Isoliquiritin Ameliorates Ulcerative Colitis in Rats through Caspase 3/HMGB1/TLR4 Dependent Signaling Pathway

  • Authors: Miao Z.1, Gu M.2, Raza F.3, Zafar H.3, Huang J.4, Yang Y.5, Sulaiman M.6, Yan J.7, Xu Y.8
  • Affiliations:
    1. Department of Gastroenterology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine
    2. Department of Nephrology, Changshu Hospital Affiliated to Nanjing University of Chinese medicine
    3. School of Pharmacy, Shanghai Jiao Tong University
    4. , Taizhou Hospital of Traditional Chinese Medicine
    5. School of Pharmacy, Jiangsu University
    6. School of Pharmacy, China Pharmaceutical University
    7. Key Laboratory for Metabolic Diseases in Chinese Medicine, First Clinical Medical College, Nanjing University of Chinese Medicine
    8. Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine
  • Issue: Vol 24, No 1 (2024)
  • Pages: 73-92
  • Section: Life Sciences
  • URL: https://j-morphology.com/1566-5232/article/view/643933
  • DOI: https://doi.org/10.2174/1566523223666230731115236
  • ID: 643933

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Abstract

Background:Isoliquiritin belongs to flavanol glycosides and has a strong antiinflammatory activity. This study sought to investigate the anti-inflammatory effect of isoliquiritin and its underlying mechanism.

Methods:The inflammatory (trinitro-benzene-sulfonic acid-TNBS-induced ulcerative colitis (UC)) model was established to ascertain the effect of isoliquiritin on the caspase-3/HMGB1/TLR4 pathway in rats. We also explored its protective effect on intestinal inflammation and its underlying mechanism using the LPS-induced inflammation model of Caco-2 cells. Besides, Deseq2 was used to analyze UCassociated protein levels.

Results:Isoliquiritin treatment significantly attenuated shortened colon length (induced by TNBS), disease activity index (DAI) score, and body weight loss in rats. A decrease in the levels of inflammatory mediators (IL-1β, I IL-4, L-6, IL-10, PGE2, and TNF-α), coupled with malondialdehyde (MDA) and superoxide dismutase (SOD), was observed in colon tissue and serum of rats after they have received isoliquiritin. Results of techniques (like western blotting, real-time PCR, immunohistochemistry, and immunofluorescence-IF) demonstrated the potential of isoliquiritin to decrease expressions of key genes in the TLR4 downstream pathways, viz., MyD88, IRAK1, TRAF6, NF-κB, p38, and JNK at mRNA and protein levels as well as inhibit HMGB1 expression, which is the upstream ligand of TLR4. Bioinformational analysis showed enteritis to be associated with a high expression of HMGB1, TLR4, and caspase-3.

Conclusion:Isoliquiritin could reduce intestinal inflammation and mucosal damage of TNBS-induced colitis in rats with a certain anti-UC effect. Meanwhile, isoliquiritin treatment also inhibited the expression of HMGB1, TLR4, and MyD88 in LPS-induced Caco-2 cells. These results indicated that isoliquiritin could ameliorate UC through the caspase-3/HMGB1/TLR4-dependent signaling pathway.

About the authors

Zhiwei Miao

Department of Gastroenterology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine

Email: info@benthamscience.net

Mingjia Gu

Department of Nephrology, Changshu Hospital Affiliated to Nanjing University of Chinese medicine

Email: info@benthamscience.net

Faisal Raza

School of Pharmacy, Shanghai Jiao Tong University

Author for correspondence.
Email: info@benthamscience.net

Hajra Zafar

School of Pharmacy, Shanghai Jiao Tong University

Email: info@benthamscience.net

Jianyi Huang

, Taizhou Hospital of Traditional Chinese Medicine

Email: info@benthamscience.net

Yuhang Yang

School of Pharmacy, Jiangsu University

Email: info@benthamscience.net

Muhammad Sulaiman

School of Pharmacy, China Pharmaceutical University

Email: info@benthamscience.net

Jing Yan

Key Laboratory for Metabolic Diseases in Chinese Medicine, First Clinical Medical College, Nanjing University of Chinese Medicine

Author for correspondence.
Email: info@benthamscience.net

Yi Xu

Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine

Author for correspondence.
Email: info@benthamscience.net

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