Wang Shuo, Liu Jinqian, Dong Jing, Fan Zongqiang, Wang Fugui, Wu Ping, Li Xiaojing, Kou Ruirui, Chen Fang
School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, Shandong, China.
School of Public Health, Shandong University, Jinan, Shandong, China.
Front Pharmacol. 2022 Aug 8;13:919898. doi: 10.3389/fphar.2022.919898. eCollection 2022.
Allyl methyl trisulfide (AMTS) is one major lipid-soluble organosulfur compound of garlic. Previous studies have reported the potential therapeutic effect of garlic on acute lung injury (ALI) or its severe condition acute respiratory distress syndrome (ARDS), but the specific substances that exert the regulatory effects are still unclear. In this study, we investigate the protective effects of AMTS on lipopolysaccharide (LPS)-induced ALI mice and explored the underlying mechanisms. In experiments, ICR mice were pretreated with 25-100 mg/kg AMTS for 7 days and followed by intratracheal instillation of LPS (1.5 mg/kg). The results showed that AMTS significantly attenuated LPS-induced deterioration of lung pathology, demonstrated by ameliorative edema and protein leakage, and improved pulmonary histopathological morphology. Meanwhile, the expression of inflammatory mediators and the infiltration of inflammation-regulation cells induced by LPS were also inhibited. experiments also revealed that AMTS could alleviate inflammation response and inhibit the exaggeration of macrophage M1 polarization in LPS-induced RAW264.7 cells. Mechanistically, we identified that AMTS treatment could attenuate the LPS-induced elevation of protein expression of p-IκBα, nuclear NF-κB-p65, COX2, iNOS, p-P38, p-ERK1/2, and p-JNK. Collectively, these data suggest that AMTS could attenuate LPS-induced ALI and the molecular mechanisms should be related to the suppression of the NF-κB and MAPKs pathways.
烯丙基甲基三硫化物(AMTS)是大蒜中的一种主要脂溶性有机硫化合物。先前的研究报道了大蒜对急性肺损伤(ALI)或其严重形式急性呼吸窘迫综合征(ARDS)的潜在治疗作用,但发挥调节作用的具体物质仍不清楚。在本研究中,我们研究了AMTS对脂多糖(LPS)诱导的ALI小鼠的保护作用,并探讨了其潜在机制。实验中,将ICR小鼠用25 - 100mg/kg AMTS预处理7天,随后气管内滴注LPS(1.5mg/kg)。结果表明,AMTS显著减轻了LPS诱导的肺病理恶化,表现为水肿和蛋白渗漏改善,并改善了肺组织病理学形态。同时,LPS诱导的炎症介质表达和炎症调节细胞浸润也受到抑制。实验还表明,AMTS可以减轻炎症反应,并抑制LPS诱导的RAW264.7细胞中巨噬细胞M1极化的加剧。机制上,我们发现AMTS处理可以减轻LPS诱导的p - IκBα、核NF - κB - p65、COX2、iNOS、p - P38、p - ERK1/2和p - JNK蛋白表达升高。总体而言,这些数据表明AMTS可以减轻LPS诱导的ALI,其分子机制应与抑制NF - κB和MAPKs途径有关。