Berberine improves colitis by triggering AhR activation by microbial tryptophan catabolites

Jing, Wanghui; Dong, Sijing; Luo, Xialin; Liu, Jingjing; Wei, Bin; Wei, Du; Yang, Lin; Luo, Hongyu; Wang, Ying; Wang, Sicen; Lü, Haitao

doi:10.1016/j.phrs.2020.105358

Cited by 126 publications

(84 citation statements)

References 54 publications

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“…In addition, microbiota analysis based on 16S rDNA revealed that berberine could alleviate intestinal disorders in rats. Berberine is also reported to mitigate DSS-mediated colitis in rats by regulating intestinal microbe-related tryptophan metabolites for activating AhR, thereby greatly improving the impaired intestinal barrier function (Jing et al, 2021). The clinic research observed that berberine administrated at 900 mg/day for 3 months could significantly decrease the Geboes grade of colonic tissue in colitis patients as well as has almost any side effect (Xu et al, 2020).…”

Section: Alkaloidsmentioning

confidence: 99%

Natural Anti-Inflammatory Compounds as Drug Candidates for Inflammatory Bowel Disease

et al. 2021

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Inflammatory bowel disease (IBD) represents chronic recurrent intestinal inflammation resulting from various factors. Crohn’s disease (CD) and ulcerative colitis (UC) have been identified as the two major types of IBD. Currently, most of the drugs for IBD used commonly in the clinic have adverse reactions, and only a few drugs present long-lasting treatment effects. Moreover, issues of drug resistance and disease recurrence are frequent and difficult to resolve. Together, these issues cause difficulties in treating patients with IBD. Therefore, the development of novel therapeutic agents for the prevention and treatment of IBD is of significance. In this context, research on natural compounds exhibiting anti-inflammatory activity could be a novel approach to developing effective therapeutic strategies for IBD. Phytochemicals such as astragalus polysaccharide (APS), quercetin, limonin, ginsenoside Rd, luteolin, kaempferol, and icariin are reported to be effective in IBD treatment. In brief, natural compounds with anti-inflammatory activities are considered important candidate drugs for IBD treatment. The present review discusses the potential of certain natural compounds and their synthetic derivatives in the prevention and treatment of IBD.

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Section: Alkaloidsmentioning

confidence: 99%

Natural Anti-Inflammatory Compounds as Drug Candidates for Inflammatory Bowel Disease

et al. 2021

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“…The decrease in Dicer expression could increase the levels of cytosolic DNA and IL-6 mRNA under oxidative stress in inflammatory bowel tissues, while berberine alleviates colitis by recovering Dicer expression to exert a preventive effect on colitis-associated tumorigenesis ( Wu et al, 2020 ). In the dextran sulfate sodium (DSS)-induced colitis model, berberine exerts its therapeutic effects by activating the mTORC1 signaling pathway to enhance the number of Treg cells and regulate the levels of intestinal microbiota-associated tryptophan metabolites and the activation of the aryl hydrocarbon receptor ( Li Q. et al, 2019 ; Jing et al, 2021 ). Similarly, berberine downregulates the levels of COX-2 mRNA, protein, as well as the concentration of prostaglandin E2 in the CRC (HT-29) cells ( Tai and Luo, 2003 ).…”

Section: Antitumor Effects and Corresponding Mechanismsmentioning

confidence: 99%

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

Chen

Liang

et al. 2022

Front. Pharmacol.

