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Ulcerative colitis (UC) is a chronic inflammatory disease of the intestines that can significantly impact quality of life and lead to various complications. Currently, 5-aminosalicylic acid derivatives, corticosteroids, immunosuppressants, and biologics are the major treatment strategies for UC, but their limitations have raised concerns. Atractylenolides (ATs), sesquiterpene metabolites found in Atractylodes macrocephala Koidz., have shown promising effects in treating UC by exerting immune barrier modulation, alleviating oxidative stress, gut microbiota regulation, improving mitochondrial dysfunction and repairing the intestinal barrier. Furthermore, ATs have been shown to possess remarkable anti-fibrosis, anti-thrombus, anti-angiogenesis and anti-cancer. These findings suggest that ATs hold important potential in treating UC and its complications. Therefore, this review systematically summarizes the efficacy and potential mechanisms of ATs in treating UC and its complications, providing the latest insights for further research and clinical applications.

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Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are chronic relapsing inflammatory gastrointestinal tract diseases of uncertain origin, which are frequently associated with zinc deficiency. Animal models have a considerable value in elucidating the process of IBD. In this study, 50 male C57BL/6 J mice were randomly assigned to five groups: control group (Con), 2,4,6-trinitrobenzenesulfonic acid (TNBS) group, and three zinc supplementation groups, namely 160 ppm group, 400 ppm group, and 1000 ppm group. The results showed that supplementation of dietary zinc with zinc oxide could effectively relieve the severity of ulcerative colitis induced by TNBS in mice. We demonstrate that the protective mechanism involves the immunomodulation of dietary zinc by increasing CD3+, CD3+CD8+, and Th2 cells, suppressing Th1 and Th17 cells, and decreasing the production of serum IL-1ß and IL-18. The dietary zinc oxide seems to be able to suppress the NF-κB/NLRP3 signaling pathway by downregulating the mRNA and protein expression of NIK, IKK, NF-κB, and NLRP3. The results suggest that dietary supplementation of zinc oxide may protect against colitis, and proper daily zinc supplementation may reduce the risk of IBD.

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Evodia rutaecarpa, the near-ripe fruit of Euodia rutaecarpa (Juss.) Benth, Euodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang, or Euodia rutaecarpa (Juss.) Benth. var. bodinieri (Dode) Huang, is a famous herbal medicine with several biological activities and therapeutic values, which has been applied for abdominalgia, abdominal distension, vomiting, and diarrhea as a complementary and alternative therapy in clinic. Indole alkaloids, particularly evodiamine (EVO), rutaecarpine (RUT), and dedhydroevodiamine (DHE), are received rising attention as the major bioactivity compounds in Evodia rutaecarpa. Therefore, this review summarizes the physicochemical properties, pharmacological activities, pharmacokinetics, and therapeutic effects on gastrointestinal diseases of these three indole alkaloids with original literature collected by PubMed, Web of Science Core Collection, and CNKI up to June 2023. Despite sharing the same parent nucleus, EVO, RUT, and DHE have different structural and chemical properties, which result in different advantages of biological effects. In their wide range of pharmacological activities, the anti-migratory activity of RUT is less effective than that of EVO, and the neuroprotection of DHE is significant. Additionally, although DHE has a higher bioavailability, EVO and RUT display better permeabilities within blood-brain barrier. These three indole alkaloids can alleviate gastrointestinal inflammatory in particular, and EVO also has outstanding anti-cancer effect, although clinical trials are still required to further support their therapeutic potential.

