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法朗西:基于 Q 标志物概念和系统药理学与生物合成研究新策略揭示的物质基础、作用机制和质量控制标准。

Franch: Substance Basis, Mechanism of Action and Quality Control Standard Revealed Based on the Q-marker Concept and New Strategy of Systemic Pharmacology and Biosynthesis Research.

机构信息

School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 613100, P.R. China.

出版信息

Curr Top Med Chem. 2024;24(23):2013-2032. doi: 10.2174/0115680266305274240723120426.

DOI:10.2174/0115680266305274240723120426
PMID:39136504
Abstract

Franch. (Ranunculaceae, Coptis), a traditional Chinese medicine (TCM) with thousands of years of clinical use history, also a natural medicine available in many countries, has wide pharmacological mechanisms and significant bioactivity according to its traditional efficacy combined with modern scientific research. The quality marker (Q-marker) of Franch. is predicted in this paper based on the chemical composition and pharmacological effects of the plant, as well as the current system pharmacology, plant relatedness, biosynthetic pathways and quantitative analysis of multi-components (QAMS). Natural medicine has the advantage of being multi-component, multi-pathway and multi-target. However, there are few reports on safety evaluation. This review predicts the Q-marker of , the safety and efficacy of is provided. Studies from 1975 to 2023 were reviewed from PubMed, Elsevier, ScienceDirect, Web of Science, SpringerLink, and Google Scholar. Alkaloids and organic acids are the two main component categories of Q-Markers. The specific alkaloids identified through predictive results include berberine, coptisine, palmatine, epiberberine, jatrorrhizine, columbamine, and berberrubine. Quinic acid and malic acid, due to their influence on the content of alkaloids and their ability to aid in identifying the active components of , are also considered Q-markers. The research strategy of "exploring chemical components, exploring pharmacological activities, constructing pharmacological mechanism network and locating biosynthetic pathways" was used to accurately screen the quality markers of in this review and summarise the quality evaluation methods and criteria. In addition, we updated the biosynthetic pathway of and refined the specific synthetic pathways of jatrorrhizine (quality markers) and epiberberine (quality markers). Finally, we summarised the quality evaluation methods of , which provide an important reference for resource evaluation and provide a key reference for the discovery of new functional chemical entities for natural medicines.

摘要

黄连(毛茛科黄连属,又称鸡爪连)是一种具有数千年临床应用历史的传统中药,也是许多国家都有的天然药物,根据其传统功效与现代科学研究相结合,具有广泛的药理机制和显著的生物活性。本文基于植物的化学成分和药理作用、当前系统药理学、植物亲缘关系、生物合成途径和多成分定量分析(QAMS),预测了黄连的质量标志物(Q-marker)。天然药物具有多成分、多途径、多靶点的优势,但安全性评价报道较少。本综述预测了黄连的 Q-marker,为其安全性和功效提供了依据。从 1975 年至 2023 年,从 PubMed、Elsevier、ScienceDirect、Web of Science、SpringerLink 和 Google Scholar 检索了研究文献。生物碱和有机酸是 Q-Marker 的两个主要成分类别。通过预测结果确定的特定生物碱包括小檗碱、黄连碱、巴马汀、表小檗碱、药根碱、汉防己甲素和小檗红碱。奎宁酸和苹果酸由于其对生物碱含量的影响及其鉴定黄连活性成分的能力,也被认为是 Q-markers。本研究采用“探索化学成分、探索药理活性、构建药理机制网络和定位生物合成途径”的研究策略,准确筛选出黄连的质量标志物,并总结了质量评价方法和标准。此外,我们更新了黄连的生物合成途径,并细化了药根碱(质量标志物)和小檗红碱(质量标志物)的具体合成途径。最后,总结了黄连的质量评价方法,为资源评价提供了重要参考,为天然药物新功能化学实体的发现提供了关键参考。

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Coptisine, the Characteristic Constituent from , Exhibits Significant Therapeutic Potential in Treating Cancers, Metabolic and Inflammatory Diseases.小檗碱,来源于黄连的特征性成分,在治疗癌症、代谢和炎症性疾病方面具有显著的治疗潜力。
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本文引用的文献

1
Malic Acid Improves Behavioral, Biochemical, and Molecular Disturbances in the Hypothalamus of Stressed Rats.苹果酸改善应激大鼠下丘脑的行为、生化和分子紊乱。
J Integr Neurosci. 2023 Jul 17;22(4):98. doi: 10.31083/j.jin2204098.
2
Coptisine Inhibits Influenza Virus Replication by Upregulating p21.小檗碱通过上调 p21 抑制流感病毒复制。
Molecules. 2023 Jul 14;28(14):5398. doi: 10.3390/molecules28145398.
3
Essential Oils: Chemistry and Pharmacological Activities.香精油:化学与药理学活动。
Biomolecules. 2023 Jul 18;13(7):1144. doi: 10.3390/biom13071144.
4
Genome-wide analysis of bHLH gene family in Coptis chinensis provides insights into the regulatory role in benzylisoquinoline alkaloid biosynthesis.黄连基因组中 bHLH 基因家族的全基因组分析揭示了其在苯丙氨酸生物合成中的调控作用。
Plant Physiol Biochem. 2023 Aug;201:107846. doi: 10.1016/j.plaphy.2023.107846. Epub 2023 Jun 24.
5
Phylogenetic analysis and functional characterization of norcoclaurine synthase involved in benzylisoquinoline alkaloids biosynthesis in Stephania tetrandra.石菖蒲中参与苄基异喹啉生物碱生物合成的诺卡考林合酶的系统发育分析和功能表征。
J Cell Physiol. 2024 Oct;239(10):e31065. doi: 10.1002/jcp.31065. Epub 2023 Jun 25.
6
Effects of Jatrorrhizine on inflammatory response induced by HO in microglia by regulating the MAPK/NF-κB/NLRP3 signaling pathway.汉防己甲素通过调控 MAPK/NF-κB/NLRP3 信号通路对 HO 诱导小胶质细胞炎症反应的影响。
Mol Neurobiol. 2023 Oct;60(10):5725-5737. doi: 10.1007/s12035-023-03385-w. Epub 2023 Jun 20.
7
Rational Engineering of ()-Norcoclaurine Synthase for Efficient Benzylisoquinoline Alkaloids Biosynthesis.理性工程化()-去甲乌药碱合酶以高效生物合成苯并异喹啉生物碱。
Molecules. 2023 May 23;28(11):4265. doi: 10.3390/molecules28114265.
8
Discovery and identification of EIF2AK2 as a direct key target of berberine for anti-inflammatory effects.发现并鉴定EIF2AK2作为小檗碱抗炎作用的直接关键靶点。
Acta Pharm Sin B. 2023 May;13(5):2138-2151. doi: 10.1016/j.apsb.2022.12.009. Epub 2022 Dec 14.
9
Berberine activates PPARδ and promotes gut microbiota-derived butyric acid to suppress hepatocellular carcinoma.小檗碱激活 PPARδ,促进肠道微生物衍生的丁酸来抑制肝癌。
Phytomedicine. 2023 Jul;115:154842. doi: 10.1016/j.phymed.2023.154842. Epub 2023 Apr 28.
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Front Genet. 2023 Mar 23;14:1151645. doi: 10.3389/fgene.2023.1151645. eCollection 2023.