Effect of charred Radix et Rhizoma Rhei in a laser-induced choroidal neovascularization murine model.

A pharmaceutical composition (patent no. WO2012079419) exhibited favorable outcomes in a clinical trial of wet age‑related macular degeneration. The aims of the present study were to explore the effects of one composition component, charred Radix et Rhizoma Rhei (CRRR), in a laser‑induced choroidal neovascularization (CNV) murine model. A total of 30 eight‑week‑old C57BL/6 mice were subjected to diode laser treatment, and CNV was induced by rupturing the Bruch's membrane. The mice were then randomly divided into two groups: the CRRR‑treated group that was administered CRRR water extract (concentration, 0.6 g/100 ml; dose, 1 ml/0.1 kg twice a day for 21 days); and the control group that was treated with saline (dose, 1 ml/0.1 kg twice a day for 21 days). The retinal tissue was subjected to quantitative polymerase chain reaction (qPCR) and western blot analysis to determine the expression levels of interleukin‑10 (IL‑10) and vascular epithelial growth factor (VEGF) at day seven following laser treatment. At weeks 2 and 3 after laser treatment, fundus fluorescein angiography was performed and graded to assess the severity of lesion leakage. Retinal flat mounts were prepared for three‑dimensional confocal microscopy at day 22 after laser treatment. At days 14 and 21 after laser treatment, no statistically significant differences were observed between the clinically relevant lesions of the CRRR‑treated and control mice. CNV volumes were not found to be significantly different between the CRRR‑treated and control mice. The expression levels of IL‑10 were significantly increased in the CRRR‑treated mice (P<0.05). However, no statistically significant differences were observed between the VEGF expression levels of the CRRR‑treated and control mice. In conclusion, CRRR did not appear to significantly inhibit CNV in this murine model. The function of CRRR in the pharmaceutical composition may be due to the effects of IL‑10 and a synergistic effect with other components of the composition. However, further investigation is required.

[1]  Qinbo Zhou,et al.  Repression of choroidal neovascularization through actin cytoskeleton pathways by microRNA-24. , 2014, Molecular therapy : the journal of the American Society of Gene Therapy.

[2]  B. Yaspan,et al.  Mechanisms of age‐related macular degeneration and therapeutic opportunities , 2014, The Journal of pathology.

[3]  Liu Jian,et al.  Current Choroidal Neovascularization Treatment , 2013, Ophthalmologica.

[4]  Shusheng Wang,et al.  Pharmaceutical composition for treating macular degeneration (WO2012079419) , 2013, Expert opinion on therapeutic patents.

[5]  C. Bell,et al.  Stroke rates after introduction of vascular endothelial growth factor inhibitors for macular degeneration: a time series analysis. , 2012, Ophthalmology.

[6]  K. Nishida,et al.  Low-Dose Lipopolysaccharide Pretreatment Suppresses Choroidal Neovascularization via IL-10 Induction , 2012, PloS one.

[7]  G. Atsumi,et al.  Pollen Typhae is a rapid hemostyptic. , 2012, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[8]  P. Lanzetta,et al.  Neovascular Age-Related Macular Degeneration , 2012, Ophthalmologica.

[9]  K. Sonoda,et al.  IL‐27 inhibits pathophysiological intraocular neovascularization due to laser burn , 2012, Journal of leukocyte biology.

[10]  Y. Jang,et al.  n-Butanol extracts of Panax notoginseng suppress LPS-induced MMP-2 expression in periodontal ligament fibroblasts and inhibit osteoclastogenesis by suppressing MAPK in LPS-activated RAW264.7 cells. , 2011, Archives of oral biology.

[11]  Jianyou Guo,et al.  Antibacterial and Anti-inflammatory Activity of Traditional Chinese Herb Pairs, Angelica sinensis and Sophora flavescens , 2011, Inflammation.

[12]  I. Cho,et al.  Fritillaria ussuriensis Extract Inhibits the Production of Inflammatory Cytokine and MAPKs in Mast Cells , 2011, Bioscience, biotechnology, and biochemistry.

[13]  Sina Farsiu,et al.  Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration , 2011, Proceedings of the National Academy of Sciences.

[14]  R. Wen,et al.  CCR3 and Choroidal Neovascularization , 2011, PloS one.

[15]  D. Charnock-Jones,et al.  The natural compound n-butylidenephthalide derived from the volatile oil of Radix Angelica sinensis inhibits angiogenesis in vitro and in vivo , 2011, Angiogenesis.

[16]  Xiumei Gao,et al.  Astragalus membranaceus extract promotes neovascularisation by VEGF pathway in rat model of ischemic injury. , 2011, Die Pharmazie.

[17]  D. T. Lau,et al.  Anti-oxidative effects of the biennial flower of Panax notoginseng against H2O2-induced cytotoxicity in cultured PC12 cells , 2010, Chinese medicine.

[18]  Yiping Wang,et al.  Traditional Chinese Medicine herbs for stopping bleeding from haemorrhoids. , 2010, The Cochrane database of systematic reviews.