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ETHNOPHARMACOLOGICAL RELEVANCE: Tou Nong Powder (TNP), a classical Chinese medicinal formula originated from the Chinese Ming Dynasty, has been applied to treat skin ulcers in patients with deficient constitutions. According to theory of traditional Chinese medicine, colonic ulcers share similar pathological conditions with skin ulcers, and consequently, TNP has been applied to ulcerative colitis (UC) safely and effectively. AIM OF STUDY: To investigate whether TNP obstructs 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced enteric inflammation through regulation of NLRP3 inflammasome and attenuating enteric pyroptosis. MATERIALS AND METHODS: Network pharmacology and UPLC-Q-TOF/MS were operated to identify compounds and pharmacological potential targets. The therapeutic effects of TNP were assessed on TNBS induced colitis via general symptoms (disease activity index, colonic weight and length) and histopathological observation. The NF-κB/NLRP3/Caspase-1/GSDMD signaling pathway regulation was investigated by Western blot and real time reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: TNP ameliorates the disease activity index, reverses the increase of colonic weight increase, alleviates colonic shortening and colonic histopathological injury. A decrease in tumor necrosis factor α (TNF-α), diamine oxidase (DAO), intercellular adhesion molecule-1 (ICAM-1), and endo-toxin (ET) were investigated in peripheral circulation. Moreover, TNP significantly obstructed the NF-κB/NLRP3/Caspase-1/GSDMD signaling pathway. CONCLUSION: TNP displays a promising therapeutic effect on UC via suppressing NF-κB/NLRP3/Caspase-1/GSDMD signaling pathway and reducing the expression of IL-1ß and IL-18.

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Background: Tong-fu therapeutic method (TFTM) is a traditional Chinese medicine treatment method for ulcerative colitis, which is a novel treatment strategies and have purgative effect. As the most representative medicinal of TFTM, Rhubarb has been reported to have a therapeutic impact on ulcerative colitis by regulating intestinal flora, anti-inflammation, and improving intestinal microcirculation. Although rhubarb has been widely used in Chinese medicine for the treatment of ulcerative colitis, the appropriate protocol is still demanded to its rational use in clinic, which promoted to evaluate the efficacy and safety for rhubarb-based therapy on ulcerative colitis. Method: Clinical trials were searched through PubMed, Cochrane Library, Web of Science, Excerpta Medica Database, Chinese National Knowledge Infrastructure, WAN FANG Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. The subgroup analyses were performed with three groups: medication, course of treatment, and route of administration. The statistical analyses were performed on Review Manager software (version 5.4.1). Results: A total of 2, 475 patients in 30 original studies were analyzed in this article. It was found that rhubarb-based therapy could increase clinical efficacy and reduce the recurrence rate. Subgroup analyses showed that rhubarb-based therapy was more effective than 5-aminosalicylic acid or sulfasalazine alone. In addition, the hypercoagulable state of ulcerative colitis could be ameliorated by decreasing platelet (PLT) and fibrinogen (FIB), and increasing prothrombin time (PT) significantly. Moreover, C-reaction protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1ß expression were significantly reduced, while IL-10 production was increased, which mediated the alleviation of intestinal inflammation stress. Conclusion: Rhubarb-based therapy could effectively improve ulcerative colitis. Of note, the rhubarb-based medicinal formulas combined with 5-ASA or SASP are more effective than the 5-ASA or SASP alone. In addition, although rhubarb has side effect, the results of our analysis showed that rhubarb-based therapy did not exhibit significant side effects. This means it has a high safety profile in clinical use. Moreover, the use of rhubarb-based therapy is recommend to use within 1-13 weeks or 3 months via administered orally or by enema, which is contributes to ensure the curative effect and avoid its toxic and side effects. As an important case of TFTM, rhubarb-based therapy provides evidence for the practical application of TFTM.

