出 处:《日用化学工业(中英文)》2024年第3期313-319,共7页China Surfactant Detergent & Cosmetics
基 金:湖北省教育厅科学研究项目(B2021262);荆楚理工学院校级科研项目(YD202106)。
摘 要:考察异橙黄酮(Isosinensetin,ISO)经皮给药对D-半乳糖(D-gal)诱导的皮肤衰老小鼠的抗衰老和抗氧化功效。将小鼠分为6组(n=12):分别为C组、D-gal组、D-gal+L-ISO组、D-gal+M-ISO组、D-gal+H-ISO组和D-gal+H-ISO+ML385组。在小鼠背部连续6周皮下注射1 g/(kg·d)的D-gal建立皮肤衰老小鼠模型。D-gal注射当天开始,C组和D-gal组小鼠背部脱毛区域涂抹雪花膏,D-gal+L-ISO组、D-gal+M-ISO组和D-gal+H-ISO组小鼠分别涂抹50,100和200 mg/kg的异橙黄酮乳膏。D-gal+H-ISO+ML385组小鼠涂抹200 mg/kg的异橙黄酮乳膏,并腹腔注射30 mg/(kg·d)核因子E2相关因子2(Nrf2)抑制剂ML385。涂抹量为2 mg/cm^(2)。经皮给药6周后,检测小鼠的体重、皮肤含水量、皮肤抗氧化指标、羟脯氨酸(HYP)和透明质酸(HA)水平。采用苏木素伊红(HE)染色观察皮肤形态。采用RT-qPCR检测皮肤中COL1A1、COL3A1、基质金属蛋白酶(MMP)-1和MMP-3的转录水平。采用Western blotting检测皮肤中Nrf2(细胞核)、Kelch样ECH相关蛋白1(Keap1)和血红素加氧酶-1(HO-1)的蛋白水平。结果显示,3个剂量的异橙黄酮经皮给药均升高了皮肤衰老小鼠的皮肤含水量,改善了皮肤形态,升高了超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)水平,降低了丙二醛(MDA)水平,升高了HYP和HA水平,升高了COL1A1和COL3A1转录水平,降低了MMP-1和MMP-3转录水平,升高了Nrf2(细胞核)和HO-1蛋白水平,降低了Keap1蛋白水平(P<0.05)。ML385减弱了异橙黄酮的抗衰老及抗氧化功效(P<0.05)。总之,异橙黄酮经皮给药通过激活Nrf2通路提高D-gal诱导的皮肤衰老小鼠的抗衰老和抗氧化能力。The study aimed to investigate the anti-aging and antioxidant effects of isosinensetin(ISO)on skin aging mice induced by D-galactose(D-gal).The mice were divided into 6 groups(n=12):C group,D-gal group,D-gal+L-ISO group,D-gal+M-ISO group,D-gal+H-ISO group and D-gal+H-ISO+ML385 group.The skin aging mouse model was established by subcutaneous injection of D-gal of 1 g/(kg·d)into the back of mice for 6 weeks.From the day of D-gal injection,mice in C group and D-gal group were applied with snow cream on their back depilation area,while mice in D-gal+L-ISO group,D-gal+M-ISO group and D-gal+H-ISO group were applied with 50,100 and 200 mg/kg isosinensetin cream,respectively.The mice in D-gal+H-ISO+ML385 group were applied with 200 mg/kg isosinensetin cream and intraperitoneally injected with 30 mg/(kg·d)nuclear factor E2 related factor 2(Nrf2)inhibitor ML385.The application amount was 2 mg/cm^(2).After 6 weeks of transdermal administration,the body weight,skin water content,skin antioxidant index,hydroxyproline(HYP)and hyaluronic acid(HA)levels were measured.The skin morphology was observed by HE staining.The transcriptional levels of COL1A1,COL3A1,matrix metalloproteinase(MMP)-1 and MMP-3 in skin were detected by RT-qPCR.The protein levels of Nrf2(nucleus),Kelch-like ECH associated Protein 1(Keap1)and heme oxygenase-1(HO-1)in skin were detected by Western blotting.The results show that all three doses of isosinensetin increases skin water content,improves skin morphology,increases superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)levels,decreases malondialdehyde(MDA)levels,increases HYP and HA levels,increases COL1A1 and COL3A1 mRNA levels,decreases MMP-1 and MMP-3 mRNA levels,increases Nrf2(nucleus)and HO-1 protein levels,and decreases Keap1 protein levels in skin aging mice(P<0.05).ML385 attenuates the anti-aging and antioxidant effects of isosinensetin(P<0.05).In short,transdermal administration of isosinensetin can improve the anti-aging and antioxidant ability of D-gal-induced skin aging m
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