scholarly journals Mechanism of QingHuaZhiXie Prescription Regulating TLR4-IECs Pathway in the Intervention of Diarrhea Predominant Irritable Bowel Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hua Huang ◽  
Ping Zhao ◽  
Meijuan Xi ◽  
Fang Li ◽  
Lijiang Ji

To investigate the effect and mechanism of QingHuaZhiXie prescription on diarrhea predominant irritable bowel syndrome (D-IBS), animal models of rats were used in this study. 48 rats were randomly divided into 6 groups, containing one control group, one animal model group (D-IBS group), and four drug intervention groups (low, medium, and high dosage of QingHuaZhiXie prescription and trimebutine maleate intervention group). Abdominal withdrawal reflex (AWR) and Bristol stool form scale were recorded; the expression levels of inflammatory factors (TNF-α and IFN-γ), pathway proteins TLR4, MyD88, NF-κB, and key proteins of tight junction between intestinal epithelial cells (IECs) were detected; the microstructure of intestinal mucosal was observed by hematoxylin and eosin (H&E) staining; MPO activity was detected with immunohistochemical analysis to reflect the inflammation of tissues. Results show that QingHuaZhiXie prescription reduced diarrhea index and intestinal hypersensitivity and intestinal tissue integrity after intervention. MPO activity in QingHuaZhiXie prescription-treated rats was significantly lower relative to their model group. The expression levels of inflammatory factors and TLR4/MyD88/NF-κB pathway proteins were repressed, and the protein levels of occludin and claudin-1 increased. Meanwhile, this study also found that the remission effect of QingHuaZhiXie prescription on D-IBS increased with its dosage increase. Hence, as a therapeutic prescription for D-IBS, QingHuaZhiXie prescription could relieve D-IBS symptoms through balancing the inflammatory factors expression by inhibiting the TLR4/MyD88/NF-κB pathway and maintaining the function and structure of IECs by improving the protein levels of JAM, occludin, claudin-1, and ZO-1.

Author(s):  
Honglin Qu ◽  
Ruilian Liu ◽  
Jiaqin Chen ◽  
Lan Zheng ◽  
Rui Chen

Objective: To investigate the role of aerobic exercise in inhibiting chronic unpredictable mild stress (CUMS) depressed mice hippocampal inflammatory response and its potential mechanisms. Methods: Fifty-four male eight-week-old C57BL/6 mice were divided as control group (CG) (18 mice) and model group (36 mice). Model group mice were treated with 13 chronic stimulating factors for 28 days to set up the CUMS depression model. Neurobehavioral assessment was performed after modeling. The mice in the model group were randomly divided into the control model group (MG) and the aerobic exercise group (EG), with 18mice in each group. The EG group carried out the adaptive training of the running platform: 10 m/min, 0° slope, and increased by 10 minutes per day for 6 days. The formal training was carried for 8 weeks with 10 m/min speed, 0° slope, 60 min/d, 6 d/Week. After the training, a neurobehavioral assessment was performed, and hippocampus IL-1β and IL-10 protein levels were detected by ELISA. RT–PCR was used to detect the expression of miR-223 and TLR4, MyD88, and NF-κB in the hippocampus. Western blot was used to detect the expression of TLR4 and phosphorylated NF-κBp65 protein in the hippocampus. Results: The hippocampus function of CUMS depression model mice was impaired. The forced swimming and forced tail suspension time were significantly prolonged, and inflammatory factors IL-1β were significantly increased in the hippocampus. Aerobic exercise significantly improves CUMS-depressed mice hippocampal function, effectively reducing depressive behavior and IL-1β levels, and increasing IL-10 levels. Besides, aerobic exercise significantly upregulates the expression level of miR-223 and inhibits the high expression of TLR4, MyD88, and NF-κB. Conclusion: Aerobic exercise significantly increases the CUMS-depressed mice hippocampus expression of miR-223, and inhibits the downstream TLR4/MyD88-NF-κB signaling pathway and the hippocampal inflammatory response, which contributes to the improvement of the hippocampal function.


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.


