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

BackgroundFructus aurantii (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...

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Main Authors: Ting-Ting Bai, Ya-Ting Xie, Quan Wan, Jin-Lian Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1544570/full
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author Ting-Ting Bai
Ting-Ting Bai
Ya-Ting Xie
Quan Wan
Jin-Lian Zhang
author_facet Ting-Ting Bai
Ting-Ting Bai
Ya-Ting Xie
Quan Wan
Jin-Lian Zhang
author_sort Ting-Ting Bai
collection DOAJ
description BackgroundFructus aurantii (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.MethodsHuman 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.Results3,5,6,7,8,3′,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.Conclusion3,5,6,7,8,3′,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.
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spelling doaj-art-d3d31e664fd04b6c8661099defbf2b7c2025-08-20T02:26:28ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15445701544570Study on the effect of 3,5,6,7,8,3′,4′-heptamethoxyflavone in Fructus Aurantii by regulating intestinal aquaporin in body fluidsTing-Ting Bai0Ting-Ting Bai1Ya-Ting Xie2Quan Wan3Jin-Lian Zhang4Department of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, ChinaMongolian College of Medicine, Inner Mongolia Medical University, Hohhot, ChinaDepartment of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, ChinaAffiliated Hospital of Inner Mongolia Minzu University, Tongliao, ChinaDepartment of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, ChinaBackgroundFructus aurantii (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.MethodsHuman 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.Results3,5,6,7,8,3′,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.Conclusion3,5,6,7,8,3′,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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1544570/full3,5,6,7,8,3′,4′-heptamethoxyflavoneFructus aurantiiaquaporinsbody fluidintestinal tract
spellingShingle Ting-Ting Bai
Ting-Ting Bai
Ya-Ting Xie
Quan Wan
Jin-Lian Zhang
Study on the effect of 3,5,6,7,8,3′,4′-heptamethoxyflavone in Fructus Aurantii by regulating intestinal aquaporin in body fluids
Frontiers in Pharmacology
3,5,6,7,8,3′,4′-heptamethoxyflavone
Fructus aurantii
aquaporins
body fluid
intestinal tract
title Study on the effect of 3,5,6,7,8,3′,4′-heptamethoxyflavone in Fructus Aurantii by regulating intestinal aquaporin in body fluids
title_full Study on the effect of 3,5,6,7,8,3′,4′-heptamethoxyflavone in Fructus Aurantii by regulating intestinal aquaporin in body fluids
title_fullStr Study on the effect of 3,5,6,7,8,3′,4′-heptamethoxyflavone in Fructus Aurantii by regulating intestinal aquaporin in body fluids
title_full_unstemmed Study on the effect of 3,5,6,7,8,3′,4′-heptamethoxyflavone in Fructus Aurantii by regulating intestinal aquaporin in body fluids
title_short Study on the effect of 3,5,6,7,8,3′,4′-heptamethoxyflavone in Fructus Aurantii by regulating intestinal aquaporin in body fluids
title_sort study on the effect of 3 5 6 7 8 3 4 heptamethoxyflavone in fructus aurantii by regulating intestinal aquaporin in body fluids
topic 3,5,6,7,8,3′,4′-heptamethoxyflavone
Fructus aurantii
aquaporins
body fluid
intestinal tract
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1544570/full
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