| Summary: | 博士 === 國立陽明大學 === 生物藥學研究所 === 99 === During the past 15 years, worldwide pharmaceutical industry has been gradually decreased on the successful rates to generate the blockbuster products. Moreover, there has followed by a substantial decline in new drug approvals and impending loss of patent protection for important medicines. Some possible reasons maybe due to limited in identifying the novel drug target or problems with the strategy of high-throughput screening of synthetic libraries. Human-experienced medicine based botanical drug discovery is a new strategy by applying human experience recorded in our ancient medicinal books or folk remedies on new drug discovery. This study aims to apply this strategy to evaluate the effect and elucidate the potential mechanisms of botanical drugs on diabetes complications and osteoporosis.
In the study of botanical drug applied to diabetes complications, we demonstrated that the extract of rhizomes from Dioscorea alata L. cv. Phyto, Dispo85E, as an HGF inducer, not only enhanced the hepatic clearance of advanced glycation end products (AGEs) by nonparenchymal cells (NPCs) but also repaired and prevented the renal and retinal damage from AGEs in two diabetic animal models. Besides, we also demonstrated the novel mechanism of HGF in endocytosis and autophagic clearance of AGEs in hepatic NPCs. This study suggests that Dispo85E is a botanical drug with a novel mechanism that enhances the clearance of AGEs through HGF-induced autophagic-lysosomal pathway and is a candidate drug for treatment of diabetic complications.
In the study of botanical drug applied to osteoporosis, we found Dispo85E can promote bone formation activity by inducing mesenchymal stem cell differentiation into osteoblasts rather than adipocytes. Besides, our in vivo data indicated that Dispo85E promotes osteoblastogenesis by increasing ALP activity and bone nodule formation in ovariectomy-induced osteoporosis mice. Microcomputed tomography (μCT) analysis also showed that Dispo85E ameliorates the deterioration of trabecular bone mineral density (tBMD) and microarchitecture of trabecular bone in ovariectomized (OVX) mice. This study suggested that Dispo85E is a botanic drug with novel mechanism that drives the linage-specific differentiation of bone marrow stromal cells and is a candidate drug for osteoporosis therapy.
Through the cooperation with research Center for Drug Discovery in National Yang-Ming University, the Dispo85E has approved by U.S. FDA for phase II clinical trials with two different indications. The recent achievement based on our rationale of human-experienced medicine based botanical drug discovery indicates that this strategy may offer a platform for botanical drug development. Besides, the novel mechanism discovered in our study can also be used as a platform of further new drug discovery.
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