Author(s):  
Saeed Yazdani Ashtiani ◽  
Mersad Amery

Background: Irritable bowel syndrome (IBS) is a common, chronic and sometimes disabling functional disorder of the gastrointestinal system and its treatment remains as health problem. Thus the aim of this study was to evaluate the Effect of multispecies probiotic supplementation, as a novel and Controversial therapeutic method on Irritable bowel syndrome. Materials and Methods: In this randomized double blind Placebo-controlled clinical trial, 60 patients with IBS were enrolled. The patients were divided randomly into two groups. Patients in intervention group received two 500 mg probiotic capsules (Familact®) and in control group, received two 500 mg placebo capsules daily for 30 consecutive days. The symptoms and quality of life were measured and compared at the beginning and just after the end of study for each case. Results: Results showed the mean score of Abdominal pain after 1 month of treatment in the probiotic group was significantly lower than the control group (1.76 ± 2.04 vs. 2.88 ± 2.25, P=0.049, respectively). While, other symptoms and quality of life did not change significantly (P>0.05). Furthermore, defecation habit and global symptoms improvement was similar after intervention in both groups and we did not observe significant differences in these items (P>0.05). Conclusion: The results of this study showed the beneficial effects of multispecies probiotic supplementation in controlling IBS patients’ abdominal pain. thus it can be prescribed as a therapeutic option in addition to standard therapy and significantly lead to better control of this symptom in the short term.


2019 ◽  
Vol 17 ◽  
pp. 205873921985368 ◽  
Author(s):  
Huimin Xue ◽  
Shan Shao

The objective of this article is to explore the clinical efficacy of acupuncture therapy of Traditional Chinese Medicine (TCM) combined with Astragalus injection in the treatment of children with diarrhea-predominant irritable bowel syndrome (IBS), and its effects on 5-hydroxytryptamine (5-HT), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) in peripheral blood. A total of 116 children with diarrhea-predominant IBS admitted to our hospital from January 2017 to January 2018 were randomly divided into two groups. The control group was treated with Astragalus injection, while the research group was treated with acupuncture therapy of TCM combined with Astragalus injection. The therapeutic effects, the concentrations of CGRP, NPY, and 5-HT in peripheral blood were compared between the two groups. The therapeutic efficacy of the study group was better than that of the control group ( P < 0.05). The concentrations of CGRP, NPY, and 5-HT in the peripheral blood of the study group were less than those of the control group ( P < 0.05). Acupuncture therapy of TCM combined with Astragalus injection has a satisfactory effect in the treatment of children with diarrhea-predominant IBS, which is worthy of more publicity and application in the clinic.


2020 ◽  
Vol 27 (5) ◽  
pp. 302-309 ◽  
Author(s):  
Masoumeh Khalighi Sikaroudi ◽  
Marjan Mokhtare ◽  
Leila Janani ◽  
Amir Hossein Faghihi Kashani ◽  
Mohsen Masoodi ◽  
...  

Objectives: This study aimed to evaluate whether vitamin D deficiency is associated with the severity of symptoms of irritable bowel syndrome (IBS) patients. Stress and gut inflammation can increase the serum level of corticotropin-releasing hormone (CRH) and interleukin-6 (IL-6), leading to a change in bowel movements. The aim of this study was to evaluate the anti-inflammatory and psychological effects of vitamin D3 supplementation on the symptom improvement of patients with a diarrhea-predominant form of IBS (IBS-D). Methods: Eighty-eight IBS-D patients (age: 18–65 years) based on Rome IV criteria who suffered from vitamin D deficiency and/or insufficiency were enrolled in this randomized, placebo-controlled trial from February 2017 to May 2018 at Rasoul-e-Akram Hospital, Tehran, Iran. Participants were randomly divided into two groups. The intervention group received 50,000 IU vitamin D3 weekly and the control group received a placebo for 9 weeks. All patients received Mebeverine 135 mg twice a day besides supplementation. The IBS Severity Score System (IBS-SSS), serum 25(OH) vitamin D3, CRH, and IL-6 were measured before and after interventions. Results: Seventy-four patients completed the study. The severity of IBS symptoms (p < 0.01) and IL-6 (p = 0.02) decreased significantly in the intervention group as compared to the control group, but there was no significant difference in the serum level of CRH. Also, in the treatment group, IBS-SSS and IL-6 were significantly reduced at the end of the study from baseline (p < 0.01 and p < 0.03, respectively). Conclusion: Our findings indicate that vitamin D3 supplementation can modulate the serum level of CRH and IL-6 and can improve symptoms in IBS-D patients. Vitamin D3 supplementation should be considered in IBS-D patients who suffer from vitamin D deficiency and/or insufficiency.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Qian Wang ◽  
Jing Lin ◽  
Peng Yang ◽  
Yingye Liang ◽  
Dongming Lu ◽  
...  

