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

2021 ◽  
Vol 12 ◽  
Author(s):  
Yulin Lu ◽  
Jingjing Huang ◽  
Yao Zhang ◽  
Zitong Huang ◽  
Weiming Yan ◽  
...  

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.

Author(s):  
Qiuke Hou ◽  
Yongquan Huang ◽  
Zhaoyang Zhu ◽  
Liu Liao ◽  
Xinlin Chen ◽  
...  

Abstract Background Tong-Xie-Yao-Fang (TXYF) has been shown to be effective in diarrhoea-predominant irritable bowel syndrome (IBS-D) patients. However, the underlying mechanism remains to be clarified. The aim of this study was to investigate the efficacy and related mechanisms of TXYF in an IBS-D rat model. Methods The IBS-D rat model was established with 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. Then, IBS-D rats were divided into control, TXYF and rifaximin groups and treated intragastrically with normal saline, TXYF and rifaximin, respectively, for 14 days. The following indicators were measured before and after treatment: defecation frequency, faecal water content (FWC) and colorectal distension (CRD). Histopathological changes in the distal colon were observed after treatment. The expression of OCLN and ZO1 in the distal colon of IBS-D rats reflected the intestinal mucosal permeability, as measured by qRT-PCR, western blot, and enzyme-linked immunosorbent assays (ELISAs). The NF-κB and Notch signalling pathways and inflammation-related factors were investigated. Results After treatment with TXYF, the defecation frequency, FWC and CRD were significantly lower than those in the model group (P < 0.05). HE staining showed that colonic epithelial cells (CECs) in the IBS-D rats displayed significant oedema, impaired intestinal mucosal integrity and an increased influx of inflammatory cells. A significant reduction in granulocyte and CEC oedema was observed after the administration of TXYF and rifaximin compared to that of the model group and blank group (P < 0.05). TXYF significantly upregulated the expression of OCLN and ZO-1 and downregulated inflammation-related factors (IL-6, IL-1β, and TNF-α and the chemokine KC) in IBS-D rats compared to those in the model group rats (P < 0.05). In terms of the NF-κB and Notch signalling pathways, the expression of NICD, p-ERK, Hes-1 and p-P65 decreased significantly in the TXYF and rifaximin groups, while the expression of ATOH1 increased significantly compared to that in the model group (P < 0.05). Conclusion TXYF can effectively improve intestinal permeability and enhance intestinal mucosal barrier function, which may be related to inhibition of the inflammatory cascade and the NF-κB and Notch signalling pathways.


2021 ◽  
Author(s):  
Masamichi Sato ◽  
Takahiro Kudo ◽  
Nobuyasu Arai ◽  
Reiko Kyodo ◽  
Kenji Hosoi ◽  
...  

Abstract Background: The correlation between small intestinal motility alteration and irritable bowel syndrome (IBS) is not well evaluated. Aims: To assess the small intestinal and colonic transits in an IBS rat model with restraint stress and determine the role of small intestinal motility in the IBS pathophysiology.Methods: Restraint stress was utilized to make adolescent IBS rat models that were evaluated for clinical symptoms, including stool frequency and diarrhea. The small intestinal motility and transit rate were also evaluated. The amounts of mRNA encoding corticotropin-releasing hormone, mast cell, and serotonin (5-Hydroxytryptamine; 5-HT) receptor 3a were quantified using real-time polymerase chain reaction (PCR); the 5-HT expression was evaluated using immunostaining.Results: Restraint stress significantly increased the number of fecal pellet outputs, stool water content, and small intestinal motility in the IBS rat models. There was no difference in real-time PCR results, but immunostaining analysis revealed that 5-HT expression in the small intestine was significantly increased in the IBS rat models.Conclusions: In the adolescent rat model of IBS with restraint stress, we observed an increase in small intestinal and colonic motility. In the small intestine, enhanced 5-HT secretion in the distal portion may be involved in increasing the small intestinal motility.


2015 ◽  
Vol 148 (4) ◽  
pp. S-585
Author(s):  
Michele Pier Luca Guarino ◽  
Giovanni Barbara ◽  
Alessia Cicenia ◽  
Annamaria Altomare ◽  
M. Raffaella Barbaro ◽  
...  

