Therapeutic Effects of Berberine Hydrochloride on Stress-Induced Diarrhea-Predominant Irritable Bowel Syndrome Rats by Inhibiting Neurotransmission in Colonic Smooth Muscle

Yulin Lu; Jingjing Huang; Yao Zhang; Zitong Huang; Weiming Yan; Tianran Zhou; Zhesheng Wang; Lu Liao; Hongying Cao; Bo Tan

doi:10.3389/fphar.2021.596686

Therapeutic Effects of Berberine Hydrochloride on Stress-Induced Diarrhea-Predominant Irritable Bowel Syndrome Rats by Inhibiting Neurotransmission in Colonic Smooth Muscle

Front Pharmacol. 2021 Sep 14:12:596686. doi: 10.3389/fphar.2021.596686. eCollection 2021.

Authors

Yulin Lu¹, Jingjing Huang¹, Yao Zhang², Zitong Huang¹, Weiming Yan³, Tianran Zhou⁴, Zhesheng Wang¹, Lu Liao¹, Hongying Cao², Bo Tan¹

Affiliations

¹ Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
² School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, China.
³ The Third Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
⁴ The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China.

Abstract

The etiology of diarrhea-predominant irritable bowel syndrome (IBS-D) is complicated and closely related to neurotransmission in the gastrointestinal (GI) tract. Developing new strategies for treating this disease is a major challenge for IBS-D research. Berberine hydrochloride (BBH), the derivative of berberine, is a herbal constituent used to treat IBS. Previous studies have shown that BBH has potential anti-inflammatory, antibacterial, analgesic, and antidiarrheal effects and a wide range of biological activities, especially in regulating the release of some neurotransmitters. A modified IBS-D rat model induced by chronic restraint stress was used in all experiments to study the effects of BBH on the GI tract. This study measured the abdominal withdrawal reflex (AWR) response to graded colorectal distention (CRD; 20, 40, 60, and 80 mmHg) and observed the fecal areas of stress-induced IBS-D model. Experiments were conducted using organ bath techniques, which were performed in vitro using strips of colonic longitudinal smooth muscle. Inhibitory and excitatory neurotransmitter agents were added to each organ bath to observe contractile responses on the strips and the treatment effect exerted by BBH. The IBS-D rat model was successfully induced by chronic restraint stress, which resulted in an increased defecation frequency and visceral hypersensitivity similar to that of humans. BBH could reduce 4-h fecal areas and AWR response to CRD in IBS-D. The stress-induced IBS-D model showed upregulated colonic mRNA expression levels of 5-hydroxytryptamine-3A receptor and downregulated expression levels of neuronal nitric oxide synthase. Meanwhile, BBH could reverse this outcome. The responses of substances that regulate the contraction induced by related neurotransmission in the longitudinal smooth muscle of IBS-D colon (including the agonist of acetylcholine, carbachol; NOS inhibitor, L-NAME; and P2Y₁ receptor antagonist, MRS2500) can be inhibited by BBH. In summary, BBH promotes defecation frequency and visceral hypersensitivity in IBS-D and exerts inhibitory effects on contractile responses in colonic longitudinal smooth muscle. Thus, BBH may represent a new therapeutic approach for treating IBS-D.

Keywords: berberine hydrochloride; colonic longitudinal smooth muscles; diarrhea-predominant irritable bowel syndrome; inhibitory effects; neurotransmission.