Inhibition of inflammasome activation via sphingolipid pathway in acute lung injury by Huanglian Jiedu decoction: An integrative pharmacology approach

Chen, Ying; Peng, Mingming; Li, Wei; Zhao, Mantong; Cao, Xia; Li, Chuanqiu; Zhang, Han; Yang, Mengru; Liang, Lanyuan; Yue, Yiming; Xia, Tianyi; Zhong, Renxing; Wang, Yi; Shu, Zunpeng

doi:10.1016/j.phymed.2022.154469

Cited by 19 publications

(4 citation statements)

References 32 publications

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“…Metabolomics techniques have been used to study metabolites associated with ALI in animals and patients with the aim of identifying disease-related biomarkers and novel drug targets ( Ding et al, 2020 ). For example, Huanglian Jiedu Decoction was shown to alleviate ALI by regulating the sphingolipid pathway to inhibit NLRP3 inflammasome activation ( Chen et al, 2022 ). The metabolomic results obtained in the present study revealed significant changes in 12 metabolites, mainly some sugar and amino acid metabolites, following EEAR treatment of ALI.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effects and mechanism of Atractylodis rhizoma in acute lung injury: Investigation based on an Integrated approach

et al. 2023

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Acute lung injury (ALI) is characterized by an excessive inflammatory response. Atractylodes lancea (Thunb.) DC. is a traditional chinese medicine with good anti-inflammatory activity that is commonly used clinically for the treatment of lung diseases in China; however, its mechanism of against ALI is unclear. We clarified the therapeutic effects of ethanol extract of Atractylodis rhizoma (EEAR) on lipopolysaccharide (LPS)-induced ALI by evaluation of hematoxylin-eosin (HE) stained sections, the lung wet/dry (W/D) ratio, and levels of inflammatory factors as indicators. We then characterized the chemical composition of EEAR by ultra-performance liquid chromatography and mass spectrometry (UPLC-MS) and screened the components and targets by network pharmacology to clarify the signaling pathways involved in the therapeutic effects of EEAR on ALI, and the results were validated by molecular docking simulation and Western blot (WB) analysis. Finally, we examined the metabolites in rat lung tissues by gas chromatography and mass spectrometry (GC-MS). The results showed that EEAR significantly reduced the W/D ratio, and tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) levels in the lungs of ALI model rats. Nineteen components of EEAR were identified and shown to act synergetically by regulating shared pathways such as the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathways. Ferulic acid, 4-methylumbelliferone, acetylatractylodinol, atractylenolide I, and atractylenolide III were predicted to bind well to PI3K, AKT and MAPK1, respectively, with binding energies < -5 kcal/mol, although only atractylenolide II bound with high affinity to MAPK1. EEAR significantly inhibited the phosphorylation of PI3K, AKT, p38, and ERK1/2, thus reducing protein expression. EEAR significantly modulated the expression of metabolites such as D-Galactose, D-Glucose, serine and D-Mannose. These metabolites were mainly concentrated in the galactose and amino acid metabolism pathways. In conclusion, EEAR alleviates ALI by inhibiting activation of the PI3K-AKT and MAPK signaling pathways and regulating galactose metabolism, providing a new direction for the development of drugs to treat ALI.

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Section: Discussionmentioning

confidence: 99%

Therapeutic effects and mechanism of Atractylodis rhizoma in acute lung injury: Investigation based on an Integrated approach

et al. 2023

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“…Activation of the TLR4/NF-kB signaling pathway results in the upregulation of NLRP3, pro-IL-1b and pro-IL-18 (55). Additionally, various stimuli such as PAMP/damage-associated molecular pattern (DAMP) indirectly activate NLRP3, leading to the assembly of NLRP3 inflammasome and activation of CASP1, which triggers the synthesis and secretion of IL-1b and IL-18 (56). Simultaneously, activated CASP1 cleaves the N-terminal sequence of GSDMD, giving rise to the production of GSDMD-N. GSDMD-N binds to the cell membrane and forms pores, facilitating the release of inflammatory cytokines and exacerbating the inflammatory response, ultimately contributing to the deterioration of ALI (57).…”

Section: Discussionmentioning

confidence: 99%

Qinhuo Shanggan oral solution resolves acute lung injury by down-regulating TLR4/NF-κB signaling cascade and inhibiting NLRP3 inflammasome activation

Tang,

Liang,

Wang

et al. 2023

Front. Immunol.

