Mollugin inhibits IL-1β production by reducing zinc finger protein 91-regulated Pro-IL-1β ubiquitination and inflammasome activity.

IF 4.8 2区 医学 Q2 IMMUNOLOGY
International immunopharmacology Pub Date : 2025-01-03 Epub Date: 2024-12-06 DOI:10.1016/j.intimp.2024.113757
Lei Song, Yi Tai, Jia Xuan Li, Shen Cao, Jing Han, Xin Zhe Liu, Sheng Cao, Ming Yue Li, Hong Xiang Zuo, Yue Xing, Juan Ma, Xuejun Jin
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引用次数: 0

Abstract

Background: Rubia cordifolia L. has been formally included in the Chinese Pharmacopoeia and utilized for centuries as a traditional Chinese medicine. Mollugin, a quinone compound, is a major active compound extracted from Rubia cordifolia L. Mollugin was reported has multiple pharmacological activity, including anti-inflammatory, anti-tumor effects. However, the anti-inflammatory mechanism is not yet clear. In this study, we explored the anti-inflammatory activity and potential mechanism of mollugin in vitro and in vivo.

Materials and methods: We explored the mechanisms that mollugin suppressed IL-1β expression through ZFP91 using various assays, including western blot, immunofluorescence, immunoprecipitation, MTT, RT-PCR, and ELISA assays in vitro. In vivo, oral administration of DSS induced colitis in mice and intraperitoneal injection of alum induced peritonitis in mice.

Results: First, the results demonstrated that mollugin dramatically suppressed IL-1β secretion through reducing ZFP91 in macrophages. Crucially, we proved that mollugin inhibited K63-linked Pro-IL-1β ubiquitination through ZFP91 and limitated Pro-IL-1β cleavage efficacy. In addition, ZFP91-mediated Caspase-8 inflammasome component expression was inhibited by mollugin. Furthermore, mollugin inhibited the assembly of the Caspase-8 inflammasome complex by downregulating ZFP91. In vivo studies further revealed that mollugin improved DSS-induced colitis and alum-induced peritonitis in mice by reducing ZFP91. Notely, mollugin significantly altered the abundance of gut flora in DSS-induced colitis mice, which in turn ameliorated the colitis.

Conclusion: We present a novel finding that mollugin inhibition of ZFP91 is a crucial regulatory step, preventing undue inflammatory responses and thereby maintaining immune homeostasis. The current study offers new insight into the development of anti-inflammatory therapeutics targeting ZFP91.

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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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