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阐明肠道微生物群驱动的串扰:在高脂血症小鼠模型中,洛贝林在协调胆固醇稳态和抗炎途径中的机制相互作用。

Elucidating the gut microbiota-driven crosstalk: mechanistic interplay of lobetyolin in coordinating cholesterol homeostasis and anti-inflammatory pathways in hyperlipidemic mice models.

作者信息

Duan Guofeng, Zhang Yuning, Liu Siyuan, Wang Siqi, Liu Jinjia, Li Lijuan, Lai Lina

机构信息

School of Pharmacy, Changzhi Medical College, Changzhi, Shanxi, China.

Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, Changzhi Medical College, Changzhi, Shanxi, China.

出版信息

Front Microbiol. 2025 Aug 19;16:1625211. doi: 10.3389/fmicb.2025.1625211. eCollection 2025.

DOI:10.3389/fmicb.2025.1625211
PMID:40904678
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12402901/
Abstract

BACKGROUND

Hyperlipidemia is a prevalent metabolic disorder closely associated with gut microbiota imbalance. In recent years, traditional Chinese medicine has demonstrated distinct advantages in the regulation of the gut microbiota and enhancement of metabolic health. This study aimed to elucidate the molecular processes by which lobetyolin modifies the gut microbiota to improve intestinal inflammation and lipid metabolism in hyperlipidemic mice.

METHODS

Forty female KM mice were randomly allocated to four groups: control, model, LBT1, and LBT2. Mice in the LBT1 and LBT2 groups received intraperitoneal injections of the corresponding concentrations of LBT for ten consecutive days, whereas mice in the control and model groups received intraperitoneal injections of physiological saline. Beginning on the eighth day, mice in the model, LBT1, and LBT2 groups received subcutaneous injections of Triton WR-1339 for three consecutive days, whereas those in the control group received subcutaneous injections of physiological saline concurrently. On the eleventh day of the experiment, serum, liver, colon, and fecal samples were collected from all mice. This study aimed to measure lipid metabolism in mouse serum and liver, assess the inflammatory status of the mouse colon, and evaluate changes in the gut microbiota.

RESULTS

Lobetyolin significantly reduced the levels of triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and total cholesterol (T-CHO) in the serum of hyperlipidemic mice. Concurrently, it elevated the levels of high-density lipoprotein cholesterol (HDL-C). The mechanism involves the reduction of endogenous cholesterol production and promotion of reverse cholesterol transport. LBT can also alleviate inflammatory responses by inhibiting the TLR4/NF-κB signaling pathway. In addition, it can regulate the balance of Th1 and Th2 immunity and enhance the immune capacity of the colon mucosa. According to the results of 16S rRNA sequencing, LBT increased the abundance of beneficial gut microbiota, such as , , and , which were positively correlated with HDL-C, IL-10, IL-4, and SIgA but negatively correlated with T-CHO, TG, LDL-C, VLDL-C, IL-6, IFN-γ, and TNF-α.

CONCLUSION

Our findings emphasize that lobetyolin exerts lipid-lowering and anti-inflammatory effects by regulating the ecological structure of the gut microbiota.

摘要

背景

高脂血症是一种常见的代谢紊乱疾病,与肠道微生物群失衡密切相关。近年来,中药在调节肠道微生物群和改善代谢健康方面显示出独特优势。本研究旨在阐明洛贝林调节肠道微生物群以改善高脂血症小鼠肠道炎症和脂质代谢的分子过程。

方法

将40只雌性KM小鼠随机分为四组:对照组、模型组、LBT1组和LBT2组。LBT1组和LBT2组小鼠连续10天腹腔注射相应浓度的LBT,而对照组和模型组小鼠腹腔注射生理盐水。从第8天开始,模型组、LBT1组和LBT2组小鼠连续3天皮下注射Triton WR-1339,而对照组小鼠同时皮下注射生理盐水。在实验的第11天,收集所有小鼠的血清、肝脏、结肠和粪便样本。本研究旨在测定小鼠血清和肝脏中的脂质代谢,评估小鼠结肠的炎症状态,并评估肠道微生物群的变化。

结果

洛贝林显著降低了高脂血症小鼠血清中甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、极低密度脂蛋白胆固醇(VLDL-C)和总胆固醇(T-CHO)的水平。同时,它提高了高密度脂蛋白胆固醇(HDL-C)的水平。其机制包括减少内源性胆固醇生成和促进胆固醇逆向转运。LBT还可通过抑制TLR4/NF-κB信号通路减轻炎症反应。此外,它可以调节Th1和Th2免疫平衡,增强结肠黏膜的免疫能力。根据16S rRNA测序结果,LBT增加了有益肠道微生物群的丰度,如 、 和 ,它们与HDL-C、IL-10、IL-4和SIgA呈正相关,但与T-CHO、TG、LDL-C、VLDL-C、IL-6、IFN-γ和TNF-α呈负相关。

结论

我们的研究结果强调,洛贝林通过调节肠道微生物群的生态结构发挥降脂和抗炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/b349de93b801/fmicb-16-1625211-g013.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/ca33a08f014e/fmicb-16-1625211-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/238ce8640226/fmicb-16-1625211-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/8896350a02e6/fmicb-16-1625211-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/00fa27bfa3ae/fmicb-16-1625211-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/54d48c90b815/fmicb-16-1625211-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/729e3496d974/fmicb-16-1625211-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/b349de93b801/fmicb-16-1625211-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/174d1c90ba5c/fmicb-16-1625211-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/cbc19294168c/fmicb-16-1625211-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/37b596d97d1d/fmicb-16-1625211-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/c20710b4c96f/fmicb-16-1625211-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/edabe96ccd12/fmicb-16-1625211-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/bcd329d00b08/fmicb-16-1625211-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/ca33a08f014e/fmicb-16-1625211-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/238ce8640226/fmicb-16-1625211-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/8896350a02e6/fmicb-16-1625211-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/00fa27bfa3ae/fmicb-16-1625211-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/54d48c90b815/fmicb-16-1625211-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/729e3496d974/fmicb-16-1625211-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a81c/12402901/b349de93b801/fmicb-16-1625211-g013.jpg

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