Efficacy and Molecular Mechanism of Quercetin on Constipation Induced by Berberine via Regulating Gut Microbiota

Author:

Cui Mengyao12,Li Ying1345,Zheng Tingting1,Chen Huan1,Wang Jinrui1,Feng Yifan1,Ye Hanyi1,Dong Zhengqi1345,Li Geng6

Affiliation:

1. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China

2. School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China

3. Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China

4. Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Beijing 100700, China

5. Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing 100700, China

6. Institute of Traditional Chinese Medicine, Chinese Academy of Traditional Chinese Medicine, Beijing 100070, China

Abstract

Berberine (BBR) is used to treat cancer, inflammatory conditions, and so on. But the side effects of BBR causing constipation should not be ignored. In clinical application, the combination of Amomum villosum Lour. (AVL) and BBR can relieve it. However, the effective ingredients and molecular mechanism of AVL in relieving constipation are not clear. A small intestine propulsion experiment was conducted in constipated mice to screen active ingredients of AVL. We further confirmed the molecular mechanism of action of the active ingredient on BBR-induced constipation. Quercetin (QR) was found to be the effective ingredient of AVL in terms of relieving constipation. QR can efficiently regulate the microbiota in mice suffering from constipation. Moreover, QR significantly raised the levels of substance P and motilin while lowering those of 5-hydroxytryptamine and vasoactive intestinal peptide; furthermore, it also increased the protein expression levels of calmodulin, myosin light-chain kinase, and myosin light chain. The use of QR in combination with BBR has an adverse effect-reducing efficacy. The study provides new ideas and possibilities for the treatment of constipation induced by BBR.

Funder

the CAMS Innovation Fund for Medical Science

Jilin Scientific and Technological Development Program

Publisher

MDPI AG

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