Parthenolide targets NLRP3 to treat inflammasome-related diseases

Liu, Liu; Feng, Lianfang; Gao, Jiahui; Hu, Jie; Li, Ang; Zhu, Yangyang; Zhang, Changlong; Qiu, Bensheng; Shen, Zuo‐Jun Max

doi:10.1016/j.intimp.2023.110229

Cited by 7 publications

(6 citation statements)

References 54 publications

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“…We performed H&E staining and PAS staining to identify the pathological changes in lung inflammation and mucus production after treatment with TVE in NA mouse model. As shown in Figure 6B, an accumulation of infiltrated cells was observed around the airways in the lung tissue of the NA mouse model, 38 whereas the number of infiltrating cells was significantly reduced in the lung tissue upon treatment with TVE or MCC950. Similarly, the analysis of the mucus produced by airway epithelial cells in the PAS staining experiment revealed a significant increase in mucus in the NA model; however, treatment with TVE or MCC950 strongly inhibited mucus production (Figure 6B).…”

Section: Resultsmentioning

confidence: 86%

“…One-way ANOVA, Bonferroni post-hoc test; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, n.s. not significant.of the NA mouse model,38 whereas the number of infiltrating cells was significantly reduced in the lung tissue upon treatment with TVE or MCC950. Similarly, the analysis of the mucus produced by airway epithelial cells in the PAS staining experiment revealed a significant increase in mucus in the NA model; however, treatment with TVE or MCC950 strongly inhibited mucus production (Figure6B).…”

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confidence: 90%

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Anti‐inflammatory effect of Trichospira verticillata via suppression of the NLRP3 inflammasome in neutrophilic asthma

Yang,

Park,

Lee

et al. 2024

J Cellular Molecular Medi

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Trichospira verticillata is an annual herb that belongs to the family Asteraceae. Trichospira verticillata extract (TVE) elicits anti‐plasmodial activity; however, there has been no detailed report about its anti‐inflammatory effects and molecular mechanisms. In addition, herbal plants exhibit anti‐inflammatory effects by suppressing the NLRP3 inflammasome. Therefore, the primary goal of this study was to examine the effects of TVE on NLRP3 inflammasome activation by measuring interleukin‐1β (IL‐1β) secretion. We treated lipopolysaccharides (LPS)‐primed J774A.1 and THP‐1 cells with TVE, which attenuated NLRP3 inflammasome activation. Notably, TVE did not affect nuclear factor‐kappa B (NF‐κB) signalling or intracellular reactive oxygen species (ROS) production and potassium efflux, suggesting that it inactivates the NLRP3 inflammasome via other mechanisms. Moreover, TVE suppressed the formation of apoptosis‐associated speck‐like protein (ASC) speck and oligomerization. Immunoprecipitation data revealed that TVE reduced the binding of NLRP3 to NIMA‐related kinase 7 (NEK7), resulting in reduced ASC oligomerization and speck formation. Moreover, TVE alleviated neutrophilic asthma (NA) symptoms in mice. This study demonstrates that TVE modulates the binding of NLPR3 to NEK7, thereby reporting novel insights into the mechanism by which TVE inhibits NLRP3 inflammasome. These findings suggest TVE as a potential therapeutic of NLRP3 inflammasome‐mediated diseases, particularly NA.

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Section: Resultsmentioning

confidence: 86%

mentioning

confidence: 90%

Anti‐inflammatory effect of Trichospira verticillata via suppression of the NLRP3 inflammasome in neutrophilic asthma

Yang,

Park,

Lee

et al. 2024

J Cellular Molecular Medi

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“…Studies have also shown that parthenolide has potential therapeutic effects for conditions such as leukemia, Alzheimer’s disease, and migraines ( Materazzi et al, 2013 ; Yang et al, 2017 ; Fan et al, 2023 ). In addition to these diseases, parthenolide has promising effects on diabetes and its related complications ( Liu et al, 2023b ). Mounting evidence also has established a close relationship between VDR signaling and diabetes, as well as diabetic nephropathy and insulin resistance.…”

Section: Natural Bioactive Compounds Targeting Vdr Activitymentioning

confidence: 99%

Modulation of the vitamin D receptor by traditional Chinese medicines and bioactive compounds: potential therapeutic applications in VDR-dependent diseases

Yao,

Oduro,

Akintibu

et al. 2024

Front. Pharmacol.

