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Withanicandrin Isolated from Datura Ferox Promotes Antinociception by Modulating the Asics and TRPS Channels and Anti-Inflammation in Adult Zebrafish
Chemistry & Biodiversity ( IF 2.3 ) Pub Date : 2024-04-19 , DOI: 10.1002/cbdv.202400538
Jéssica Bezerra Maciel 1 , Hortência Ribeiro Liberato 1 , Antônio Wlisses da Silva 1 , João Pedro Vieira da Silva 1 , Francisco das Chagas L Pinto 2 , Emanuela de Lima Rebouças 1 , Francisco Sydney Henrique da Silva 3 , Maria Kueirislene Amâncio Ferreira 1 , Marcia Machado Marinho 4 , Emmanuel Silva Marinho 1, 5 , Otília Deusdênia Loiola Pessoa 2 , Paulo Goberlânio de Barros Silva 6 , Andrelina Noronha Coelho-de-Souza 3 , Maria Izabel Florindo Guedes 7 , Andreia Ferreira de Castro Gomes 8 , Jane Eire Silva Alencar de Menezes 1 , Hélcio Silva Dos Santos 1, 4
Affiliation  

This is the first study to analyze the anti-inflammatory and antinociceptive effect of withanicandrin, isolated from Datura Ferox leaves, and the possible mechanism of action involved in adult zebrafish (ZFa). To this end, the animals were treated intraperitoneally (i. p.) with withanicandrin (4; 20 and 40 mg/kg; 20 μL) and subjected to locomotor activity and acute toxicity. Nociception tests were also carried out with chemical agents, in addition to tests to evaluate inflammatory processes induced by κ-Carrageenan 1.5 % and a Molecular Docking study. As a result, withanicandrin reduced nociceptive behavior by capsaicin at a dose of 40 mg/kg and by acid saline at doses of 4 and 40 mg/kg, through neuromodulation of TRPV1 channels and ASICs, identified through blocking the antinociceptive effect of withanicandrin by the antagonists capsazepine and naloxone. Furthermore, withanicandrin caused an anti-inflammatory effect through the reduction of abdominal edema, absence of leukocyte infiltrate in the liver tissue and reduction of ROS in thel liver tissue and presented better affinity energy compared to control morphine (TRPV1) and ibuprofen (COX-1 and COX-2).

中文翻译:


从曼陀罗中分离出的醉茄甙通过调节成年斑马鱼的 Asics 和 TRPS 通道以及抗炎作用来促进镇痛作用



这是第一项分析从曼陀罗叶中分离出的酒茄甙的抗炎和抗伤害作用的研究,以及对成年斑马鱼(ZFa)的可能作用机制。为此,对动物进行腹膜内(ip)处理withanicandrin (4;20和40mg/kg;20μL)并进行运动活动和急性毒性。除了评估 κ-卡拉胶 1.5% 诱导的炎症过程的测试和分子对接研究之外,还使用化学试剂进行了伤害感受测试。结果,通过 TRPV1 通道和 ASIC 的神经调节,醉茄甙减少了剂量为 40 mg/kg 的辣椒素和剂量为 4 和 40 mg/kg 的盐水的伤害感受行为,这是通过阻断醉茄甙的抗伤害作用来确定的。拮抗剂辣椒西平和纳洛酮。此外,与对照吗啡 (TRPV1) 和布洛芬 (COX-1) 相比,醉茄碱通过减少腹部水肿、消除肝组织中的白细胞浸润以及减少肝组织中的 ROS 产生抗炎作用,并呈现出更好的亲和能。和 COX-2)。
更新日期:2024-04-19
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