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

Abstract

The incidence of ulcerative colitis (UC) is rising worldwide. As a refractory and recurrent disease, UC could seriously affect the patients’ quality of life. However, current clinical medical treatments for UC are accompanied by various side effects, especially for long-term applications. Here, the underlying efficacy of cyclodextrins (CDs) was studied. As common excipients, CDs endow proven safety for long-term applications. Results of predictive methods derived from network pharmacology prompted the potential anti-inflammatory effects of CDs by oral administration. 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. 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. Conclusively, the study showed the therapeutic application prospects of CDs in UC treatment and indicated the feasibility and advantages of developing ‘new’ therapeutic activities of ‘old’ ingredients.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cyclodextrin
• network pharmacology
• acute ulcerative colitis
• anti-inflammatory
• intestinal flora

Author contributions

Weiqin Wang was responsible for the predictive analysis and experiments design, data analysis, and article writing. Xuefeng Li was responsible for the animal and cell experiments and participated in data analysis. Hangyi Wu participated in the data analysis. Fanli Shi participated in animal dissection and cell sample collection. Huixia Lv and Zhenhai Zhang were responsible for the supervision, project administration, funding acquisition, and revision of the article. All authors approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was financially supported by the National Natural Science Foundation of China (81673830), Six Talent Peaks Project of Jiangsu Province (YY053), Major Project and Double First-Class Innovative Team (CPU2018GY28), and National Science and Technology Major Project (2017zx09101001005).