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枳壳黄酮促进胃肠动力的机制:基于有机与无机内源性物质结合的视角

Mechanism of Fructus Aurantii Flavonoids Promoting Gastrointestinal Motility: From Organic and Inorganic Endogenous Substances Combination Point of View.

作者信息

Wang Shuai, Bao Yong-Rui, Li Tian-Jiao, Yu Ting, Chang Xin, Yang Guan-Lin, Meng Xian-Sheng

机构信息

School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.

Component Medicine Engineering Research Center of Liaoning Province, Dalian 116600, China.

出版信息

Pharmacogn Mag. 2017 Jul-Sep;13(51):372-377. doi: 10.4103/pm.pm_179_16. Epub 2017 Jul 19.

Abstract

BACKGROUND

Fructus Aurantii (FA) derived from the dried, and unripe fruit of L. is one of the commonly used traditional Chinese medicines to treat gastrointestinal motility dysfunction diseases. According to the literature research, FA flavonoids (FAF) are important active ingredients of FA promoting gastrointestinal motility, but the exact material basis and mechanism of action are still not very clear.

OBJECTIVE

This experiment was designed to illustrate the material basis of FAF promoting gastrointestinal motility and explore the mechanism of action from an organic and inorganic combination point of view.

MATERIALS AND METHODS

In this experiment, high-performance liquid chromatography (HPLC) method was used to analyze the composition and content of FAF. Based on the prominent prokinetic effect of FAF on mice, the mechanism of action was speculated through a combination of HPLC coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) and inductively coupled plasma mass spectrometry (ICP-MS).

RESULTS

With the method of HPLC, ten dominating components of FAF including neoeriocitrin, narirutin, rhoifolin, naringin, hesperidin, neohesperidin, neoponcirin, naringenin, hesperetin, and nobiletin accounting for more than 86% of FAF were identified. Combined HPLC-QTOF-MS with ICP-MS, the endogenous substances with difference in the blood of mice were analyzed, in which 4-dimethylallyltryptophan, corticosterone, phytosphingosine, sphinganine, LysoPC (20:4(5Z, 8Z, 11Z, 14Z)), LysoPC(18:2 (9Z, 12Z)), and Ca, Mg, Zn metal ions had significant changes, involving tryptophan metabolism, corticosterone metabolism, sphingolipid metabolism, and other pathways.

CONCLUSION

The results preliminarily elaborated the mechanism of FAF promoting gastrointestinal motility from an organic and inorganic point of view, which provide valuable information for researching and developing new multi-component Chinese medicine curing gastrointestinal underpower associated diseases.

SUMMARY

Fructus Aurantii flavonoids are one of the main components of Fructus Aurantii that possess prominent gastrointestinal motility promoting efficacyThe mainly material basis of Fructus Aurantii flavonoids promoting gastrointestinal motility were neoeriocitrin, narirutin, rhoifolin, naringin, hesperidin, neohesperidin, neoponcirin, naringenin, hesperetin, and nobiletinFructus Aurantii flavonoids can regulate the content of 4-dimethylallyltryptophan, corticosterone, phytosphingosine, sphinganine, LysoPC (20:4(5Z, 8Z, 11Z, 14Z)), LysoPC.(18:2(9Z, 12Z)) and Ca, Mg, Zn-metal ions, through tryptophan metabolism, corticosterone metabolism, sphingolipid metabolism, and other pathways to present its gastrointestinal motility promoting efficacy. FA: Fructus Aurantii; FAF: Fructus Aurantii flavonoids; HPLC: High performance liquid chromatography; HPLC-QTOF-MS: High performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry; ICP-MS: Inductively coupled plasma mass spectrometry; PCA: Principal components analysis; CG: Control group; FAFLG: Low-dosage group of Fructus Aurantii flavonoids; FAFMG: Middle-dosage group of Fructus Aurantii flavonoids; FAFHG: High-dosage group of Fructus Aurantii flavonoids; DPG: Domperidone group.

摘要

背景

枳实来源于酸橙干燥未成熟果实,是治疗胃肠动力障碍性疾病常用的传统中药之一。据文献研究,枳实黄酮是枳实促进胃肠动力的重要活性成分,但确切物质基础及作用机制尚不完全明确。

目的

本实验旨在阐明枳实黄酮促进胃肠动力的物质基础,并从有机和无机结合角度探讨其作用机制。

材料与方法

本实验采用高效液相色谱法分析枳实黄酮的组成及含量。基于枳实黄酮对小鼠显著的促胃肠动力作用,通过高效液相色谱-四极杆飞行时间质谱联用(HPLC-QTOF-MS)及电感耦合等离子体质谱(ICP-MS)联用推测其作用机制。

结果

采用高效液相色谱法鉴定出枳实黄酮中含量占比超过86%的10种主要成分,包括新橙皮苷、柚皮芸香苷、异鼠李素-3-O-芸香糖苷、柚皮苷、橙皮苷、新橙皮苷、新枳苷、柚皮素、橙皮素及川陈皮素。结合HPLC-QTOF-MS与ICP-MS分析小鼠血液中差异内源性物质,其中4-二甲基烯丙基色氨酸、皮质酮、植物鞘氨醇、鞘氨醇、溶血磷脂酰胆碱(20:4(5Z, 8Z, 11Z, 14Z))、溶血磷脂酰胆碱(18:2(9Z, 12Z))以及钙、镁、锌金属离子有显著变化,涉及色氨酸代谢、皮质酮代谢、鞘脂代谢等途径。

结论

本研究结果从有机和无机角度初步阐明了枳实黄酮促进胃肠动力的机制,为研发治疗胃肠动力不足相关疾病的新型多组分中药提供了有价值的信息。

总结

枳实黄酮是枳实具有显著促胃肠动力功效的主要成分之一。枳实黄酮促胃肠动力的主要物质基础为新橙皮苷、柚皮芸香苷、异鼠李素-3-O-芸香糖苷、柚皮苷、橙皮苷、新橙皮苷、新枳苷、柚皮素、橙皮素及川陈皮素。枳实黄酮可通过色氨酸代谢、皮质酮代谢、鞘脂代谢等途径调节4-二甲基烯丙基色氨酸、皮质酮、植物鞘氨醇、鞘氨醇、溶血磷脂酰胆碱(20:4(5Z, 8Z, 11Z, 14Z))、溶血磷脂酰胆碱(18:2(9Z, 12Z))以及钙、镁、锌金属离子的含量,从而发挥其促胃肠动力功效。 FA:枳实;FAF:枳实黄酮;HPLC:高效液相色谱;HPLC-QTOF-MS:高效液相色谱-四极杆飞行时间质谱联用;ICP-MS:电感耦合等离子体质谱;PCA:主成分分析;CG:对照组;FAFLG:枳实黄酮低剂量组;FAFMG:枳实黄酮中剂量组;FAFHG:枳实黄酮高剂量组;DPG:多潘立酮组。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6fa/5551352/81a8ed2d3122/PM-13-372-g001.jpg

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