Evaluation of Indigo Naturalis Prepared Using a Novel Method - Anti-Inflammatory Activities Against Colonic Cancer Cell Lines

Sep 22, 2026

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Ulcerative colitis (UC) is a chronic inflammatory bowel disease in which long-term inflammation of colonic tissues is closely linked to cancerous transformation. Indigo naturalis prepared using a novel method (NIN) has shown beneficial effects on inflammatory and cancerous colonic cells, but the mechanism remained unclear. This study used the HT-29 colonic cancer cell line to model an inflammatory cancer state, finding that NIN reduced pro-inflammatory IL-1β, restored MUC2-mediated mucin secretion function, and inhibited HT-29 proliferation. Mechanistic experiments indicated that NIN activates AhR signaling to upregulate Rnf43, suppress β-catenin/Wnt signaling, and downregulate Axin2 and Lgr5, with effects blocked by the AhR antagonist CH223191.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Introduction

Ulcerative colitis and cancer transformation

Traditional Chinese medicine and Indigo Naturalis (IN)

Role of AhR and Wnt/β-catenin signaling

Study objective and approach

Wiley Mediators of Inflammation Volume 2026, Article ID 1141244, 11 pages [https://doi.org/10.1155/mi/1141244](https://doi.org/10.1155/mi/1141244) Research Article Evaluation of Indigo Naturalis Prepared Using a Novel Method: Anti-Inﬂammatory Activities Against Colonic Cancer Cell Lines Xianxiang Xu , Lin Lin , Wenjie Ning , Xinyi Zhou , Aftab Ullah , Xiaoping Huang , Huiyong Yang , Xunxun Wu , and Yong Diao School of Medicine, Huaqiao University, 269 Chenghua North Road, Quanzhou 362021, China Correspondence should be addressed to Xianxiang Xu; [xuxianxiang@hqu.edu.cn](xuxianxiang@hqu.edu.cn) Received 9 March 2025; Revised 6 December 2025; Accepted 12 December 2025 Academic Editor: Coman Cristin Copyright © 2026 Xianxiang Xu et al. Mediators of Inﬂammation published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Ulcerative colitis (UC) is a chronic inﬂammatory bowel disease (IBD), and cancerous transformation of UC is closely associated with chronic inﬂammation of colonic tissues. Indigo naturalis (IN) prepared using a novel method (NIN) has exhibited beneﬁcial efﬁcacy against inﬂammatory and cancerous colonic cells. However, the underlying mechanism still remains to be elucidated. This study aimed to construct an inﬂammation model by the HT-29 colonic cancer cell line and to investigate the effect of NIN on an inﬂammatory cancer state and the possible mechanism. The results showed that NIN could reduce the increased expression of pro-inﬂammatory cytokine IL-1β in the inﬂammatory cancer cells and attenuate the inﬂammatory response; elevate the low expression of MUC2 in the inﬂammatory cancer state and restore the mucin secretion function; and inhibit the proliferation of HT-29 cells. Based on the activation ofthe aryl hydrocarbon receptor (AhR) signaling pathway, NIN increases the expression of the Wnt/β-catenin signaling pathway inhibitor Rnf43, inhibits the expression of nonphosphorylated β-catenin, and reduces the level of the pathway downstream target gene Axin2, which in turn inhibits the Wnt/β-catenin signaling pathway and inhibits the expression of Lgr5, a stem cell gene of colorectal cancer (CAC) . The production of the above effects of NIN was blocked by the AhR antagonist CH223191 . The in vitro studies veriﬁed that NIN alleviated UC by activing AhR signaling pathway, which in turn inhibited the Wnt/β-catenin signaling pathway. The possible mechanism of NIN on UC could be explained starting from the inﬂammation-cancer transformation. Furthermore, comprehensive research is expected between inﬂammation and cancer development. Keywords: aryl hydrocarbon receptor (AhR); indigo naturalis prepared using a novel method (NIN); inﬂammation-cancer transformation; ulcerative colitis 1. Introduction Ulcerative colitis (UC) is an inﬂammatory disease of the gastrointestinal tract, which is characterized with a wide range of lesions, a tendency to recur, and a tendency to become cancerous [1, 2] . Transformation of UC to cancer is strongly associated with chronic inﬂammation in colonic tissues, and patients with chronic UC are at a higher risk of developing colorectal cancer (CAC)[3, 4]. Inﬂammatory stress at the site, and the presence of intestinal microbiota and cytokines contribute to the inﬂammatory bowel disease (IBD) and colitis-associated CAC [5, 6] . The patients face an increased risk of developing CAC. In Asian UC patients, malignant transformation typically begins 10–20 years post-diagnosis, whereas in North American CAC patients, the risk signiﬁcantly escalates after 30 years [7] . Effectively managing chronic inﬂammation and mucosal damage in UC is vital to mitigate the risk of cancerous transformation [8] . Despite advances, controlling this progression remains a signiﬁcant challenge in UC treatment [9] .

FAQs

What effect does NIN have on inflammatory cancer cells in this study?

NIN reduces increased IL-1β expression and attenuates the inflammatory response in the inflammatory cancer state.

How does NIN influence mucin secretion and MUC2 levels?

NIN elevates low MUC2 expression in the inflammatory cancer state and restores mucin secretion function.

What mechanism explains the action of NIN in UC-related inflammation?

NIN activates AhR signaling, which inhibits the Wnt/β-catenin pathway by increasing Rnf43 and reducing β-catenin downstream targets; the effects are blocked by the AhR antagonist CH223191.

Sep 22, 2026

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