Bufotenines-loaded liposome exerts anti-inflammatory, analgesic effects and reduce gastrointestinal toxicity through altering lipid and bufotenines metabolism

• Published in: Biomedicine & pharmacotherapy Vol. 153; p. 113492
• Main Authors: Shen, Lili, Lv, Xiang, Yang, Xin, Deng, Shuangbing, Liu, Lina, Zhou, Jing, Zhu, Yuyu, Ma, Hongyue
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.09.2022; Elsevier
• Subjects: Analgesia; Anti-inflammation; Bufotenines; Gastrointestinal irritation; Lipid metabolism; Liposome; EE; Gastrointestinal irritation; HPWT; NS; DL; Liposome; MRM; PWMT; TNF; COX; Bufotenines; IL-6; Anti-inflammation; Analgesia; LOX; UPLC; CYP450; LA; EPA; ESI; Lipid metabolism; CPWL
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113492

Bufotenines, a natural component from toad venom, showed great potential for development as a novel anti-inflammation and analgesia agent, but the potential toxicity limited its clinic use. In this paper, bufotenines-loaded liposome was prepared and optimized. Then, the therapeutic effects and drug safety of bufotenines-liposome were investigated against inflammation and pain on animal models, with a focus on gastrointestinal toxicity. Bufotenines and its liposome significantly increased paw withdrawal mechanical threshold (PWMT) in Von Frey test and hot paw withdrawal latency (HPWL) in hot-plate test. Moreover, intestinal absorption in vitro and pathological analysis in vivo showed that total bufotenines-loaded liposome significantly reduced the gastrointestinal irritation through reducing exposure of total bufotenines on intestinal tissue. High-sensitivity lipidomics analysis revealed the effect of total bufotenines-loaded liposome were be related to the down-regulation of inflammatory mediators from cyclooxygenase (COX) and lipoxygenase (LOX), the up-regulation of cytochrome P450 (CYP450), and other pathways, thus regulating lipid metabolism pathway and ultimately reducing gastrointestinal irritation. This study shows that liposome-loaded bufotenines has anti-inflammatory, analgesic effects and achieves toxicity reduction. These results provide systematic evidences for efficacy and safety of toad venom active ingredients. •Bufotenines is a kind of natural product with proven anti-inflammation and analgesic activities.•Liposome represents a powerful delivery system for reducing gastrointestinal irritation.•Highly sensitive lipidomics reveals the disorder of inflammatory mediators in gastrointestinal stimulation.