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Background: Hepatic fibrosis is a health challenge due to the absence of satisfactory therapy, especially at the cirrhosis stage. Dahuang Zhechong pill (DHZCP)-based therapy is reportedly a successful treatment for hepatic fibrosis and is even beneficial for the treatment of cirrhosis. Hence, a systematic review and clinical evidence assessment of DHZCP-based therapy should be performed, and clinical recommendations based on its efficacy for the treatment of hepatic fibrosis should be generated. With respect to potential indicators, the comparative value of the hepatic function, spleen thickness, and portal vein internal diameter should be evaluated. Materials and methods: PubMed, the Excerpta Medica Database, the Cochrane Library, the Web of Science, the WanFang Database, the Chinese Scientific Journal Database, and the Chinese National Knowledge Infrastructure database were searched to identify clinical trials. Three subgroup analyses were performed based on the stage of disease, medication use, and the course of treatment. Statistical analyses were performed using Review Manager 5.4. Results: A total of 18 studies including 1,494 patients were evaluated. The DHZCP-based therapy was effective in reducing the plasma levels of hyaluronic acid, and laminin, procollagen III, and IV collagen were also reduced irrespective of the hepatitis stage or the presence of hepatic cirrhosis. Abnormalities in alanine aminotransferase, aspartate aminotransferase, albumin, and total bilirubin were reversed. A 6-month course of treatment was the most beneficial DHZCP-based therapy regimen. Alanine aminotransferase improvement was more obvious in patients with cirrhosis, and alanine aminotransferase was reduced significantly in patients with hepatic cirrhosis. With respect to pharmacological mechanisms, DHZCP-based therapy could inhibit hepatic stellate cell growth and activation, reduce inflammation, and prevent extracellular matrix formation. Hepatic portal hypertension and splenomegaly were ameliorated significantly in the DHZCP-based therapy group. Conclusion: Dahuang Zhechong pill-based therapy has demonstrated efficacy as a treatment for hepatic fibrosis and cirrhosis. A 6-month course of treatment is the recommended option for DHZCP-based therapy in clinical practice. The combination of DHZCP-based therapy and entecavir is a favorable treatment for hepatic cirrhosis.

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Ulcerative colitis is a chronic and relapsing inflammatory bowel disease without satisfactory therapy available recently. Renshen Baidu powder (RSBDP) is a classic Chinese medicinal formula used since Chinese Song dynasty and has been proven as an effective treatment of ulcerative colitis in clinics. However, the active ingredients and the molecular mechanism have not been fully disclosed. It is imperative to explore the active ingredients and the mechanism of RSBDP. In this study, the potential active components for ulcerative colitis treatment in RSBDP were determined and predicted in silicon, and its molecular mechanisms were also presented, in which the PI3K/Akt/NF-κB signaling pathway was recognized to be vital. Basically, the pharmacodynamics and mechanistic studies of RSBDP for ulcerative colitis were implemented on TNBS-induced experimental rats. The results showed that RSBDP could ameliorate the disease activity index and colon weight, as well as improve colonic shortening and colon histology. In addition, the tumor necrosis factor-α (TNF-α), diamine oxidase, intercellular adhesion molecule-1, and endotoxin in serum were also reduced. It is worth mentioning that the PI3K/Akt/NF-κB signaling pathway was inhibited after RSBDP administration via inhibiting the phosphorylation of proteins. In conclusion, RSBDP effectively ameliorates TNBS-induced colitis rats by inhibiting the PI3K/Akt/NF-κB signaling pathway.

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[This corrects the article DOI: 10.3389/fmed.2021.766126.].

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Background: The combination of probiotics and traditional Chinese medicine (TCM) is a prospective therapy for ulcerative colitis (UC), and its efficacy and safety need to be urgently evaluated. Objective: This study aims to comprehensively assess the efficacy and safety of probiotics combined with TCM for the treatment of UC. Methods: The Pubmed, EMBASE, Cochrane library, China Academic Journals (CNKI), Wan-fang database, Chinese biomedical literature service system (CBM), and Chinese Science and Technology Journals (CQVIP) were searched. Subgroup analysis were designed in accordance with different control drugs, treatment courses, and types of probiotics. The Review Manager software (version 5.4.1) was utilized for statistical analysis. Results: 14 original studies containing 1,154 patients were analyzed and showed that probiotics with TCM was more effective than 5-aminosalicylic acid (5-ASA), probiotics or TCM used individually. Moreover, probiotics combined with TCM could inhibit the intestinal inflammation, reduce the recurrence rate and the incidence of adverse events. The subgroup analysis showed that a mixture of different probiotics was more effective than a single strain. Conclusion: It is suggested that probiotics combined with TCM could effectively control clinical symptoms, inhibit intestinal inflammatory response, and finally slow down the disease progress and reduce the disease recurrence with less adverse events. The mixture of different probiotics used in conjunction with individually tailored TCM is a potential clinical strategy for UC.

