巴西红山茄（Apocynaceae）是一种树，在巴西尤其是亚马逊地区有分布，被当地土著和克里奥人民使用于民间草药治疗疟疾、麻风病、风湿病、癌症、糖尿病和炎症性疾病。然而，到目前为止，还没有科学报告证明其作为抗炎和愈伤剂的流行用途。本研究旨在分离吲哚类生物碱，并研究巴西红山茄树皮水乙醇提取物（An）的安全性、抗炎和愈伤特性。化合物通过不同的色谱学方法分离，并通过广泛的光谱分析确定结构。安全性通过体外使用三甲基四唑盐酸盐（MTT）试剂对小鼠成纤维母细胞（3T3）和猴肾细胞（Vero E6）株系进行评估，以及溶血试验的评估，并通过急性毒性模型进行体内评估，小鼠通过胃内给予2000毫克/千克的安，以内服的方式给予单次剂量，对行为、血液学和生化参数进行评估。抗水肿效应通过角叉菜胶导致的爪水肿模型进行监测，治疗动物通过胃内给予50、100和200毫克/千克的安，量化水肿百分比（0-4小时），测定髓过氧化物酶（MPO）和促炎症细胞因子（TNF-α、IL-6和IL-1β）水平。抗炎活性通过藏红花空气囊模型进行展示，治疗动物通过胃内给予50、100和200毫克/千克的安，确定白细胞数量、MPO、总蛋白和细胞因子水平。此外，愈合潜力通过皮肤创伤模型进行评估，治疗小鼠在伤口区域接受50、100和200毫克/毫升的安，拍摄伤口皮肤照片并计算面积。总共，在An中分离出五种化合物，包括一种新的8,9-蒲公英木素葡萄糖苷和四种已知的吲哚类生物碱。MTT和溶血试验表明，所有浓度的提取物都没有细胞毒性。急性毒性模型也显示使用提取物后没有毒性迹象或对行为、生化和血液学参数的显著变化。在水肿模型中，An显著减少了水肿百分比，以及MPO和促炎症细胞因子的水平。以同样的方式，An在藏红花空气囊实验中显示出减少白细胞迁移（主要是多形核细胞）、总蛋白、MPO和细胞因子浓度的效果。此外，An还展示了愈伤效应，减少了皮肤创伤面积。我们的结果首次证明了巴西红山茄的抗炎和愈伤特性，证明了其在传统医学中的使用的合理性。此外，包括体外细胞毒性和体内急性毒性测试，这些结果表明了该提取物的使用安全性。版权所有©2023。由Elsevier B.V.出版。

Aspidosperma nitidum Benth (Apocynaceae) is a tree found in Brazil especially in the Amazonia region, known as "carapanaúba", being used by indigenous and cabloco population in folk medicine in the treatment of malaria, leprosy, rheumatism, cancer, diabetes and inflammatory disorders. However, there are no scientific reports, up to now, to evidence its popular use as anti-inflammatory and healing agent.This study aimed to isolate indole alkaloids, as well as investigate the safety, anti-inflammatory and healing properties of hydroethanol extract from the stem barks of Aspidosperma nitidum Benth (An).The compounds were isolated using diverse chromatographic methodologies and the structures were determined by extensive spectroscopic analyses. The safety was evaluated in vitro through 3-methyl-[4-5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay using murine fibroblast (3T3) and monkey kidney (Vero E6) cell lines and by the hemolytic assay, as well as, in vivo, through acute toxicity model, which the mice received a single dose of 2000 mg/kg of An, by intra-gastric (i.g.) route, and behavioral, hematological and biochemical parameters were evaluated. The anti-edematogenic effect was monitored through carrageenan-induced paw edema model, in which the rodents were treated with 50, 100 and 200 mg/kg of An by i. g., the percentage of edema (0-4 h), myeloperoxidase (MPO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) levels were quantified. The anti-inflammatory activity was demonstrated through the zymosan-air-pouch model, in which the animals were treated with 50, 100 and 200 mg/kg of An by i. g, and the leukocytes number, MPO, total protein and cytokines levels were determined. In addition, the healing potential was evaluated through a skin wound model, in which the mice received 50, 100 and 200 mg/mL of An in wound area, and the wound skins were photographed and the area calculated.In total, five compounds were isolated in the An, being a new 8,9-dinorneolignan glucoside and four known indole alkaloids. The MTT and hemolytic assays, in all concentrations of the extract, demonstrated not be cytotoxic. Acute toxicity model also evidenced no sign of toxicity or significant changes on the behavior, biochemical and hematological parameters after use of the extract. In the edematogenic model, the An reduced significantly the percentage of edema, as well as, the MPO and pro-inflammatory cytokines levels. The same form, An revealed to be efficient in decreasing the leukocytes migration (mainly polymorphonuclears), total proteins, MPO and cytokines concentrations in the zymosan-air-pouch assay. Moreover, the An revealed a healing effect, reducing the area of the skin wound.Ours results evidence in the first time, the anti-inflammatory and healing property of An, justifying its use in traditional medicine. Moreover, include cytotoxicity in vitro and acute toxicity in vivo tests, which indicate the safety of use of the extract.Copyright © 2023. Published by Elsevier B.V.