Relationship between serum miR-505,miR-15 and endoscopic activity of ulcerative colitis / 中国内镜杂志

Objective To investigate the relationship between serum miR-505,miR-15 and endoscopic activity of ulcerative colitis(UC).Methods 98 patients with UC from May 2020 to May 2022 were selected as the observation group,and 80 patients with irritable bowel syndrome(IBS)were selected as the control group during the same period.The modified Mayo score was used to evaluate the endoscopic activity in patients with UC,and the relationship among the changes of serum miR-505 and miR-15 levels and the endoscopic activity in patients with UC was analyzed.Results The level of serum miR-505 in observation group was lower than that in control group,while the level of miR-15 in observation group was higher than that in control group(P<0.05).The level of serum miR-505 in patients with active UC was lower than that in patients with the healing stage,while the level of serum miR-15 in patients with active UC was higher than that in patients with healing stage(P<0.05).The serum miR-505 level of E3 type was lower than that of E2 type and E1 type,and the serum miR-15 level of E3 type was higher than that of E2 type and E1 type(P<0.05).The Mayo score of type E3 was higher than that of type E2 and E1(P<0.05).Pearson correlation analysis showed that serum miR-505 was negatively correlated with Mayo score(r =-0.51,P<0.05),while serum miR-15 was positively correlated with Mayo score(r = 0.54,P<0.05).Receiver operator characteristic curve(ROC curve)results showed that the cut-off value of miR-505 was 0.93,and the area under the curve(AUC)for evaluating the endoscopic activity of patients with UC was 0.67(95%CI:0.659～0.785),and the sensitivity and specificity were 73.24%and 68.55%,respectively.The cut-off value of miR-15 was 0.85,and the AUC for evaluating the endoscopic activity of patients with UC was 0.69(95%CI:0.672～0.814),and the sensitivity and specificity were 76.38%and 69.72%,respectively.The AUC for the joint evaluation of UC by both was 0.82(95%CI:0.809～0.912),and the sensitivity and specificity were 84.56%and 68.49%,respectively.Conclusion Serum miR-505 levels decrease and serum miR-15 levels increase in UC patients than IBS,and the level is closely related to patients'pathological conditions and endoscopic activity.Combined detection of serum miR-505 and miR-15 has a good value in evaluating endoscopic activity in UC patients.

Role of Intestinal Tight Junction in Ulcerative Colitis and Traditional Chinese Medicine Treatment： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC）， a disease that affects the colon or rectum， is characterized by long-term recurrent inflammation and eventually leads to ulcers in the inner wall of the intestine. The disease has a high incidence and is difficult to be cured， which causes severe physical and mental discomfort and economic burden to the patients. Therefore， it is urgent to develop new therapies with high cure rate and low side effect. The pathological mechanism of UC is complex and involves multiple factors. The intestinal mucosal barrier damage is the main pathological basis of UC， which is a hot topic and a new research direction. Intestinal tight junction （TJ）， as the structural basis of the intestinal mucosal mechanical barrier， can actively regulate mucosal function and play a key role in the pathogenesis of UC. Traditional Chinese medicine （TCM） can regulate TJ protein via multiple pathways and multiple targets， repair the intestinal mucosal barrier， and thus block the progression of UC. Studies have demonstrated that Chinese herbal medicines and their components， Chinese medicine compound prescriptions， and Chinese medicine preparations can treat UC by regulating TJ protein to maintain the function and reduce the permeability of intestinal epithelium， providing a new therapeutic strategy for UC. Although TCM has unique advantages that western medicine cannot replace by mediating TJ protein expression in UC， a comprehensive review of this field remains to be carried out. Focusing on the status of UC and TCM syndrome differentiation and treatment， we retrieved relevant articles with ''ulcerative colitis''， ''tight junction''， and ''Chinese medicine'' as the keywords， and summarized the relationship of TJ and its key target proteins with UC to clarify the critical role of TJ in UC pathophysiology. Furthermore， we summarized the Chinese medicines regulating TJ in the treatment of UC in recent years， aiming to provide a theoretical basis for the development of drugs for this disease.

Effects of Huangqin Tang on NLRP3/Caspase-1 pathway in mice model of ulcerative colitis / 中国中药杂志

The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1β, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1β, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1β, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1β, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.

