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甜橙 var. 酸橙 Engl. 抑制 3T3-L1 细胞和秀丽隐杆线虫中的脂质积累,并预防高脂肪饮食喂养的小鼠肥胖。

Citrus aurantium L. var. amara Engl. inhibited lipid accumulation in 3T3-L1 cells and Caenorhabditis elegans and prevented obesity in high-fat diet-fed mice.

机构信息

College of Food and Bioengineering, South China University of Technology, Guangzhou, 510640, China.

College of Food and Bioengineering, South China University of Technology, Guangzhou, 510640, China.

出版信息

Pharmacol Res. 2019 Sep;147:104347. doi: 10.1016/j.phrs.2019.104347. Epub 2019 Jul 14.

DOI:10.1016/j.phrs.2019.104347
PMID:31315066
Abstract

Natural products with anti-obesity effects and few side effects have attracted great attention recently. Citrus aurantium L. var. amara Engl. (CAVA) is popularly consumed as an edible and medicinal resource in China. However, its anti-obesity effects were poorly understood. The anti-obesity effects of CAVA extracts were systematically evaluated using 3T3-L1 cells, Caenorhabditis elegans (C. elegans) and high fat diet (HFD)-fed mice. Flavonoid-rich (EA) extracts with neohesperidin, hesperidin and naringin comprising 32.15%, were isolated from CAVA. EA extracts treatment significantly inhibited differentiation of 3T3-L1 preadipocytes by modulating lipid metabolism-related mediators. EA extracts supplementation also inhibited antioxidant responses in C. elegans by decreasing reactive oxygen species generation and malonaldehyde value, and increasing superoxide dismutase content. EA extracts feeding markedly decreased triglyceride (TG) content, and affected expression of genes involved in lipid and glucose metabolism in wild type C. elegans. TG content in mdt-15 (XA7702) mutants was not decreased by EA extracts administration, suggesting that EA extracts treatment might inhibit lipid accumulation in C. elegans dependent on mdt-15. EA extracts intervention further reduced body weight gain and modulated plasma biochemical parameters in HFD-fed mice. EA extracts treatment prevented HFD-induced epididymal adipose hypertrophy, liver oxidative injuries and steatosis. EA extracts administration also strongly prevented HFD-induced reduction of gut microbial diversity, decreased the Firmicutes-to-Bacteroidetes ratio and the Erysipelotrichaceae abundance, and enhanced the Bifidobacteriace abundance in HFD-fed mice. EA extracts from blossoms of CAVA were excellent antiobesogenic candidates that acted through multiple mechanisms that acted simultaneously.

摘要

具有减肥效果且副作用小的天然产物最近受到了极大关注。在中国,酸橙(Citrus aurantium L. var. amara Engl.)作为一种食用和药用资源被广泛食用。然而,其减肥效果尚未被充分了解。本研究采用 3T3-L1 细胞、秀丽隐杆线虫(Caenorhabditis elegans)和高脂饮食(high fat diet,HFD)喂养小鼠系统评价酸橙提取物的减肥作用。从酸橙中分离得到富含黄酮类化合物(flavonoid-rich,EA)的提取物,其中包含新橙皮苷、橙皮苷和柚皮苷,分别占 32.15%。EA 提取物处理可通过调节脂代谢相关介质显著抑制 3T3-L1 前体脂肪细胞的分化。EA 提取物补充还可通过减少活性氧(reactive oxygen species,ROS)生成和丙二醛(malonaldehyde value,MDA)值以及增加超氧化物歧化酶(superoxide dismutase,SOD)含量抑制秀丽隐杆线虫的抗氧化反应。EA 提取物喂养显著降低了野生型秀丽隐杆线虫的甘油三酯(triglyceride,TG)含量,并影响了脂质和葡萄糖代谢相关基因的表达。然而,在 mdt-15(XA7702)突变体中,EA 提取物的添加并不能降低 TG 含量,表明 EA 提取物处理可能依赖于 mdt-15 抑制秀丽隐杆线虫的脂质积累。EA 提取物干预还进一步降低了 HFD 喂养小鼠的体重增加并调节了其血浆生化参数。EA 提取物处理可防止 HFD 诱导的附睾脂肪肥大、肝脏氧化损伤和脂肪变性。EA 提取物给药还可强烈防止 HFD 诱导的肠道微生物多样性降低、厚壁菌门(Firmicutes)/拟杆菌门(Bacteroidetes)比值降低和红螺菌科(Erysipelotrichaceae)丰度降低,并增加 HFD 喂养小鼠中的双歧杆菌科(Bifidobacteriaceae)丰度。酸橙花 EA 提取物是极好的抗肥胖候选物,可通过多种同时作用的机制发挥作用。

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