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2019000007-20190152.pdf
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ヘスペレチン誘導体の老眼進行遅延効果および白内障発症予防効果の解明
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ヘスペレチン ユウドウタイ ノ ロウガン シンコウ チエン コウカ オヨビ ハクナイショウ ハッショウ ヨボウ コウカ ノ カイメイ
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Hesuperechin yūdōtai no rōgan shinkō chien kōka oyobi hakunaishō hasshō yobō kōka no kaimei
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Effect of hesperetin derivatives on the development of cataracts and presbyopia.
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中澤, 洋介
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ナカザワ, ヨウスケ
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Nakazawa, Yosuke
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慶應義塾大学薬学部専任講師
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Research team head
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慶應義塾大学
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ケイオウ ギジュク ダイガク
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Keiō gijuku daigaku
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2020
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学事振興資金研究成果実績報告書
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2019
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研究代表者らは、みかんの果皮に豊富に含まれている天然型フラバノンであるヘスペリジンに着目し、その白内障および老眼予防効果を検討したものである。
白内障は、水晶体が白濁し視機能が大きく低下する疾患である。高齢者に頻発する眼疾患であり、80歳以上でほぼ100%の人に発症すると言われている。視機能の低下に伴い、運動行動意欲の低下を引き遅し、ひいては生活の質(Quality of Life)を大きく低下させ、社会問題にもなっている。老眼もまた、頻発する眼疾患であり、早い人で40歳代で発症する。本採択研究は、ヘスペリジンおよびその誘導体をラットおよびマウスに投与し、検討した。
具体的には、亜セレン酸ナトリウムを13日齢ラットに投与し白内障モデル動物を作成した。そのラットに胃ゾンデ法あるいは自由引水により、ヘスペリジンを経口摂取させ、一定期間後の水晶体弾性度、水晶体抗酸化物質の濃度と活性を測定した。
その結果、α‑glucosyl hesperidin の処理により、白内障の進行が有意に抑制されることが明らかとなった。また水晶体の抗酸化物質であるグルタチオンやアスコルビン酸の濃度の低下抑制がみとめられた。さらにin vitroの検討より、ヘスペリジン誘導体が水晶体上皮細胞のアポトーシスを抑制することがあきらかとなり、これが抗白内障効果へ繋がる可能性が示唆された。
Hesperetin is a natural flavonoid with robust antioxidant properties. Our previous study reported that hesperetin can prevent cataract formation. However, an important consideration regarding hesperetin consumption is the limited bioavailability due to its poor solubility. The present study investigated the anti‑cataract effects of α‑glucosyl hesperidin in vivo and in vitro using a selenite‑induced cataract model.
Cataracts refers to a clouding of the lens of the eye, which affect vision and remain a major cause of blindness in the world. In this study, we determined whether anti‑cataract properties of these derivatives could be altered by linking fatty acids. SD rats (age, 13 days) were orally administered PBS or α‑glucosyl hesperidin on days 0, 1 and 2. Sodium selenite was subcutaneously administered to the rats 4 h after the first oral administration on day 0. Antioxidant levels in the lens and blood were measured on day 6. In vitro, human lens epithelial cells were treated with sodium selenite and/or hesperetin for 24 h and analyzed for apoptosis markers using sub‑G1 population and Annexin V‑FITC/propidium iodide staining and DNA ladder formation.
As the result, α‑glucosyl hesperidin treatment significantly reduced the severity of selenite‑induced cataract. The level of antioxidants was significantly reduced in the selenite‑treated rats compared with in the controls; however, they were normalized with α‑glucosyl hesperidin treatment. In vitro, hesperetin could significantly reduce the number of cells undergoing apoptosis induced by sodium selenite in human lens epithelial cell lines.
Overall, oral consumption of α‑glucosyl hesperidin could delay the onset of selenite‑induced cataract, at least in part by modulating the selenite‑induced cell death in lens epithelial cells.
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