Traditional Chinese Medicine Intervention in Ulcerative Colitis via NLRP3-Mediated Pyroptosis Pathway： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC） mainly occurs in the colon and rectum， with complex pathological mechanism. The occurrence of ulcerative colitis is associated with the uncontrollable inflammatory response of the intestine. The Western medicine therapy of UC mainly uses glucocorticoids and immunosuppressants to reduce intestinal inflammation. While blocking the progress of UC to a certain extent， it causes severe adverse reactions. More and more studies have confirmed that traditional Chinese medicine （TCM） has obvious advantages in the prevention and treatment of UC and can significantly reduce the recurrence of the disease. Pyroptosis， a novel form of cell death， can destroy cell structure， release intracellular pro-inflammatory substances， and mediate intestinal immune response in UC. TCM can promote pyroptosis （removing excess） or inhibit pyroptosis （replenishing deficiency）， which is consistent with the regulation of Yin and Yang. TCM plays a role in the treatment of UC mainly by inhibiting pyroptosis （replenishing deficiency） and reducing intestinal immune response. In recent years， a large number of studies have been carried out to decipher the mechanism of TCM in the treatment of UC via NOD-like receptor protein domain 3 （NLRP3）-mediated pyroptosis pathway. The results have demonstrated that NLRP3 pathway is the key target of TCM in the treatment of UC. However， a comprehensive summary remains to be carried out on the inhibition of NLRP3-mediated pyroptosis pathway by TCM in the treatment of UC. Therefore， we retrieved the articles in this field in recent years with the keywords "pyroptosis"， "NLRP3"， "ulcerative colitis"， and "Chinese medicine". The Chinese medicines regulating NLRP3 pathway mainly have the functions of clearing heat and drying dampness， harmonizing Qi and blood， moving Qi and dredging fu-organs， and invigorating spleen and removing dampness. The findings can help researchers to fully understand the mechanism of TCM in the treatment of UC via the NLRP3 pathway and provide a theoretical basis for the treatment of UC and further drug development.

Traditional Chinese Medicine Intervention in Ulcerative Colitis Based on TLR4 Signaling Pathway： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC） is a disease that affects the mucosal and submucosal layers of the colon and is characterized by inflammation of the intestinal mucosa. The incidence of UC is increasing year by year， and it is complex and refractory， severely impacting the physical and mental health of patients. The pathological mechanism of this disease is complex， with immune responses and uncontrollable inflammatory reactions in the intestine being important physiopathologic mechanisms. Toll-like receptor 4 （TLR4）， as a transmembrane signaling receptor， plays a key role in mediating immune responses and inflammatory reactions in the development of UC. Currently， the treatment of UC mainly relies on salicylic acids， glucocorticoids， and other agents to reduce intestinal inflammation. While these drugs can partially inhibit the progression of the disease， they often come with significant adverse effects and the potential for relapse upon discontinuation. Traditional Chinese medicine （TCM） offers multiple pathways， effects， and targets for regulating the TLR4 pathway， suppressing inflammatory responses， and effectively intervening in the progression of UC. This approach has become a hot topic in the prevention and treatment of UC. Numerous studies have shown that TCM treatment of UC has unique advantages. TCM can enhance immune defenses， suppress inflammatory responses， promote intestinal mucosal healing， and maintain the balance of the intestinal microbiota by regulating the TLR4 signaling pathway， thereby effectively treating UC， with substantial progress achieved. However， there is currently a lack of comprehensive reviews on the role of TCM in regulating the TLR4 signaling pathway for the treatment of UC. Therefore， this article systematically summarized the relationship between the TLR4 signaling pathway and UC， as well as the role of TCM in this context， by reviewing relevant literature from recent years， aiming to provide new insights into the potential treatment and new drug development for UC.

Establishment and Evaluation of Ulcerative Colitis Animal Model in Combination of Disease and Syndrome / 中国实验方剂学杂志

Ulcerative colitis （UC） is one of the main manifestations of inflammatory bowel disease. Because of its lingering and refractory nature， it has become a major public health challenge worldwide. In the treatment of UC， traditional Chinese medicine （TCM） effectively relieves clinical syndromes， shortens the treatment period， reduces the frequency of recurrence， improves the quality of life， and reduces the occurrence of complications. To study the specific mechanism of TCM in the treatment of UC and screen out suitable drugs under the guidance of syndrome differentiation， the suitable UC animal model in the combination of disease and syndrome is used as an important method. This paper summarized and compared the UC animal model in the combination of disease and syndrome from five aspects， including selection of model animal species， sexual selection， preparation methods of UC animal model in the combination of disease and syndrome， indicators of model evaluation， and the main mechanism of TCM intervention in UC animal model in the combination of disease and syndrome. This paper aimed to provide references for the establishment of the optimal UC animal model in the combination of disease and syndrome. Research shows that UC syndrome mainly studied at present includes damp-heat syndrome， spleen deficiency syndrome， spleen-kidney Yang deficiency syndrome， spleen deficiency and dampness accumulation syndrome， liver depression and spleen deficiency syndrome， and cold-heat mixed syndrome.In the modeling method， the etiology simulation method is mainly used to first copy the syndrome type before the chemical agents or immune preparations were used to induce the disease model，and rats were often selected as the research objects，and the replication cycle was 7 to 28 days.The selected chemical reagents were mainly 5% dextran sulfate sodium（DSS） free drink, 2,4,6-trinitrobenzenesulfonic acid（TNBS） 100 mg·kg-1 and 50% ethanol 0.25 mL mixed reagent enema.This model replication method can take into account both UC pathogenesis characteristics of pathology of western medicine and TCM， syndrome type of traditional Chinese medicine and western medicine for interpretation pathological changes and TCM treatment of UC associated mechanism is of great significance， and help to help toestablish the optimal condition in combination with UC animal models for reference， for further research on prevention and treatment of UC specific mechanism of action of TCM model basis.

