title: Sipjeondaebo-tang, a traditional herbal formula, inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy.
abstract: Retinal neovascularization is a common pathology in age-related macular degeneration, retinopathy of prematurity and proliferative diabetic retinopathy. Platelet derived growth factor (PDGF) is a vasoactive factor and has been implicated in proliferative retinopathies. Oxygen-induced retinopathy in the mouse is the standard experimental model of proliferative retinopathies. Sipjeondaebo-tang (SDT) is the most widely used traditional herbal formula in East Asia, also known as Shi-Quan-Da-Bu-Tang in Chinese and Juzen-taiho-to in Japanese. SDT has been known to exert anti-angiogenic activities in several tumor models, but the role of SDT in proliferative retinopathies remains unclear. Thus, the object of the present study is to examine the mechanism of action and efficacy of SDT on retinal neovascularization in oxygen-induced ischemic retinopathy (OIR) mice. Neonatal mice at postnatal day 7 (P7) were exposed to 75% concentration of oxygen for 5 days (P7-P12), and then returned to room air from P12 to P17 to induce retinal neovascularization. SDT were administered once per day for 5 consecutive days (P12-P16) by intraperitoneal injection. Retinal neovascularization was measured at P17. We used a protein array to evaluate the expression levels of angiogenic factors. Inhibitory activity of SDT on PDGF-BB/PDGFRβ interaction was evaluated in vitro. Retinal neovascularization in the OIR mice was significantly decreased by SDT. SDT decreased the expression levels of PDGF-BB protein and VEGF mRNA. Moreover, SDT dose-dependently inhibited PDGF-BB/PDGFRβ interaction (IC50 = 388.82 ± 7.31 µg/ml). In conclusion, SDT is a potent inhibitor of retinal neovascularization through inhibiting the pro-angiogenic effect of PDGF-BB.
authors.affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine.
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Lee
authors.forename: Chan-Sik
authors.initials: CS
authors.lastname: Kim
authors.forename: Eunjin
authors.initials: E
authors.lastname: Sohn
authors.forename: Kyuhyung
authors.initials: K
authors.lastname: Jo
authors.forename: Hye Ryeng
authors.initials: HR
authors.lastname: Lim
authors.forename: Sun Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
authors.forename: Junghyun
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D000077214:Becaplermin; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000009:adverse effects*; D011485:Protein Binding / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C063587:juzentaihoto; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D010100:Oxygen