Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia

Ethnopharmacological relevance: Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in “Synopsis of Golden Chamber” (Han Dynasty in the 3rd century) and the Zhizhu pill in “Differentiation on Endogenous” in Jin Dynasty (1,115–1,234). ZZKZ contains...

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Main Authors: Zhuanglong Xiao, Jing Xu, Jun Tan, Shengyan Zhang, Nian Wang, Ruiyun Wang, Pengcheng Yang, Tao Bai, Jun Song, Zhaohong Shi, Wenliang Lyu, Lei Zhang, Xiaohua Hou
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.1026660/full
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author Zhuanglong Xiao
Jing Xu
Jing Xu
Jing Xu
Jun Tan
Shengyan Zhang
Nian Wang
Ruiyun Wang
Pengcheng Yang
Tao Bai
Jun Song
Zhaohong Shi
Wenliang Lyu
Lei Zhang
Xiaohua Hou
author_facet Zhuanglong Xiao
Jing Xu
Jing Xu
Jing Xu
Jun Tan
Shengyan Zhang
Nian Wang
Ruiyun Wang
Pengcheng Yang
Tao Bai
Jun Song
Zhaohong Shi
Wenliang Lyu
Lei Zhang
Xiaohua Hou
author_sort Zhuanglong Xiao
collection DOAJ
description Ethnopharmacological relevance: Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in “Synopsis of Golden Chamber” (Han Dynasty in the 3rd century) and the Zhizhu pill in “Differentiation on Endogenous” in Jin Dynasty (1,115–1,234). ZZKZ contains four botanical drugs, including Citrus × Aurantium L [Rutaceae; Aurantii Fructus Immaturus], Atractylodes Macrocephala Koidz. [Compositae; Rhizoma Atractylodis Macrocephalae], Bupleurum Chinense DC [Apiaceae; Radix Bupleuri Chinensis], and Crataegus Pinnatifida Bunge [Rosaceae; Fructus Crataegi Pinnatifidae], which have been widely used in clinical therapy for functional dyspepsia (FD).Aim of the study: This study aimed to evaluate the pharmacological effects and mechanisms of action of ZZKZ on gastric hypersensitivity and motor dysfunction in a rat model of FD.Materials and methods: FD was induced in Sprague-Dawley rats by neonatal gastric irritation with 0.1% iodoacetamide. The FD rats were treated with ZZKZ (0.5 g/kg, 1.0 g/kg, or 1.5 g/kg respectively) by gavage for 7 days, while domperidone (3 mg/kg) acted as treatment control. Body weight gain, food intake, gastric emptying, and intestinal propulsion were also measured. Ex vivo gastric smooth muscle activity recordings and greater splanchnic afferent (GSN) firing recordings were employed to evaluate gastric motility and sensation. Particularly, the role of 5-HT in the action of ZZKZ in improving gastric dysmotility and hypersensitivity was explored.Results: ZZKZ promoted weight gain, food intake, gastric emptying, and intestinal propulsion in FD rats. ZZKZ promoted spontaneous and ACh-induced contractions of gastric smooth muscle strips in FD rats, alleviated spontaneous activity, and chemical (acid perfusion) and mechanical (intragastric distension) stimulated GSN firing in FD rats. ZZKZ ameliorated gastric smooth muscle contraction and GSN firing induced by 5-HT in FD rats. ZZKZ stimulated the release of serum 5-HT, with reduced 5-HT3 receptor and increased 5-HT4 receptor mRNA expression in the guts of FD rats.Conclusion: This study demonstrated that ZZKZ improves FD-related gastric hypersensitivity and motor dysfunction and should be an effective compound for relieving FD symptoms. The gastric 5-HT system with lower 5-HT3 activity and increased 5-HT4 distribution is involved in the mechanisms of ZZKZ underlying the treatment of FD.
