Ulcerative colitis (UC), a major subtype of inflammatory bowel disease (IBD) alongside Crohn’s disease, is characterized by a relapsing and remitting course of mucosal inflammation with classic symptoms including bloody diarrhea, rectal urgency, tenesmus, and abdominal pain.
In a previous study, the team of Prof. Lv at the China Pharmaceutical University (Nanjing) investigated an inclusion complex composed of γ-cyclodextrin (γ-CD) as the host molecule and epigallocatechin-3-gallate (EGCG) as the guest molecule for the treatment of UC. Surprisingly, they found that γ-CD alone exhibited significant therapeutic effects in a dextran sulfate sodium (DSS)-induced acute UC mouse model. [1] Specifically, γ-CD inhibited the overproduction of pro-inflammatory cytokines and modulated gut microbiota composition.
RAW264.7 cell experiments verified that CDs could inhibit the excessive secretion of TNF-α (β-CD > α-CD ≈ γ-CD), IL-6, and NO (α-CD > β-CD ≈ γ-CD) as predicted [2]. In mice with DSS-induced acute UC, oral administration of CDs could effectively mitigate the pathological damage of colon tissue and reduce the level of inflammatory mediators. Moreover, 16S rRNA sequencing displayed that gut microbes disturbed by DSS were significantly regulated by CDs.
In a recent study the therapeutic effects of HPBCD and SBEBCD on UC were explored via RAW264.7 cell experiments and DSS-induced acute UC mice assays [3]. Mechanistic investigations were conducted through network pharmacology, molecular docking, Caco-2 monolayer transepithelial electrical resistance (TEER) assays, and 16S rRNA sequencing of gut microbiota. Treatment with HPBCD or SBEBCD reduced pro-inflammatory cytokines (NO, IL-6, and TNF-α) levels to 77.8 %-96.3 % of LPS-induced values in RAW264.7 cells. Compared with the DSS-induced UC model group, both HPBCD and SBEBCD treatment groups showed significantly reduced levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) (P < 0.01, P < 0.001). Network pharmacology predicted them to act on proteins related to inflammation. Molecular docking analysis revealed that HPBCD and SBEBCD could function as “buffer”, demonstrating a tendency to form stable inclusion complexes with intestinal epithelial disruptors (N-acetyl-DL-tryptophan (N-AT) and adenosine 5′-monophosphate monohydrate (AMP)). 16S rRNA sequencing analysis demonstrated that both SBEBCD and HPBCD administration significantly modulated the dysbiotic gut microbiota composition in DSS-treated mice.
References
[1] Weiqin Wang, Xuefeng Li, Fanli Shi, Zhenhai Zhang, Huixia Lv (2023) Study on the preparation of EGCG-γ-Cyclodextrin inclusion complex and its drug-excipient combined therapeutic effects on the treatment of DSS-induced acute ulcerative colitis in mice. International Journal of Pharmaceutics 630, 122419.
https://doi.org/10.1016/j.ijpharm.2022.122419
[2] Wang, W., Li, X., Wu, H., Shi, F., Zhang, Z., & Lv, H. (2023). Explore the underlying oral efficacy of α-, β-, γ-Cyclodextrin against the ulcerative colitis using in vitro and in vivo studies assisted by network pharmacology. Journal of Biomolecular Structure and Dynamics 42(10), 4985–5000. https://doi.org/10.1080/07391102.2023.2239901
[3] Lan Zhang, Fang Li, Huanhuan Wang, Bin Chen, Yongzhi Hua, Zhentao An (2025) Study on the Ameliorative effects of Hydroxypropyl Betadex and Betadex Sulfobutyl ether sodium on acute ulcerative colitis induced by DSS in Mice. Carbohydrate Polymer Technologies and Applications 10, 100825.
https://doi.org/10.1016/j.carpta.2025.100825