Research - Bilberry / Vaccinium myrtillus
Ginkgo biloba Extract and Bilberry Anthocyanins Improve Visual Function in Patients with Normal Tension Glaucoma
Seong Hee Shim,1 Joon Mo Kim,1 Chul Young Choi,1 Chan Yun Kim,2 and Ki Ho Park3,4
1Department of Ophthalmology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
2Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.
3Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.
4Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul, Korea.
Abstract
Ginkgo biloba extract (GBE) and anthocyanins are considered beneficial for various vascular diseases. This study was performed to evaluate the effect of GBE and anthocyanins on visual function in patients with normal tension glaucoma (NTG) based on the vascular theory of mechanisms of glaucomatous optic nerve damage. Retrospective analysis was carried out by a chart review of 332 subjects (209 men and 123 women) who were treated with anthocyanins (n=132), GBE (n=103), or no medication (control, n=97). Humphrey Visual Field (HVF) test, logarithm of the minimal angle of resolution best-corrected visual acuity (logMAR BCVA), intraocular pressure, blood pressure, and fasting blood glucose were determined before and after treatment. Complete ocular and systemic examinations were performed. The mean follow-up duration was 23.82±9.84 (range, 12–59) months; the mean anthocyanin treatment duration was 24.32±10.43 (range, 6–53) months, and the mean GBE treatment duration was 23.81±10.36 months (range, 6–59) months. After anthocyanin treatment, the mean BCVA for all eyes improved from 0.16 (±0.34) to 0.11 (±0.18) logMAR units (P=.008), and HVF mean deviation improved from −6.44 (±7.05) to −5.34 (±6.42) (P=.001). After GBE treatment, HVF mean deviation improved from −5.25 (±6.13) to −4.31 (±5.60) (P=.002). A generalized linear model demonstrated that the final BCVA was not affected by demographic differences among the groups. These results suggest that anthocyanins and GBE may be helpful in improving visual function in some individuals with NTG.
Source : Journal of Medicinal Food
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Vaccinium myrtillus (Bilberry) Extracts Reduce Angiogenesis In Vitro and In Vivo
Nozomu Matsunaga1, Yuichi Chikaraishi1, Masamitsu Shimazawa1, Shigeru Yokota2 and Hideaki Hara1
1Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585 and 2Wakasa Seikatsu Co. Ltd, 22 Naginataboko-cho, Shijo-Karasuma, Shimogyo-ku, Kyoto 600-8008, Japan
Vaccinium myrtillus (Bilberry) extracts (VME) were tested foreffects on angiogenesis in vitro and in vivo. VME (0.3–30µg ml–1) and GM6001 (0.1–100 µM; a matrixmetalloproteinase inhibitor) concentration-dependently inhibitedboth tube formation and migration of human umbilical vein endothelialcells (HUVECs) induced by vascular endothelial growth factor-A(VEGF-A). In addition, VME inhibited VEGF-A-induced proliferationof HUVECs. VME inhibited VEGF-A-induced phosphorylations ofextracellular signal-regulated kinase 1/2 (ERK 1/2) and serine/threonineprotein kinase family protein kinase B (Akt), but not that ofphospholipase C (PLC). In an in vivo assay, intravitreal administrationof VME inhibited the formation of neovascular tufts during oxygen-inducedretinopathy in mice. Thus, VME inhibited angiogenesis both invitro and in vivo, presumably by inhibiting the phosphorylationsof ERK 1/2 and Akt. These findings indicate that VME may beeffective against retinal diseases involving angiogenesis, providingit can reach the retina after its administration. Further investigationswill be needed to clarify the major angiogenesis-modulatingconstituent(s) of VME.
Introduction
Angiogenesis is the process by which blood vessels are formedfrom pre-existing ones. In adults, physiological angiogenesisis observed only at restricted sites, such as the endometriumand ovarian follicle, and it is normally transient. However,abnormal angiogenesis causes many ocular diseases, such as diabeticretinopathy (1), age-related macular degeneration (2) and neovascularglaucoma (3). Previous studies have revealed that angiogenesisis explicitly increased by several growth factors, such as VEGF(4), basic fibroblast growth factor (5) and platelet-derivedgrowth factor (6).
Galardy et al. (7) reported that a carcinoma extract implantedin the rat cornea can be used to stimulate angiogenesis fromthe vessels of the limbus, and also that continuous administrationof GM6001, a broad-spectrum matrix metalloproteinase (MMP) inhibitor,reduced both the vessel number and vessel area. More recently,Koike et al. (8) found that GM6001 decreases tubulogenesis inmicrovascular endothelial cells from young humans. These findingssuggest that MMP plays a pivotal role in angiogenesis, and thatMMP inhibitors may be effective angiostatic agents.
Vaccinium myrtillus (Bilberry), a member of the Ericaceous family,can be found in the mountains and forests of Europe and NorthAmerica. Vaccinium myrtillus extracts (VME) containing 15 differentanthocyanins (9,10) have been shown to possess potent antioxidantproperties (9), stabilize collagen fibers and promote collagenbiosynthesis (11) and inhibit platelet aggregation (12). Animalstudies have demonstrated VME to be of benefit in improvingvascular tone, blood flow and vasoprotection (13,14). When administeredto healthy subjects or to patients with visual disorders, VME(either alone or in combination with β-carotene and vitaminE) induces a significant improvement in night vision, a quickeradaptation to darkness and a more rapid restoration of visualacuity following exposure to a flash of bright light (11). Hence,bilberries (or VME) have been utilized as a popular edible aidor supplement for asthenopia and improved visual function. Furthermore,an extract of V. myrtillus fruits (a low concentration of anthocyanosidesin a highly purified extract) has been reported to induce significantimprovements in ophthalmoscopic and angiographic images in diabeticor hypertensive patients (15), but it has remained unclear whetherit inhibits angiogenesis.
Roy et al. (16) noted that in the human keratinocytes cell-lineHaCaT, VEGF expression is decreased by a variety of berry seeds,such as bilberry, raspberry, strawberry, blueberry and optiberry(a blend of wild blueberry, strawberry, cranberry and raspberryseeds, and elderberry and wild bilberry samples). They alsoobserved that optiberry inhibits the tube formation among humanmicrovascular endothelial cells induced by basement proteinsfrom mouse tumors. These findings suggest that certain berryseeds have inhibitory actions against angiogenesis, although,the precise mechanism remains unclear. We therefore examinedthe in vitro effects of VME on the angiogenesis (tube formation,and cell proliferation and migration) and phosphorylation ofextracellular signal-regulated kinase 1/2 (ERK 1/2), phospholipaseC (PLC) and serine/threonine protein kinase family protein kinaseB (Akt) that are induced by vascular endothelial growth factor-A(VEGF-A). We also evaluated the in vivo effects of VME on oxygen-induced retinopathy in mice.
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