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The Vitamin D receptor (VDR) is a crucial nuclear receptor that plays a vital role in various physiological functions. To a larger extent, the genomic effects of VDR maintain general wellbeing, and its modulation holds implications for multiple diseases. Current evidence regarding using vitamin D or its synthetic analogs to treat non-communicable diseases is insufficient, though observational studies suggest potential benefits. Traditional Chinese medicines (TCMs) and bioactive compounds derived from natural sources have garnered increasing attention. Interestingly, TCM formulae and TCM-derived bioactive compounds have shown promise in modulating VDR activities. This review explores the intriguing potential of TCM and bioactive compounds in modulating VDR activity. We first emphasize the latest information on the genetic expression, function, and structure of VDR, providing a comprehensive understanding of this crucial receptor. Following this, we review several TCM formulae and herbs known to influence VDR alongside the mechanisms underpinning their action. Similarly, we also discuss TCM-based bioactive compounds that target VDR, offering insights into their roles and modes of action.

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“…The wide range of biological activities shown by PTL is mainly attributed to the α-exo-methylene-γ-butyrolactone moiety present in its structure [4,5]. In fact, α-exo-methylene is able to react with nucleophilic cysteines from biomolecules through a Michael addition (Figure 1) [6][7][8] to form a covalent bond.…”

Section: Introductionmentioning

confidence: 99%

“…structure [4,5]. In fact, α-exo-methylene is able to react with nucleophilic cysteines from biomolecules through a Michael addition (Figure 1) [6][7][8] to form a covalent bond.…”

Section: Introductionmentioning

confidence: 99%

Regioselective and Stereoselective Synthesis of Parthenolide Analogs by Acyl Nitroso-Ene Reaction and Their Biological Evaluation against Mycobacterium tuberculosis

Gioia,

Ruggieri,

Biela

et al. 2023

IJMS

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Historically, natural products have played a major role in the development of antibiotics. Their complex chemical structures and high polarity give them advantages in the drug discovery process. In the broad range of natural products, sesquiterpene lactones are interesting compounds because of their diverse biological activities, their high-polarity, and sp3-carbon-rich chemical structures. Parthenolide (PTL) is a natural compound isolated from Tanacetum parthenium, of the family of germacranolide-type sesquiterpene lactones. In recent years, parthenolide has been studied for its anti-inflammatory, antimigraine, and anticancer properties. Recently, PTL has shown antibacterial activities, especially against Gram-positive bacteria. However, few studies are available on the potential antitubercular activities of parthenolide and its analogs. It has been demonstrated that parthenolide’s biological effects are linked to the reactivity of α-exo-methylene-γ-butyrolactone, which reacts with cysteine in targeted proteins via a Michael addition. In this work, we describe the ene reaction of acylnitroso intermediates with parthenolide leading to the regioselective and stereoselective synthesis of new derivatives and their biological evaluation. The addition of hydroxycarbamates and hydroxyureas led to original analogs with higher polarity and solubility than parthenolide. Through this synthetic route, the Michael acceptor motif was preserved and is thus believed to be involved in the selective activity against Mycobacterium tuberculosis.

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Parthenolide targets NLRP3 to treat inflammasome-related diseases

Cited by 7 publications

References 54 publications

Anti‐inflammatory effect of Trichospira verticillata via suppression of the NLRP3 inflammasome in neutrophilic asthma

Anti‐inflammatory effect of Trichospira verticillata via suppression of the NLRP3 inflammasome in neutrophilic asthma

Modulation of the vitamin D receptor by traditional Chinese medicines and bioactive compounds: potential therapeutic applications in VDR-dependent diseases

Regioselective and Stereoselective Synthesis of Parthenolide Analogs by Acyl Nitroso-Ene Reaction and Their Biological Evaluation against Mycobacterium tuberculosis

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