Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University, Chengdu, China.
Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Phytother Res. 2018 Aug;32(8):1521-1529. doi: 10.1002/ptr.6080. Epub 2018 Apr 19.
Astragalus polysaccharides (APS), one of the major active components in Astragalus membranaceus, is an effective immunomodulator used in the treatment of immunological diseases in China. However, the anti-infective action and mechanism of APS is not fully known. In the present study, we found that APS induced the expression of human cathelicidin antimicrobial peptide LL-37, a key host anti-infective molecule, in both mRNA and protein levels in respiratory epithelial cells HBE16 and A549. Furthermore, the lysate and supernatant from APS-treated HBE16 cells both exhibited an obvious antibacterial action, which was partially neutralizated by LL-37 monoclonal antibody. In addition, APS also significantly elevated the phosphorylation of p38 MAPK and JNK and caused the degradation of IκBα. Specific inhibitors of p38 MAPK, JNK, or NF-κB obviously abolished APS-induced LL-37 synthesis and antibacterial activity, respectively. Taken together, our results confirmed the enhancement of APS on LL-37 induction and antibacterial action in respiratory epithelial cells, which may be attributed to activation of p38 MAPK/JNK and NF-κB pathways. Furthermore, these results also supported the clinical application of APS in the treatment of infectious diseases.
黄芪多糖（APS）是黄芪的主要活性成分之一，是一种有效的免疫调节剂，在中国用于治疗免疫性疾病。然而，APS 的抗感染作用及其机制尚不完全清楚。在本研究中，我们发现 APS 在呼吸道上皮细胞 HBE16 和 A549 中诱导人防御素抗菌肽 LL-37 的表达，这是一种关键的宿主抗感染分子，在 mRNA 和蛋白水平上均有表达。此外，APS 处理的 HBE16 细胞的裂解物和上清液均表现出明显的抗菌作用，该作用可被 LL-37 单克隆抗体部分中和。此外，APS 还显著提高了 p38 MAPK 和 JNK 的磷酸化水平，并导致 IκBα的降解。p38 MAPK、JNK 或 NF-κB 的特异性抑制剂明显消除了 APS 诱导的 LL-37 合成和抗菌活性。综上所述，我们的研究结果证实了 APS 增强呼吸道上皮细胞中 LL-37 的诱导和抗菌作用，这可能归因于 p38 MAPK/JNK 和 NF-κB 通路的激活。此外，这些结果还支持了 APS 在治疗感染性疾病中的临床应用。
