI team reported encouraging results2 in mice with a second flavonoid from Dalbergia sissoo, ‘dalberg phenol’, in mice with their ovaries removed. These mice had a marked increase in body weight and loss of bone volume, but DGP treatment increased bone biomechanical strength and new bone formation. They said the extract possibly acted by increasing bone-making or ‘osteoblastic’ activities and decreasing bone resorption or ‘osteoclastic’ activities.
The bark of the second plant that yielded a rapid fracture-healing agent, the Himalayan elm (Ulmus wallichiana) is used as traditional medicine to treat fractures in the region.
Initial pharmacological investigations by CDRI scientists showed that the bark extract contains three chemical compounds that prevent menopausal bone loss and promote bone-forming cells. They also inhibited formation of fatty tissue. .
CSIR-CDRI signed a research and licensing agreement in 2012 with M/s Kemxtree LLC, USA), a Nostrum group company, for further development of the molecules as a rapid fracture-healing oral drug.
1. Kushwaha, P. et al. A novel therapeutic approach with Caviunin-based isoflavonoid that en routes bone marrow cells to bone formation via BMP2/Wnt-β-catenin signaling. Cell Death Dis. (2014) doi: 10.1038/cddis.2014.350
2. Gautam, J. et al. Neoflavonoid dalbergiphenol from heartwood of Dalbergia sissoo acts as bone savior in an estrogen withdrawal model for osteoporosis. Menopause (2015) doi: 10.1097/GME.0000000000000453