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黄芩-黄连提取物单煎液与合煎液对大鼠急性酒精性肝损伤的影响及机制初步研究

Primary study on the effects and mechanisms of separate and combined decoctions of Scutellaria baicalensis Georgi - Coptis chinensis Franch extracts in relieving acute alcoholic liver injury in rats.

作者信息

Shen Yingyan, Zhao Yixin, Zhong Chunxue, Huang Hanmei, Yang Zaiqing, Wu Mingxing, Lu Lingzhi, Yang Rongping, Ke Xiumei

机构信息

Key Laboratory Breeding Base of Systematic Research and Utilization on Chinese Meterial, Medical Resources Co-founded by Sichuan Province and Ministry of Science and Technology, Chengdu University of Traditional Chinese Medicine, Chendu, China.

Chongqing Key Laboratory of Chinese Medicine New Drug Screening, Southwest University, Chongqing, China.

出版信息

J Ethnopharmacol. 2024 Apr 24;324:117790. doi: 10.1016/j.jep.2024.117790. Epub 2024 Jan 20.

DOI:10.1016/j.jep.2024.117790
PMID:38253276
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Scutellaria baicalensis Georgi (SBG) and Coptis chinensis Franch (CCF) are traditional herbal medicine pairs used for clearing heat and eliminating dampness, stopping diarrhea, and detoxification. Traditionally, these two herbs are combined and decocted together, but the modern preparation procedures separate them to avoid the large amount of precipitation generated from co-decoction. Thus, a conflict lies between the traditional and modern extraction processes of Scutellaria baicalensis Georgi - Coptis chinensis Franch (SBG-CCF).

AIM OF STUDY

There is a conflict between traditional medical practices of SBG-CCF and the modern formulation industry. In this study, we investigated the differences in the effects and mechanisms of SBG-CCF extracted by decocting separately and combining decoctions, as well as the scientific effectiveness of traditional and modern treatment methods on both. Acute alcoholic liver injury (ALI) rats were used as the pathological model.

MATERIALS AND METHODS

SD rats were divided into 8 groups, including blank group, model group, low, medium, and high dose groups of SBG-CCF separated decoction, low, medium, and high dose groups of SBG-CCF combined decoction. Acute alcoholic liver injury model was induced in rats by gradually increasing the dose of alcohol through gavage everyday using white wine with an alcohol content 52%. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) were used as indicators to assess the intervention effect of SBG-CCF. And the potential active ingredients of SBG-CCF and the targets related to ALI were screened using network pharmacology, and the prediction results of network pharmacology were verified by quantitative real-time fluorescence PCR (qRT-PCR).

RESULTS

SBG-CCF decoction alone and six combinations of decoctions have different degrees of improvement on alcoholic liver injury, with significant efficacy in the middle-dose group, and the combined decoction was superior to the individual decoction. SBG-CCF gavage can reduce the activity of AST, ALT, TC, TG, LDH, and MDA in the serum and liver of ALI rats, while increasing the levels of SOD and GSH. Network pharmacological analysis identified 39 active components, mainly flavonoids and alkaloids. Enrichment analysis suggested that SBG-CCF may treat ALI through the regulation of tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), interleukin-17 (IL-17), apoptosis, and the Toll-like receptor signaling pathways. The key targets in the Disease-Signaling Pathway-Target Network were MAPK8, IKBKB, MAPK10, MAPK3, MAPK1, and AKT1. qRT-PCR results indicated that targets regulating inflammation and lipid metabolism are MAPK8, MAPK10, MAPK3, and AKT1.

CONCLUSION

SBG-CCF separately extracts and combines decoction can alleviate acute alcoholic liver injury, and the effect of combined decoction is more significant than separate decoction, implying that the precipitate produced by the combination of the two is also an active substance. The resistance mechanism of SBG-CCF ALI may be related to the modulation of lipid metabolism, inhibition of lipid peroxidation, and oxidative stress. SBG-CCF has the characteristics of multi-component, multi-pathway, and multi-target resistance to ALI.

摘要

民族药理学相关性

黄芩(SBG)和黄连(CCF)是用于清热燥湿、止泻和解毒的传统草药对。传统上,这两种草药一起配伍煎煮,但现代制备工艺将它们分开以避免合煎产生大量沉淀。因此,黄芩 - 黄连(SBG - CCF)的传统与现代提取工艺之间存在冲突。

研究目的

SBG - CCF的传统医学实践与现代制剂行业之间存在冲突。在本研究中,我们研究了分别煎煮和合煎提取的SBG - CCF在效果和机制上的差异,以及传统和现代治疗方法对两者的科学有效性。以急性酒精性肝损伤(ALI)大鼠作为病理模型。

材料与方法

将SD大鼠分为8组,包括空白组、模型组、SBG - CCF分煎的低、中、高剂量组,SBG - CCF合煎的低、中、高剂量组。通过每天用酒精含量为52%的白酒灌胃逐渐增加酒精剂量诱导大鼠急性酒精性肝损伤模型。采用天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆固醇(TC)、甘油三酯(TG)、乳酸脱氢酶(LDH)、丙二醛(MDA)、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)作为指标评估SBG - CCF的干预效果。并利用网络药理学筛选SBG - CCF的潜在活性成分和与ALI相关的靶点,通过定量实时荧光PCR(qRT - PCR)验证网络药理学的预测结果。

结果

SBG - CCF单独煎煮及六种合煎组合对酒精性肝损伤均有不同程度改善,中剂量组疗效显著,且合煎优于分煎。SBG - CCF灌胃可降低ALI大鼠血清和肝脏中AST、ALT、TC、TG、LDH和MDA的活性,同时提高SOD和GSH水平。网络药理学分析鉴定出39种活性成分,主要为黄酮类和生物碱类。富集分析表明,SBG - CCF可能通过调节肿瘤坏死因子(TNF)、丝裂原活化蛋白激酶(MAPK)、白细胞介素 - 17(IL - 17)、凋亡和Toll样受体信号通路治疗ALI。疾病 - 信号通路 - 靶点网络中的关键靶点为MAPK8、IKBKB、MAPK10、MAPK3、MAPK1和AKT1。qRT - PCR结果表明,调节炎症和脂质代谢的靶点为MAPK8、MAPK10、MAPK3和AKT1。

结论

SBG - CCF分煎和合煎均可减轻急性酒精性肝损伤,且合煎效果比分煎更显著,这意味着两者合煎产生的沉淀物也是一种活性物质。SBG - CCF抗ALI的作用机制可能与调节脂质代谢、抑制脂质过氧化和氧化应激有关。SBG - CCF对ALI具有多成分、多途径、多靶点的抗性特点。

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