Total flavonoids of Inula japonica alleviated the inflammatory response and oxidative stress in LPS-induced acute lung injury via inhibiting the sEH activity: Insights from lipid metabolomics

Zhang, Juan; Zhang, Min; Zhang, Wenhao; Zhu, Qi-Meng; Huo, Xiaokui; Sun, Cheng‐Peng; Ma, Xiaochi; Xiao, Haitao

doi:10.1016/j.phymed.2022.154380

Cited by 13 publications

(7 citation statements)

References 40 publications

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“…IKKβ-mediated NF-κB pathway is a key signal transduction pathway involved in inflammatory response, angiogenesis, invasiveness, metastasis, and immune escape [39][40][41][42][43][44][45][46]. After this signaling pathway is activated by inflammatory factors, it promotes the expression of inflammatory factors at the transcriptional level as well, thus forming a loop and producing an amplification effect to aggravate inflammation response [47][48][49][50][51]. In the case of the colitis-associated cancer (CAC) mouse model, IKKβ genetic deletion in intestinal epithelial cells greatly reduces the incidence of tumors through the increase of apoptosis [52], while its KO in the macrophage significantly reduces tumor size by suppressing the expression of pro-inflammatory factors [53,54].…”

Section: The Ikkβ Mechanismmentioning

confidence: 99%

IκB kinase β (IKKβ): Structure, transduction mechanism, biological function, and discovery of its inhibitors

Zhang¹,

Zhang²,

Li³

et al. 2023

Int. J. Biol. Sci.

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The effective approach to discover innovative drugs will ask natural products for answers because of their complex and changeable structures and multiple biological activities. Inhibitory kappa B kinase beta (IKKβ), known as IKK2, is a key regulatory kinase responsible for the activation of NF-κB through its phosphorylation at Ser177 and Ser181 to promote the phosphorylation of inhibitors of kappa B (IκBs), triggering their ubiquitination and degradation to active the nuclear factor kappa-B (NF-κB) cascade. Chemical inhibition of IKKβ or its genetic knockout has become an effective method to block NF-κB-mediated proliferation and migration of tumor cells and inflammatory response. In this review, we summarized the structural feature and transduction mechanism of IKKβ and the discovery of inhibitors from natural resources (e.g. sesquiterpenoids, diterpenoids, triterpenoids, flavonoids, and alkaloids) and chemical synthesis (e.g. pyrimidines, pyridines, pyrazines, quinoxalines, thiophenes, and thiazolidines). In addition, the biosynthetic pathway of novel natural IKKβ inhibitors and their biological potentials were discussed. This review will provide inspiration for the structural modification of IKKβ inhibitors based on the skeleton of natural products or chemical synthesis and further phytochemistry investigations.

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Section: The Ikkβ Mechanismmentioning

confidence: 99%

IκB kinase β (IKKβ): Structure, transduction mechanism, biological function, and discovery of its inhibitors

Zhang¹,

Zhang²,

Li³

et al. 2023

Int. J. Biol. Sci.

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“…While under continuous viral infection and the storm of inflammatory factors, the reduction of antioxidant defense such as superoxide dismutase (SOD), reduced glutathione (GSH), accompanied by the accelerated production of ROS and RNS, led to the occurrence of redox imbalance [ 23 ]. Redox imbalance triggers oxidative stress and AECs suffer oxidative damage, causing an increase in the levels of oxidized glutathione (GSSG) and the lipid peroxidation product malondialdehyde (MDA) [ 24 , 25 ]. Oxidative stress also induces AECs transdifferentiate to fibroblasts via epithelial-mesenchymal transition (EMT) [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Pulmonary redox imbalance drives early fibroproliferative response in moderate/severe coronavirus disease-19 acute respiratory distress syndrome and impacts long-term lung abnormalities