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[This corrects the article DOI: 10.3389/fphar2021.714287.].

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Ulcerative Colitis (UC) is a chronic inflammatory bowel disease. The prolonged course of UC and the lack of effective treatment management make it difficult to cure, affecting the health and life safety of patients. Although UC has received more attention, the etiology and pathogenesis of UC are still unclear. Therefore, it is urgent to establish an updated and comprehensive understanding of UC and explore effective treatment strategies. Notably, sufficient evidence shows that the intestinal microbiota plays an important role in the pathogenesis of UC, and the treating method aimed at improving the balance of the intestinal microbiota exhibits a therapeutic potential for UC. This article reviews the relationship between the genetic, immunological and microbial risk factors with UC. At the same time, the UC animal models related to intestinal microbiota dysbiosis induced by chemical drugs were evaluated. Finally, the potential value of the therapeutic strategies for restoring intestinal microbial homeostasis and treating UC were also investigated. Comprehensively, this study may help to carry out preclinical research, treatment theory and methods, and health management strategy of UC, and provide some theoretical basis for TCM in the treatment of UC.

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Background: The combination of strengthening Qi and eliminating pathogens is an available therapeutic principle in traditional Chinese medicine (TCM) for primary liver cancer (PLC) at middle-advanced stage. However, there is a lack of reasonable evidence to support the proper application of this therapeutic principle. This meta-analysis aims to evaluate the efficacy and safety of Chinese medicinal formulas (CMFs), including two subgroup analyses of the principle of strengthening Qi and eliminating pathogens. Method: Clinical trials were obtained through searching of EMBASE, Web of Science, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, and two clinical trial registries. The randomized controlled trials with the combination of CMFs and transcatheter arterial chemoembolization (TACE) in the experiment group were acceptable, in contrast to the TACE alone in the control group. The statistics analysis was performed on Review Manager 5.4. Results: A total of eligible 24 trials were accessed in this work. Overall, CMFs could improve the survival duration of 6 months, 1 year, and 2 years, Karnofsky Performance Status, tumor objective response rate (ORR), AFP, and symptom. In the subgroup analysis, trials complying with the principle of single strengthening Qi did not show any significant difference in increasing tumor ORR. Meanwhile, the principle of combined strengthening Qi and eliminating pathogens was uncertain in improving symptoms and 1-year and 2-year survival time. In addition, the outcome indexes of ALT and AST were heterogeneous. In last, the total occurrence of adverse events could not be reduced via using CMFs. Patients treated with CMFs exhibited liver injury, fever, and white blood cell decline, with mild events occurring more frequently and severe events occurring less. Conclusion: CMFs are an effective treatment method to cure PLC at the middle-advanced stage. Adopting the principle of single strengthening Qi presents better efficacy in the long term by prolonging the survival duration. Following the principle of combined strengthening Qi and eliminating pathogens could be more beneficial to patients in short term by lessening the tumor size. CMFs have the advantage of reducing certain serious adverse events.

