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Curcumin and hesperetin attenuate D-galactose-induced brain senescence in vitro and in vivo

Nutrition Research and Practice 2020년 14권 5호 p.438 ~ 452
이지혜, Kim Yoo-Sun, 김은주, 김예린, 김유리,
소속 상세정보
이지혜 ( Lee Ji-Hye ) - Ewha Womans University Department of Nutritional Science and Food Management
 ( Kim Yoo-Sun ) - Ewha Womans University Department of Nutritional Science and Food Management
김은주 ( Kim Eun-Ju ) - Ewha Womans University Department of Nutritional Science and Food Management
김예린 ( Kim Ye-Rin ) - Ewha Womans University Department of Nutritional Science and Food Management
김유리 ( Kim Yu-Ri ) - Ewha Womans University Department of Nutritional Science and Food Management

Abstract


BACKGROUND/OBJECTIVES: Brain senescence causes cognitive impairment and neurodegeneration. It has also been demonstrated that curcumin (Cur) and hesperetin (Hes), both antioxidant polyphenolic compounds, mediate anti-aging and neuroprotective effects. Therefore, the objective of this study was to investigate whether Cur, Hes, and/or their combination exert anti-aging effects in D-galactose (Dg)-induced aged neuronal cells and rats.

MATERIALS/METHODS: SH-SY5Y cells differentiated in response to retinoic acid were treated with Cur (1 μM), Hes (1 μM), or a combination of both, followed by 300 mM Dg. Neuronal loss was subsequently evaluated by measuring average neurite length and analyzing expression of β-tubulin III, phosphorylated extracellular signal-regulated kinases, and neurofilament heavy polypeptide. Cellular senescence and related proteins, p16 and p21, were also investigated, including their regulation of antioxidant enzymes. In vivo, brain aging was induced by injecting 250 mg/kg body weight (b.w.) Dg. The effects of supplementing this model with 50 mg/kg b.w. Cur, 50 mg/kg b.w. Hes, or a combination of both for 3 months were subsequently evaluated. Brain aging was examined with a step-through passive avoidance test and apoptosis markers were analyzed in brain cortex tissues.

RESULTS: Cur, Hes, and their combination improved neuron length and cellular senescence by decreasing the number of β-gal stained cells, down-regulated expression of p16 and p21, and up-regulated expression of antioxidant enzymes, including superoxide dismutase 1, glutathione peroxidase 1, and catalase. Administration of Cur, Hes, or their combination also tended to ameliorate cognitive impairment and suppress apoptosis in the cerebral cortex by down-regulating Bax and poly (ADP-ribose) polymerase expression and increasing Bcl-2 expression.

CONCLUSIONS: Cur and Hes appear to attenuate Dg-induced brain aging via regulation of antioxidant enzymes and apoptosis. These results suggest that Cur and Hes may mediate neuroprotective effects in the aging process, and further study of these antioxidant polyphenolic compounds is warranted.

키워드

Curcumin; hesperetin; brain; aging; D-galactose

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