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3,5,6,7,8,3',4'-七甲氧基黄酮通过调节机体体液中的肠道水通道蛋白的作用研究。

Study on the effect of 3,5,6,7,8,3',4'-heptamethoxyflavone in by regulating intestinal aquaporin in body fluids.

作者信息

Bai Ting-Ting, Xie Ya-Ting, Wan Quan, Zhang Jin-Lian

机构信息

Department of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, China.

Mongolian College of Medicine, Inner Mongolia Medical University, Hohhot, China.

出版信息

Front Pharmacol. 2025 May 19;16:1544570. doi: 10.3389/fphar.2025.1544570. eCollection 2025.

Abstract

BACKGROUND

(FA) can cause the drying of body fluids, although the specific mechanism of this process remains unclear. FA is used to promote stagnation and eliminate flatulence in traditional Chinese medicine. 3,5,6,7,8,3',4'-heptamethoxyflavone is the active metabolite in FA, and it contributes to the drying process. This paper presents an investigation into the underlying mechanisms of the effect of 3,5,6,7,8,3',4'-heptamethoxyflavone on body fluids through regulating the Aquaporin pathway.

METHODS

Human small intestinal epithelial cells (FHs74lnt), human colon histiocytes (CCD018Co), a normal mouse, and an AQP3 knockout mouse, were used in the study. Indicators included the water consumption, diet, and fecal water content of the mice, as well as pathological changes in the small intestinal and colon tissues and the relative expression of AQP3, AQP5, AQP7, and AQP11 mRNA in those tissues, and protein expression. ALD and ADH hormone levels, and the AQP3 upstream receptor genes AVPR1 and AVPR2 were also used as indicators for examination.

RESULTS

3,5,6,7,8,3',4'-heptamethoxyflavone has a strong desiccating impact on body fluids, causing an increase in water intake and a rise in the water content of feces. Additionally, animal experiments have suggested a connection to histological damage in the colon and small intestine, including lymphocyte infiltration, mucosal laminae breakage, and local ulceration. Additionally, the expression of the proteins Aquaporin 3, 5, 7, and 11 in the intestinal tissues may be regulated by 3,5,6,7,8,3',4'-heptamethoxyflavone. This metabolite also increases the expression of upstream receptor genes, allowing them to bind more easily to antidiuretic hormone and aldosterone, such as arginine vasopressin receptors 1 and 2. A number of changes in water intake and fecal water content were observed in response to 3,5,6,7,8,3',4'-heptamethoxyflavone in experiments conducted on Aquaporin3-/- mice. The control of water secretion and absorption in the body is thus impacted by alternating the Aquaporin 3 water channels.

CONCLUSION

3,5,6,7,8,3',4'-heptamethoxyflavone may affect upstream receptor genes, including AVPR1 and AVPR2, and promote their binding to ALD and ADH, which in turn affects the opening and closing of the AQP3 water channel to regulate water secretion and absorption in the body.

摘要

背景

(黄酮醋酸酯,FA)可导致体液干燥,尽管这一过程的具体机制尚不清楚。在传统中医中,FA被用于行气消胀。3,5,6,7,8,3',4'-七甲氧基黄酮是FA中的活性代谢产物,它促成了干燥过程。本文通过调节水通道蛋白途径,对3,5,6,7,8,3',4'-七甲氧基黄酮对体液影响的潜在机制进行了研究。

方法

本研究使用了人小肠上皮细胞(FHs74lnt)、人结肠组织细胞(CCD018Co)、正常小鼠和水通道蛋白3基因敲除小鼠。指标包括小鼠的饮水量、饮食量、粪便含水量,以及小肠和结肠组织的病理变化、这些组织中AQP3、AQP5、AQP7和AQP11 mRNA的相对表达及蛋白表达。醛固酮(ALD)和抗利尿激素(ADH)水平,以及AQP3上游受体基因AVPR1和AVPR2也作为检测指标。

结果

3,5,6,7,8,3',4'-七甲氧基黄酮对体液有强烈的干燥作用,导致饮水量增加和粪便含水量升高。此外,动物实验表明其与结肠和小肠的组织学损伤有关,包括淋巴细胞浸润、黏膜层破损和局部溃疡。此外,3,5,6,7,8,3',4'-七甲氧基黄酮可能调节肠道组织中水通道蛋白3、5、7和11的表达。这种代谢产物还增加了上游受体基因的表达,使其更容易与抗利尿激素和醛固酮结合,如精氨酸血管加压素受体1和2。在对水通道蛋白3基因敲除小鼠进行的实验中,观察到3,5,6,7,8,3',4'-七甲氧基黄酮导致了饮水量和粪便含水量的一些变化。因此,通过改变水通道蛋白3水通道,影响了体内水的分泌和吸收的控制。

结论

3,5,6,7,8,3',4'-七甲氧基黄酮可能影响包括AVPR1和AVPR2在内的上游受体基因,并促进它们与ALD和ADH的结合,进而影响AQP3水通道的开闭,以调节体内水的分泌和吸收。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467b/12127768/4b555035e024/fphar-16-1544570-g001.jpg

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