Ding Wanting, Sun Yuan, Tuohudaali Wulipan, Li Chenyang, Yao Yuhan, Zhao Jun
School of Pharmacy, Xinjiang Medical University, Urumqi 830011, China.
Xinjiang Key Laboratory for Uighur Medicine, Institute of Materia Medica of Xinjiang, Urumqi 830004, China.
Int J Mol Sci. 2025 Jun 19;26(12):5912. doi: 10.3390/ijms26125912.
This study aimed to investigate the preventive effects of isostrictiniin (ITN) from against acute lung injury (ALI) through lipopolysaccharide (LPS)-induced ALI mice and LPS-induced A549 cells. Compared with the model group, ITN (50 and 100 mg/kg) significantly reduced the lung indexes, W/D rates, BALF WBC counts, and total protein contents in ALI mice ( < 0.05), as well as the blood neu counts ( < 0.01), while increasing the blood lym counts ( < 0.01). ITN (50 and 100 mg/kg) also markedly decreased the lung tissue TNF-α, IL-6, IL-1β, MDA, and MPO activities in ALI mice ( < 0.01) and enhanced the SOD and GSH levels ( < 0.01). Additionally, ITN (50 and 100 mg/kg) significantly improved lung histopathological damage in ALI mice. Moreover, ITN (10 and 25 µM) significantly reduced the NO, PGE2, IL-1β, IL-6, TNF-α, and MDA levels in LPS-induced A549 cells ( < 0.01) while significantly increasing the SOD and GSH activities ( < 0.01). After LPS-induced A549 cells, the Keap1, p-JNK/JNK, p-ERK1/2/ERK1/2, p-P38/P38, p-IκBα/IκBα, and p-NF-κBp65/NF-κB p65 levels were significantly upregulated ( < 0.05), whereas the Nrf2 and HO-1 protein expressions were downregulated ( < 0.05). After treatment with ITN (25 μM), the changes in these relative protein expressions in LPS-induced A549 cells were significantly reversed ( < 0.05). The above results indicate that ITN has a better preventive effect against ALI, and its mechanisms are related to the regulation of the Keap1-Nrf2/HO-1 and MAPK/NF-κB signaling pathways.
本研究旨在通过脂多糖（LPS）诱导的急性肺损伤（ALI）小鼠和LPS诱导的A549细胞，研究异斯垂亭宁（ITN）对ALI的预防作用。与模型组相比，ITN（50和100 mg/kg）显著降低了ALI小鼠的肺指数、湿干比、支气管肺泡灌洗液（BALF）白细胞计数和总蛋白含量（P<0.05），以及血液中性粒细胞计数（P<0.01），同时增加了血液淋巴细胞计数（P<0.01）。ITN（50和100 mg/kg）还显著降低了ALI小鼠肺组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、丙二醛（MDA）和髓过氧化物酶（MPO）活性（P<0.01），并提高了超氧化物歧化酶（SOD）和谷胱甘肽（GSH）水平（P<0.01）。此外，ITN（50和100 mg/kg）显著改善了ALI小鼠的肺组织病理损伤。此外，ITN（10和25 μM）显著降低了LPS诱导的A549细胞中一氧化氮（NO）、前列腺素E2（PGE2）、IL-1β、IL-6、TNF-α和MDA水平（P<0.01），同时显著提高了SOD和GSH活性（P<0.01）。LPS诱导A549细胞后， Kelch样环氧氯丙烷相关蛋白1（Keap1）磷酸化的c-Jun氨基末端激酶/总c-Jun氨基末端激酶（p-JNK/JNK）、磷酸化的细胞外信号调节激酶1/2/总细胞外信号调节激酶1/2（p-ERK1/2/ERK1/2）、磷酸化的p38丝裂原活化蛋白激酶/总p38丝裂原活化蛋白激酶（p-P38/P38）、磷酸化的IκBα/总IκBα和磷酸化的核因子κB p65/总核因子κB p65水平显著上调（P<0.05），而核因子E2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）蛋白表达下调（P<0.05）。用ITN（25 μM）处理后，LPS诱导的A549细胞中这些相对蛋白表达的变化得到显著逆转（P<0.05）。上述结果表明，ITN对ALI具有较好的预防作用，其机制与调节Keap1-Nrf2/HO-1和丝裂原活化蛋白激酶/核因子κB（MAPK/NF-κB）信号通路有关。
