Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, PR China.
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, PR China.
J Pharmacol Sci. 2019 Apr;139(4):377-384. doi: 10.1016/j.jphs.2019.03.002. Epub 2019 Mar 14.
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by inflammation, multifocal fibrotic lesions and excessive collagen deposition with limited therapies. As a major bioactive compound in garlic, S-allyl-l-cysteine (SAC) is a neuroprotective drug candidate to prevent cognitive decline, however, its anti-pulmonary fibrotic activity remains unknown. Here, we investigated whether SAC could attenuate bleomycin (BLM)-induced pulmonary fibrosis and inflammation in mice. Our results showed that SAC dose-dependently reduced the infiltration of inflammatory cells, pulmonary lesions and collagen deposition in BLM treated mice with downregulated mRNA expression levels of fibrotic genes including alpha smooth muscle actin (α-SMA), fibronectin, collagen I and collagen III as well as the protein level of α-SMA. In addition, SAC could also reduce the mRNA expression of inflammatory mediators such as TNF-α and iNOS. Furthermore, higher phosphorylation of AKT and NF-κB p65 in IPF patient samples and murine samples was verified by immunohistochemistry while SAC could decrease the phosphorylation level of AKT and NF-κB p65 in mice stimulated with BLM. These findings, for the first time, indicate that SAC might mediate AKT/NF-κB signaling pathway to inhibit BLM-induced pulmonary fibrosis and support the potential role of SAC as an anti-pulmonary fibrosis agent.
特发性肺纤维化（IPF）是一种进行性和致命性肺部疾病，其特征为炎症、多灶性纤维化病变和过量的胶原沉积，治疗方法有限。S-烯丙基-L-半胱氨酸（SAC）作为大蒜中的一种主要生物活性化合物，是一种神经保护药物候选物，可预防认知能力下降，然而，其抗肺纤维化活性尚不清楚。在这里，我们研究了 SAC 是否可以减轻博莱霉素（BLM）诱导的小鼠肺纤维化和炎症。我们的结果表明，SAC 可剂量依赖性地减少 BLM 处理小鼠的炎症细胞浸润、肺损伤和胶原沉积，并下调纤维化基因（包括α平滑肌肌动蛋白（α-SMA）、纤维连接蛋白、I 型和 III 型胶原）的 mRNA 表达水平以及α-SMA 的蛋白水平。此外，SAC 还可以降低 TNF-α和 iNOS 等炎症介质的 mRNA 表达。此外，通过免疫组化验证了 IPF 患者样本和小鼠样本中 AKT 和 NF-κB p65 的磷酸化水平升高，而 SAC 可以降低 BLM 刺激的小鼠中 AKT 和 NF-κB p65 的磷酸化水平。这些发现首次表明，SAC 可能通过 AKT/NF-κB 信号通路来抑制 BLM 诱导的肺纤维化，并支持 SAC 作为抗肺纤维化药物的潜在作用。
