Therapeutic Effects of Berberine Hydrochloride on Stress-Induced Diarrhea-Predominant Irritable Bowel Syndrome Rats by Inhibiting Neurotransmission in Colonic Smooth Muscle.
Therapeutic Effects of Berberine Hydrochloride on Stress-Induced Diarrhea-Predominant Irritable Bowel Syndrome Rats by Inhibiting Neurotransmission in Colonic Smooth Muscle.
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DOI：
10.3389/fphar.2021.596686
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发表时间：
2021
影响因子：
5.6
通讯作者：
Tan B
中科院分区：
文献类型：
--
作者：
Lu Y;Huang J;Zhang Y;Huang Z;Yan W;Zhou T;Wang Z;Liao L;Cao H;Tan B
肠易激综合征（IBS-D）的病因复杂，与胃肠道神经传递密切相关。开发治疗这种疾病的新策略是IBS-D研究的主要挑战。盐酸小檗碱（BBH）是小檗碱的衍生物，是一种用于治疗IBS的草药成分。已有研究表明，BBH具有潜在的抗炎、抗菌、镇痛、抗炎作用和广泛的生物学活性，特别是在调节某些神经递质的释放方面。在所有实验中使用慢性束缚应激诱导的改良IBS-D大鼠模型来研究BBH对胃肠道的影响。本研究测定了大鼠对分级结直肠扩张（CRD; 20、40、60和80 mmHg）的腹缩反射（AWR）反应，并观察了应激诱导的IBS-D模型的粪便面积。使用器官浴技术进行实验，所述器官浴技术使用结肠纵向平滑肌条在体外进行。将抑制性和兴奋性神经递质剂加入每个器官浴中，以观察条上的收缩反应和BBH施加的治疗效果。通过慢性束缚应激成功地诱导了IBS-D大鼠模型，其导致排便频率增加和内脏高敏感性类似于人类。BBH可降低IBS-D患者4 h粪便面积和对CRD的AWR反应。应激诱导的IBS-D模型显示结肠5-羟色胺-3A受体mRNA表达水平上调，神经元型一氧化氮合酶表达水平下调。与此同时，BBH可以扭转这一结果。BBH可抑制调节IBS-D结肠纵向平滑肌中相关神经传递诱导的收缩的物质（包括乙酰胆碱激动剂卡巴胆碱、NOS抑制剂L-NAME和P2 Y1受体拮抗剂MRS 2500）的反应。综上所述，BBH促进IBS-D的排便频率和内脏高敏感性，并对结肠纵向平滑肌的收缩反应产生抑制作用。因此，BBH可能代表治疗IBS-D的新治疗方法。
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.
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DOI：
10.1080/17474124.2017.1298442
发表时间：
2017-01-01
影响因子：
3.9
作者：
Corsetti, Maura;Whorwell, Peter
通讯作者：
Whorwell, Peter
DOI：
10.1152/ajpgi.00448.2009
发表时间：
2010-07-01
影响因子：
4.5
作者：
Gil, Victor;Gallego, Diana;Jimenez, Marcel
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Jimenez, Marcel
影响因子：
24.5
作者：
Akbar A;Yiangou Y;Facer P;Walters JR;Anand P;Ghosh S
通讯作者：
Ghosh S
影响因子：
3.5
作者：
Balestra, B.;Vicini, R.;Barbara, G.
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Barbara, G.
DOI：
10.1152/ajpgi.00164.2011
发表时间：
2011-09-01
影响因子：
4.5
作者：
Chaudhury, Arun;He, Xue-Dao;Goyal, Raj K.
通讯作者：
Goyal, Raj K.