熊果苷通过调节 PCNA/Bax 蛋白对氧化偶氮甲烷诱导的大鼠结肠异常隐窝病灶具有化学保护作用。
Chemoprotective effect of arbutin on azoxymethane-induced aberrant crypt foci in rat colon via modulation of PCNA/Bax protein.
发表日期:2024
作者:
K A Ahmed, S H Shareef, T A Faraj, M A Abdulla, S K Najmaldin, N F S Agha, R K Kheder
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
熊果苷因其抗菌、抗氧化和抗炎特性而被用于传统疗法中,以治疗多种综合症。本研究旨在评估熊果苷对氧化偶氮甲烷 (AOM) 诱导的大鼠结肠异常隐窝病灶 (ACF) 的化学预防作用。设五组大鼠:正常对照组(每周一次皮下注射无菌磷酸盐缓冲盐水,连续两周)和2-5组,每周皮下接种15mg/kg AOM,连续两周。 AOM 对照组和 5-氟尿嘧啶 (5-FU) 对照组每天使用饲管口服 10% 吐温,持续 8 周。治疗组每天喂食30和60 mg/kg熊果苷,持续2个月。 AOM 对照组的 ACF 除了多层细胞外还存在异常细胞核,且不存在杯状细胞。阴性对照组显示球形细胞和位于基底位置的细胞核。组织学检查显示 5-FU 参考组的结肠组织中 AFC 细胞数量减少。与 AOM 对照相比,熊果苷喂养的动物表现出增殖细胞核抗原 (PCNA) 下调和 Bax 蛋白上调。与 AOM 对照组相比,饲喂熊果苷的大鼠结肠组织匀浆中的超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 活性显着增加。总之,熊果苷具有显着降低 ACF、下调 PCNA 蛋白和上调 Bax 蛋白的能力,对结直肠癌具有治疗作用。此外,熊果苷可显着增加 SOD 和 CAT,并降低丙二醛 (MDA) 水平,这可能是由于其抗增殖和抗氧化特性。
Arbutin is utilized in traditional remedies to cure numerous syndromes because of its anti-microbial, antioxidant, and anti-inflammatory properties. This study aimed to evaluate chemopreventive effects of arbutin on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) in rats. Five groups of rats were used: normal control group (rats injected hypodermically with sterile phosphate-buffered saline once per week for two weeks) and groups 2-5, which were subcutaneously inoculated with 15 mg/kg AOM once a week for two weeks. AOM control and 5-fluorouracil (5-FU) control groups were fed 10% Tween orally daily for 8 weeks using a feeding tube. The treated groups were fed 30 and 60 mg/kg arbutin every day for 2 months. ACF from the AOM control group had aberrant nuclei in addition to multilayered cells and an absence of goblet cells. The negative control group displayed spherical cells and nuclei in basal positions. Histological examination revealed a reduced number of AFC cells from colon tissues of the 5-FU reference group. Arbutin-fed animals showed down-regulation of proliferating cell nuclear antigen (PCNA) and up-regulation of Bax protein compared to AOM control. Rats fed with arbutin displayed a significant increase of superoxide dismutase (SOD) and catalase (CAT) activities in colon tissue homogenates compared to the AOM control group. In conclusion, arbutin showed therapeutic effects against colorectal cancer, explained by its ability to significantly decrease ACF, down-regulate PCNA protein, and up-regulate Bax protein. In addition, arbutin significantly increased SOD and CAT, and decreased malondialdehyde (MDA) levels, which might be due to its anti-proliferative and antioxidant properties.