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基于网络药理学分析探讨半夏泻心汤对三硝基苯磺酸诱导溃疡性结肠炎大鼠作用的潜在机制。

Exploration of the potential mechanism of Banxia Xiexin Decoction for the effects on TNBS-induced ulcerative colitis rats with the assistance of network pharmacology analysis.

机构信息

Experiment Center of Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

出版信息

J Ethnopharmacol. 2021 Sep 15;277:114197. doi: 10.1016/j.jep.2021.114197. Epub 2021 May 15.

DOI:10.1016/j.jep.2021.114197
PMID:34004261
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Banxia Xiexin Decoction (BXD), an ancient TCM prescription originating from Treatise on Febrile Diseases (Shang Han Lun) of the Han Dynasty, has been widely used in modern clinical practice, especially for gastrointestinal diseases, including ulcerative colitis (UC). However, the modern decoction method of BXD differs from that of the original method. Thus, an exploration of the influence of the different decoction methods on the pharmacological effects is interesting and significant.

AIM OF THE STUDY

This study aimed to systematically compare the pharmacological effects of extracts of BXD on TNBS induce UC rats that were prepared by different methods, the ancient method and the modern method. The findings may provide important information for the further mechanical exploration of the classical prescription, contributing to the rational application and enhancing the understanding of BXD in modern applications or scientific research.

METHODS

Fifty-four SD rats were randomly divided into the following nine groups at n = 6/group: control group; model group; salicylazosulfapyridine group; BXD ancient extraction method's low-dose group (BXD-AED-L, 3.6 g BXD-AED/kg), medium-dose group (BXD-AED-M, 7.2 g BXD-AED/kg), and high-dose group (BXD-AED-H, 14.4 g BXD-AED/kg); and BXD modern extraction method's low-dose group (BXD-MED-L, 1 g BXD-MED/kg), medium-dose group (BXD-MED-M, 2 g BXD-MED/kg), and high-dose group (BXD-MED-H, 4 g BXD-MED/kg). All the groups, except the control group, were rectally injected with 70 mg/kg ethanol solution containing TNBS (2,4,6-trinitrobenzenesulfonic acid) to establish the UC models. The pharmacological evaluations including disease activity index, colon weight index, macroscopic and histological evaluation of colon damage, and inflammatory cytokine levels (IL-4, IL-10, IL-1β, TNF-α, and IL-6)were measured. In the network pharmacology analysis, the "herbs-components-targets-disease" network was constructed and visually analyzed with which the targets with a strong correlation with UC were screened out.

RESULTS

The results showed that both BXD-AED and BXD-MED might alleviate the severity of UC with different degrees according to the majority of indices that were evaluated. At similar doses, the BXD-AED groups performed better compared with the BXD-MED groups. With the assistance of the network pharmacology analysis, some key active components (quercetin, baicalein, wogonin, and baicalin) related to the anti-UC/inflammation were screened out. The contents of the components in BXD-AED were higher than those in BXD-MED. The joint results of the study indicated that BXD, an ancient TCM compound prescription, is an effective drug candidate for the modern treatment of UC.

摘要

民族药理学相关性

半夏泻心汤(BXD)是一种源自汉代《伤寒论》的古老中药方剂,在现代临床实践中被广泛应用,尤其用于胃肠道疾病,包括溃疡性结肠炎(UC)。然而,BXD 的现代煎煮方法与原始方法不同。因此,探索不同煎煮方法对药理作用的影响是有趣且有意义的。

研究目的

本研究旨在系统比较不同方法制备的 BXD 提取物对 TNBS 诱导的 UC 大鼠的药理作用,包括古代方法和现代方法。研究结果可能为进一步深入探讨经典方剂提供重要信息,有助于促进 BXD 在现代应用或科学研究中的合理应用和加深理解。

方法

54 只 SD 大鼠随机分为 9 组,每组 6 只:对照组;模型组;柳氮磺胺吡啶组;BXD 古代提取方法低剂量组(BXD-AED-L,3.6g BXD-AED/kg)、中剂量组(BXD-AED-M,7.2g BXD-AED/kg)和高剂量组(BXD-AED-H,14.4g BXD-AED/kg);BXD 现代提取方法低剂量组(BXD-MED-L,1g BXD-MED/kg)、中剂量组(BXD-MED-M,2g BXD-MED/kg)和高剂量组(BXD-MED-H,4g BXD-MED/kg)。除对照组外,其余各组均经直肠给予含 70mg/kg 乙醇溶液的 TNBS(2,4,6-三硝基苯磺酸),建立 UC 模型。通过疾病活动指数、结肠重量指数、结肠损伤的宏观和组织学评价以及炎症细胞因子水平(IL-4、IL-10、IL-1β、TNF-α 和 IL-6)评估进行药理学评价。在网络药理学分析中,构建了“草药-成分-靶点-疾病”网络,并对其进行了可视化分析,筛选出与 UC 相关性较强的靶点。

结果

结果表明,BXD-AED 和 BXD-MED 均可在不同程度上缓解 UC 的严重程度,根据大多数评估指标。在相似的剂量下,BXD-AED 组的表现优于 BXD-MED 组。借助网络药理学分析,筛选出与抗 UC/抗炎相关的一些关键活性成分(槲皮素、黄芩素、汉黄芩素和黄芩苷)。BXD-AED 中的成分含量高于 BXD-MED。研究结果表明,BXD 作为一种古老的中药复方制剂,是一种治疗 UC 的有效药物候选物。

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