Effects of astragaloside Ⅳ on inflammatory response and percentage of peripheral blood Th17 cells in mice with ulcerative colitis / 中国中药杂志

This study aimed to investigate the anti-inflammatory effect of astragaloside Ⅳ in mice with ulcerative colitis(UC) and its effect on the percentage of peripheral blood T helper(Th17) cells. Following the establishment of UC mouse model with 2% sodium dextran sulfate(DSS), mice in the positive control group and low-and high-dose astragaloside Ⅳ groups were treated with corresponding drugs by gavage. Disease activity index(DAI) was calculated, and serum interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), and transforming growth factor-β(TGF-β) levels were assayed by ELISA. The pathological changes in colon tissue were observed by HE staining, and Th17/regulatory T cells(Treg) ratio in the peripheral blood was determined by flow cytometry. Western blot was conducted for detecting the relative protein expression levels of forkhead box protein P3(Foxp3) and retinoic acid-related orphan nuclear receptor γT(ROR-γt). The findings demonstrated that in normal mice, the colonic structure was intact. The goblet cells were not reduced and the glands were neatly arranged, with no mucosal erosion, bleeding, or positive cell infiltration. In the model group, the colonic mucosal structure was seriously damaged, manifested as disordered arrangement or missing of glands, vascular dilatation, congestion, and massive inflammatory cell infiltration. The pathological injury of colon tissue was alleviated to varying degrees in drug treatment groups. Compared with the normal group, the model group exhibited elevated percentage of Th17 cells, increased IL-17 and TNF-α content, up-regulated relative ROR-γt protein expression, lowered TGF-β, reduced percentage of Treg cells, and down-regulated relative Foxp3 protein expression. The comparison with the model group showed that DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the positive control group, low-dose astragaloside Ⅳ group, and high-dose astragaloside Ⅳ group were decreased, while TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression were increased. The DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the low-dose astragaloside Ⅳ group were higher than those in the positive control group, whereas the content of TGF-β, percentage of Treg cells, and relative Foxp3 protein expression were lower. DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, relative ROR-γt protein expression in the high-dose astragaloside Ⅳ group declined in contrast to those in the low-dose astragaloside Ⅳ group, while the TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression rose. There was no significant difference between the positive control group and the high-dose astragaloside Ⅳ group. Astragaloside Ⅳ is able to inhibit inflammatory response and diminish the percentage of Th17 cells in mice with UC.

Fish Oil Improves Dysbiosis of Host-microbial Interaction and Maintains Remission in Colitis Mice / 中国生物化学与分子生物学报

n-3 polyunsaturated fatty acids (PUFAs) play an active role in controlling the progression of ulcerative colitis (UC), but its mechanism is not very clear. In this study, we compared the effects of fish oil (the main component is n-3 PUFAs) in the mouse model with acute and chronic colitis induced by dextran sulfate sodium (DSS). Male C57BL/6J mice were randomly divided into six groups, and each group had ten mice. The alleviating effect of fish oil on chronic colitis was significantly better than acute colitis as indicated by the following analysis: the weight loss of mice (P < 0. 05), decreased disease activity index (DAI) score (P<0. 05), colonic edema, colon length index and histopathological score (P < 0. 05), and serum pro-inflammatory factor levels like IL-1β, TNF-α, and IL-6 (P < 0. 01). Moreover, fish oil promoted the level of serum anti-inflammatory factor IL-10 (P<0. 05). The treatment of fish oil increased the n-3 PUFA concentration in the intestinal epithelium of mice (P < 0. 01), especially EPA (P<0. 05). 16S rRNA sequencing of feces revealed that fish oil significantly increased the relative abundance of butyrate-producing flora (Clostridiales) and probiotics (Bifidobacteriales) in the feces of the maintained remission model group, reduce the proportion of aerobic, parthenogenic anaerobic and pathogenic, and improved the disorder of glycan biosynthesis and metabolism and oxidative phosphorylation (P<0. 05). Compared with the induced remission fish oil group, fish oil treatment led to an elevated expression of mechanical barrier and energy metabolism pathway proteins in the maintained remission fish oil group. Our results showed that fish oil exerted a more potent inhibitory effect in the remission mice model, which may be related to effectively strengthening the mechanical barrier, improving the composition and function of intestinal microbiota and concentration of butyric acids and improving dysbiosis of host-microbial interaction.