Yang,

Tan,

et al. 2024

Ann. Intensive Care

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Background COVID-19-associated pulmonary fibrosis remains frequent. This study aimed to investigate pulmonary redox balance in COVID-19 ARDS patients and possible relationship with pulmonary fibrosis and long-term lung abnormalities. Methods Baseline data, chest CT fibrosis scores, N-terminal peptide of alveolar collagen III (NT-PCP-III), transforming growth factor (TGF)-β1, superoxide dismutase (SOD), reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) were first collected and compared between SARS-CoV-2 RNA positive patients with moderate to severe ARDS (n = 65, COVID-19 ARDS) and SARS-CoV-2 RNA negative non-ARDS patients requiring mechanical ventilation (n = 63, non-ARDS). Then, correlations between fibroproliferative (NT-PCP-III and TGF-β1) and redox markers were analyzed within COVID-19 ARDS group, and comparisons between survivor and non-survivor subgroups were performed. Finally, follow-up of COVID-19 ARDS survivors was performed to analyze the relationship between pulmonary abnormalities, fibroproliferative and redox markers 3 months after discharge. Results Compared with non-ARDS group, COVID-19 ARDS group had significantly elevated chest CT fibrosis scores (p < 0.001) and NT-PCP-III (p < 0.001), TGF-β1 (p < 0.001), GSSG (p < 0.001), and MDA (p < 0.001) concentrations on admission, while decreased SOD (p < 0.001) and GSH (p < 0.001) levels were observed in BALF. Both NT-PCP-III and TGF-β1 in BALF from COVID-19 ARDS group were directly correlated with GSSG (p < 0.001) and MDA (p < 0.001) and were inversely correlated with SOD (p < 0.001) and GSH (p < 0.001). Within COVID-19 ARDS group, non-survivors (n = 28) showed significant pulmonary fibroproliferation (p < 0.001) with more severe redox imbalance (p < 0.001) than survivors (n = 37). Furthermore, according to data from COVID-19 ARDS survivor follow-up (n = 37), radiographic residual pulmonary fibrosis and lung function impairment improved 3 months after discharge compared with discharge (p < 0.001) and were associated with early pulmonary fibroproliferation and redox imbalance (p < 0.01). Conclusions Pulmonary redox imbalance occurring early in COVID-19 ARDS patients drives fibroproliferative response and increases the risk of death. Long-term lung abnormalities post-COVID-19 are associated with early pulmonary fibroproliferation and redox imbalance. Graphical abstract

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“…[9] and emphasized the potent activity of sesquiterpenoids against the cancer cells in vitro. Except for the cytotoxic or antiproliferative action, the preparations from the plants of the subtribe are often investigated for their anti-inflammatory [10][11][12], antidiabetic [13][14][15], antilipidemic [16][17][18], vasorelaxant/antihypertensive [19,20], anti-oxidative stress [21][22][23] and hepatoprotective [24][25][26] activities in vivo. Recently, their efficacy in the prevention of depression-like behavior in rodents has been also explored [27,28].…”

Section: Introductionmentioning

confidence: 99%

Polyphenols of the Inuleae-Inulinae and Their Biological Activities: A Review

Malarz,

Michalska,

Stojakowska

2024

Preprint

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Polyphenols are ubiquitous plant metabolites that demonstrate biological activities essential to the plant-environment interactions. They are of interest to plant food consumers, as well as to the food, pharmaceutical and cosmetic industry. The class of the plant metabolites comprises both widespread (chlorogenic acids, luteolin, quercetin) and unique compounds of diverse chemical structures but of the common biosynthetic origin. Polyphenols, next to sesquiterpenoids are regarded as the major class of the Inuleae-Inulinae metabolites responsible for the pharmacological activity of medicinal plants from the subtribe (Blumea spp., Dittrichia spp., Inula spp., Pulicaria spp. and others). Recent decades have brought a rapid development of molecular and analytical techniques which resulted in better understanding of the taxonomic relationships within the Inuleae tribe and in a plethora of data concerning the chemical constituents of the Inuleae-Inulinae. The current taxonomical classification has introduced changes in the well-established botanical names and rearranged the genera based on molecular plant genetic studies. The newly created chemical data together with the earlier phytochemical studies may provide some complementary information on biochemical relationships within the subtribe. Moreover, they may at least partly explain pharmacological activities of the plant preparations traditionally used in therapy. The current review aimed to systematize the knowledge on the polyphenols of the Inulae-Inulinae.

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Total flavonoids of Inula japonica alleviated the inflammatory response and oxidative stress in LPS-induced acute lung injury via inhibiting the sEH activity: Insights from lipid metabolomics

Cited by 13 publications

References 40 publications

IκB kinase β (IKKβ): Structure, transduction mechanism, biological function, and discovery of its inhibitors

IκB kinase β (IKKβ): Structure, transduction mechanism, biological function, and discovery of its inhibitors

Pulmonary redox imbalance drives early fibroproliferative response in moderate/severe coronavirus disease-19 acute respiratory distress syndrome and impacts long-term lung abnormalities

Polyphenols of the Inuleae-Inulinae and Their Biological Activities: A Review

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