Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education; Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, P.R. China.
Key Laboratory of Tropical Translational Medicine of Ministry of Education; Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, College of Pharmacy, Hainan Medical University, Haikou 571199, P. R. China.
Food Funct. 2022 Aug 1;13(15):8254-8273. doi: 10.1039/d2fo00595f.
Oxidative stress interferes with blood glucose homeostasis, leading to insulin resistance (IR) and hyperglycemia, which eventually induce type 2 diabetes (T2DM). Fermented noni ( L.) fruit juice (FNJ) is a traditional folk medicine in Polynesia as well as a functional food supplement with a variety of health benefits. In this study, the efficacy and mechanism of FNJ in improving oxidative stress and IR were investigated under the synergistic effect of Nrf2/ARE pathway and gut flora and . , insulin resistant HepG2 cells were established with 50 mM high glucose, and 25 μM rosiglitazone (ROSI) was used as a positive control. , male C57BLKS mice in the CON group were fed a normal diet and C57BLKS/J-db/db (db/db) mice were treated with 10 mg kg d ROSI and 6.5 and 13 mL kg d FNJ for 8 weeks, respectively. The results showed that 3-5% FNJ markedly improved IR by increasing glucose uptake and consumption and ameliorated oxidative stress up-regulating the expression of related antioxidant enzymes such as SOD and GPx and attenuating ROS and MDA in IR-HepG2 cells. , db/db mice exhibited hyperglycemia, hyperinsulinemia, and oxidative stress, whereas FNJ significantly inverted those conditions. Moreover, FNJ supplementation notably increased the gut microbiota diversity of T2DM mice and remodeled the gut microbial composition to suppress microbial disorder. Specifically, FNJ increased the ratio of F/B and lowered the Proteobacteria abundance at the phylum level. The db/db mice were enriched in Enterobacteriaceae, Klebsiella, and Klebsiella-pneumonia, while FNJ feeding significantly up-regulated Rikenellaceae. In addition, western blotting and qPCR experiments showed that FNJ promoted the expression of Nrf2, HO-1, IRS1, PI3K, AKT, and GLUT4 and reduced the JNK level both and . These results confirmed that FNJ had a protective effect on oxidative stress and IR by activating Nrf2/ARE signaling pathway and regulating gut flora in db/db mice and IR-HepG2 cells.
氧化应激干扰血糖稳态，导致胰岛素抵抗（IR）和高血糖，最终诱发 2 型糖尿病（T2DM）。发酵诺丽（L.）果浆（FNJ）是波利尼西亚的传统民间药物，也是一种具有多种健康益处的功能性食品补充剂。在这项研究中，研究了 FNJ 在 Nrf2/ARE 通路和肠道菌群协同作用下改善氧化应激和 IR 的功效和机制。使用 50mM 高葡萄糖建立胰岛素抵抗 HepG2 细胞，25μM 罗格列酮（ROSI）作为阳性对照。在 CON 组中，雄性 C57BLKS 小鼠喂食正常饮食，C57BLKS/J-db/db（db/db）小鼠分别用 10mgkg d ROSI 和 6.5 和 13mLkg d FNJ 治疗 8 周。结果表明，3-5%FNJ 可通过增加葡萄糖摄取和消耗显著改善 IR，并改善氧化应激，上调相关抗氧化酶如 SOD 和 GPx 的表达，减轻 IR-HepG2 细胞中的 ROS 和 MDA。在 db/db 小鼠中，FNJ 显著降低了空腹血糖、胰岛素、胰岛素抵抗指数和 MDA，同时增加了 SOD、GPx 和 GSH 的活性。db/db 小鼠表现出高血糖、高胰岛素血症和氧化应激，而 FNJ 显著逆转了这些情况。此外，FNJ 补充显著增加了 T2DM 小鼠的肠道微生物多样性，并重塑了肠道微生物组成，以抑制微生物紊乱。具体而言，FNJ 增加了 F/B 的比例，并降低了门水平的变形菌门丰度。db/db 小鼠富集了肠杆菌科、克雷伯氏菌和肺炎克雷伯菌，而 FNJ 喂养显著上调了理研菌科。此外，western blotting 和 qPCR 实验表明，FNJ 促进了 Nrf2、HO-1、IRS1、PI3K、AKT 和 GLUT4 的表达，并降低了 JNK 水平。这些结果证实，FNJ 通过激活 Nrf2/ARE 信号通路和调节 db/db 小鼠和 IR-HepG2 细胞中的肠道菌群，对氧化应激和 IR 具有保护作用。
