Costunolide alleviates HKSA-induced acute lung injury via inhibition of macrophage activation

Chen, Yun-tian; Du, Yao; Zhao, Bo; Gan, Li-xing; Yu, Kaikai; Sun, Lei; Wang, Jian; Qian, Feng

doi:10.1038/s41401-018-0192-6

Cited by 22 publications

(10 citation statements)

References 35 publications

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“…Lung tissue homogenates were mixed with thiobarbituric acid, and the MPO activity in the supernatant was detected using a spectrophotometer by measuring the absorbance changes of lung tissues per gram 48 …”

Section: Methodsmentioning

confidence: 99%

NLRP3 Inflammasome Activation by MicroRNA-495 Promoter Methylation May Contribute to the Progression of Acute Lung Injury

Ying

Mao

Yao

2019

Molecular Therapy - Nucleic Acids

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Acute lung injury (ALI) is a pulmonary disorder that causes acute respiratory failure, thus leading to relative high mortality worldwide. However, the molecular mechanisms of ALI remain largely unknown. MicroRNA (miRNA)-dependent control of gene expression at a post-transcriptional level has been recently reported. Herein, we identify a candidate miRNA, miR-495, that affects the progression of ALI. Alveolar macrophages (NR8383) were treated with 1 mg/mL lipopolysaccharide (LPS) to establish a cell-injury model. Combined with the data from western blot, methylation-specific PCR, methylated DNA immunoprecipitation, and chromatin immunoprecipitation assays, NLRP3 inflammasome activation and methylation-dependent repression of miR-495 were found in LPS-exposed NR8383 cells. Dual-luciferase reporter gene assay and miR-495 gain-offunction experiments confirmed that NLRP3 was a target of miR-495. Next, the expression of miR-495 and NLRP3 was overexpressed or silenced to assess their effects on NLRP3 inflammasome activation, alveolar macrophage inflammation, and pyroptosis in vitro. As demonstrated, overexpressed miR-495 alleviated alveolar macrophage inflammation and pyroptosis and inhibited NLRP3 inflammasome activation by negatively regulating the NLRP3 gene. Consistently, elevated miR-495 alleviated lung injury and reduced the neutrophil infiltration and inflammation in rat models of LPS-induced ALI. Taken together, the data in our study demonstrated that methylation of the miR-495 promoter could downregulate miR-495, whose elevation could attenuate the activation of the NLRP3 inflammasome to protect against ALI, which provides novel therapeutic targets for ALI treatment.

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Section: Methodsmentioning

confidence: 99%

NLRP3 Inflammasome Activation by MicroRNA-495 Promoter Methylation May Contribute to the Progression of Acute Lung Injury

Ying

Mao

Yao

2019

Molecular Therapy - Nucleic Acids

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“…Additionally, costunolide dose-dependently reduced inflammatory cytokine expression in murine bone marrow-derived macrophages and alveolar macrophages stimulated by lipoteichoic acid or HKSA. These effects of costunolide were related to inhibition of the MAPK signaling pathway [ 232 ].…”

Section: Natural Compounds That Exert Anti-ali Effectsmentioning

confidence: 99%

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

Zhou

et al. 2021

Pharmacological Research

248

121

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“…Its anti-inflammatory action has been well documented in vitro [84,100] and in vivo, appearing to be linked to NF-κB pathway inhibition [101]. For example, costunolide (3) is able to suppress inflammatory angiogenesis [102], alleviating gastric ulcers [103], and acute lung and liver damage [104][105][106][107].…”

Section: Biosynthesis Of Costunolide (mentioning

confidence: 99%

Applications of Sesquiterpene Lactones: A Review of Some Potential Success Cases

et al. 2020

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Sesquiterpene lactones, a vast range of terpenoids isolated from Asteraceae species, exhibit a broad spectrum of biological effects and several of them are already commercially available, such as artemisinin. Here the most recent and impactful results of in vivo, preclinical and clinical studies involving a selection of ten sesquiterpene lactones (alantolactone, arglabin, costunolide, cynaropicrin, helenalin, inuviscolide, lactucin, parthenolide, thapsigargin and tomentosin) are presented and discussed, along with some of their derivatives. In the authors’ opinion, these compounds have been neglected compared to others, although they could be of great use in developing important new pharmaceutical products. The selected sesquiterpenes show promising anticancer and anti-inflammatory effects, acting on various targets. Moreover, they exhibit antifungal, anxiolytic, analgesic, and antitrypanosomal activities. Several studies discussed here clearly show the potential that some of them have in combination therapy, as sensitizing agents to facilitate and enhance the action of drugs in clinical use. The derivatives show greater pharmacological value since they have better pharmacokinetics, stability, potency, and/or selectivity. All these natural terpenoids and their derivatives exhibit properties that invite further research by the scientific community.

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Costunolide alleviates HKSA-induced acute lung injury via inhibition of macrophage activation

Cited by 22 publications

References 35 publications

NLRP3 Inflammasome Activation by MicroRNA-495 Promoter Methylation May Contribute to the Progression of Acute Lung Injury

NLRP3 Inflammasome Activation by MicroRNA-495 Promoter Methylation May Contribute to the Progression of Acute Lung Injury

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

Applications of Sesquiterpene Lactones: A Review of Some Potential Success Cases

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