Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China; The Research Centre for Chinese Medicine Innovation, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Biomed Pharmacother. 2024 Jul;176:116901. doi: 10.1016/j.biopha.2024.116901. Epub 2024 Jun 15.
Amauroderma rugosum (AR) is a medicinal mushroom commonly used to treat inflammation, gastric disorders, epilepsy, and cancers due to its remarkable anti-inflammatory and anti-oxidative properties. This study was designed to evaluate the pharmacological effects of AR and its underlying mechanism of action against ulcerative colitis (UC) in vitro and in vivo.
A UC mouse model was established by administration of dextran sulfate sodium (DSS). AR extract was administered intragastrically to mice for 7 days. At the end of the experiment, histopathology, macrophage phenotype, oxidative stress, and inflammatory status were examined in vivo. Furthermore, RAW 264.7, THP-1, and Caco-2 cells were used to elucidate the mechanism of action of AR in vitro.
AR extract (0.5-2 mg/mL) significantly suppressed lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-induced M1 macrophage (pro-inflammatory) polarization in both RAW 264.7 and THP-1 cells. LPS-induced pro-inflammatory mediators (nitric oxide, TNF-α, IL-1β, MCP-1, and IL-6) were reduced by AR extract in a concentration-dependent manner. Similarly, AR extract downregulated MAPK signaling activity in LPS-stimulated RAW 264.7 cells. AR extract elicited a concentration-dependent increase in the mRNA expression of M2 (anti-inflammatory) phenotype markers (CD206, Arg-1, Fizz-1, and Ym-1) in RAW 264.7 cells. Moreover, AR extract suppressed DSS-induced ROS generation and mitochondrial dysfunction in Caco-2 cells. The in vivo experiment revealed that AR extract (200 mg/kg) increased colon length compared to the DSS-treated group. In addition, disease activity index, spleen ratio, body weight, oxidative stress, and colonic inflammation were markedly improved by AR treatment in DSS-induced UC mice. Finally, AR suppressed M1 and promoted M2 macrophage polarization in UC mice.
The AR extract protected against DSS-induced UC by regulating macrophage polarization and suppressing oxidative stress. These valuable findings suggest that adequate intake of AR can prevent and/or treat UC.
皱柄白马鞍菌（AR）是一种药用蘑菇，由于其显著的抗炎和抗氧化特性，常用于治疗炎症、胃病、癫痫和癌症。本研究旨在评估 AR 的药理作用及其在体内和体外对抗溃疡性结肠炎（UC）的作用机制。
通过给予葡聚糖硫酸钠（DSS）建立 UC 小鼠模型。AR 提取物通过灌胃给予小鼠 7 天。实验结束时，在体内检查组织病理学、巨噬细胞表型、氧化应激和炎症状态。此外，还使用 RAW 264.7、THP-1 和 Caco-2 细胞在体外阐明 AR 的作用机制。
AR 提取物（0.5-2mg/mL）显著抑制脂多糖（LPS）和干扰素-γ（IFN-γ）诱导的 RAW 264.7 和 THP-1 细胞中 M1 巨噬细胞（促炎）极化。AR 提取物以浓度依赖性方式降低 LPS 诱导的促炎介质（一氧化氮、TNF-α、IL-1β、MCP-1 和 IL-6）。同样，AR 提取物下调 LPS 刺激的 RAW 264.7 细胞中 MAPK 信号活性。AR 提取物在浓度依赖性方式下增加 RAW 264.7 细胞中 M2（抗炎）表型标志物（CD206、Arg-1、Fizz-1 和 Ym-1）的 mRNA 表达。此外，AR 提取物抑制 DSS 诱导的 Caco-2 细胞中 ROS 生成和线粒体功能障碍。体内实验表明，AR 提取物（200mg/kg）与 DSS 处理组相比，增加了结肠长度。此外，AR 处理可显著改善 DSS 诱导的 UC 小鼠的疾病活动指数、脾比、体重、氧化应激和结肠炎症。最后，AR 抑制 UC 小鼠中 M1 并促进 M2 巨噬细胞极化。
AR 提取物通过调节巨噬细胞极化和抑制氧化应激来保护 DSS 诱导的 UC。这些有价值的发现表明，适量摄入 AR 可以预防和/或治疗 UC。
