School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, China; Shandong Key University Laboratory of Pharmaceutics & Drug Delivery Systems, 44 West Wenhua Road, Jinan, Shandong 250012, China.
School of Basic Medical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, China.
Int Immunopharmacol. 2020 Apr;81:106273. doi: 10.1016/j.intimp.2020.106273. Epub 2020 Mar 5.
The garlic-derived organosulfur compound S-allylmercaptocysteine (SAMC) has been reported to exhibit anti-inflammatory and anti-oxidative activities, whereas its potential therapeutic effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) is unknown. In this study, we focused on exploring the therapeutic effects of SAMC on LPS-induced ALI mice and the involvement of underlying molecular mechanisms. BalB/c mice were treated with SAMC (10, 30 and 60 mg/kg) or positive control N-acetylcysteine (NAC, 500 mg/kg) by gavage after intratracheal instillation of LPS for 30 min and were sacrificed 24 h after LPS administration. Our results indicate that the treatment with SAMC not only ameliorated the histological changes but also decreased LPS-triggered lung edema. Moreover, SAMC displayed an anti-inflammatory effect through reducing inflammatory cells infiltration, myeloperoxidase (MPO) formation and inhibiting pro-inflammatory cytokines/mediator production including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) via suppressing the activation of nuclear factor-kappaB (NF-κB) signaling pathway. Furthermore, SAMC attenuated oxidative stress evoked by LPS via diminishing malondialdehyde (MDA) formation and reversing glutathione (GSH) and superoxide dismutase (SOD) depletion. Meanwhile, SAMC up-regulated expressions of endogenous antioxidant/detoxifying proteins including heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1(NQO1) through reversing the suppression of Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway. Our results demonstrate that SAMC effectively attenuated LPS-induced ALI which was largely dependent upon inhibition of inflammation and oxidative stress via NF-κB and Keap1/Nrf2 signaling pathways.
大蒜衍生的有机硫化合物 S-烯丙基巯基半胱氨酸（SAMC）已被报道具有抗炎和抗氧化作用，但其对脂多糖（LPS）诱导的急性肺损伤（ALI）的潜在治疗作用尚不清楚。在这项研究中，我们专注于探索 SAMC 对 LPS 诱导的 ALI 小鼠的治疗作用及其潜在的分子机制。 BALB/c 小鼠经气管内滴注 LPS 30 分钟后，给予 SAMC（10、30 和 60mg/kg）或阳性对照 N-乙酰半胱氨酸（NAC，500mg/kg）灌胃，LPS 给药后 24 小时处死。结果表明，SAMC 治疗不仅改善了组织学变化，而且减轻了 LPS 触发的肺水肿。此外，SAMC 通过减少炎症细胞浸润、髓过氧化物酶（MPO）形成以及抑制肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX2）等促炎细胞因子/介质的产生，发挥抗炎作用，其机制与抑制核因子-κB（NF-κB）信号通路的激活有关。此外，SAMC 通过减少丙二醛（MDA）的形成以及逆转谷胱甘肽（GSH）和超氧化物歧化酶（SOD）的耗竭，减轻 LPS 引起的氧化应激。同时，SAMC 通过逆转 Kelch 样 ECH 相关蛋白 1（Keap1）/核因子红细胞 2 相关因子 2（Nrf2）信号通路的抑制，上调血红素加氧酶-1（HO-1）和 NAD（P）H：醌氧化还原酶 1（NQO1）等内源性抗氧化/解毒蛋白的表达。我们的研究结果表明，SAMC 可有效减轻 LPS 诱导的 ALI，其作用主要依赖于通过 NF-κB 和 Keap1/Nrf2 信号通路抑制炎症和氧化应激。