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Changrong Zhang ◽  
Yongquan Huang ◽  
Peiwu Li ◽  
Xinlin Chen ◽  
Fengbin Liu ◽  
...  

Abstract Background Ginger or ginger extracts have been used in traditional medicine relieve pain caused by diarrhea predominant irritable bowel syndrome (IBS-D), but few data exists about its effectiveness. This present study was to validate the effect of ginger on visceral pain, and to further explore the possible underlying mechanism by which ginger is used to relieve IBS-D intestinal hypersensitivity. Methods First, the IBS-D rat model was established by chemical stimulation and acute and chronic pressure stimulation. Then, different dose of ginger were administrated to IBS-D rats and evaluate the defecation frequency, fecal water content (FWC) and abdominal withdrawal reflex (AWR) scores in IBS-D rats. Further, the IBS-D rats were sacrificed to collecte the colonic tissues to evaluate the effect of ginger administration on its pathology and changes of pro-inflammatory factors, and changes of NF-κB pathway. Second, the ginger was taken to HPLC analysis and 6-gingerol was choosen to further experiment. Then, IBS-D rats were treated with different dose of 6-gingerol, and the behavioral evaluation were to evaluate the effect of 6-gingerol on IBS-D rats. Further, colonic epithelial cells (CECs) were collectted and to evaluate the effect of 6-gingerol on the expression of inflammatory factors and changes of NF-κB pathway. Results The IBS-D rat model was successfully established by chemical stimulation and acute and chronic pressure stimulation. And ginger treatment significantly reduced the defecation frequency, fecal water content and AWR scores in IBS-D rats. Histopathological analysis showed that ginger treatment can significantly reduce colonic edema and promote the recovery of inflammation in IBS-D rats, and the effect is equivalent to rifaximin. Elisa and RT-qPCR showed that ginger inhibited the expression of proinflammatory factors (TNF-α, IL-6, iNOS) in IBS-D rats. Western blot showed IkBα was up-regulated while p-p65 was inhibited under ginger treatment. HPLC analysis showed that 6-gingerol was the main component of ginger, which could improve clinical symptoms in IBS-D rats. Western blot and RT-qPCR showed that 6-gingerol inhibited the expression of proinflammatory factors (TNF-α, IL-6, iNOS) in CECs, and inhibition of IκBα degradation and phosphorylation of p65 involved in NF-κB pathway. Conclusion Ginger and ginger extract could relieve intestinal hypersensitivity of IBS-D by inhibiting proinflammatory response.


Gut ◽  
1986 ◽  
Vol 27 (9) ◽  
pp. 1014-1017 ◽  
Author(s):  
P J Whorwell ◽  
E W Lupton ◽  
D Erduran ◽  
K Wilson

2014 ◽  
Vol 146 (5) ◽  
pp. S-83
Author(s):  
Michele Pier Luca Guarino ◽  
Giovanni Barbara ◽  
Annamaria Altomare ◽  
M. Raffaella Barbaro ◽  
Silvia Cocca ◽  
...  

2020 ◽  
Vol 5 (01) ◽  
pp. 87-97
Author(s):  
Darshana . ◽  
Amitabh Singh

Grahani Dosha is vitiation of Agni i.e. functional derangement of Grahani regarding production of Pachaka Pitta (enzymes responsible for digestion) and also holding (Grahana) of Ama (food) for digestion. Grahani in Ayurveda is called as Pittadhara kala which is the seat of Agni responsible for digestion of food and situated above Nabhi. The part of small intestine and large intestine lying between Amashaya and Pakwashaya should be considered as Grahani. This part is also described as the sole site of Pitta. Various disorders of GI tract like irritable bowel syndrome (IBS) can be considered under heading of Grahani Roga. Both the formulations Nagradya Churna and Bhunimbadya churna are highly effective, promote appetite, digestion and remove Ama Dosha from the system by increasing the power of Agni. Madhu is Yogabahi and it helps to initiate the absorption through intestine properly. Total 40 patients of Grahani were registered and randomly divided into 2 groups for clinical trial of 45days. Result of the study revealed that both the formulations produced significant results in almost all cases barring a few patients who were suffering from longer period.


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