This study set out to investigate the effect of massage on the Toll-like receptor 4 (TLR4) signalling pathway in the dorsal root ganglia of rats that had undergone spinal nerve ligation (SNL), with the hypothesis that massage could be used as an analgesic. Forty female SD rats were randomly divided into 5 groups: the control group, sham-operated group, model group, sham massage group, and massage group. There were 8 rats in each group. SNL rat models were established in the model group, sham massage group, and massage group. Rats in the sham-operated group underwent surgery to expose the vertebral nerves, but no further procedures were performed. The control group consisted of intact animals. The rats in the massage group underwent massage using a massage simulation machine once a day for 14 d in succession; the hind limbs of the rats in the sham massage group were gently touched with a cloth bag once a day for 14 continuous days. The rats in the control group, the sham-operated group, and the model group did not receive any intervention and were observed for 14 d. Paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) of rats in each group were detected 1 d before modelling and at 1, 3, 7, and 14 d after modelling. Fourteen days after modelling, the expression levels of TLR4, IRAK1, TRAF6, TNF-α, and IL-6 were detected in all rats. The PWTL and PWMT of SNL rats were decreased, while these parameters were elevated after massage. SNL rats showed higher levels of TLR4, IRAK1, TRAF6, IL-6, and TNF-α, and massage effectively lowered the expression levels of these molecules. Inhibiting activation of the TLR4 signalling pathway, which can reduce the release of inflammatory factors, may be one mechanism by which massage treats neuropathic pain.


2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Lin Zhang ◽  
Hua Peng ◽  
Jin Xu ◽  
Yixin Xu ◽  
You Yin ◽  
...  

Objective. To investigate the effects of Dendrobium officinale polysaccharides (DOPS) on the expression of inflammatory factors IL-1β and TNF-α and the MKP-1/MAPK signal pathway. Methods. PTZ-induced epileptic rat models were established. The rats were randomly divided into four groups: the control group, the DOPS group, the model group, and the DOPS intervention group. RT-PCR was used to measure the mRNA expression of IL-1β and TNF-α in the hippocampi of all groups; western blot was used to measure the protein expression of IL-1β and TNF-α and phosphorylation of ERK1/2, JNK, p38, and MKP-1 in the hippocampi of all groups at weeks 1, 2, 3, and 4 after modeling. Results. At weeks 1, 2, 3, and 4 after modeling, there were no significant differences between the control group and the DOPS group in the mRNA and protein expression of IL-1β and TNF-α and phosphorylation of ERK1/2, JNK, p38, and MKP-1 (all P>0.05); the mRNA and protein expression of IL-1β and TNF-α and phosphorylation of ERK1/2, JNK, and p38 were significantly increased, while the phosphorylation of MKP-1 was decreased in the model group compared with the control group. The mRNA and protein expression of IL-1β and TNF-α and phosphorylation of ERK1/2, JNK, and p38 were significantly decreased, while the phosphorylation of MKP-1 was increased in the DOPS intervention group compared with the model group. Conclusion. DOPS can reduce PTZ-induced brain inflammation and seizures of epileptic rats by inhibiting IL-1β, TNF-α, and MAPK signal pathways.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 416
Author(s):  
Clara Nilholm ◽  
Ewa Larsson ◽  
Emily Sonestedt ◽  
Bodil Roth ◽  
Bodil Ohlsson

Dietary advice constitutes a treatment strategy for irritable bowel syndrome (IBS). We aimed to examine the effect of a starch- and sucrose-reduced diet (SSRD) on gastrointestinal symptoms in IBS patients, in relation to dietary intake and systemic inflammatory parameters. IBS patients (n = 105) were randomized to a 4-week SSRD intervention (n = 80) receiving written and verbal dietary advice focused on starch and sucrose reduction and increased intake of protein, fat and dairy, or control group (n = 25; habitual diet). At baseline and 4 weeks, blood was sampled, and participants filled out IBS-SSS, VAS-IBS, and Rome IV questionnaires and dietary registrations. C-reactive protein and cytokines TNF-α, IFN-γ, IL-6, IL-8, IL-10, and IL-18 were analyzed from plasma. At 4 weeks, the intervention group displayed lower total IBS-SSS, ‘abdominal pain’, ‘bloating/flatulence’ and ‘intestinal symptoms´ influence on daily life’ scores (p ≤ 0.001 for all) compared to controls, and a 74%, responder rate (RR = ΔTotal IBS-SSS ≥ −50; RRcontrols = 24%). Median values of sucrose (5.4 vs. 20 g), disaccharides (16 vs. 28 g), starch (22 vs. 82 g) and carbohydrates (88 vs. 182 g) were lower for the intervention group compared to controls (p ≤ 0.002 for all), and energy percentages (E%) of protein (21 vs. 17 E%, p = 0.006) and fat (47 vs. 38 E%, p = 0.002) were higher. Sugar-, starch- and carbohydrate-reductions correlated weakly-moderately with total IBS-SSS decrease for all participants. Inflammatory parameters were unaffected. IBS patients display high compliance to the SSRD, with improved gastrointestinal symptoms but unaltered inflammatory parameters. In conclusion, the SSRD constitutes a promising dietary treatment for IBS, but needs to be further researched and compared to established dietary treatments before it could be used in a clinical setting.