Clinical Efficacy of Kuijietong Against Mild to Moderate Active Ulcerative Colitis / 中国实验方剂学杂志

Objective:To re-evaluate the intervention effect of Kuijietong（KJT） on ulcerative colitis（UC）. Method:Sixty patients with mild-to-moderate UC in the active stage were enrolled and randomized into a KJT group （<italic>n</italic>=30） and a sulfasalazine （SASP） group （<italic>n</italic>=30）. Patients in the KJT group were treated with KJT granules， one bag divided in two daily doses， once in the morning and once in the evening， while those in the SASP group received SASP， 1 g per time， four times per day. Then the clinical efficacy was evaluated. Result:According to the modified Mayo score，the clinical remission rates of the KJT group and SASP group were determined to be 46.7% （14/30）and 40% （12/30），exhibiting no significant difference between the two groups （<italic>P</italic>>0.05）. The clinical effective rate of the KJT group was 83.3% （25/30），which was better than 60% （18/30） of the SASP group （<italic>P</italic><0.05）. The mucosal healing rate in the KJT group was 36.7% （11/30）， not significantly different from 30% （9/30） in the SASP group. In the alleviation of UC symptoms，the score of large intestine dampness heat syndrome in the KJT group was remarkably better than that in the SASP group （<italic>P</italic><0.05），but there was no significant difference in inflammatory bowel disease questionnaire （IBDQ） score between the two groups. In terms of physical and chemical indexes，serum erythrocyte sedimentation rate （ESR） in the KJT group after intervention was lower than that in the SASP group （<italic>P</italic><0.05），whereas the interleukin-10 （IL-10） level was higher（<italic>P</italic><0.05）. The comparison between the two groups revealed no significant difference in C-reactive protein （CRP）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， CD4⁺ T cells and regulatory T （Treg） cells after intervention. During the intervention，no obvious adverse reactions were found in the two groups，indicating good safety. Conclusion:KJT is not inferior to SASP in relieving mild-to-moderate UC in the active stage.

Gegen Qinliantang Alleviates Ulcerative Colitis via Cell Signaling Pathways： A Review / 中国实验方剂学杂志

Gegen Qinliantang， a classic traditional Chinese medicine（TCM） compound， has been verified in modern research to possess various pharmacological effects such as anti-inflammation，anti-oxidative stress，protecting intestinal mucosal barrier， and regulating intestinal flora and immune response. Ulcerative colitis （UC） is a chronic idiopathic inflammatory disease involving the colorectal mucosa， which mainly results from genetic susceptibility， intestinal mucosal barrier damage， abnormal immune response， intestinal flora disturbance， and bile acid metabolism disorders. By reviewing the literature published in recent years， this paper sorted out the relevant pathways and mechanisms involved in the treatment of UC by Gegen Qinliantang to provide ideas for further clinical and basic research. This literature review uncovered that Gegen Qinliantang exerted the therapeutic effects against UC mainly via interleukin-6（IL-6）/Janus tyrosine kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3） signaling pathway， Toll like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB） signaling pathway，Notch signaling pathway， and matrix metalloproteinase-9（MMP-9）/p38 mitogen-activated protein kinase（p38 MAPK） signaling pathway. Gegen Qinliantang regulates the intercellular molecular transmission in multiple pathways to protect the intestinal mucosal barrier， adjust the immune response and anti-oxidative stress， and relieve UC， demonstrating the multi-target， multi-mechanism， and multi-pathway advantages of TCM compounds.

