Jeong Yun-Jeong, Shin Jae-Moon, Bae Young-Seuk, Cho Hyun-Ji, Park Kwan-Kyu, Choe Jung-Yoon, Han Sang-Mi, Moon Sung-Kwon, Kim Wun-Jae, Choi Yung Hyun, Kim Cheorl-Ho, Chang Hyeun-Wook, Chang Young-Chae
Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea; School of Life Sciences, KNU Creative BioResearch Group (BK21 plus program), Kyungpook National University, Daegu 702-701 Republic of Korea.
Int Immunopharmacol. 2015 Apr;25(2):400-5. doi: 10.1016/j.intimp.2015.02.021. Epub 2015 Feb 21.
Bee venom is a natural ingredient produced by the honey bee (Apis mellifera), and has been widely used in China, Korea and Japan as a traditional medicine for various diseases such as arthritis, rheumatism, and skin diseases However, the regulation of the underlying molecular mechanisms of the anti-arthritis by bee venom and its major peptides is largely unknown. In this study, we investigated the potential molecular mechanisms underlying the anti-arthritis effect of bee venom and its major peptides, melittin and apamin, in tumor necrosis factor-α (TNF-α) responsive C57BL/6 mice chondrocyte cells. The bee venom and melittin significantly and selectively suppressed the TNF-α-mediated decrease of type II collagen expression, whereas the apamin had no effects on the type II collagen expression. We, furthermore, found that the bee venom and melittin inhibited the protein expression of matrix metalloproteinase (MMP)-1 and MMP-8, which suggests that the chondroprotective effect of bee venom may be caused by melittin. The inhibitory effects of melittin on the TNF-α-induced MMP-1 and MMP-8 protein expression were regulated by the inhibition of NF-kB and AP-1. In addition, melittin suppressed the TNF-α-induced phosphorylation of Akt, JNK and ERK1/2, but did not affect the phosphorylation of p38 kinase. These results suggest that melittin suppresses TNF-α-stimulated decrease of type II collagen expression by the inhibiting MMP-1 and MMP-8 through regulation of the NF-kB and AP-1 pathway and provision of a novel role for melittin in anti-arthritis action.
蜂毒是蜜蜂（西方蜜蜂）产生的一种天然成分，在中国、韩国和日本已被广泛用作治疗关节炎、风湿病和皮肤病等各种疾病的传统药物。然而，蜂毒及其主要肽类抗关节炎的潜在分子机制在很大程度上尚不清楚。在本研究中，我们调查了蜂毒及其主要肽类蜂毒肽和蜂毒明肽在肿瘤坏死因子-α（TNF-α）反应性C57BL/6小鼠软骨细胞中抗关节炎作用的潜在分子机制。蜂毒和蜂毒肽显著且选择性地抑制了TNF-α介导的II型胶原蛋白表达的降低，而蜂毒明肽对II型胶原蛋白表达没有影响。此外，我们发现蜂毒和蜂毒肽抑制了基质金属蛋白酶（MMP）-1和MMP-8的蛋白表达，这表明蜂毒的软骨保护作用可能是由蜂毒肽引起的。蜂毒肽对TNF-α诱导的MMP-1和MMP-8蛋白表达的抑制作用是通过抑制NF-κB和AP-1来调节的。此外，蜂毒肽抑制了TNF-α诱导的Akt、JNK和ERK1/2的磷酸化，但不影响p38激酶的磷酸化。这些结果表明，蜂毒肽通过调节NF-κB和AP-1途径抑制MMP-1和MMP-8，从而抑制TNF-α刺激的II型胶原蛋白表达的降低，并为蜂毒肽在抗关节炎作用中提供了新的作用。
