Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine of Chonbuk National University Hospital, Chonbuk National University, Jeonju, Jeonbuk 561‑180, Republic of Korea.
Int J Mol Med. 2013 Oct;32(4):971-7. doi: 10.3892/ijmm.2013.1468. Epub 2013 Aug 9.
Inflammatory cytokines, matrix metalloproteinases (MMPs) and cyclooxygenase (COX)-2 released from rheumatoid arthritis synovial fibroblasts (RASFs) are involved in the destruction of both articular bone and cartilage. Kaempferol has been reported to act as an antioxidant and anti-inflammatory agent by inhibiting nitric oxide synthase and COX enzymes. The aim of the present study was to determine the effects of kaempferol on the interleukin-1β (IL-1β)-induced proliferation of RASFs and the production of MMPs, COX and prostaglandin E2 (PGE2) by RASFs. The proliferation of the RASFs stimulated with IL-1β and treated with/without kaempferol was evaluated by CCK-8 assay. The expression of MMPs, TIMP metallopeptidase inhibitor-1 (TIMP-1), COXs, PGE2 and that of intracellular MAPK signaling molecules, including p-ERK, p-p38, p-JNK and nuclear factor-κB (NF-κB) was examined by immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and ELISA under the conditions described above. Kaempferol inhibited the proliferation of both unstimulated and IL-1β‑stimulated RASFs, as well as the mRNA and protein expression of MMP-1, MMP-3, COX-2 and PGE2 induced by IL-1β. Kaempferol also inhibited the phosphorylation of ERK-1/2, p38 and JNK, as well as the activation of NF-κB induced by IL-1β. These results indicate that kaempferol inhibits synovial fibroblast proliferation, as well as the production of and MMPs, COX‑2 and PGE2, which is involved in articular inflammation and destruction in rheumatoid arthritis (RA). Our data suggest that kaempferol may be a novel therapeutic agent for the treatment of RA.
炎症细胞因子、基质金属蛋白酶 (MMPs) 和环氧化酶 (COX)-2 从类风湿关节炎滑膜成纤维细胞 (RASFs) 释放出来，参与关节骨和软骨的破坏。山柰酚已被报道通过抑制一氧化氮合酶和 COX 酶来发挥抗氧化和抗炎作用。本研究旨在确定山柰酚对白细胞介素-1β (IL-1β) 诱导的 RASFs 增殖以及 MMPs、COX 和前列腺素 E2 (PGE2) 的产生的影响。通过 CCK-8 测定评估经 IL-1β 刺激并用/不用山柰酚处理的 RASFs 的增殖。通过免疫印迹或半定量逆转录聚合酶链反应 (RT-PCR) 和 ELISA 检查 MMPs、TIMP 金属肽酶抑制剂-1 (TIMP-1)、COXs、PGE2 以及细胞内 MAPK 信号分子，包括 p-ERK、p-p38、p-JNK 和核因子-κB (NF-κB) 的表达在上文所述条件下。山柰酚抑制未受刺激和 IL-1β 刺激的 RASFs 的增殖，以及 MMP-1、MMP-3、COX-2 和 PGE2 的 mRNA 和蛋白表达，这些表达是由 IL-1β 诱导的。山柰酚还抑制 ERK-1/2、p38 和 JNK 的磷酸化，以及 NF-κB 的激活，这些都是由 IL-1β 诱导的。这些结果表明，山柰酚抑制滑膜成纤维细胞增殖，以及参与类风湿关节炎 (RA) 关节炎症和破坏的 MMPs、COX-2 和 PGE2 的产生。我们的数据表明，山柰酚可能是治疗 RA 的一种新的治疗剂。
