Wang Zengfa, Yang Fengling, Wang Yi, Geng Xiaoyu, Zhang Jinyu, Wang Xinming, Liu Chang, Danso Blessing, Chen Jingbo, Pozzolini Marina, Zu Xianpeng, Xiao Liang, Zhang Jing
College of Traditional Chinese Medicinal Materials, Jilin Agricultural University, Changchun, 130118, China; Faculty of Naval Medicine, Naval Medical University, Shanghai, 200433, China.
Faculty of Naval Medicine, Naval Medical University, Shanghai, 200433, China.
Toxicon. 2025 Mar;256:108266. doi: 10.1016/j.toxicon.2025.108266. Epub 2025 Jan 28.
The toxicity of jellyfish Rhopilema esculentum (R. esculentum), an edible jellyfish that releases venom, has been controversial. The aim of this comprehensive study was to investigate the toxic effects of jellyfish tentacle extract (TE), which was evaluated in vivo and in vitro using ICR mice and RAW264.7 cells respectively. A library of natural compounds was screened for their ability to antagonize phospholipase A (PLA) activity to identify potential protective agents and mechanisms. Of the 20 natural compounds evaluated, baicalein was found to have the strongest PLA antagonistic and cytoprotective effects. In vivo, experiments showed that TE at a dose of 7.02 mg/kg only resulted in a 50% survival rate in mice. However, pretreatment with 30 mg/kg baicalein significantly increased the survival rate to 75%, while also attenuating TE-induced cardiac and hepatic injuries, and ameliorating TE-induced elevations in LDH, CK-MB, and AST levels. In vitro studies found that baicalein reduced cellular ROS and MDA levels, increased the expression of CAT, SOD, and GSH/GSSG to enhance cellular antioxidant defenses against TE-induced oxidative stress, and also inhibited TE-induced upregulation of TNF-α, IL-6, IL-1β, and CXCL10. Importantly, baicalein was found to modulate dysregulated MAPK and NF-κB signaling pathways disrupted by TE. Taken together, these findings suggest that baicalein can antagonize R. esculentum toxin-induced oxidative stress and apoptosis by modulating ROS/MAPK/NF-κB, which provides a viable therapeutic strategy to control the deleterious effects of jellyfish stings and associated inflammation.
食用水母海蜇（Rhopilema esculentum）会释放毒液，其毒性一直存在争议。本综合研究的目的是调查水母触手提取物（TE）的毒性作用，分别使用ICR小鼠和RAW264.7细胞在体内和体外对其进行评估。筛选了一个天然化合物库，以研究它们拮抗磷脂酶A（PLA）活性的能力，从而确定潜在的保护剂和作用机制。在评估的20种天然化合物中，发现黄芩苷具有最强的PLA拮抗作用和细胞保护作用。在体内，实验表明，剂量为7.02 mg/kg的TE仅导致小鼠50%的存活率。然而，用30 mg/kg黄芩苷预处理可显著提高存活率至75%，同时减轻TE诱导的心脏和肝脏损伤，并改善TE诱导的乳酸脱氢酶（LDH）、肌酸激酶同工酶（CK-MB）和天冬氨酸转氨酶（AST）水平升高。体外研究发现，黄芩苷降低了细胞内活性氧（ROS）和丙二醛（MDA）水平，增加了过氧化氢酶（CAT）、超氧化物歧化酶（SOD）的表达以及谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）比值，以增强细胞对TE诱导的氧化应激的抗氧化防御能力，并且还抑制了TE诱导的肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和CXC趋化因子配体10（CXCL10）的上调。重要的是，发现黄芩苷可调节被TE破坏的丝裂原活化蛋白激酶（MAPK）和核因子-κB（NF-κB）信号通路失调。综上所述，这些发现表明黄芩苷可通过调节ROS/MAPK/NF-κB拮抗海蜇毒素诱导的氧化应激和细胞凋亡，这为控制水母蜇伤的有害影响及相关炎症提供了一种可行的治疗策略。
