研究动态
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Casearia sylvestris 变种lingua (Càmbess.) Eichler 叶水提取物通过粘液生成、抗氧化和抗炎作用改善 TNBS 诱导的 IBD 大鼠的结肠炎症。

Casearia sylvestris var. lingua (Càmbess.) Eichler leaves aqueous extract improves colon inflammation through mucogenic, antioxidant and anti-inflammatory actions in TNBS- induced IBD rats.

发表日期:2024 May 25
作者: Karuppusamy Arunachalam, Monica Steffi Matchado, Amilcar Sabino Damazo, Claudia Andrea Lima Cardoso, Thiago Luis Aguayo de Castro, Adrivanio Baranoski, Silvia Cordeiro das Neves, Domingos Tabajara de Oliveira Martins, Valter Aragão do Nascimento, Rodrigo Juliano Oliveira
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

Casearia sylvestris 变种lingua (Cambess.) Eichler 是杨柳科的一员,由于其多功能的治疗特性,在不同文化的传统医学中占有重要地位。从历史上看,土著社区利用植物的不同部分,包括叶子、树皮和根,来解决各种健康问题。 C. sylvestris var. 的传统用途lingua 涵盖胃肠道疾病、呼吸道感染、伤口愈合、炎症和胃溃疡的治疗。药理学研究表明该植物具有抗菌、抗炎、抗氧化、镇痛、胃保护和免疫调节作用。这标志着樟子松对抗溃疡性结肠炎有效性的第一份科学验证报告。该报告旨在通过临床前实验确认该植物的传统用途。这项工作使用了樟子松的水提取物。舌叶 (AEC) 在大鼠和 HT-29(人结直肠癌细胞系)模型中评估急性抗溃疡性结肠炎功效。为了确定 AEC 的次级代谢产物,采用二极管阵列检测器液相色谱 (LC-DAD) 研究进行了。使用 2,4,6-三硝基苯磺酸(TNBS,30 mg/0.25 mL EtOH 30% v/v)灌肠引起急性结肠炎。花了三天时间给予 C. sylvestris var。林瓜提取物以 3、30 和 300 mg/kg 的剂量口服灌胃。使用相同的路线向车辆和幼稚组输送蒸馏水。第四天处死动物后,取出肠组织进行组织学检查和生化测试评估,例如超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)、过氧化氢酶(CAT)、丙二醛(MDA)、亚硝酸盐/硝酸盐、髓过氧化物酶 (MPO) 活性。此外,还对肠组织进行了白细胞介素 1 β (IL-1β)、肿瘤坏死因子 α (TNF-α) 和白细胞介素 10 (IL-10) 检测。此外,MTT 测定用于评估 AEC 对 HT-29 细胞活力的影响。此外,还进行了分子对接研究,以将一些潜在的靶蛋白与 AEC 中发现的化学物质进行比较。LC-DAD 分析确定了 AEC 中的五种化合物(咖啡酸、鞣花酸、阿魏酸、没食子酸和槲皮素)。预施用 AEC(3;30;300 mg/kg)和美沙拉秦(500 mg/kg)可降低宏观评分(55%、47%、45% 和 52%,p < 0.001)和溃疡面积(70.3%) 、70.5%、57% 和 56%,p < 0.001)。与结肠炎组相比,它还增加了 SOD、GSH 和 CAT 活性 (p < 0.01),同时降低了 MDA (p < 0.001)、亚硝酸盐/硝酸盐 (p < 0.05) 和 MPO (p < 0.001) 活性。关于炎症标志物,观察到显着的调节:与对照组相比,AEC(3、30 和 300 mg/kg)降低了 IL-1β 和 TNF-α 水平(p < 0.001),增加了 IL-10 水平(p < 0.001)。结肠炎组。 AEC 抑制 HT-29 细胞的活力,IC50 为 195.90 ± 0.01 μg/mL(48 小时)。在分子对接分析过程中,槲皮素、没食子酸、阿魏酸、咖啡酸和鞣花酸表现出一致的结合亲和力,与 3w3l (TLR8) 和 3ds6 (MAPK14) 复合物形成稳定的相互作用。这些结果表明肠道粘原性、 C. sylvestris var. 的抗炎和抗氧化特性。舌叶提取物可能参与其对溃疡性结肠炎的治疗作用。计算机研究的结果表明槲皮素和鞣花酸可能分别以有益的方式与 P38 和 TLR8 相互作用。版权所有 © 2024。由 Elsevier B.V. 出版。
Casearia sylvestris var. lingua (Cambess.) Eichler, a member of the Salicaceae family, holds a prominent place in traditional medicine across various cultures due to its versatile therapeutic properties. Historically, indigenous communities have utilized different parts of the plant, including leaves, bark, and roots, to address a wide array of health conditions. Traditional uses of C. sylvestris var. lingua encompasses the treatment of gastrointestinal disorders, respiratory infections, wound healing, inflammation, and stomach ulcers. Pharmacological studies have demonstrated the plant's antimicrobial, anti-inflammatory, antioxidant, analgesic, gastroprotective, and immunomodulatory effects. This signifies the first scientific validation report for