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Cucurbitacin B alleviates DSS-induced experimental colitis by targeting ZNF70 to suppress the NLRP3/STAT3 signaling
Shen Cao1, Yuhan Wang2, Yi Tai1
1Molecular Medicine Research Center, College of Pharmacy, Ministry of Education Key Laboratory of Changbai Mountain Natural Resources and Functional Molecules), Yanbian University, Yanji, 133002, Jilin Province, China.
Abstract:
Ulcerative colitis (UC) is an inflammatory disease characterized by lifelong involvement and a complex pathogenesis. Due to the limitations of current treatment modalities, there remains a pressing need to discover new medications for the management of UC. Cucurbitacin B (CuB) is a tetracyclic triterpenoid derived from Lagenaria siceraria (Molina) Standl., exhibiting pharmacological activities including hepatoprotective, anti-inflammatory, and anti-tumor properties. In this study, we conducted a comprehensive evaluation of the anti-inflammatory activity of CuB in both DSS-induced experimental colitis in vivo and macrophage models in vitro. Our results indicate that CuB exerts an anti-inflammatory effect by regulating the assembly of the NLRP3 inflammasome and the activation of p-STAT3 via ZNF70, thereby reducing the release of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Such results indicate that CuB can effectively prevent the development of UC and offer new insights for its management.
Insights
Cucurbitacin B (CuB) effectively reduces inflammation in ulcerative colitis (UC) models by regulating the NLRP3 inflammasome and p-STAT3 pathways. This natural compound offers potential for new UC treatments.
Area of Science:
- Pharmacology
- Immunology
- Gastroenterology
Background:
- Ulcerative colitis (UC) is a chronic inflammatory bowel disease with complex pathogenesis.
- Current UC treatments have limitations, necessitating novel therapeutic strategies.
- Cucurbitacin B (CuB), a natural triterpenoid, possesses known anti-inflammatory properties.
Purpose of the Study:
- To evaluate the anti-inflammatory efficacy of Cucurbitacin B (CuB) in experimental models of ulcerative colitis.
- To elucidate the molecular mechanisms underlying CuB's anti-inflammatory effects.
Main Methods:
- In vivo assessment using DSS-induced experimental colitis in mice.
- In vitro studies utilizing macrophage models.
- Analysis of NLRP3 inflammasome assembly and p-STAT3 activation.
- Quantification of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).
Main Results:
- CuB demonstrated significant anti-inflammatory effects in both in vivo and in vitro models.
- CuB regulated NLRP3 inflammasome assembly and p-STAT3 activation via ZNF70.
- CuB reduced the release of key pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α.
Conclusions:
- Cucurbitacin B exhibits potent anti-inflammatory activity relevant to ulcerative colitis management.
- CuB's mechanism involves modulation of the NLRP3 inflammasome and STAT3 signaling pathways.
- CuB presents a promising therapeutic candidate for preventing UC development and progression.
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