背景:HymenaeaeriogyneBenth(豆科)通常被称为“Jatoba”。尽管它在民间医学中用于治疗炎症性疾病,没有描述显示其抗炎潜力。
目的:从这个意义上说,这项研究旨在评估H.eriogyne的树皮和叶提取物的抗炎和抗蛇毒血清作用。
方法:通过角叉菜胶诱导的爪水肿和酵母聚糖诱导的气囊模型进行体内抗炎活性,评估水肿的作用,白细胞迁移,蛋白质浓度,促炎细胞因子的水平,丙二醛(MDA)和MPO活性。在体外研究了抗蛇毒血清的酶促作用(蛋白水解,磷脂酶和透明质酸酶)Bothropsbrazili和B.leucurus毒,以及在体内对白斑芽孢杆菌诱导的爪水肿模型的影响。此外,在计算机上研究了其标记物(astilbin和芦丁)对髓过氧化物酶(MPO)活性的影响。对于分子对接,AutodockVina,Biovia探索工作室,使用Chimera1.16软件。
结果:毛线菌的提取物、树皮和叶显示出很高的抗炎作用,所有评估的炎症参数均降低。与叶提取物相比,树皮提取物显示出优异的结果,表明了astilbin浓度的影响,树皮较高,抗炎作用。此外,只有黑毛虫树皮提取物能够降低丙二醛,表明相关的抗氧化作用。关于体外抗蛇毒血清的作用,提取物(树皮和叶子)揭示了抑制蛋白水解的能力,两种毒液的磷脂酶和透明质酸酶作用,对B.leucurus毒液有更大的效果。在体内,根结线虫的树皮和叶提取物(50-200mg/kg)显示出抗水肿活性,减少MPO和促炎细胞因子的释放,表明存在可用于控制由毒液诱导的炎症过程的生物活性成分。在计算机模拟分析中,astilbin和芦丁显示出9种可能的位置和朝向MPO的方向的可逆相互作用,具有-9.5和-10.4kcal/mol的亲和力,并且与Phe407,Gln91,His95和Arg239相互作用,是MPO的重要活动袋。芦丁表现出与MPO的更有效的相互作用类型。
结论:该方法首次揭示了H.eriogyne树皮和叶提取物在体内的抗炎作用,以及它的抗虫潜力。此外,在MPO下,作为抗氧化剂的药理学原的不同作用以及astilbin和芦丁的不同作用揭示了H.eriogyne提取物中存在的生物活性化合物的不同抗炎机制,具有新的药理药物的潜力。
BACKGROUND: Hymenaea eriogyne Benth (Fabaceae) is popularly known as \"Jatobá\". Despite its use in folk medicine to treat inflammatory disorders, there are no descriptions that show its anti-inflammatory potential.
OBJECTIVE: In this sense, this study aimed to evaluate the anti-inflammatory and antivenom action of bark and leaves extract of H. eriogyne.
METHODS: The in vivo anti-inflammatory activity was conducted by carrageenan-induced paw edema and zymosan-induced air pouch models, evaluating the edematogenic effect, leukocyte migration, protein concentration, levels of pro-inflammatory cytokines, malondialdehyde (MDA) and MPO activity. The antivenom potential was investigated in vitro on the enzymatic action (proteolytic, phospholipase and hyaluronidase) of Bothrops brazili and B. leucurus venom, as well as in vivo on the paw edema model induced by B. leucurus. Furthermore, the influence of its markers (astilbin and rutin) on myeloperoxidase (MPO) activity was investigated in silico. For molecular docking, AutodockVina, Biovia Discovery Studio, and Chimera 1.16 software were used.
RESULTS: The extracts and bark and leaves of H. eriogyne revealed a high anti-inflammatory effect, with a reduction in all inflammatory parameters evaluated. The bark extract showed superior results when compared to the leaf extract, suggesting the influence of the astilbin concentration, higher in the bark, on the anti-inflammatory action. In addition, only the H. eriogyne bark extract was able to reduce MDA, indicating an associated antioxidant effect. Regarding the in vitro antivenom action, the extracts (bark and leaves) revealed the ability to inhibit the proteolytic, phospholipase and hyaluronidase action of both bothropic venom, with a greater effect against B. leucurus venom. In vivo, extracts from the bark and leaves of H. eriogyne (50 - 200 mg/kg) showed antiedematogenic activity, reducing the release of MPO and pro-inflammatory cytokines, indicating the presence of bioactive components useful in controlling the inflammatory process induced by the venom. In the in silico assays, astilbin and rutin showed reversible interactions of 9 possible positions and orientations towards MPO, with affinities of -9.5 and -10.4 kcal/mol and interactions with Phe407, Gln91, His95 and Arg239, important active pockets of MPO. Rutin demonstrated more effective types of interactions with MPO.
CONCLUSIONS: This approach reveals for the first time the anti-inflammatory action of H. eriogyne bark and leaf extracts in vivo, as well as its antiophidic potential. Moreover, the distinct effect of pharmacogens as antioxidant agents and distinct effect of astilbin and rutin under MPO sheds light on the different anti-inflammatory mechanisms of bioactive compounds present in H. eriogyne extracts, with high potential for the prospection of new pharmacological agents.