Wang Bixu, Lin Yue, Zhou Mingyuan, Fu Siyu, Zhu Bingqi, Chen Yuchi, Ding Zhishan, Zhou Fangmei
School of Medical Techonology and Information Engineering, Zhejiang Chinese Medical University, No.548, Binjiang District, Hangzhou 310053, Zhejiang, People's Republic of China.
Biomed Pharmacother. 2022 Nov;155:113755. doi: 10.1016/j.biopha.2022.113755. Epub 2022 Sep 28.
Tetrastigma Hemsleyanum Diels et Gilg (Sanyeqing, SYQ), a traditional herb native to China, has been widely used in the treatment of inflammatory diseases, febrile convulsions and dysentery. Previous studies have demonstrated the hypoglycemic, anti-inflammatory and anti-pyretic effects of polysaccharides from SYQ (SYQP). However, the role of SYQP in acute lung injury (ALI) remained unknown. Our present study aimed to explore the protective effects of SYQP in ALI and explained its underlying mechanism. In vivo, Balb/c mice were intragastrically administered with SYQP and dexamethasone (DXMS) for 14 days which were intratracheally instilled (IT) with LPS at the last day. In vitro, A549 cells were pretreated with SYQP, DXMS or TAK-242, following by LPS stimulation for 24 h. The histopathological results showed that SYQP remarkably alleviated pulmonary macrophage infiltration and myeloperoxidase (MPO) levels. Additionally, SYQP evidently suppressed wet/dry (W/D) ratio of lung and white blood cells (WBC) in bronchoalveolar lavage fluid (BALF). Moreover, SYQP markedly reduced TNF-α, IL-6, IL-1β and COX-2 levels both in vivo and in vitro. Meanwhile, SYQP significantly attenuated oxidative stress through upregulating the levels of SOD and GSH-Px and downregulating the expressions of MDA and LDH in vivo, which was confirmed by in vitro results that SYQP could increase SOD activity and decrease MDA and NO contents. Importantly, a decline in protein expressions of TLR4, COX-2, NF-κB p50, phospho-NF-κB p65 and phospho-IκB-α was detected in vivo and in vitro. Taken together, our results demonstrated that SYQP ameliorated LPS-induced ALI by alleviating inflammation and oxidative stress via attenuating TLR4/COX-2/NF-κB signaling pathway.
三叶崖爬藤（Tetrastigma Hemsleyanum Diels et Gilg，中药名三叶青，SYQ）是一种原产于中国的传统草药，已被广泛用于治疗炎症性疾病、高热惊厥和痢疾。先前的研究已经证明了三叶青多糖（SYQP）具有降血糖、抗炎和退热作用。然而，SYQP在急性肺损伤（ALI）中的作用尚不清楚。我们目前的研究旨在探讨SYQP对ALI的保护作用，并解释其潜在机制。在体内实验中，Balb/c小鼠连续14天灌胃给予SYQP和地塞米松（DXMS），最后一天经气管内注入（IT）脂多糖（LPS）。在体外实验中，A549细胞先用SYQP、DXMS或TAK-242预处理，然后用LPS刺激24小时。组织病理学结果显示，SYQP显著减轻了肺部巨噬细胞浸润和髓过氧化物酶（MPO）水平。此外，SYQP明显抑制了肺组织的湿/干（W/D）比值以及支气管肺泡灌洗液（BALF）中的白细胞（WBC）数量。此外，SYQP在体内和体外均显著降低了肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和环氧化酶-2（COX-2）水平。同时，SYQP通过上调超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）水平以及下调丙二醛（MDA）和乳酸脱氢酶（LDH）的表达，在体内显著减轻了氧化应激，体外实验结果也证实SYQP可增加SOD活性并降低MDA和一氧化氮（NO）含量。重要的是，在体内和体外均检测到Toll样受体4（TLR4）、COX-2、核因子κB p50（NF-κB p50）、磷酸化核因子κB p65（phospho-NF-κB p65）和磷酸化核因子κB抑制蛋白α（phospho-IκB-α）的蛋白表达下降。综上所述，我们的结果表明，SYQP通过减弱TLR4/COX-2/NF-κB信号通路减轻炎症和氧化应激，从而改善LPS诱导的ALI。