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BACKGROUND: Ulcerative colitis (UC) is a chronic non-specific intestinal inflammatory disease characterized by continuous and diffuse inflammatory response of colonic mucosa. Steroid-dependent UC is an important type of UC. Chinese herbal medicine is widely used in treating steroid-dependent UC in China. However, there is no systematic review and meta-analysis to collate and evaluate the evidence of these studies. The purpose of this research is to provide evidence of the efficacy and safety of Chinese herbal medicine in treating steroid-dependent UC. METHODS AND ANALYSIS: Six databases, including 3 English databases and 3 Chinese databases will be searched. In addition, other grey literatures and ongoing studies will also be searched. Two researchers will independently select eligible studies by reading titles, abstracts and full texts according to the inclusion and exclusion criteria. Risk of bias assessment will be conducted by 2 independent reviewers using Cochrane risk-of-bias tool. The outcomes include steroid-free remission rate, Total clinical effective rate, Incidence of adverse events, Disease activity index (modified Mayo score), Results of enteroscopy (Baron score) and mucosa (geboes index score). Heterogeneity between studies will be assessed by Cochrane X and I tests. We will conduct subgroup analysis and meta-regression to explore the source of heterogeneity. We will also evaluate the stability of the results through sensitivity analysis and publication bias through funnel plot and Egger test. RESULTS: The results will be published in peer-reviewed journals. CONCLUSION: Our meta-analysis and systematic evaluation results will confirm whether Chinese herbal medicine is effective in the treatment of steroid-dependent UC. It will provide more ideas for future research. OSF REGISTRATION NUMBER: DOI: 10.17605/OSF.IO/YP79Z.

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BACKGROUND: Ulcerative colitis (UC), an important type of inflammatory bowel disease, is mainly characterized by persistent and diffuse inflammatory response of colonic mucosa. Many studies have explored the effects and mechanisms of Chinese herbal medicine (CHM) in UC animal models. However, there is no systematic review and meta-analysis to evaluate and summarize these studies. The purpose of this study is to provide precise evidence of the effects and mechanisms of CHM in treating UC. METHODS: Six databases, including 3 English databases and 3 Chinese databases will be searched. Two researchers will independently select eligible studies by reading titles, abstracts, and full texts according to the inclusion and exclusion criteria. Risk of bias assessment will be conducted by 2 independent reviewers using SYRCLE's risk of bias tool. The outcomes include total clinical effective rate, adverse events, disease activity index, interleukin-1ß (IL-1ß), IL-4, IL-6, IL-17; colombosa damage index, colonic mucosa damage index; myeloperoxidase; epidermal growth factor; transforming growth factor-ß1; and histopathological score. Heterogeneity between studies will be assessed by Cochrane X and I tests. We will conduct subgroup analysis to explore the subgroup effects. We will also evaluate the stability of the results through sensitivity analysis and publication bias through funnel plot and Egger test. RESULTS: The results will be published in peer-reviewed journals. CONCLUSION: This study can help us to understand the effects and possible mechanisms of CHM for UC. For further clinical researches, this study can help us to better look for possible effective medicines for clinical use. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/YU5FN.

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The incidence of inflammatory bowel disease (IBD), which predominantly comprises Crohn's disease and ulcerative colitis, is increasing worldwide. However, the treatment of IBD still faces great challenges. The involved NF-κB is the main signaling pathway in human IBD and thus is a prime target. There is abundant evidence that Tou Nong San (TNS), which is a traditional Chinese medicinal decoction used for treating sores and carbuncles, has a positive effect on the inflammation. This study investigated the effects of oral administration of TNS on colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and the underlying mechanism(s). Quality control of the major compounds in TNS was performed by high-performance liquid chromatography, and six chemical constituents were identified in aqueous extracts. TNS led to improvements in weight loss and water and food intake in rats. The macroscopic and microscopic scores of rat tissues greatly decreased. Protein and mRNA levels of proinflammatory cytokines, including interleukin-17 (IL-17), tumour necrosis factor-α, IL-1ß, and IL6, involved in the NF-κB signaling pathway were greatly reduced. The results suggest that the anti-inflammatory effect of TNS is associated with the regulation of the NF-κB signaling pathway, which contributes to the network pharmacological effect of TNS on human IBD in clinical practice.