Evaluation of the Potential Therapeutic Effects of HPβCD and SBEβCD in a Mouse Model of Acute Ulcerative Colitis

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A Nanjing, China based research group designed a tailored investigation [1] based on a surprising previous study [2]. In they preceding work they 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 Ulcerative Colitis (UC). They found that γ-CD alone exhibited significant therapeutic effects in a dextran sulfate sodium (DSS)-induced acute UC mouse model. Specifically, γ-CD inhibited the overproduction of pro-inflammatory cytokines and modulated gut microbiota composition. This finding was found particularly promising, as cyclodextrin derivatives are known for their long-term safety, low production costs, and widespread use in the pharmaceutical and food industries. As a continuation of the work the group planned to study the effect of Hydroxypropyl Betadex (HPβCD) and Betadex Sulfobutyl Ether Sodium (SBEβCD) on acute UC. HPβCD and SBEβCD demonstrate both enhanced aqueous solubility and superior safety profiles relative to other cyclodextrin derivatives.

It is very likely that the paper published based on the follow-up study [1] is the first occurence of investigating the potential of HPβCD and SBEβCD in treating UC. HPβCD and SBEβCD exhibited dose-dependent inhibition of pro-inflammatory mediators, suppressing: (i) LPS-induced cytokine release (NO, IL-6, TNF-α) to 77.896.3 % baseline in vitro (P < 0.05), and (ii) DSS-induced TNF-α, IL-6, and IL-1β to 66.4–85.1 % in vivo (P < 0.01, P < 0.001). Network pharmacology analysis identified key inflammatory proteins as potential molecular targets of HPβCD and SBEβCD. Molecular docking studies demonstrated their capacity to form stable inclusion complexes with epithelial disruptors, suggesting a buffering mechanism that may protect intestinal barrier integrity. rRNA sequencing analysis demonstrated that both HPβCD and SBEβCD administration significantly modulated the dysbiotic gut microbiota composition in DSS-treated mice. These findings provided a new perspective on the application of HPβCD and SBEβCD and opened up new possibilities for the development of novel therapeutic strategies for UC.

[1] Lan Zhang, Fang Li, Huanhuan Wang, Bin Chen, Yongzhi Hua, Zhentao An. 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 2025;10:100825 https://doi.org/10.1016/j.carpta.2025.100825

[2] Wang W, Li X, Shi F, Zhang Z, Lv H. 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. Int J Pharm. 2023 Jan 5;630:122419. https://doi.org/10.1016/j.ijpharm.2022.122419

Cartoon illustration created using Microsoft Copilot’s AI image generation.

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