Abstract：
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.
摘要：
Bufotenines,一种来自蟾蜍毒液的天然成分,显示出作为一种新型的抗炎和镇痛药物的巨大发展潜力，但潜在的毒性限制了其临床应用。在本文中,制备并优化了负载丁酚的脂质体。然后，在动物模型上研究了布福替尼脂质体对炎症和疼痛的治疗效果和药物安全性，重点关注胃肠道毒性。Bufotenins及其脂质体在VonFrey测试中显着增加了爪退缩机械阈值（PWMT），在热板测试中热爪退缩潜伏期（HPWL）。此外，体外肠吸收和体内病理分析表明，总丁酚胺脂质体通过减少总丁酚胺在肠组织上的暴露，显着降低了胃肠道刺激。高敏脂质组学分析显示负载总丁酚胺的脂质体的作用与环氧合酶（COX）和脂氧合酶（LOX）的炎症介质的下调有关，细胞色素P450（CYP450）的上调，和其他途径，从而调节脂质代谢途径，最终减少胃肠道刺激。这项研究表明，脂质体负载的bufotenines具有抗炎作用，镇痛效果，实现毒性降低。这些结果为蟾毒活性成分的有效性和安全性提供了系统的证据。
