Shugan Decoction Alleviates Colonic Dysmotility in Female SERT-Knockout Rats by Decreasing M3 Receptor Expression

Wang, Yinshu; Duan, Ying; Wang, Enkang; Meng, Yangyang; Bi, Zijuan; Sun, Shuai; Zhang, Chaochao; Fan, Haiting; Yuan, Judy Chia Chun

doi:10.3389/fphar.2020.01082

Cited by 6 publications

(9 citation statements)

References 28 publications

(29 reference statements)

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“…e present study showed that 5-HT induced colonic contractility was increased in the IBS group. e data was consistent with one recent study; the tension due to the ACh-induced colonic smooth muscle contractility was greater in serotonin reuptake transporter-knocked out rats than in wild-type rats [48]. Pretreatment with HJE and PEP inhibited the 5-HTinduced hypercontractility of the colon in the IBS rats.…”

Section: Discussionsupporting

confidence: 92%

Ameliorative Effects of Humulus japonicus Extract and Polysaccharide-Rich Extract of Phragmites rhizoma in Rats with Gastrointestinal Dysfunctions Induced by Water Avoidance Stress

Thein

Choi

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Chronic stress can cause the gastrointestinal disorders characterized by an altered bowel movement and abdominal pain. Studies have shown that Humulus japonicus extract (HJE) has anti-inflammatory and antidiarrheal effects, and Phragmites rhizoma extract (PEP) has antioxidative and antistress effects. The present study aimed to investigate the possible effects of HJE and PEP in rat models with stress-induced gastrointestinal dysfunctions. The rats were exposed to water avoidance stress (WAS, 1 h/day) for 10 days to induce gastrointestinal disorders. We found that WAS significantly increased fecal pellet output during 1 h stress, gastric emptying, colonic contractility, and permeability compared to the normal rats. Pretreatment with HJE and PEP (0.25 and 0.5 mL/kg, both administered separately) improved the increased gastric emptying and colonic contractility induced by electrical field stimulation, acetylcholine, and serotonin and also alleviated the increased colonic permeability. HJE and PEP also increased the claudin-1 and occludin expressions, reduced by WAS. WAS increased the concentration of TNF-α and TBARS and reduced FRAP. HJE and PEP recovered these effects. HJE and PEP improved the gastrointestinal disorders induced by WAS by upregulating the tight junction protein, possibly acting on cholinergic and serotonergic receptors to abolish the colonic hypercontractility and hyperpermeability and degradation of inflammatory cytokines via an antioxidant effect.

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Section: Discussionsupporting

confidence: 92%

Ameliorative Effects of Humulus japonicus Extract and Polysaccharide-Rich Extract of Phragmites rhizoma in Rats with Gastrointestinal Dysfunctions Induced by Water Avoidance Stress

Thein

Choi

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…In the present study, we confirmed the VH and found dysmotility in female slc6a4 −/− rats. Moreover, we have reported the increased sensibility of colonic muscle strips to acetylcholine (ACh) isolated from female SERT KO rats, which may be related to the increased expression of muscarinic receptor 3 (M3 receptor) 41 . We can therefore utilize female slc6a4 −/− rats as a reliable IBS animal model.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, we have reported the increased sensibility of colonic muscle strips to acetylcholine (ACh) isolated from female SERT KO rats, which may be related to the increased expression of muscarinic receptor 3 (M3 receptor). 41 We can therefore utilize female slc6a4 −/− rats as a reliable IBS animal model. Recent studies have reported that the serotonin system is involved in VH and gastrointestinal dysmotility.…”

Section: Discussionmentioning

confidence: 99%

Female serotonin transporter‐knockout rat: A potential model of irritable bowel syndrome

Zhang

Meng

et al. 2021

The FASEB Journal

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Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease. Although visceral hypersensitivity (VH) and disturbed gastrointestinal motility are typical pathophysiological features of IBS, the pathological mechanisms underlying this disease remain unclear. Serotonin system abnormalities are considered to play an important role in the pathomechanisms of IBS. Here, we hypothesize that similar alterations, including VH and colonic motility, induced by serotonin transporter (SERT) knockout result from altered serotonin signaling. We sought to determine the molecular mechanism underlying VH and colonic dysmotility induced by SERT knockout. We found that female SERT (slc6a4)‐knockout (KO; ie, slc6a4−/−) rats exhibited lower pain pressure thresholds (PPTs) than wild‐type (WT; ie, slc6a4+/+) rats in response to colorectal distension (CRD). Significantly increased fecal pellet output and reduced concentration of serum tryptophan were observed in the female SERT KO rats. The concentrations of 5‐hydroxytryptamine (5‐HT) in platelet‐rich plasma (PRP) and serum in SERT KO rats were lower than those in WT rats, but the numbers of enterochromaffin cells (ECs) and the concentrations of 5‐HT in colon of SERT KO rats were higher than those of WT rats. Finally, increased expression levels of 5‐HT1B receptors, 5‐HT2C receptors, 5‐HT3A receptors, 5‐HT3B receptors, 5‐HT6 receptors, 5‐HT7 receptors, and glycosylated dopamine transporters (DATs) were found in the female SERT KO rats. We concluded that alterations in the serotonin system induced by the knockout of slc6a4 might result in VH and accelerated gastrointestinal motility in female SERT KO rats, which can be used as an animal model of IBS.