[19]  Michael B Horsley,et al.  Retinal nerve fiber layer thickness in patients receiving chronic anti-vascular endothelial growth factor therapy. , 2010, American journal of ophthalmology.

[20]  H. Moon,et al.  Curcumin inhibits TNFα-induced lectin-like oxidised LDL receptor-1 (LOX-1) expression and suppresses the inflammatory response in human umbilical vein endothelial cells (HUVECs) by an antioxidant mechanism , 2010, Journal of enzyme inhibition and medicinal chemistry.

[21]  Ji-Seon Seo,et al.  A modified preparation (LMK03) of the oriental medicine Jangwonhwan reduces Abeta(1-42) level in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease. , 2010, Journal of ethnopharmacology.

[22]  Margarida Saraiva,et al.  The regulation of IL-10 production by immune cells , 2010, Nature Reviews Immunology.

[23]  J. Ko,et al.  The protective action of radix Astragalus membranaceus against hapten-induced colitis through modulation of cytokines. , 2009, Cytokine.

[24]  Da-peng Li,et al.  Synergistic antioxidant activities of eight traditional Chinese herb pairs. , 2009, Biological & pharmaceutical bulletin.

[25]  C. Rao,et al.  Curcumin protects retinal cells from light-and oxidant stress-induced cell death. , 2009, Free radical biology & medicine.

[26]  Takuhiro Yamaguchi,et al.  Cerebrovascular accidents in ranibizumab. , 2009, Ophthalmology.

[27]  Zong-fang Li,et al.  Up-regulation of Toll-like receptor 4 was suppressed by emodin and baicalin in the setting of acute pancreatitis. , 2009, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[28]  H. Kaplan,et al.  Is there tachyphylaxis to intravitreal anti-vascular endothelial growth factor pharmacotherapy in age-related macular degeneration? , 2008, Ophthalmology.

[29]  C. Regillo,et al.  Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. , 2008, American journal of ophthalmology.

[30]  Youngnim Choi,et al.  Anti-inflammatory effects of BT-201, an n-butanol extract of Panax notoginseng, observed in vitro and in a collagen-induced arthritis model. , 2007, Clinical nutrition.

[31]  Xingbin Yang,et al.  Component and antioxidant properties of polysaccharide fractions isolated from Angelica sinensis (OLIV.) DIELS. , 2007, Biological & pharmaceutical bulletin.

[32]  David T. Shima,et al.  Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. , 2007, The American journal of pathology.

[33]  J. Garcia-Arumi,et al.  Photodynamic therapy with intravitreal triamcinolone in predominantly classic choroidal neovascularization: one-year results of a randomized study. , 2006, Ophthalmology.

[34]  G. Shah,et al.  COMBINED PHOTODYNAMIC THERAPY WITH VERTEPORFIN AND INTRAVITREAL BEVACIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION , 2006, Retina.

[35]  P. Elsner,et al.  Assessment of anti‐inflammatory activity of Poria cocos in sodium lauryl sulphate‐induced irritant contact dermatitis , 2006, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[36]  R. Apte,et al.  Macrophages Inhibit Neovascularization in a Murine Model of Age-Related Macular Degeneration , 2006, PLoS medicine.

[37]  G. Peyman,et al.  Applications of liposomes in ophthalmology. , 2005, Survey of ophthalmology.

[38]  T. Peto,et al.  The epidemiology of age-related macular degeneration. , 2004, American journal of ophthalmology.

[39]  G. Ooi,et al.  Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer. , 2003, Respiratory medicine.

[40]  S. Shih,et al.  Nonvascular role for VEGF: VEGFR-1, 2 activity is critical for neural retinal development. , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[41]  K. Lee,et al.  Research and future trends in the pharmaceutical development of medicinal herbs from Chinese medicine , 2000, Public Health Nutrition.

[42]  M. Gillies,et al.  Exudative macular degeneration and intravitreal triamcinolone: 18 month follow up. , 1998, Australian and New Zealand journal of ophthalmology.

[43]  B. Aggarwal,et al.  Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits TNF-induced NF-κB activation, IκB degradation, and expression of cell surface adhesion proteins in human vascular endothelial cells , 1998, Oncogene.

[44]  N. Andrews,et al.  A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. , 1991, Nucleic acids research.

[45]  F. Ferris,et al.  Age-related macular degeneration and blindness due to neovascular maculopathy. , 1984, Archives of ophthalmology.

[46]  H. Kanayama,et al.  A new antitumor polysaccharide from the mycelia of Poria cocos wolf. , 1983, Chemical & pharmaceutical bulletin.

[47]  Y. Kwan,et al.  The angiogenic effects of Angelica sinensis extract on HUVEC in vitro and zebrafish in vivo , 2008, Journal of cellular biochemistry.

[48]  Ivana K. Kim,et al.  The FASEB Journal • Research Communication Endogenous endostatin inhibits choroidal neovascularization , 2022 .