2021 ◽  
Vol 31 (4) ◽  
pp. 271-279
Author(s):  
Sepideh Shakernejad ◽  
◽  
Javad Khalatbari ◽  
Majid-Mahmoud Alilou ◽  
◽  
...  

Introduction: Irritable bowel syndrome is the most common, costly, and disabling dysfunction of the gastrointestinal tract. Mental disorders can be one of the main factors in the onset, continuation, or exacerbation of gastrointestinal signs and symptoms in people with this syndrome. Commitment and acceptance therapy is a mixture of four approaches of awareness, acceptance, commitment, and behavior change, and its overall goal is to achieve psychological flexibility to move towards thought-based behavior. This treatment focuses less on reducing symptoms and more on improving the quality of life. Objective: This study aimed to determine the effectiveness of acceptance and commitment-based therapy on the immune function and activity limitations in patients with irritable bowel syndrome. Materials and Methods: This study was a quasi-experimental research with a pre-test, post-test design and a control group. Thirty patients with irritable bowel syndrome were randomly selected from those referred to a hospital clinic in Tabriz City, Iran. They were randomly divided into the intervention and control groups (15 in each group). The intervention group received acceptance and commitment group therapy for 8 sessions, while the control group did not receive any intervention. Both groups were assessed before and after the intervention, and in the follow-up phase using the activity limitations subscale of quality of life questionnaires (to measure activity limitations) and stool calprotectin test to assess safety performance. Data analysis was performed using descriptive statistics indices (mean and standard deviation) and analysis of variance with repeated measures, Bonferroni test, and analysis of covariance to test the study hypotheses. Results: The Mean±SD age of the intervention group was 34.53±18.38 years, and the Mean±SD age of the control group was 42.80±17.97 years. The significance levels of Levene’s and the Shapiro-Wilk test for all variables were greater than 0.05. Based on the results, the Mean±SD score of the activity limitations variable in the intervention group was 7.53±4.24 in the pre-test, 17.66±3.41 in the post test, and 17.26±3.65 in the follow-up. According to the results, activity limitations (P=0.027) and safety performance (P=0.034) were significantly different before and after the intervention. Conclusion: The present study’s findings show that acceptance and commitment-based therapy can play an influential role in improving patients’ immune function and promoting their activity limitations. Therefore, this treatment is recommended as a complementary therapy in patients with irritable bowel syndrome.


Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 340
Author(s):  
Fernando Salvador ◽  
Beatriz Lobo ◽  
Lidia Goterris ◽  
Carmen Alonso-Cotoner ◽  
Javier Santos ◽  
...  

Background: The aim of the present study is to describe the occurrence of Blastocystis sp. detection among asymptomatic subjects and patients with irritable bowel syndrome in order to evaluate the potential association between irritable bowel syndrome and the parasitic infection. Methods: Cross-sectional study where adult patients with irritable bowel syndrome diagnosed according to Rome IV criteria were included. A control group was formed by asymptomatic subjects older than 18 years. Exclusion criteria were: immunosuppressive condition or having received any drug with demonstrated activity against Blastocystis sp. within the last 6 months before study inclusion. Epidemiological and clinical information was collected from all included participants. Two stool samples were obtained from all participants: one sample for microscopic examination and one sample for Blastocystis sp. PCR detection. Blastocystis sp. infection was defined by the positivity of any of the diagnostic techniques. Results: Seventy-two participants were included (36 asymptomatic subjects and 36 patients with irritable bowel syndrome). Thirty-five (48.6%) were men, and median age of participants was 34 (IQR 29–49) years. The overall rate of Blastocystis sp. carriage was 27.8% (20/72). The prevalence assessed through microscopic examination was 22.2% (16/72), while the prevalence measured by PCR was 15.3% (11/72). When comparing the presence of Blastocystis sp. between asymptomatic subjects and IBS patients, we did not find any statistically significant difference (36.1% vs. 19.4% respectively, p = 0.114). Conclusions: regarding the occurrence of Blastocystis sp., no differences were found between asymptomatic participants and patients with irritable bowel disease irrespective of the diagnostic technique performed.


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