Effect of Sishenwan， Baitouweng Tang， and Lianlitang on Ulcerative Colitis in Rats / 中国实验方剂学杂志

Objective:To explore the mechanism of Sishenwan， Baitouweng Tang， and Lianlitang in the treatment of ulcerative colitis （UC）， and compare their efficacies on UC in rats. Method:Ninety SD rats of SPF grade were randomly divided into blank group （distilled water， 2 mL·d^-1） and experimental group. The rats in the experimental groups were administered with 2，4，6-trinitrobenzene sulfonic acid （TNBS） by clysis to induce the UC model. Subsequently， the model rats were divided into a model group （distilled water， 2 mL·d^-1）， positive group ［sulfasalazine （SASP）， 0.4 g·kg^-1·d^-1］， Sishenwan group （1.76 g·kg^-1·d^-1）， a Baitouweng Tang group （1.40 g·kg^-1·d^-1）， and Lianlitang group （2.13 g·kg^-1·d^-1） according to the random number table. The rats in each group were dosed at 2 mL·d^-1 for 14 days. The pathological score for colonic mucosa was detected. Cytokines were detected by the cytokine chip. The enzyme-linked immunosorbent assay （ELISA） was used to detect the free triiodothyronine （FT₃）， glucagon-like peptide-1 （GLP-1）， and corticosterone （CORT） in plasma， and neurotensin （NT）， substance P （SP）， vasoactive intestinal peptide （VIP）， and somatostatin （SST） in colon tissues. Result:Compared with the normal group， the model group showed increased colon mass-length ratio and pathological score for colonic mucosa （<italic>P</italic><0.01）， infiltration of massive lymphocytes， disordered or absent intestinal villi， elevated levels of cytokine-induced neutrophil chemoattractant-1/2<italic>α</italic>/<italic>β</italic>/3 （CINC-1/2<italic>α</italic>/<italic>β</italic>/3）， interleukin-1<italic>α</italic> （IL-1<italic>α</italic>）， interferon-inducible protein-10 （IP-10） and other factors in colon tissues （<italic>P</italic><0.05）， dwindled CORT and GLP-1 levels in plasma （<italic>P</italic><0.05）， and increased SP content in colon tissues （<italic>P</italic><0.05）. Compared with the results in the model group， the mucosal injury in the colon of rats in each drug group was relieved. The levels of IL-1<italic>α</italic>， IP-10， lipopolysaccharide-inducible CXC chemokine （LIX）， and L-selectin of rats in the Lianlitang group and Sishenwan group were reduced （<italic>P</italic><0.05）， and the CINC-3 and IL-17 levels were diminished in the Baitouweng Tang group （<italic>P</italic><0.05）. The levels of CINC-1/3， IL-1<italic>α</italic>， and IP-10 were reduced in the SASP group （<italic>P</italic><0.05）. The plasma FT₃ was up-regulated in the Lianlitang group， and the plasma GLP-1 levels were elevated in the three Chinese medicine groups （<italic>P</italic><0.05）. The VIP content in colon tissues of the Sishenwan group and Baitouweng Tang group was down-regulated （<italic>P</italic><0.05）， and the SST content in colon tissues of the SASP group was significantly up-regulated （<italic>P</italic><0.01）. Conclusion:The intervention of Lianlitang and Sishenwan on UC was significant， and the underlying mechanism of action might be related to inflammation inhibition and immune balance by regulating the cytokine network. The efficacy of Lianlitang was predominant， followed by Sishenwan and Baitouweng Tang.

Shaoyaotang Treats Ulcerative Colitis by Inhibiting HIF-1α and Regulating Th17/Treg Balance / 中国实验方剂学杂志

Objective:To explore the effect of hypoxia-inducible factor （HIF）-1<italic>α</italic> on T helper 17 （Th17）/regulatory T cell （Treg） balance in ulcerative colitis and the intervention mechanism of Shaoyaotang. Method:Forty-eight SD rats were randomly divided into normal group （normal saline）， model group， mesalazine group （0.42 g·kg^-1）， Shaoyaotang group （11.1 g·kg^-1）， inhibitor group ［2-methoxyestradiol （2ME₂）， 0.015 g·kg^-1］， and Shaoyaotang+inhibitor group. The ulcerative colitis model was induced by 2，4，6-trinitrobenzene sulfonic acid （TNBS）. The rats in all groups received corresponding treatments for 7 d， and the general condition and disease activity index （DAI） were observed. Hematoxylin-eosin （HE） staining was used to observe histopathological changes of the colon. Enzyme-linked immunosorbent assay （ELISA） was employed to detect serum levels of interleukin （IL）-10， IL-17， and IL-23 in rats. Western blot was used to detect the expression levels of forkhead box protein 3 （FoxP3）， retinoic acid-related orphan receptor <italic>γ</italic>t （ROR<italic>γ</italic>t）， and HIF-1<italic>α</italic> proteins in the colon tissue. Result:Compared with the normal group， the model group showed elevated disease activity index （DAI） score and pathological score for intestinal mucosa （<italic>P</italic><0.01）， reduced serum IL-10 level （<italic>P</italic><0.01）， up-regulated IL-17 and IL-23 levels （<italic>P</italic><0.01）， increased ROR<italic>γ</italic>t and HIF-1<italic>α</italic> expression （<italic>P</italic><0.01）， and decreased FoxP3 protein expression （<italic>P</italic><0.01）. Compared with the model group， the Shaoyaotang group displayed diminished DAI score and pathological score for intestinal mucosa （<italic>P</italic><0.05， <italic>P</italic><0.01）， increased serum IL-10 level （<italic>P</italic><0.01）， decreased IL-17 and IL-23 levels （<italic>P</italic><0.01）， dwindled protein levels of ROR<italic>γ</italic>t and HIF-1<italic>α </italic>（<italic>P</italic><0.01）， and up-regulated expression of FoxP3 （<italic>P</italic><0.01）. Compared with the inhibitor group， the Shaoyaotang group and the Shaoyaotang+inhibitor group exhibited significant differences in the expression of ROR<italic>γ</italic>t， FoxP3， and HIF-1<italic>α</italic> proteins （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Shaoyaotang could effectively treat ulcerative colitis， and the underlying mechanism of action might be related to the regulation of Th17/Treg rebalance by inhibiting HIF-1<italic>α</italic>.

