南美洲的亚马逊雨林地区和中美洲的热带森林中可以找到毛红壳（学名：Virola elongata (Benth.) War.，樟科），在马托格罗索州被称为"mucuíba"。该树种的茎皮浸膏从传统上被用于治疗各种健康问题，包括胃溃疡、感染、炎症和其他疾病。在科学文献中，毛红壳表现出抗溃疡、胃护理、抗增生、抗有丝分裂和精神活性等药理性质。然而，值得注意的是，毛红壳的安全性尚未得到充分确定。 为评估毛红壳茎皮的水乙醇浸膏（HEVe）在体内和体外实验模型中的毒性。HEVe由茎皮粉末浸泡于70%的水乙醇溶液中（1:10 w/v）获得。通过Alamar蓝实验评估HEVe（3.125-200 μg/mL）对中国仓鼠卵巢上皮细胞（CHO-k1）和人胃腺癌细胞（AGS）的细胞毒性作用。通过微核试验评估HEVe（10、30或100 μg/mL）对CHO-k1细胞的遗传毒性。通过单剂量口服给药（2000 mg/kg）评估HEVe的急性毒性。通过在大鼠中连续30天给予口服300、600和1200 mg/kg的浸膏评估HEVe的亚急性毒性。对毒理学参数的临床观察每6天记录一次。处理结束后，采集血液进行血液学和生化分析，并取出一些组织进行宏观和组织病理学分析。 HEVe在CHO-k1和AGS细胞中没有显示细胞毒性（IC50 > 200 μg/mL），也没有在CHO-k1细胞中引起DNA损伤。在单剂量口服给药（2000 mg/kg）的小鼠中，HEVe未导致死亡，雄性小鼠体重变化减少（33.03%，p < 0.05），胃的相对重量增加（12.82%，p < 0.05），雌性小鼠脾脏的相对重量增加（25.00%，p < 0.01）。在亚急性毒性评估中，HEVe在30天内未导致动物死亡。观察到HEVe治疗组中，300和600 mg/kg浸膏组在第6天的饮水量分别减少36.65%和34.12%，并且600 mg/kg HEVe处理的动物的尿液排出量在整个实验过程中显示出增加（p < 0.05），在第12天时达到最大值46.72%。血细胞计数显示300 mg/kg剂量降低（p < 0.05）淋巴细胞的绝对数量，而300、600或1200 mg/kg HEVe剂量将全血中的红细胞计数降低24.84%（p < 0.01）、16.72%（p < 0.05）和22.14%（p < 0.01），并分别降低单核细胞（p < 0.05）的绝对数量59.77%、65.51%和79.81%。至于生化参数，在最高剂量下，发现血糖水平增加22.41%（p < 0.05），而肌酐在300 mg/kg剂量下降低44.71%（p < 0.05）。在接受三个剂量测试的动物中，AST和碱性磷酸酶的血浆水平与溶剂组相比显示降低（p < 0.05）。然而，观察到的血液学和生化变化均在这种动物物种的生理限度范围内。在30天内，给予的三个剂量的HEVe未观察到动物器官的宏观和组织病理学变化。 结果显示，HEVe在体外未显示细胞毒性或遗传毒性。在啮齿动物中，HEVe在急性和亚急性毒性试验中证明是安全的。大鼠中未观察到明显不良反应剂量（NOAEL）大于1200 mg/kg p.o.。 版权所有 © 2023 合作出版Elsevier B.V.。

Virola elongata (Benth.) War. (Myrsticaceae), referred to as "mucuíba" in Mato Grosso, is a native tree species that can be found in the Amazon Rainforest regions of South America and the Tropical Forests of Central America. The macerated extracts from the stem bark of this tree have been traditionally used to address various health issues, including gastric ulcers, infections, inflammations, and other ailments. In scientific literature, V. elongata has demonstrated pharmacological properties such as antiulcer, gastroprotective, antiproliferative, antimitotic, and psychoactive effects. Nevertheless, it is important to note that the safety profile of V. elongata has not been thoroughly established.To evaluate the toxicity of the hydroethanolic extract of the stem bark of Virola elongata (HEVe) in experimental models in vivo and in vitro.HEVe was obtained by macerating the stem bark powder in 70% hydroethanolic solution (1:10 w/v). The cytotoxicity of HEVe (3.125-200 μg/mL) was evaluated by Alamar blue assay in Chinese hamster ovary epithelial cells (CHO-k1) and human gastric adenocarcinoma (AGS). Genotoxicity assessment of HEVe (10, 30, or 100 μg/mL) was performed in CHO-k1 cells by the micronucleus test. The acute toxicity of HEVe was assessed by single-dose oral administration (2000 mg/kg) in mice of both sexes. The subacute toxicity of HEVe was assessed by oral administration of 300, 600, and 1200 mg/kg of the extract over 30 days in rats. Clinical observations of toxicological parameters were noted and pooled every 6 days. After the treatment period, blood was collected for hematological and biochemical analyses, and some organs were removed for macroscopic and histopathological analyses.HEVe did not show cytotoxicity in CHO-k1 and AGS cells (IC50 > 200 μg/mL) and did not cause DNA damage in CHO-k1 cells. Oral administration of HEVe in a single dose of 2000 mg/kg did not result in the death of the mice, with a reduction in body weight variation (33.03%, p < 0.05) and an increase in the relative weight of the stomach (12 .82%, p < 0.05) in male mice, and increased relative weight of the spleen (25.00%, p < 0.01) in female mice. In the assessment of subacute toxicity, HEVe did not result in the death of the animals over the 30 days. A reduction (p < 0.05) in water consumption of 36.65% and 34.12% was observed in the groups treated with 300 and 600 mg/kg, respectively, of HEVe on D6., and the urine excretion of animals treated with 600 mg/kg of HEVe showed an increase (p < 0.05) throughout the experiment, with a maximum value of 46.72% on D12. The blood counts showed that the dose of 300 mg/kg reduced (p < 0.05) the absolute number of lymphocytes, while the doses of 300, 600, or 1200 mg/kg of HEVe reduced the red blood cell count in whole blood by 24.84% (p < 0.01), 16.72% (p < 0.05), and 22.14% (p < 0.01), and the absolute number of monocytes (p < 0.05) in 59.77%, 65.51%, and 79.81%, respectively. As for the biochemical parameters, the glucose level found increased by 22.41% (p < 0.05) only at the highest dose, while creatinine was reduced by 44.71% (p < 0.05) at the dose of 300 mg/kg of HEVe. In animals treated with the three doses tested, plasma levels of AST and alkaline phosphatase showed a reduction (p < 0.05) with the vehicle group. However, the hematological and biochemical changes observed are within the physiological limits for this animal species. No macroscopic and histopathological changes were observed in the organs of the animals treated with the three doses of HEVe within 30 days.The results showed that HEVe did not show cytotoxicity or genotoxicity in vitro. HEVe proved to be safe in rodents in both acute and subacute toxicity tests. In rats, the no-observed-adverse-effect level (NOAEL) dose was greater than 1200 mg/kg p.o. in rats.Copyright © 2023. Published by Elsevier B.V.