Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2018 | Research article

Dendrobium nobile Lindley and its bibenzyl component moscatilin are able to protect retinal cells from ischemia/hypoxia by dowregulating placental growth factor and upregulating Norrie disease protein

Authors: Wen-Haur Chao, Ming-Yi Lai, Hwai-Tzong Pan, Huei-Wen Shiu, Mi-Mi Chen, Hsiao-Ming Chao

Published in: BMC Complementary Medicine and Therapies | Issue 1/2018

Abstract

Background

Presumably, progression of developmental retinal vascular disorders is mainly driven by persistent ischemia/hypoxia. An investigation into vision-threatening retinal ischemia remains important. Our aim was to evaluate, in relation to retinal ischemia, protective effects and mechanisms of Dendrobium nobile Lindley (DNL) and its bibenzyl component moscatilin. The therapeutic mechanisms included evaluations of levels of placental growth factor (PLGF) and Norrie disease protein (NDP).

Methods

An oxygen glucose deprivation (OGD) model involved cells cultured in DMEM containing 1% O₂, 94% N₂ and 0 g/L glucose. High intraocular pressure (HIOP)-induced retinal ischemia was created by increasing IOP to 120 mmHg for 60 min in Wistar rats. The methods included electroretinogram (ERG), histopathology, MTT assay and biochemistry.

Results

When compared with cells cultured in DMEM containing DMSO (DMSO+DMEM), cells subjected to OGD and pre-administrated with DMSO (DMSO+OGD) showed a significant reduction in the cell viability and NDP expression. Moreover, cells that received OGD and 1 h pre-administration of 0.1 μM moscatilin (Pre-OGD Mos 0.1 μM) showed a significant counteraction of the OGD-induced decreased cell viability. Furthermore, compared with the DMSO+OGD group (44.54 ± 3.15%), there was significant elevated NDP levels in the Pre-OGD Mos 0.1 μM group (108.38 ± 29.33%). Additionally, there were significant ischemic alterations, namely reduced ERG b-wave, less numerous retinal ganglion cells, decreased inner retinal thickness, and reduced/enhanced amacrine’s ChAT/Müller’s GFAP or vimentin immunolabelings. Moreover, there were significantly increased protein levels of HIF-1α, VEGF, PKM2, RBP2 and, particularly, PLGF (pg/ml; Sham vs. Vehicle: 15.11 ± 1.58 vs. 39.53 ± 5.25). These ischemic effects were significantly altered when 1.0 g/Kg/day DNL (DNL1.0 + I/R or I/R+ DNL1.0) was applied before and/or after ischemia, but not vehicle (Vehicle+I/R). Of novelty and significance, the DNL1.0 action mechanism appears to be similar to that of the anti-PLGF Eylea [PLGF (pg/ml); DNL1.0 vs. Eylea+I/R: 19.93 ± 2.24 vs. 6.44 ± 0.60].

Conclusions

DNL and moscatilin are able to protect against retinal ischemic/hypoxic changes respectively by downregulating PLGF and upregulating NDP. Progression of developmental retinal vascular disorders such as Norrie disease due to persistent ischemia/hypoxia might be thus prevented.

Available only for authorised users

Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, et al. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell. 2004;116(6):883–95. 15035989CrossRefPubMed

Nikopoulos K, Venselaar H, Collin RW, Riveiro-Alvarez R, Boonstra FN, Hooymans JM, et al. Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP. Hum Mutat. 2010;31(6):656–66. https://doi.org/10.1002/humu.21250.CrossRefPubMed

Wu JH, Liu JH, Ko YC, Wang CT, Chung YC, Chu KC, et al. Haploinsufficiency of RCBTB1 is associated with coats disease and familial exudative vitreoretinopathy. Hum Mol Genet. 2016;25(8):1637–47. https://doi.org/10.1093/hmg/ddw041.CrossRefPubMed

Wang Y, Rattner A, Zhou Y, Williams J, Smallwood PM, Nathans J. Norrin/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity. Cell. 2012;151:1332–44. https://doi.org/10.1016/j.cell.2012.10.042.CrossRefPubMedPubMedCentral

Luhmann UFO, Lin J, Acar N, Lammel S, Feil S, Grimm C, et al. Role of the Norrie disease pseudoglioma gene in sprouting angiogenesis during development of the retinal vasculature. Invest Ophthalmol Vis Sci. 2005;46:3372–82. https://doi.org/10.1167/iovs.05-0174.CrossRefPubMed

Chao HM, Chuang MJ, Liu JH, Liu XQ, Ho LK, Pan WH, et al. Baicalein protects against retinal ischemia by antioxidation, antiapoptosis, downregulation of HIF-1α, VEGF, and MMP-9 and upregulation of HO-1. J Ocul Pharmacol Ther. 2013;29(6):539–49. https://doi.org/10.1089/jop.2010.0063. CrossRefPubMedPubMedCentral

