Suppression of NLRP3 inflammasome by Platycodin D via the TLR4/MyD88/NF-κB pathway contributes to attenuation of lipopolysaccharide induced acute lung injury in rats

Wu, Yongcan; Huang, Demei; Wang, Xiaomin; Pei, Caixia; Xiao, Wei; Wang, Fei; Wang, Zhenxing

doi:10.1016/j.intimp.2021.107621

Cited by 26 publications

(21 citation statements)

References 49 publications

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“…Triterpenoids, procyanidin B2, significantly suppressed the activation of NLRP3 inflammasome in the lung tissue induced by paraquat in the rat model ( Jiang et al, 2018 ). Platycodin D are protective against LPS-induced ALI by inhibiting NLRP3 and NF-κB signaling pathway ( Wu et al, 2021 ). Flavonoids, chlorogenic acid, markedly decreased activity of inducible nitric oxide synthase (iNOS) in lung tissues, so it prevented nitric oxide (NO) release in response to LPS ( Zhang et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Qingwenzhike Prescription Alleviates Acute Lung Injury Induced by LPS via Inhibiting TLR4/NF-kB Pathway and NLRP3 Inflammasome Activation

Zhang

Wang

et al. 2021

Front. Pharmacol.

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Background: Acute lung injury (ALI) is characterized by dysfunction of the alveolar epithelial membrane caused by acute inflammation and tissue injury. Qingwenzhike (QWZK) prescription has been demonstrated to be effective against respiratory viral infections in clinical practices, including coronavirus disease 2019 (COVID-19) infection. So far, the chemical compositions, protective effects on ALI, and possible anti-inflammatory mechanisms remain unknown.Methods: In this study, the compositions of QWZK were determined via the linear ion trap/electrostatic field orbital trap tandem high-resolution mass spectrometry (UHPLC-LTQ-Orbitrap MS). To test the protective effects of QWZK on ALI, an ALI model induced by lipopolysaccharide (LPS) in rats was used. The effects of QWZK on the LPS-induced ALI were evaluated by pathological changes and the number and classification of white blood cell (WBC) in bronchoalveolar lavage fluid (BALF). To investigate the possible underlying mechanisms, the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP-1), interleukin-1β (IL-1β), interleukin-18 (IL-18), and immunoregulatory-related factors interferon-γ (IFN-γ) were detected by ELISA. Furthermore, the expression of Toll-like receptor 4 (TLR4), p-IKKα/β, IKKα, IKKβ, p-IκBα, IκBα, p-NF-κB, nuclear factor-κB (NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, pro-caspase-1, apoptosis-associated speck-like protein containing CARD (ASC), and β-actin were tested by Western blot.Results: A total of 99 compounds were identified in QWZK, including 33 flavonoids, 23 phenolic acids, 3 alkaloids, 3 coumarins, 20 triterpenoids, 5 anthraquinones, and 12 others. ALI rats induced by LPS exhibited significant increase in neutrophile, significant decrease in lymphocyte, and evidently thicker alveolar wall than control animals. QWZK reversed the changes in WBC count and alveolar wall to normal level on the model of ALI induced by LPS. ELISA results revealed that QWZK significantly reduced the overexpression of proinflammatory factors IL-6, TNF-α, MCP-1, IL-1β, IL-18, and IFN-γ induced by LPS. Western blot results demonstrated that QWZK significantly downregulated the overexpression of TLR4, p-IKKα/β, p-IκBα, p-NF-κB, NLRP3, cleaved caspase-1, and ASC induced by LPS, which suggested that QWZK inhibited TLR4/NF-κB signaling pathway and NLRP3 inflammasomes.Conclusions: The chemical compositions of QWZK were first identified. It was demonstrated that QWZK showed protective effects on ALI induced by LPS. The possible underlying mechanisms of QWZK on ALI induced by LPS was via inhibiting TLR4/NF-kB signaling pathway and NLRP3 inflammasome activation. This work suggested that QWZK is a potential therapeutic candidate for the treatments of ALI and pulmonary inflammation.

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Section: Discussionmentioning

confidence: 99%

Qingwenzhike Prescription Alleviates Acute Lung Injury Induced by LPS via Inhibiting TLR4/NF-kB Pathway and NLRP3 Inflammasome Activation

Zhang

Wang

et al. 2021

Front. Pharmacol.