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Acute lung injury (ALI) is a common condition, particularly in the COVID-19 pandemic, which is distinguished by sudden onset of respiratory insufficiency with tachypnea, oxygen-refractory cyanosis, reduced lung compliance and diffuse infiltration of pulmonary alveoli. It is well-established that increasing activity of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling axis and the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation are associated with the pathogenesis of ALI. Since ALI poses a huge challenge to human health, it is urgent to tackle this affliction with therapeutic intervention. Qinhuo Shanggan oral solution (QHSG), a traditional Chinese herbal formula, is clinically used for effective medication of various lung diseases including ALI, with the action mechanism obscure. In the present study, with the rat model of lipopolysaccharide (LPS)-induced ALI, QHSG was unveiled to ameliorate ALI by alleviating the pathological features, reversing the alteration in white blood cell profile and impeding the production of inflammatory cytokines through down-regulation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. In LPS-stimulated RAW264.7 mouse macrophages, QHSG was discovered to hinder the generation of inflammatory cytokines by lessening TLR4/NF-κB signaling pathway activity and weakening NLRP3 inflammasome activation. Taken together, QHSG may resolve acute lung injury, attributed to its anti-inflammation and immunoregulation by attenuation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. Our findings provide a novel insight into the action mechanism of QHSG and lay a mechanistic foundation for therapeutic intervention in acute lung injury with QHSG in clinical practice.

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“…Huazhuo Quyu Formula, composed of Rheum palmatum L. (Da huang), Coptis chinensis Franch. The essential active compound that inhibited liver inflammatory processes and vascular hyperplasia regulated the cell cycle and suppressed both the activation and proliferation of hepatic stellate cells [10].…”

Section: Araliopsis Soyauxii Engl (Rutaceae)mentioning

confidence: 99%

Obacunone, a Promising Phytochemical Triterpenoid: Research Progress on Its Pharmacological Activity and Mechanism

Zhou,

Gu,

et al. 2024

Molecules

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Obacunone, a natural triterpenoid, is an active component of the herbs Dictamnus dasycarpus Turcz. and Phellodendron amurense Rupr, and an indicator of the herbs’ quality. Owing to its multiple health benefits, several studies have investigated the multi-targeting potential action mechanisms of obacunone. To summarize recent developments on the pharmacological actions of obacunone and focus on the underlying molecular mechanisms and signaling networks, we searched PubMed, Europe PMC, Wiley Online Library, Web of Science, Google Scholar, Wanfang Medical Network, and China National Knowledge Infrastructure for articles published prior to March 2024. Existing research indicates obacunone has great potential to become a promising therapeutic option against tumors, fibrotic diseases, bone and cholesterol metabolism diseases, and infections of pathogenic microorganisms, among others. The paper contributes to providing up-to-date references for further research and clinical applications of obacunone.

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Inhibition of inflammasome activation via sphingolipid pathway in acute lung injury by Huanglian Jiedu decoction: An integrative pharmacology approach

Cited by 19 publications

References 32 publications

Therapeutic effects and mechanism of Atractylodis rhizoma in acute lung injury: Investigation based on an Integrated approach

Therapeutic effects and mechanism of Atractylodis rhizoma in acute lung injury: Investigation based on an Integrated approach

Qinhuo Shanggan oral solution resolves acute lung injury by down-regulating TLR4/NF-κB signaling cascade and inhibiting NLRP3 inflammasome activation

Obacunone, a Promising Phytochemical Triterpenoid: Research Progress on Its Pharmacological Activity and Mechanism

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