Beck SC, Feng Y, Sothilingam V, Garrido MG, Tanimoto N, Acar N, et al. Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease. PLoS One. 2017;12(6):e0178753. https://doi.org/10.1371/journal.pone.0178753.CrossRefPubMedPubMedCentral

Tan S, Geng S, Liu JH, Pan WH, Wang LX, Liu HK, et al. Xue-Fu-Zhu-Yu decoction protects rats against retinal ischemia by downregulation of HIF-1α and VEGF via inhibition of RBP2 and PKM2. BMC Complement Altern Med. 2017;17(1):365. https://doi.org/10.1186/s12906-017-1857-2. CrossRefPubMedPubMedCentral

Wurm A, Iandiev I, Uhlmann S, Wiedemann P, Reichenbach A, Bringmann A, et al. Effects of ischemia-reperfusion on physiological properties of Müller glial cells in the porcine retina. Invest Ophthalmol Vis Sci. 2011;52(6):3360–7. https://doi.org/10.1167/iovs.10-6901.CrossRefPubMed

10.

Liu JH, Wann H, Chen MM, Pan WH, Chen YC, Liu CM, et al. Baicalein significantly protects human retinal pigment epithelium cells against H₂O₂-induced oxidative stress by scavenging reactive oxygen species and downregulating the expression of matrix metalloproteinase-9 and vascular endothelial growth factor. J Ocul Pharmacol Ther. 2010;26(5):421–9. https://doi.org/10.1089/jop.2010.0063.CrossRefPubMed

11.

Luo W, Hu H, Chang R, Zhong J, Knabel M, O'Meally R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell. 2011;145(5):732–44. https://doi.org/10.1016/j.cell.2011.03.054.CrossRefPubMedPubMedCentral

12.

Qi L, Zhu F, Li SH, Si LB, Hu LK, Tian H. Retinoblastoma binding protein 2 (RBP2) promotes HIF-1α-VEGF-induced angiogenesis of non-small cell lung cancer via the Akt pathway. PLoS One. 2014;9(8):e106032. https://doi.org/10.1371/%20journal.pone.0106032.CrossRefPubMedPubMedCentral

13.

Mesquita J, Castro-de-Sousa JP, Vaz-Pereira S, Neves A, Passarinha LA, Tomaz CT. Vascular endothelial growth factors and placental growth factor in retinal vasculopathies: current research and future perspectives. Cytokine Growth Factor Rev. 2018;39:102–15. https://doi.org/10.1016/j.cytogfr.2017.11.005.CrossRefPubMed

14.

Lam Y, Ng TB, Yao RM, Shi J, Xu K, Sze SC, et al. Evaluation of chemical constituents and important mechanism of pharmacological biology in dendrobium plants. Evid Based Complement Alternat Med. 2015;2015:841752. https://doi.org/10.1155/2015/841752. CrossRefPubMedPubMedCentral

15.

Liu YN, Pan SL, Peng CY, Huang DY, Guh JH, Chen CC, et al. Moscatilin repressed lipopolysaccharide-induced HIF-1alpha accumulation and NF-kappaB activation in murine RAW264.7 cells. Shock. 2010;33(1):70–5. https://doi.org/10.1097/shk.0b013e3181a7ff4a.CrossRefPubMed

16.

Tsai AC, Pan SL, Liao CH, Guh JH, Wang SW, Sun HL, et al. Moscatilin, a bibenzyl derivative from the India orchid Dendrobrium loddigesii, suppresses tumor angiogenesis and growth in vitro and in vivo. Cancer Lett. 2010;292(2):163–70. https://doi.org/10.1016/j.canlet.2009.11.020.CrossRefPubMed

17.

Chen CA, Chen CC, Shen CC, Chang HH, Chen YJ. Moscatilin induces apoptosis and mitotic catastrophe in human esophageal cancer cells. J Med Food. 2013;16(10):869–77. https://doi.org/10.1089/jmf.2012.2617.CrossRefPubMedPubMedCentral

18.

Li Y, Li F, Gong Q, Wu Q, Shi J. Inhibitory effects of dendrobium alkaloids on memory impairment induced lipopolysaccharide in rats. Planta Med. 2011;77(2):117–21. https://doi.org/10.1055/s-0030-1250235.CrossRefPubMed

19.

Sun J, Zhang F, Yang M, Zhang J, Chen L, Zhan R, et al. Isolation of α-glucosidase inhibitors including a new flavonol glycoside from Dendrobium devonianum. Nat Prod Res. 2014;28(21):1900–5. https://doi.org/10.1080/14786419.2014.955495.CrossRefPubMed

20.

Yoon MY, Hwang JH, Park JH, Lee MR, Kim HJ, Park E, et al. Neuroprotective effects of SG-168 against oxidative stress-induced apoptosis in PC12 cells. J Med Food. 2011;14(1–2):120–7. https://doi.org/10.1089/jmf.2010.1027.CrossRefPubMed

21.

