Qin Tan,Xuanxuan An,Shuang Pan,Shujun Zhen,Yongmei Hu,Xiaoli Hu
Clioquinol (CQ) is not only used to treat skin diseases, but also CQ is a potential pharmaceutical for the treatment of neurodegenerative diseases. However, only a few researches report the detection of CQ. Thus, it is of great significance to accurately quantify CQ. Herein, we developed a CQ fluorescent sensor by Cu 2+ and carbon dots (CDs). Cu 2+ adsorbed on the surface of CDs preventing the non-radiative recombination of the holes in the valence band and the excited electrons in the CDs conduction band , which brings about an increase in the fluorescence intensity of CDs. However, a complex is formed owing to the strong affinity with Cu 2+ and CQ causing that Cu 2+ is disrobed from the CDs surface and then it quenched the fluorescence of CDs through inner filter effect (IFE). The CDs + Cu 2+ system displays preferable sensitivity and high selectivity toward CQ in a range of 40.0–400.0 μmol L −1 with a detection limit of 4.7 μmol L −1 . In addition, the strategy is employed for the quantification of CQ in clioquinol cream with satisfactory results.
In recent years, studies have shown a close relationship between cardiomyocyte death and ferroptosis. Clioquinol (CQ) can inhibit ferroptosis. Porous lipid-poly (lactic-co-glycolic acid) (PLGA) microbubbles (MBs) were prepared by double emulsification (W 1 /O/W 2 ) using 1,2-dioctadecanoyl-sn-glycero-3-phophocholine and PLGA as raw materials. Porous lipid-PLGA MBs were used as carriers to prepare CQ/PLGA MBs containing CQ. CQ/PLGA had the advantages of high drug loading, good biocompatibility, and sustained release. Our results showed that CQ/PLGA improved the effect of CQ and reduced its cytotoxicity. Under low-frequency ultrasound with certain parameters, CQ/PLGA showed steady-state cavitation, which increased the membrane permeability of mouse cardiomyocyte HL-1 to a certain extent and further prevented the process of ferroptosis in mouse cardiomyocyte HL-1.
Peipei Chen,Yunshu Wang,Huaiping Tang,Chao Zhou,Zhuo Liu,Shenghan Gao,Tingting Wang,Yun Xu,Sen-Lin Ji
The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC 50 ) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.
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