Yang Shuai, Duan Hongwei, Zeng Jianlin, Yan Zhenxing, Niu Tian, Ma Xiaofei, Zhang Yong, Hu Junjie, Zhang Lihong, Zhao Xingxu
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, Gansu, China; Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou, 730070, Gansu, China.
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, Gansu, China; Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou, 730070, Gansu, China.
J Ethnopharmacol. 2025 Jan 13;339:119157. doi: 10.1016/j.jep.2024.119157. Epub 2024 Nov 26.
Lonicerae japonicae flos (LJF), the dried flower bud or newly bloomed flower of Lonicera japonica Thunb., is widely used in Traditional Chinese medicine (TCM), exhibiting anti-inflammatory and immune-enhancing properties. Luteolin (Lut) is a major bioactive component of LJF, demonstrating a regulatory role in immune disorders. However, the specific role of Lut in regulating macrophage-mediated intestinal inflammation and its underlying molecular mechanisms have not yet been fully explored.
This study was designed to explore whether Lut alleviates Ulcerative colitis (UC) in mice and to elucidate its underlying mechanism in intestinal inflammation.
Mice were administered Dextran sodium sulfate (DSS) for 7 d to establish a UC model, followed by oral administration of Lut (12.5, 25, and 50 mg/kg body weight). RNA-sequencing (RNA-Seq) was used to screen signaling pathways. RAW264.7 cells were cultured and treated with Lut (6.25, 12.5, and 25 μM) and lipopolysaccharide (LPS, 1 μg/mL) for 24 h. To examine the role of the AMP-activated protein kinase (AMPK)/Peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway, the cells were treated with compound C (an AMPK inhibitor) and GW9662 (a PPARγ antagonist).
Lut suppressed the inflammation of DSS-induced colitis in vivo, attenuated DSS-induced clinical man-ifestations, reversed colon length reduction, and reduced histological injury. Lut induced a shift in the macrophage phenotype from classical (M1) to alternative (M2) by suppressing M1 marker gene expression and enhancing M2 marker gene expression following DSS or LPS induction. RNA-seq revealed that PPARγ was involved in the regulation of macrophages by Lut. Furthermore, the polarization effect of Lut on macrophages was shown to be mediated through the AMPK-PPARγ signaling pathway.
These findings indicate that Lut effectively ameliorates UC in mice through the activation of the AMPK-PPARγ signaling pathway, leading to the inhibition of macrophage M1 polarization and promotion of M2 polarization. This study provides insight into future research on the utilization of Lut-rich TCM dietary supplements as a prophylactic treatment strategy in the prevention of UC.
金银花（LJF），即忍冬科植物忍冬干燥的花蕾或初开的花，在传统中药（TCM）中被广泛应用，具有抗炎和增强免疫的特性。木犀草素（Lut）是金银花的主要生物活性成分，在免疫紊乱中发挥调节作用。然而，Lut在调节巨噬细胞介导的肠道炎症中的具体作用及其潜在分子机制尚未得到充分探索。
本研究旨在探讨Lut是否能减轻小鼠溃疡性结肠炎（UC），并阐明其在肠道炎症中的潜在机制。
给小鼠连续7天给予葡聚糖硫酸钠（DSS）以建立UC模型，随后口服Lut（12.5、25和50mg/kg体重）。采用RNA测序（RNA-Seq）筛选信号通路。培养RAW264.7细胞，并用Lut（6.25、12.5和25μM）和脂多糖（LPS，1μg/mL）处理24小时。为了研究AMP激活的蛋白激酶（AMPK）/过氧化物酶体增殖物激活受体γ（PPARγ）信号通路的作用，用化合物C（一种AMPK抑制剂）和GW9662（一种PPARγ拮抗剂）处理细胞。
Lut在体内抑制了DSS诱导的结肠炎炎症，减轻了DSS诱导的临床表现，逆转了结肠长度缩短，并减少了组织学损伤。Lut通过抑制DSS或LPS诱导后的M1标记基因表达并增强M2标记基因表达，诱导巨噬细胞表型从经典（M1）向替代（M2）转变。RNA-seq显示PPARγ参与了Lut对巨噬细胞的调节。此外，Lut对巨噬细胞的极化作用被证明是通过AMPK-PPARγ信号通路介导的。
这些发现表明，Lut通过激活AMPK-PPARγ信号通路有效改善小鼠UC，导致巨噬细胞M1极化的抑制和M2极化的促进。本研究为未来利用富含Lut的中药膳食补充剂作为预防UC的预防性治疗策略的研究提供了思路。