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“…The ingredients of SGD were analyzed by HPLC as reported in our previous study (Wang et al, 2020 ). Briefly, Saikosaponin A, paeoniflorin, 5-O-methylvisammioside, hesperidin, or cimicifugoside was dissolved in methanol and obtained 1 mg/mL of standard solution separately.…”

Section: Methodsmentioning

confidence: 99%

No synergistic effect of fecal microbiota transplantation and shugan decoction in water avoidance stress-induced IBS-D rat model

Meng

Feng²,

Hang³

et al. 2022

Front. Microbiol.

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BackgroundIt has been reported that 5-hydroxytryptamine (5-HT, serotonin) metabolism is involved in the pathogenesis of irritable bowel syndrome (IBS) and that either Shugan decoction (SGD) or fecal microbiota transplantation (FMT) can alleviate the symptoms of IBS in patients and animal models. But the synergistic effect of FMT and SGD on 5-HT metabolism and IBS symptoms has not been investigated.AimThe main purpose of this study is to observe the synergistic effect of FMT with SGD on symptoms and 5-HT metabolism in IBS-D rats induced by water avoidance stress (WAS). Moreover, the possible material basis of the FMT was investigated.MethodsIn experiment I, rats were randomly divided into seven groups. Control group: routine feeding; WAS→ Control group: routine feeding with fecal microbiota liquid (FML) 1 (derived from rats in WAS group) gavage since the fourth day; WAS group: 10 days WAS with routine feeding; SGD group: 10 days WAS with SGD gavage since the fourth day on the base of routine feeding; Control→ WAS group: 10 days WAS with FML2 (derived from rats in Control group) gavage since the fourth day with routine feeding; SGD→ WAS group: 10 days WAS with FML3 (derived from rats in SGD group) gavage since the fourth day with routine feeding; SGD + (Control→ WAS) group: 10 days WAS with SGD and FML2 (derived from rats in Control group) gavage since the fourth day with routine feeding. In experiment II, rats were randomly divided into three groups. Control group: routine feeding; Control→ WAS group: 10 days WAS with FML2 gavage since the fourth day with routine feeding; FControl→ WAS group: 10 days WAS with FML2 filtrate gavage since the fourth day. The number of fecal pellets output (FPT) and the pain pressure threshold (PPT) were recorded. The histological changes in colon mucosa were observed by hematoxylin-eosin (HE) stain. The number of enterochromaffin cells (ECs), the content of 5-HT, and the expression of serotonin reuptake transporter (SERT) protein in the colon were measured by immunofluorescence or western blotting.ResultsCompared with that in the control group, the PPT and the expression of SERT in the WAS group and that in the WAS→ Control group were decreased with the increased number of ECs and the level of 5-HT in colon. But the FPT was not increased in the WAS→ Control group although that was increased in the WAS group. Compared with that in the WAS group, the FPT, the PPT, the number of ECs, the level of 5-HT, and the expression of SERT protein in colon in the SGD group, control→ WAS group, SGD→ WAS group, and SGD+(Control→ WAS) group were all recovered. The recovery of these indicators in the Control→ WAS group and that in the FControl→ WAS group was not significantly different.ConclusionNo synergistic effect of SGD with FMT on IBS symptoms induced by WAS was found. The metabolites of intestinal microbiota may be the main active substances of the FML derived from normal rats to alleviate WAS-induced IBS symptoms.

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Shugan Decoction Alleviates Colonic Dysmotility in Female SERT-Knockout Rats by Decreasing M3 Receptor Expression

Cited by 6 publications

References 28 publications

Ameliorative Effects of Humulus japonicus Extract and Polysaccharide-Rich Extract of Phragmites rhizoma in Rats with Gastrointestinal Dysfunctions Induced by Water Avoidance Stress

Ameliorative Effects of Humulus japonicus Extract and Polysaccharide-Rich Extract of Phragmites rhizoma in Rats with Gastrointestinal Dysfunctions Induced by Water Avoidance Stress

Female serotonin transporter‐knockout rat: A potential model of irritable bowel syndrome

No synergistic effect of fecal microbiota transplantation and shugan decoction in water avoidance stress-induced IBS-D rat model

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