Effect of acupoint thread-embedding on tight junction of intestinal mucosa epithelium in rats with ulcerative colitis / 中国针灸

OBJECTIVE@#To observe the effect of acupoint thread-embedding on tight junction of intestinal mucosal epithelial barrier in rats with ulcerative colitis (UC) under the state of "deficiency and stasis", and to explore its mechanism.@*METHODS@#Sixty male SD rats were randomly divided into a control group (@*RESULTS@#Compared with the control group, in the model group the body weight was decreased (@*CONCLUSION@#The thread-embedding could repair the tight junction of intestinal mucosa epithelium and reduce the permeability of intestinal mucosa epithelium, which may be related to the decrease of the expression of CaMKⅡ, MLCK and other protein kinases.

Pharmacological effects of Huangqin Decoction prepared from roots of multi-originated peony on ulcerative colitis in mice:a comparative study / 中国中药杂志

Huangqin Decoction(HQD) is a classic prescription for treating dysentery in the Treatise on Cold Damage and now is mainly used for the treatment of ulcerative colitis(UC). Since there are no requirements on specific Paeonia species, both Paeoniae Radix Alba(white peony root, WPR) and Paeoniae Radix Rubra(red peony root, RPR) are clinically used in HQD now. Although the two types of peony roots are close in origin and similar in primary components, the medicinal properties and efficacies are different. Furthermore, the systematic comparative analysis on the efficacy differences in treating UC of HQD with the roots of multi-originated peony has been seldom reported. This study compared and evaluated the pharmacological effects of HQD prepared from the roots of multi-originated peony, including WPR, RPR-l(derived from P. lactiflora), and RPR-v(derived from P. veitchii) based on the mouse model of UC induced by dextran sodium sulfate(DSS) by animal behaviors, pathological section(colon), and cytokine expression(IL-1β and IL-6), aiming to provide evidence for the identification of the original resource of peony root in HQD. The results indicated that all HQD samples prepared from WPR, RPR-l, and RPR-v could improve the symptoms of UC. Compared with the HQD-WPR, HQD-RPR-l and HQD-RPR-v were significantly different in weight loss, colon length, and disease activity index(DAI) score, but there was no significant difference between HQD-RPR-l and HQD-RPR-v. Moreover, HQD-RPR-v exhibited the most significant improvement in the pathological morphology of colonic tissue and mucosal defects. According to the previous comparative analysis of chemical profiling and content distribution of HQD prepared from the roots of multi-originated peony, RPR-v in HQD was potent in protecting against UC, which was presumedly attributed to a large number of monoterpene glycosides and galloyl glucoses. This study provided a scientific basis for the determination of peony root in HQD and its clinical medication.

