Astragalus polysaccharide ameliorates lipopolysaccharide-induced cell injury in ATDC5 cells via miR-92a/KLF4 mediation

• Published in: Biomedicine & pharmacotherapy 2019-10, Vol.118, p.109180
• Main Authors: Fan, Lei, Li, Ming, Cao, Fu-Yang, Zeng, Zhi-Wei, Li, Xiao-Bin, Ma, Chao, Ru, Jing-Tao, Wu, Xue-Jian
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Astragalus Plant - chemistry; Cell Line; Cell Survival - drug effects; Chondrocytes - drug effects; Chondrocytes - immunology; Chondrocytes - metabolism; Chondrocytes - pathology; Down-Regulation; Drugs, Chinese Herbal - isolation & purification; Drugs, Chinese Herbal - pharmacology; Gene Expression - drug effects; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors - genetics; Mice; MicroRNAs - genetics; NF-kappa B - antagonists & inhibitors; Osteoarthritis; Polysaccharides - isolation & purification; Polysaccharides - pharmacology; RNA, Small Interfering - genetics; Up-Regulation
• ISSN: 1950-6007
• DOI: 10.1016/j.biopha.2019.109180

Astragalus polysaccharide (APS) is a traditional Chinese herbal medicine with anti-inflammatory and anti-aging activities. This study aimed to explore the effect and associated mechanisms of APS on LPS-induced injury in ATDC5 cells, to evaluate the potential of APS for use as an adjuvant therapy for osteoarthritis (OA). ATDC5 cells were pre-treated with APS and stimulated with lipopolysaccharide (LPS). Cell viability, ROS generation as well as the expression of IL-6, TNF-α, iNOS and Cox-2 were evaluated by performing CCK8 assay, ROS detection, ELISA, western blot and qRT-PCR. The expression of NF-κB and p38MAPK signal pathways related proteins and KLF4 was measured through western blot. LPS increased the expression of IL-6 and TNF-α, elevated the expression of Cox-2, iNOS and increased ROS generation. APS treatment significantly alleviated LPS-induced damage in ATDC5 cells. Besides, miR-92a was down-regulated while KLF4 was up-regulated by APS. At the same time, the targeting relationship between miR-92a and KLF4 was demonstrated. The inhibitory effects of APS on LPS-induced injury in ATDC5 cells were attenuated by the combination of KLF4 siRNA. In addition, LPS induced NF-κB and p38MAPK signal pathways were decreased by APS treatment. Also, the inhibitory effect of APS on NF-κB and p38MAPK signal pathways was reversed by KLF4 siRNA. The present study reveals that APS protects ATDC5 cells against LPS induced-injury by regulation of miR-92a/KLF4 axis and suppressing NF-κB and p38MAPK signal pathways.