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“…After reviewing all of the publications, 10 studies were excluded because of missing outcome data ( Ehrhart et al, 2000 ; Tawadros et al, 2007 ; Nader and Baraka, 2012 ; An et al, 2014 ; Wang et al, 2015 ; Liu and Chen, 2016 ; Shen et al, 2017 ; Ni et al, 2019 ; Wang et al, 2019 ; Yang et al, 2019 ), and another 12 studies were excluded because multiple interventions were investigated ( Murakami et al, 2000 ; Lin et al, 2011 ; Li et al, 2014b ; Li et al, 2016a ; Li et al, 2016b ; Baradaran Rahimi et al, 2019 ; Ye et al, 2019 ; Duan et al, 2020 ; Yue et al, 2020 ; Choi et al, 2021 ; Zhang et al, 2021 ; Liu et al, 2022 ). In conclusion, 16 studies were included in this meta-analysis, as described below ( Shi et al, 2007 ; Yang et al, 2011 ; Chen et al, 2014 ; Yang et al, 2014 ; Yuan et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Li et al, 2018b ; Luo et al, 2019 ; Ren et al, 2019 ; Zhang et al, 2020 ; Ali et al, 2021 ; Dikmen et al, 2021 ; Li et al, 2021 ; Wang et al, 2021 ; Wu et al, 2021 ) ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Rats ranged in age from 6 to 8 weeks and in weight from 90 to 350 g. In terms of intervention, diterpenoid, monoterpenoid, sesquiterpenoid, and triterpenoid were used in seven studies ( Shi et al, 2007 ; Yang et al, 2011 ; Yang et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Li et al, 2018b ; Luo et al, 2019 ), three studies ( Yuan et al, 2014 ; Ren et al, 2019 ; Li et al, 2021 ), two studies ( Ali et al, 2021 ; Wang et al, 2021 ), and four studies ( Chen et al, 2014 ; Zhang et al, 2020 ; Dikmen et al, 2021 ; Wu et al, 2021 ), respectively. In addition, 13 studies used male rats ( Shi et al, 2007 ; Yang et al, 2011 ; Chen et al, 2014 ; Yang et al, 2014 ; Yuan et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Luo et al, 2019 ; Ren et al, 2019 ; Zhang et al, 2020 ; Dikmen et al, 2021 ; Li et al, 2021 ; Wang et al, 2021 ), whereas three studies did not report gender ( Li et al, 2018b ; Ali et al, 2021 ; Wu et al, 2021 ). Sprague Dawley rats were used in 11 studies ( Shi et al, 2007 ; Yang et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Li et al, 2018b ; Luo et al, 2019 ; Ren et al, 2019 ; Ali et al, 2021 ; Li et al, 2021 ; Wang et al, 2021 ; Wu et al, 2021 ) and Wistar rats in five studies ( Yang et al, 2011 ; Chen et al, 2014 ; Yuan et al, 2014 ; Zhang et al, 2020 ; Dikmen et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…In one study, datasets with more than three independent groups, namely, a control group, a low terpenoid dosage group, and a high terpenoid dosage group, were defined. A single control group was compared with various groups that investigated different terpenoid dosages in eight studies ( Yang et al, 2011 ; Chen et al, 2014 ; Yang et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Ren et al, 2019 ; Wang et al, 2021 ; Wu et al, 2021 ). To avoid a redundant expansion in the meta-analysis sample size, the number of samples in the control group in each study was divided by those in the matched groups.…”

Section: Methodsmentioning

confidence: 99%

“…Acute lung injury (ALI) is an acute inflammatory disease that disrupts the lung’s endothelial and epithelial barriers ( Manicone, 2009 ). It is associated with systemic inflammatory response syndrome and multiple organ dysfunction syndrome ( Wu et al, 2021 ). ALI, which is characterized by pulmonary edema and severe hypoxia, has also been regarded as the leading cause of death in patients with sepsis, imposing an enormous health burden worldwide each year ( Schingnitz et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of terpenoids in attenuating pulmonary edema in acute lung injury: A meta-analysis of animal studies

et al. 2022

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Background: The clinical efficiency of terpenoids in treating human acute lung injury (ALI) is yet to be determined. The lipopolysaccharide-induced rat model of ALI is a well-established and widely used experimental model for studying terpenoids’ effects on ALI. Using a systematic review and meta-analysis, the therapeutic efficiency of terpenoid administration on the lung wet-to-dry weight ratio in rats was investigated.Methods: Using the Cochrane Library, Embase, and PubMed databases, a comprehensive literature search for studies evaluating the therapeutic efficacy of terpenoids on ALI in rats was conducted. The lung wet-to-dry weight ratio was extracted as the main outcome. The quality of the included studies was assessed using the Systematic Review Center for Laboratory Animal Experimentation’s risk of bias tool.Results: In total, 16 studies were included in this meta-analysis. In general, terpenoids significantly lowered the lung wet-to-dry weight ratio when compared with the control vehicle (p = 0.0002; standardized mean difference (SMD): −0.16; 95% confidence interval (CI): −0.24, −0.08). Subgroup analysis revealed that low dose (≤10 μmol/kg) (p < 0.0001; SMD: −0.68; 95% CI: −1.02, −0.34), intraperitoneal injection (p = 0.0002; SMD: −0.43; 95% CI: −0.66, −0.20), diterpenoid (p = 0.004; SMD: −0.13; 95% CI: −0.23, −0.04), and triterpenoid (p = 0.04; SMD: −0.28; 95% CI: −0.54, −0.01) significantly lowered the lung wet-to-dry weight ratio when compared with the control vehicle.Conclusion: A low dose of diterpenoid and triterpenoid administered intraperitoneally is effective in alleviating ALI. This systematic review and meta-analysis provides a valuable mirror for clinical research aiming at the advancement of terpenoids for preventive and therapeutic use.Systematic Review Registration: CRD42022326779

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Phytochemicals as Modulators of Toll-Like Receptors: An Immunopharmacological Perspective

Chakraborty,

Chatterjee,

Chakraborty

et al. 2024

Medicinal Plants and Antimicrobial Therapies

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Suppression of NLRP3 inflammasome by Platycodin D via the TLR4/MyD88/NF-κB pathway contributes to attenuation of lipopolysaccharide induced acute lung injury in rats

Cited by 26 publications

References 49 publications

Qingwenzhike Prescription Alleviates Acute Lung Injury Induced by LPS via Inhibiting TLR4/NF-kB Pathway and NLRP3 Inflammasome Activation

Qingwenzhike Prescription Alleviates Acute Lung Injury Induced by LPS via Inhibiting TLR4/NF-kB Pathway and NLRP3 Inflammasome Activation

Efficacy of terpenoids in attenuating pulmonary edema in acute lung injury: A meta-analysis of animal studies

Phytochemicals as Modulators of Toll-Like Receptors: An Immunopharmacological Perspective

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