10

10.1021/acs.jmedchem.5b01227 Tauroursodeoxycholate [PubMed] [CrossRef] [Google Scholar] Muranaka, K. , Yanagi, Y. , Tamaki, Y. , Takahashi, H. , Usui, T. , Ohashi, K. , Senda, T. (2005). bevacizumab, aflibercept, and ranibizumab, have been administered intravitreally in clinical trials. The drugs caused significant neovascularization suppression and vision loss stability (Campa & Harding,?2011; Frampton,?2013; Garcia\Layana et?al.,?2015). It is noteworthy that this intravitreal administration of anti\VEGF brokers has Tauroursodeoxycholate been associated with adverse effects (Diago et?al.,?2009; Fintak et?al.,?2008). When anti\VEGF brokers are administered intravitreally repeatedly, ocular complications, such as endophthalmitis, traumatic cataracts, ocular inflammation, retinal detachment, intraocular pressure elevation, and vitreous hemorrhage, can occur at a high incidence (Falavarjani & Nguyen,?2013). Novel agents using other administration routes are thus increasingly considered (Cammalleri et?al.,?2017; Honda et?al.,?2010; Meredith et?al.,?2015; Takahashi et?al.,?2008). Some food supplements and its ingredients have been considered to be inhibitors of ocular angiogenesis (Sulaiman, Basavarajappa, & Corson,?2014) and retinal degeneration (Dal Monte et?al.,?2018; Locri, Cammalleri, Dal Monte, Rusciano, & Bagnoli, 2019). Thunb. has been used as a functional food to treat several diseases, such as edema and inflammation in Korea and Japan (Kimura, But, Guo, & Sung,?1997). The leaves of have various phytochemicals such as Tauroursodeoxycholate aucubin, quercetin, and kaempferol (Bernini, Iavarone, & Trogolo,?1984; Iwashina, Kamenosono, & Hatta,?1997). Recently, we reported that and its bioactive compound, aucubin, showed potent pharmacological effects on dry eye disease (Kang, Jung, & Kim,?2018). The antiangiogenic abilities of around the neovascular retinal diseases have not been described in reports, according to our research. To elucidate this, we examined the antiangiogenic activities of an ethanolic extract of (AJE) in p300 an oxygen\induced ischemic retinopathy (OIR) model. The ability of aucubin, kaempferol, and quercetin to inhibit retinal vascular hyperpermeability stimulated by administering exogenous VEGF intravitreally in rats was also assessed. 2.?MATERIALS AND METHODS 2.1. AJE preparation The leaves and stems of were cultivated and collected in Geoje, Kyungsangnamdo, South Korea. Jeonbuk National University’s (Jeonju, South Korea) herbarium has the voucher specimen (No. JBNU\AJE2018). The leaves (700?g) and stems (350?g) of were extracted with 30% ethanol (10.5?L) at 85C. The extraction took 3?hr with 175?g sample gotten by concentration and freeze\drying. AJE was qualitatively and quantitatively assessed with high\performance liquid chromatography (HPLC). Tauroursodeoxycholate AJE contained 59.7??1.5?mg/g aucubin (Physique?1). Open in a separate window Physique 1 HPLC profile of an extract of rats that are 7?weeks old were bought from Koatech and anesthetized using isoflurane. A total of 4?l of a single dose of 100?ng VEGF164 (R&D Systems) was administered into the vitreous cavity of one eye with a microinjector (Hamilton). The other eye was injected with the same volume of physiological saline. The following five groups of rats were then created as follows: (a) rats injected intravitreally; (b) rats injected intravitreally and treated with 100?mg of AJE per kg body weight; (c) rats injected intravitreally and exposed to 100?mg of aucubin per body weight; (d) rats injected intravitreally and treated with 100?mg per kg body weight of quercetin; and (e) rats injected intravitreally and treated with 100?mg per kg body weight of kaempferol. After the rats were injected intraocularly, AJE, quercetin, aucubin, and kaempferol were administered once every day for 3?days. The quantification of the extravasated tracer dye was done using a method described previously (Jung, Kim, Kim, Kim, & Cho,?2015). 2.7. Statistical analysis One\way analysis of variance then Tukey’s multiple comparison test was applied for group data analysis. A statistically significant difference was indicated by a (Iwashina et?al.,?1997). To determine how AJE influences the induction of vascular pathological change by VEGF in retinas, fluorescein angiography was carried out in exogenous VEGF, with the rats injected intravitreally. The control samples retained fluorescence dye in the vessels. When exogenous VEGF was administered intravitreally, it caused leakage in.