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Cancer is a serious disease with an increasing number of reported cases and high mortality worldwide. Gastrointestinal cancer defines a group of cancers in the digestive system, e.g., liver cancer, colorectal cancer, and gastric cancer. Coptidis Rhizoma (C. Rhizoma; Huanglian, in Chinese) is a classical Chinese medicinal botanical drug for the treatment of gastrointestinal disorders and has been shown to have a wide variety of pharmacological activity, including antifungal, antivirus, anticancer, antidiabetic, hypoglycemic, and cardioprotective effects. Recent studies on C. Rhizoma present significant progress on its anticancer effects and the corresponding mechanisms as well as its clinical applications. Herein, keywords related to C. Rhizoma, cancer, gastrointestinal cancer, and omics were searched in PubMed and the Web of Science databases, and more than three hundred recent publications were reviewed and discussed. C. Rhizoma extract along with its main components, berberine, palmatine, coptisine, magnoflorine, jatrorrhizine, epiberberine, oxyepiberberine, oxyberberine, dihydroberberine, columbamine, limonin, and derivatives, are reviewed. We describe novel and classic anticancer mechanisms from various perspectives of pharmacology, pharmaceutical chemistry, and pharmaceutics. Researchers have transformed the chemical structures and drug delivery systems of these components to obtain better efficacy and bioavailability of C. Rhizoma. Furthermore, C. Rhizoma in combination with other drugs and their clinical application are also summarized. Taken together, C. Rhizoma has broad prospects as a potential adjuvant candidate against cancers, making it reasonable to conduct additional preclinical studies and clinical trials in gastrointestinal cancer in the future.

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“…In addition, the study also clarifies the role of AhR activation as the primary mechanism of this benefit, consistent with the attenuation of colitis through other AhR activators in multiple animal models. [46][47][48][49][50][51][52][53][54][55][56][57] Limitations of this study are its open-label nature and small sample size. Further investigation with a well-controlled study and an adequate number of patients to evaluate the use of a colon-targeted AhR agonist in patients with treatment-refractory UC is warranted.…”

Section: Discussionmentioning

confidence: 97%

Treatment-refractory ulcerative colitis responsive to indigo naturalis

Saiki

Andreasson

Grimes

et al. 2021

BMJ Open Gastroenterol

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BackgroundIndigo naturalis (IN) is an herbal medicine that has been used for ulcerative colitis with an unclear mechanism of action. Indigo and indirubin, its main constituents, are ligands of the aryl hydrocarbon receptor (AhR). We assessed the safety, efficacy, and colon AhR activity of IN given orally to patients with treatment-refractory ulcerative colitis. The role of AhR in IN benefit was further evaluated with an AhR antagonist in a murine colitis model.MethodsThis open-label, dose-escalation study sequentially treated 11 patients with ulcerative colitis with either IN 500 mg/day or 1.5 g/day for 8 weeks, followed by a 4-week non-treatment period. The primary efficacy endpoint was clinical response at week 8, assessed by total Mayo score. Secondary endpoints included clinical remission, Ulcerative Colitis Endoscopic Index of Severity, quality of life, and colon AhR activity measured by cytochrome P450 1A1 (CYP1A1) RNA expression.ResultsTen of 11 (91%) patients, including 8/9 (89%) with moderate-to-severe disease, achieved a clinical response. Among these 10 patients, all had failed treatment with 5-aminosalicylic acid, 8 patients with a tumour necrosis factor (TNF)-alpha inhibitor, and 6 patients with TNF-alpha inhibitor and vedolizumab. Five patients were corticosteroid dependent. Clinical response was observed in all five patients who had been recommended for colectomy. Three patients achieved clinical remission. All patients experienced improved endoscopic severity and quality of life. Four weeks after treatment completion, six patients had worsened partial Mayo scores. Four patients progressed to colectomy after study completion. Colon CYP1A1 RNA expression increased 12 557-fold at week 8 among six patients evaluated. No patient discontinued IN due to an adverse event. Concomitant administration of 3-methoxy-4-nitroflavone, an AhR antagonist, in a murine colitis model abrogated the benefit of IN.ConclusionIN is a potentially effective therapy for patients with treatment-refractory ulcerative colitis. This benefit is likely through AhR activation.Trial registration numberNCT02442960.

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Berberine improves colitis by triggering AhR activation by microbial tryptophan catabolites

Cited by 126 publications

References 54 publications

Natural Anti-Inflammatory Compounds as Drug Candidates for Inflammatory Bowel Disease

Natural Anti-Inflammatory Compounds as Drug Candidates for Inflammatory Bowel Disease

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

Treatment-refractory ulcerative colitis responsive to indigo naturalis

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