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spelling doaj.art-0800eb8c365244e4943d0b485899cc852022-12-22T02:50:09ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.10266601026660Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsiaZhuanglong Xiao0Jing Xu1Jing Xu2Jing Xu3Jun Tan4Shengyan Zhang5Nian Wang6Ruiyun Wang7Pengcheng Yang8Tao Bai9Jun Song10Zhaohong Shi11Wenliang Lyu12Lei Zhang13Xiaohua Hou14Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaClinical College of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, ChinaDepartment of Chinese Medicine, Hubei College of Chinese Medicine, Jingzhou, ChinaDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastroenterology, The First Hospital of Wuhan (Wuhan Integrated TCM and Western Medicine Hospital), Wuhan, ChinaDepartment of Gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastroenterology, The First Hospital of Wuhan (Wuhan Integrated TCM and Western Medicine Hospital), Wuhan, ChinaClinical College of Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, ChinaDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaEthnopharmacological relevance: Zhizhu Kuanzhong (ZZKZ) is a traditional Chinese medicine modified from classic formula Zhizhu decoction in “Synopsis of Golden Chamber” (Han Dynasty in the 3rd century) and the Zhizhu pill in “Differentiation on Endogenous” in Jin Dynasty (1,115–1,234). ZZKZ contains four botanical drugs, including Citrus × Aurantium L [Rutaceae; Aurantii Fructus Immaturus], Atractylodes Macrocephala Koidz. [Compositae; Rhizoma Atractylodis Macrocephalae], Bupleurum Chinense DC [Apiaceae; Radix Bupleuri Chinensis], and Crataegus Pinnatifida Bunge [Rosaceae; Fructus Crataegi Pinnatifidae], which have been widely used in clinical therapy for functional dyspepsia (FD).Aim of the study: This study aimed to evaluate the pharmacological effects and mechanisms of action of ZZKZ on gastric hypersensitivity and motor dysfunction in a rat model of FD.Materials and methods: FD was induced in Sprague-Dawley rats by neonatal gastric irritation with 0.1% iodoacetamide. The FD rats were treated with ZZKZ (0.5 g/kg, 1.0 g/kg, or 1.5 g/kg respectively) by gavage for 7 days, while domperidone (3 mg/kg) acted as treatment control. Body weight gain, food intake, gastric emptying, and intestinal propulsion were also measured. Ex vivo gastric smooth muscle activity recordings and greater splanchnic afferent (GSN) firing recordings were employed to evaluate gastric motility and sensation. Particularly, the role of 5-HT in the action of ZZKZ in improving gastric dysmotility and hypersensitivity was explored.Results: ZZKZ promoted weight gain, food intake, gastric emptying, and intestinal propulsion in FD rats. ZZKZ promoted spontaneous and ACh-induced contractions of gastric smooth muscle strips in FD rats, alleviated spontaneous activity, and chemical (acid perfusion) and mechanical (intragastric distension) stimulated GSN firing in FD rats. ZZKZ ameliorated gastric smooth muscle contraction and GSN firing induced by 5-HT in FD rats. ZZKZ stimulated the release of serum 5-HT, with reduced 5-HT3 receptor and increased 5-HT4 receptor mRNA expression in the guts of FD rats.Conclusion: This study demonstrated that ZZKZ improves FD-related gastric hypersensitivity and motor dysfunction and should be an effective compound for relieving FD symptoms. The gastric 5-HT system with lower 5-HT3 activity and increased 5-HT4 distribution is involved in the mechanisms of ZZKZ underlying the treatment of FD.https://www.frontiersin.org/articles/10.3389/fphar.2022.1026660/fullZhizhu Kuanzhong capsulefunctional dyspepsiagastrointestinal motilitygreater splanchnic afferents5-hydroxytryptamine
spellingShingle Zhuanglong Xiao
Jing Xu
Jing Xu
Jing Xu
Jun Tan
Shengyan Zhang
Nian Wang
Ruiyun Wang
Pengcheng Yang
Tao Bai
Jun Song
Zhaohong Shi
Wenliang Lyu
Lei Zhang
Xiaohua Hou
Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia
Frontiers in Pharmacology
Zhizhu Kuanzhong capsule
functional dyspepsia
gastrointestinal motility
greater splanchnic afferents
5-hydroxytryptamine
title Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia
title_full Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia
title_fullStr Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia
title_full_unstemmed Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia
title_short Zhizhu Kuanzhong, a traditional Chinese medicine, alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia
title_sort zhizhu kuanzhong a traditional chinese medicine alleviates gastric hypersensitivity and motor dysfunction on a rat model of functional dyspepsia
topic Zhizhu Kuanzhong capsule
functional dyspepsia
gastrointestinal motility
greater splanchnic afferents
5-hydroxytryptamine
url https://www.frontiersin.org/articles/10.3389/fphar.2022.1026660/full
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