| Osteoporosis, which has been defined as a state of low bone mass, is one of the most serious disorder associated with aging. According to the theory of Chinese traditional medicine, the formulations used to tonify the kidney and strengthen the bone are always useful in the treatment of osteoporosis syndrome. So 29 kinds of crude drugs from this type of formulation were selected and the aqueous ext. and MeOH ext. of them were screened for their antiosteoporotic activity on stimulation of proliferation of osteoblast-like cell lines UMR106, among all the ext., the water ext. of rhizomes of Dioscorea spongiosa showed the strongest stimulatory activity.As we know, the imbalance between the bone formation related to the osteoblast closely and bone resorption related to the osteoclast closely, make the osteoporosis occur. So a good agent for anti-osteoporosis should be effective both to osteoblast and to osteoclast. Therefore, the water ext. of D. spongiosa, together with another 10 ext showed the stronger stimulatory activity on osteoblast, were screened further on its inhibitory activity on formation of osteoclast multinuclear cell. It also showed the stronger activity in this in vitro experiment. Then, the result of in vivo experiment revealed that it prevented the decrease of BMD of the spinal vertebra, trabecular mineral content, trabecular density, cortical mineral content of proximal tibia in OVX rat significantly.The water ext. of D. spongiosa was subjected to the chromatographic separation on Dion 101 column to get H20,30%, 60%, 90%EtOH fractions successively, among them, the 90%EtOH fraction showed the strongest anti-osteoporotic activity, both on stimulation of osteoblast proliferation and inhibition of osteoclast formation, and also showed the inhibitory activity on bone resorption induced by PTH. In vivo experiment, it can prevent the decrease in total mineral content, total density, trabecular mineral content, trabecular density, cortical mineral content and the anti-twist strength of the proximal tibia in OVX rat significantly. So it was further separated by a series of chromatography to afford 28 compounds, in which, 3 new diarylheptanoids and 6 new steroid saponins.Diarylheptanoids and lignans were evaluated their anti-osteoporotic activity both on the inhibition of the osteoclast formation and on bone resorption induced by PTH, while the glycosides were perfermed only on bone resorption induced by PTH due to small amount of some of them. All the diarylheptanoid and lignan compounds can inhibit the formation of osteoclast significantly but did not show any cytotoxic to cells, while they also showed the inhibitory activity on bone resorption significantly. Interestingly, 2 showed strong inhinition in both experiment, while 1 showed only weakactivity on the osteoclast formation, but no activity on bone resorption, though they are diasteromers. It seems that they acted on the receptors of the osteoclast, where the stereochemistry is crucial for the activity. Among steroid saponin compounds, some compounds behaved the inhibitory activity on osteoclast formation but they also showed the cytotoxic also. 3 saponins and 1 glycoside possessed the inhibition on bone resorption and compound 21, the major compound of this fraction, showed the strongest activity among the glycosides. So it was supposed to do in vivo experiment in OVX mice. From the result data, compound 21, showed the inhibitory activity on the decrease of total mineral content, total mineral density, trabecular mineral density, cortical mineral content, cortical mineral density, cortical thickness and the anti-twist strength of the proximal tibia, and total mineral content, total mineral density, trabecular mineral density, cortical mineral content, cortical mineral density of the distal femora in OVX mice.Comparison the in vivo activity of 90%EtOH fraction and compound 21 with estradiol, indicated the 90% EtOH fraction behaved the stronger activity on total mineral content, total density, trabecular mineral content, trabecular d... |
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