Pan LH, Li XF, Wang MN, Zha XQ, Yang XF, Liu ZJ, et al. Comparison of hypoglycemic and antioxidative effects of polysaccharides from four different Dendrobium species. Int J Biol Macromol. 2014;64:420–7. https://doi.org/10.1016/j.ijbiomac.2013.12.024.CrossRefPubMed

22.

Gong CY, Lu B, Yang L, Wang L, Ji LL. Bibenzyl from Dendrobium inhibits angiogenesis and its underlying mechanism. Yao Xue Xue Bao. 2013;48(3):337–42. PMID: 23724644PubMed

23.

Kowitdamrong A, Chanvorachote P, Sritularak B, Pongrakhananon V. Moscatilin inhibits lung cancer cell motility and invasion via suppression of endogenous reactive oxygen species. Biomed Res Int. 2013;2013:765894. https://doi.org/10.1155/2013/765894.CrossRefPubMedPubMedCentral

24.

Van Bergen NJ, Wood JP, Chidlow G, Trounce IA, Casson RJ, Ju WK, Weinreb RN, Crowston JG. Recharacterization of the RGC-5 retinal ganglion cell line. Invest Ophthalmol Vis Sci. 2009;50(9):4267–72. https://doi.org/10.1167/iovs.09-3484.CrossRefPubMed

25.

Tasca CI, Dal-Cim T, Cimarosti H. In vitro oxygen-glucose deprivation to study ischemic cell death. Methods Mol Biol. 2015;1254:197–210. https://doi.org/10.1007/978-1-4939-2152-2_15.CrossRefPubMed

26.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1–2):55–63. https://doi.org/10.1016/0022-1759(83)90303-4.CrossRefPubMed

27.

Engvall E, Perlmann P. Enzyme-linked immunosorbent (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry. 1971;8:871–4. PMID: 5135623CrossRefPubMed

28.

Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, et al. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150:76–85. PMID: 3843705CrossRefPubMed

29.

Ho C, Chen C. Moscatilin from the orchid Dendrobrium loddigesii is a potential anticancer agent. Cancer Investig. 2003;21(5):729–36. https://doi.org/10.1081/CNV-120023771.CrossRef

30.

Drenser KA. Wnt signaling pathway in retinal vascularization. Eye Brain. 2016;8:141–6. https://doi.org/10.2147/EB.S94452.CrossRefPubMedPubMedCentral

31.

Braunger BM, Ohlmann A, Koch M, Tanimoto N, Volz C, Yang Y, et al. Constitutive overexpression of Norrin activates Wnt/β-catenin and endothelin-2 signaling to protect photoreceptors from light damage. Neurobiol Dis. 2013;50:1–12. https://doi.org/10.1016/j.nbd.2012.09.008.CrossRefPubMed

32.

Dailey WA, Drenser KA, Wong SC, Cheng M, Vercellone J, Roumayah KK, et al. Norrin treatment improves ganglion cell survival in an oxygen-induced retinopathy model of retinal ischemia. Exp Eye Res. 2017;164:129–38. https://doi.org/10.1016/j.exer.2017.08.012.CrossRefPubMed

33.

Miyazawa M, Shimamura H, Nakamura S, Sugiura W, Kosaka H, Kameoka H. Moscatilin from Dendrobium nobile, a naturally occurring bibenzyl compound with potential antimutagenic activity. J Agric Food Chem. 1999;47(5):2163–7. PMID: 10552513CrossRefPubMed

Title: Dendrobium nobile Lindley and its bibenzyl component moscatilin are able to protect retinal cells from ischemia/hypoxia by dowregulating placental growth factor and upregulating Norrie disease protein
Authors: Wen-Haur Chao
Ming-Yi Lai
Hwai-Tzong Pan
Huei-Wen Shiu
Mi-Mi Chen
Hsiao-Ming Chao
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2018
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-018-2256-z

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Dendrobium nobile Lindley and its bibenzyl component moscatilin are able to protect retinal cells from ischemia/hypoxia by dowregulating placental growth factor and upregulating Norrie disease protein

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2018

Identification of antitumoral agents against human pancreatic cancer cells from Asteraceae and Lamiaceae plant extracts

Emotional release and physical symptom improvement: a qualitative analysis of self-reported outcomes and mechanisms in patients treated with neural therapy

Profile of osteopathic practice in Spain: results from a standardized data collection study

Extract of Stellerachamaejasme L(ESC) inhibits growth and metastasis of human hepatocellular carcinoma via regulating microRNA expression

(R)-α-Lipoic acid inhibits fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro

Sheng Jiang San, a traditional multi-herb formulation, exerts anti-influenza effects in vitro and in vivo via neuraminidase inhibition and immune regulation