Effect of Nrf2/HO-1 signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis in mice / 中国中药杂志

The present study aimed to explore the effect of nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis(UC). After the UC model was induced by 3% dextran sodium sulfate(DSS), experimental animals were randomly divided into control group, model group, salazosulfapyridine(SASP) group, and low-and high-dose Sishen Pills groups. Drug intervention(ig) was performed for seven consecutive days during modeling. On the 7 th day, the mice were euthanized. The body weight and colon length were recorded, and the histopathological changes of the colon were observed by HE staining. Serum interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and reactive oxygen species(ROS) were detected by ELISA. The protein and mRNA expression of Nrf2, HO-1, and NADPH quinine oxidoreductase-1(NQO-1) was determined by Western blot and reverse transcription-polymerase chain reaction(RT-PCR). Compared with the normal group, the model group exhibited reduced body weight, colon length, and T-AOC, increased IL-6, TNF-α, MDA, and ROS, and diminished protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. Compared with the model group, the SASP group and high-dose Sishen Pills group showed elevated body weight, colon length, and T-AOC, lowered IL-6, TNF-α, MDA, and ROS levels, and increased protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. As assessed by HE staining, Sishen Pills could improve the pathological changes of the colon. The findings suggested that Sishen Pills could protect the colon against UC induced by 3% DSS. The specific mechanism of action may be related to the anti-inflammatory and anti-oxidative stress effects by the activation of the Nrf2/HO-1 signaling pathway.

Mechanism of Potentilla discolor in treating UC by regulating mitochondrial autophagy / 中国中药杂志

To evaluate the therapeutic effect of Potentilla discolor on 2,4,6-trinitrobenzensulfonic acid(TNBS)-induced experimental ulcerative colitis(UC) in rats and to determine its therapeutic mechanism through mitochondrial autophagy, immune cells, and cytokines. A rat model of UC was established by TNBS-ethanol enema. Rats were divided into six groups: control, UC model, sulfasalazine(positive drug), and high-dose, moderate-dose, and low-dose ethanol extract groups. After 14-day continuous administration of the corresponding drugs, the disease activity index(DAI) and hematoxylin and eosin(HE) were evaluated. The morphological structure of mitochondria was observed by using transmission electron microscope(TEM), mitophagy-related mRNA expression was detected by using Real-time quantitative polymerase chain reaction(qRT-PCR), immune cell differentiation in rat serum was detected by using flow cytometry(FCM), and cytokine expression in colon tissues of rats was detected by protein microarray. The results showed that compared with the model group, each dose group of P. discolor could significantly reduce the DAI of UC model rats, and decrease the degree of inflammatory cells infiltration in the colon tissue of UC model rats. Meanwhile the expressions of T cells and Th cells in the serum increased significantly, the expression of Tc cells in the serum decreased significantly. Transmission electron microscope found that there was fusion of mitochondria and lysosomes in the colon tissue of the administration group. The expressions of mitochondrial autophagy related genes NF-κB, p62 and parkin were significantly increased in colon tissues. The results of protein chip showed that compared with the model group, the high dose group of P. discolor could significantly regulate the expression of cytokines. In conclusion, these results suggested that P. discolor improved TNBS-induced acute ulcerative colitis in rats by regulating the mitochondrial autophagy and the inflammatory factor expression.

Expressions and effects of serum miR-23a-3p and miR-27a-3p in mice with ulcerative colitis / 上海交通大学学报（医学版）

Objective: To explore the expression levels of miR-23a-3p and miR-27a-3p in the sera of mice with ulcerative colitis (UC) and their potential action mechanisms. Methods: Twenty C57BL/6 mice were randomly divided into the control group and the model group with 10 mice in each group. The model group mice were induced orally by water with 5% dextran sulfate sodium (DSS) for 7 d. During the induction period, the general condition, fecal morphology and occult blood status of the mice were observed. After 7 d, the whole blood and colon tissues of mice were collected, and the colon lengths and wet weights were measured. The expressions of miR-23a-3p and miR-27a-3p in the sera were detected by qRT-PCR. The expressions of peroxisome proliferator-activated receptor γ, coactivator-1α (PPARGC1A), PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2), B-cell lymphoma-2 (BCL-2), BCL-2 associated X protein (BAX), cytochrome c (CYT-C) and cleaved cysteine-containing aspartate-specific protease (cleaved-caspase-3) were detected by Western blotting. Results: After DSS induction, the model group mice showed mental depression, weight loss, diarrhea, and bloody stool, whose colon lengths were shortened and colon wet weights decreased. The UC model was constructed successfully. In the model group, the expressions of miR-23a-3p and miR-27a-3p in the sera decreased significantly (P<0.05), and the expressions of PPARGC1A, PHLPP2, BAX, CYT-C and cleavedcaspase- 3 in the colon tissues increased significantly (P<0.05), but BCL-2 decreased (P<0.05). Conclusion: The expressions of miR-23a-3p and miR- 27a-3p are low in the sera of UC mice, which may be involved in the occurrence and development of UC by up regulating the expressions of PPARGC1A and PHLPP2 in the colons and triggering mitochondrial pathway to induce apoptosis.

