Yinyin Ye1, Yuwei Wang2, Yanlang Yang2, Liangfei Tao3. 1. Department of Nephrology, Yijishan Hospital of Wannan Medical College, # 92 Zheshan Road, Wuhu, 241002, Anhui Province, People's Republic of China. pangyakefp@163.com. 2. Department of Nephrology, Yijishan Hospital of Wannan Medical College, # 92 Zheshan Road, Wuhu, 241002, Anhui Province, People's Republic of China. 3. Medical Emergency Center, #158 Yueming Road, Baoshan District, Shanghai, 201900, People's Republic of China. liangfeitao212@sina.com.
Abstract
OBJECTIVE: The currently available anti-inflammatory drugs often cause diverse side effects with long-term use. Exploring anti-inflammatory drugs with better efficacy and lower toxicity presents an ongoing challenge. Aloperine is an alkaloid extracted from the leaves and seeds of Sophora alopecuroides L. However, the anti-inflammatory effects of Aloperine have not been fully elucidated. This study aimed to investigate whether Aloperine suppresses lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages. METHODS: RAW264.7 macrophages were stimulated with LPS (1 μg/mL) in the presence or absence of Aloperine (50 and 100 μM). mRNA expression was measured by real-time PCR, and protein expression was assessed by western blot analysis. The secretion of pro-inflammatory cytokines was measured by ELISA. The levels of nitric oxide (NO) and reactive oxygen species (ROS) were measured by staining. The transcriptional activity of NF-κB was assayed by a luciferase activity assay. RESULTS: The results proved that Aloperine inhibited the expression of LPS-induced pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-17A (IL-17A)] in macrophages. Treatment with Aloperine inhibited NO production through suppressing inducible nitric oxide synthase (iNOS) expression and the secretion of prostaglandin E2 (PGE2) by inhibiting cyclooxygenase 2 (COX-2) expression. Aloperine prevented LPS-induced oxidative stress by reducing the generation of ROS. Furthermore, aloperine significantly reduced Toll-like receptor 4 (TLR4) and myeloid differentiation factor (Myd-88) levels and prevented the nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated macrophages. CONCLUSION: Taken together, our findings show that Aloperine could suppress LPS-induced macrophage activation by inhibiting the TLR4/Myd-88/NF-κB pathway.
OBJECTIVE: The currently available anti-inflammatory drugs often cause diverse side effects with long-term use. Exploring anti-inflammatory drugs with better efficacy and lower toxicity presents an ongoing challenge. Aloperine is an alkaloid extracted from the leaves and seeds of Sophora alopecuroides L. However, the anti-inflammatory effects of Aloperine have not been fully elucidated. This study aimed to investigate whether Aloperine suppresses lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages. METHODS:RAW264.7 macrophages were stimulated with LPS (1 μg/mL) in the presence or absence of Aloperine (50 and 100 μM). mRNA expression was measured by real-time PCR, and protein expression was assessed by western blot analysis. The secretion of pro-inflammatory cytokines was measured by ELISA. The levels of nitric oxide (NO) and reactive oxygen species (ROS) were measured by staining. The transcriptional activity of NF-κB was assayed by a luciferase activity assay. RESULTS: The results proved that Aloperine inhibited the expression of LPS-induced pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-17A (IL-17A)] in macrophages. Treatment with Aloperine inhibited NO production through suppressing inducible nitric oxide synthase (iNOS) expression and the secretion of prostaglandin E2 (PGE2) by inhibiting cyclooxygenase 2 (COX-2) expression. Aloperine prevented LPS-induced oxidative stress by reducing the generation of ROS. Furthermore, aloperine significantly reduced Toll-like receptor 4 (TLR4) and myeloid differentiation factor (Myd-88) levels and prevented the nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated macrophages. CONCLUSION: Taken together, our findings show that Aloperine could suppress LPS-induced macrophage activation by inhibiting the TLR4/Myd-88/NF-κB pathway.
Authors: A J Dannenberg; N K Altorki; J O Boyle; C Dang; L R Howe; B B Weksler; K Subbaramaiah Journal: Lancet Oncol Date: 2001-09 Impact factor: 41.316