Jung Haesoo, Kim Yong Soo, Jung Da-Min, Lee Kyeong-Seob, Lee Jung-Min, Kim Kee K
Department of Biochemistry, Chungnam National University, Daejeon, Republic of Korea.
Dong Seo Medical Research Institute, Namyangju-si, Gyeonggi-do, Republic of Korea.
Anim Cells Syst (Seoul). 2022 Jul 18;26(4):158-165. doi: 10.1080/19768354.2022.2099971. eCollection 2022.
Melittin is a major component of bee venom; it is widely used in traditional medicine because of its therapeutic effects, such as anti-inflammatory effects. However, melittin has limited medical applications owing to its adverse effects, such as high cytotoxicity. In this study, we investigated the physiological activities of various hydrolyzed melittin-derived peptides to eliminate the cytotoxicity of melittin and enhance its efficacy. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay confirmed that melittin-derived peptides showed antioxidant activity comparable to that of melittin. Moreover, unlike melittin, which showed high cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, the melittin-derived peptides showed negligible cytotoxicity. Among the melittin-derived peptides, the peptide composed of sequence TTGLPALISWIKRKRQQ (P1) showed inhibitory effects on the mRNA expression of inflammatory cytokines and phosphorylation of IκBα, similar to the effects of melittin in RAW 264.7 cells. Degranulation of RBL-2H3 cells was analyzed using a β-hexosaminidase release assay to confirm the allergenic activity of melittin and P1, which showed remarkably reduced allergenicity of P1 compared to that of melittin. These results indicate that P1 maintained the anti-inflammatory effects of melittin while reducing its cytotoxicity and allergic reactions. In conclusion, the melittin-derived peptide P1 efficiently decreased the adverse effects while maintaining the beneficial effects of melittin, making it suitable for therapeutic applications.
蜂毒肽是蜂毒的主要成分；由于其具有抗炎等治疗作用，在传统医学中被广泛应用。然而，蜂毒肽因其具有高细胞毒性等不良反应，医学应用受到限制。在本研究中，我们研究了各种水解蜂毒肽衍生肽的生理活性，以消除蜂毒肽的细胞毒性并增强其疗效。2,2'-联氮-双-(3-乙基苯并噻唑啉-6-磺酸)（ABTS）自由基清除试验证实，蜂毒肽衍生肽具有与蜂毒肽相当的抗氧化活性。此外，与在3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺苯基)-2H-四唑内盐（MTS）试验中表现出高细胞毒性的蜂毒肽不同，蜂毒肽衍生肽的细胞毒性可忽略不计。在蜂毒肽衍生肽中，由序列TTGLPALISWIKRKRQQ（P1）组成的肽对RAW 264.7细胞中炎性细胞因子的mRNA表达和IκBα的磷酸化具有抑制作用，类似于蜂毒肽的作用。使用β-己糖胺酶释放试验分析RBL-2H3细胞的脱颗粒情况，以确认蜂毒肽和P1的致敏活性，结果显示与蜂毒肽相比，P1的致敏性显著降低。这些结果表明，P1在降低蜂毒肽细胞毒性和过敏反应的同时，保持了其抗炎作用。总之，蜂毒肽衍生肽P1在保持蜂毒肽有益作用的同时有效降低了其不良反应，使其适用于治疗应用。