C. sylvestris regarding its effectiveness against ulcerative colitis. The report aims to affirm the traditional use of this plant through pre-clinical experiments.This work uses an aqueous extract from C. sylvestris var. lingua leaves (AECs) to evaluate the acute anti-ulcerative colitis efficacy in rat and HT-29 (human colorectal cancer cell line) models.To determine the secondary metabolites of AECs, liquid chromatography with a diode array detector (LC-DAD) study was carried out. 2,4,6-trinitrobenzenesulfonic acid (TNBS, 30 mg/0.25 mL EtOH 30% v/v) was used as an enema to cause acute colitis. Three days were spent giving the C. sylvestris var. lingua extract orally by gavage at dosages of 3, 30, and 300 mg/kg. The same route was used to deliver distilled water to the vehicle and naïve groups. After the animals were sacrificed on the fourth day, intestinal tissues were taken for histological examination and evaluation of biochemical tests such as those measuring superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA), nitrite/nitrate, myeloperoxidase (MPO) activity. Additionally, interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10), were conducted on the intestinal tissues. Additionally, an MTT assay was used to evaluate the effect of AECs on the viability of HT-29 cells. Additionally, a molecular docking study was carried out to compare some potential target proteins with identified chemicals found in AECs.LC-DAD analysis identified five compounds (caffeic acid, ellagic acid, ferulic acid, gallic acid, and quercetin) in AECs. Pre-administration of AECs (3; 30; 300 mg/kg) and mesalazine (500 mg/kg) reduced macroscopic scores (55%, 47%, 45%, and 52%, p < 0.001) and ulcerated areas (70.3%, 70.5%, 57%, and 56%, p < 0.001), respectively. It also increased SOD, GSH, and CAT activities (p < 0.01), while decreasing MDA (p < 0.001), nitrite/nitrate (p < 0.05), and MPO (p < 0.001) activities compared to the colitis group. Concerning inflammatory markers, significant modulations were observed: AECs (3, 30, and 300 mg/kg) lowered levels of IL-1β and TNF-α (p < 0.001) and increased IL-10 levels (p < 0.001) compared to the colitis groups. The viability of HT-29 cells was suppressed by AECs with an IC50 of 195.90 ± 0.01 μg/mL (48 h). During the molecular docking analysis, quercetin, gallic acid, ferulic acid, caffeic acid, and ellagic acid demonstrated consistent binding affinities, forming stable interactions with the 3w3l (TLR8) and the 3ds6 (MAPK14) complexes.These results imply that the intestinal mucogenic, anti-inflammatory, and antioxidant properties of the C. sylvestris var. lingua leaf extract may be involved in its therapeutic actions for ulcerative colitis. The results of the in silico study point to the possibility of quercetin and ellagic acid interacting with P38 and TLR8, respectively, in a beneficial way.Copyright © 2024. Published by Elsevier B.V.