Melittin-derived peptides exhibit variations in cytotoxicity and antioxidant, anti-inflammatory and allergenic activities

Abstract

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.

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The RNA ligation method using modified splint DNAs significantly improves the efficiency of circular RNA synthesis

“…The protein in the acrylamide gel was transferred to the NC membrane using a Mini Trans-Blot Electrophoretic Transfer Cell (Bio-Rad). The blotted membrane was blocked with 5% skim milk in TBST for 1 h. HRP-conjugated goat anti-human IgG Fc cross-adsorbed secondary antibody (1:5000 diluted in TBST containing 5% skim milk) was bound for 1 h. After washing five times with TBST, the experimental results were imaged using ECL (Jung et al 2022 ).…”

Recent advances in melittin-based nanoparticles for antitumor treatment: from mechanisms to targeted delivery strategies

“…Previous studies have indicated that the activation of peripheral P2X and P2Y receptors, transient receptor potential (TRP) vanilloid receptor 1 (TRPV1) and canonical TRP channels might be involved in the pathophysiological processing of MLT-induced hypersensitivity [ 87 , 88 ]. However, the molecular mechanisms by which the innate immune system initiates allergic responses remain largely undiscovered [ 89 ].…”