Clinical Significance of the Ratio of Neutrophil to Lymphocyte in the Differential Diagnosis of Primary Ulcerative Colitis and the Judgment of Its Severity / 现代检验医学杂志

Objective To investigate the clinical impact of neutrophil to lymphocyte ratio (NLR) in the diagnosis of ulcerative colitis.Methods The study included 97 patients with ulcerative colitis (UC) and 95 patients with irritable bowel syndrome (IBS) from June 2009 to June 2016.The differences of NLR between the two groups were analyzed and the result of sensitivity and specificity were calculated.The differencesn of NLR were analyzed between the groups of different severity and in different lesionsseparately.Results NLR were significantly higher in ulcerative colitis than in irritable bowel syndrome (t=2.327,P＜0.021).Sensitivity was 69.1 ％ and specificity was 75.8 ％.There was statistic different in groups of different severity determination of newly diagnosed ulcerative colitis (F=8.221,P=0.001)and there was no statistic different between different lesions (F=0.737,P=0.483).Conclusion NLR is valuable in the diagnosis of UC and IBS can determine the degree of inflammation of ulcerative colitis.

Effects of Deoxyschisandrin on Hemorrheology and Coagulation Function in Ulcerative Colitis Mice / 现代生物医学进展

Objective:To observe the effects of Deoxyschisandrin on hemorrheology and coagulation function in ulcerative colitis (UC)mice.Methods:Trinitrobenzenesulfonic acid (TNBS)induced UC mice model was prepared.And then UC mice were randomly divided into model group,positive control group,high,medium,and low dose groups of deoxyschisandrin (80,40,20mg/kg),and in addition,a normal control group was set up.There were 10 mice in each group respectively.UC mice were intragastricly administrated with different concentration of deoxyschisandrin in medication group,or with equal volume distilled water in normal group or model group,respectively.The blood viscosity was determined by blood rheometer,and the bleeding time (BT)and the clotting time (CT)were also observed through the methods of tail cutting and blood coagulation in glass plates accordingly.Results:Compared with model group,the BT (P ＜ 0.01)and CT (P ＜ 0.05)were significantly prolonged,and the blood viscosity was decreased obviously (P ＜ 0.05) in UC mice after administrated with different concentration deoxyschisandfin for 14 days.And the effects in high dose group were strongest and similar to those in the positive group.Conclusions:Deoxyschisandrin can improve hemorrheology and coagulation function in UC mice.

Regulatory effect of Tripterygium wilfordii polycoride (TWP) towards TLR4/MyD88 independent pathway in TNBS/ethanol ulcerative colitis (UC) rat model / 中国中药杂志

In order to study the regulatory effect of Tripterygium wilfordii polycoride (TWP) towards TLR4/MyD88 independent pathway in TNBS/ethanol ulcerative colitis (UC) rat model, TNBS/ethanol enema was adopted to build TNBS/ethanol UC rat model. After the successful modeling procedure, 90 male Wistar rats are were divided into 6 groups, including namely normal group, model group, TWP low, middle, high dose groups (3, 6, 12 mg•kg⁻¹)and azathioprine (AZA) group (6 g•kg⁻¹), with 15 rats in each group. All rats in each group were administrated with corresponding medicines for 14 days. After 14 days of administration, corresponding colon tissues were taken for general and microscopic evaluation. Western blotting analysis and RT-PCR were adopted to test the mRNA and protein expressions of TLR4/MyD88 independent pathway-related molecules, namely TLR4, TRAM, TRIF, NF-κB and IFN-γ. The results showed that DAI, general and microscopic evaluations all indicated that TNBS/ethanol UC rat model was successful. TWP can improve UC-related clinical manifestation and heal colonic mucosa, which was equal to AZA. RT-PCR and WB results showed that the expression of TLR4/MyD88 independent pathway-related molecules in model group were significantly superior to that in normal group at either mRNA or protein level (P<0.01). Compared with model group, TWP can inhibit the expression of each node in TLR4/MyD88 independent pathway in a dose-dependent manner. The inhibitory effect of TWP with high dose towards the above molecules was inferior to that in model group at either mRNA or protein level (P<0.05). The inhibitory effect of TWP with high dose towards upstream molecules of TLR4/MyD88 independent pathway (TLR4, TRAM, TRIF, NF-κB) was slightly superior to AZA group at either mRNA or protein level. However, such inhibitory effect towards terminal inflammatory cytokines (IFN-γ) was inferior to AZA group at either mRNA or protein level. All the above differences had no statistical significance. Therefore, in TNBS/ethanol UC rat model, TLR4/MyD88 independent pathway took part in regulating inflammation. TWP exerted its anti-inflammation effect by inhibiting the expression of TLR4/MyD88 independent pathway in a dose-dependent manner.