Therapeutic potential of IKK-β inhibitors from natural phenolics for inflammation in cardiovascular diseases

Zhou, Peng; Fang, Hua; Wang, Xiang; Huang, Jinling

doi:10.1007/s10787-019-00680-8

Cited by 25 publications

(16 citation statements)

References 177 publications

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“…In the LIQ60 group, the cell viability was dramatically increased up to 92.06 ± 2.09% of normal control (100%). It was reported that LIQ increased cell viability via its anti-inflammatory [ 38 ], antioxidant, and antiapoptosis activity [ 20 , 23 ]. The current results further confirmed the safety of LIQ indicated in the previous publication [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

Liquiritin from Radix Glycyrrhizae Protects Cardiac Mitochondria from Hypoxia/Reoxygenation Damage

Thu

Yen

2021

Journal of Analytical Methods in Chemistry

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Aims. The purpose of this study was to evaluate the protective effect of liquiritin (LIQ) from Radix Glycyrrhizae on cardiac mitochondria against hypoxia/reoxygenation (HR) injury. Methods. H9C2 cells were subject to the HR model. LIQ purified from Radix Glycyrrhizae (purity > 95%) was administrated to reoxygenation period. Cell viability, mitochondrial mass, mitochondrial membrane potential, reactive oxygen species, and mitochondrial Ca2⁺ level were then assessed by using Cell Counting kit-8 and suitable fluorescence probe kits. Results. LIQ administration remarkably reduced the rate of HR damage via increasing H9C2 cell viability level and preserving mitochondria after HR. Particularly, 60 μM of LIQ posthypoxic treatment markedly reduced cell death in HR-subjected H9C2 cell groups ( p < 0.05 ). Interestingly, posthypoxic treatment of LIQ significantly prevented the loss of mitochondrial membrane potential, the decrease in mitochondrial mass, the increase in reactive oxygen species production, and the elevation of mitochondrial Ca2⁺ level in HR-treated H9C2 cells. Conclusion. The present study provides for the first time the cardioprotective of LIQ posthypoxic treatment via reducing H9C2 cell death and protecting cardiac mitochondria against HR damage.

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Section: Resultsmentioning

confidence: 99%

Liquiritin from Radix Glycyrrhizae Protects Cardiac Mitochondria from Hypoxia/Reoxygenation Damage

Thu

Yen

2021

Journal of Analytical Methods in Chemistry

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“…Previous studies have reported that FGF10 is a vital regulator of the NF-κB-dependent inflammatory response (22,23). IKBα is a major inhibitor of NF-κB and may remove NF-κB complexes in nuclei (36). NF-κB is comprised of p50 and p65 subunits and is activated by p65, which may promote the secretion of the inflammatory cytokines IL-1β, IL-6 and TNF-α (37,38).…”

Section: Discussionmentioning

confidence: 99%

miR‑9 alleviated the inflammatory response and apoptosis in caerulein‑induced acute pancreatitis by regulating FGF10 and the NF‑κB signaling pathway

et al. 2021

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MicroRNAs (miRs) have been implicated in the development of acute pancreatitis (AP). However, the role and potential mechanism of miR-9 in AP progression remains unclear. Caerulein-treated AR42J cells were used as a cellular model of AP. Results revealed caerulein triggered an inflammatory response by promoting the secretion of inflammatory cytokines [tumor necrosis factor-α, interleukin (IL) 1β and IL-6], as evidenced by ELISA. Furthermore, caerulein-induced apoptosis was reported by flow cytometry and western blot assays. Additionally, miR-9 expression was downregulated by caerulein treatment, as demonstrated by reverse transcription quantitative PCR. However, miR-9 overexpression reduced the inflammatory response and apoptosis in caerulein-treated AR42J cells. miR-9 knockdown resulted in opposite effects. Furthermore, fibroblast growth factor (FGF) 10 was validated to be targeted via miR-9 by luciferase, RNA immunoprecipitation and RNA pull-down assays. Results demonstrated increased FGF10 expression in caerulein-treated AR42J cells and that FGF10 over expression exacerbated the caerulein-induced inflammatory response and apoptosis, while its knockdown had the opposite effect. Additionally, FGF10 reversed the effect of miR-9 on caerulein-induced injury in AR42J cells. Results demonstrated that miR-9 inhibited the expression of the nuclear factor κB (NF-κB) pathway-related proteins by downregulating FGF10. As a result, miR-9 decreased inflammatory response and apoptosis in caerulein-treated AR42J cells by targeting FGF10 and blocking NF-κB signaling, suggesting that miR-9 may serve as a novel target for AP treatment.

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“…Briefly, the IKK-β enzyme’s 3D structure (PDB ID: 4KIK) was downloaded from the RCSB Protein Data Bank ( ) with X-ray diffraction resolutions of 2.83 Å [ 38 , 39 ]. The obtained PDB file was prepared with the Protein Preparation Wizard of Schrodinger suite 2018 using OPLS3e force-field (Schrödinger Suite; Epik version 4.6; Impact version 8.1; Prime module, Schrödinger, LLC, New York, NY, USA, 2018).…”

Section: Methodsmentioning

confidence: 99%

Methylenedioxy Piperamide-Derived Compound D5 Regulates Inflammatory Cytokine Secretion in a Culture of Human Glial Cells

Shahbazi

Zakerali

2022

Molecules

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Neuroinflammation is the cornerstone of most neuronal disorders, particularly neurodegenerative diseases. During the inflammatory process, various pro-inflammatory cytokines, chemokines, and enzymes—such as interleukin 1-β (IL1-β), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), inducible nitric oxide synthases (iNOS), inhibitory kappa kinase (IKK), and inducible nitric oxide (NO)—are over-expressed in response to every stimulus. Methods: In the present study, we focused on the anti-neuroinflammatory efficacy of (2E,4E)-N,5-bis(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienamide, encoded D5. We investigated the efficacy of D5 on the upstream and downstream products of inflammatory pathways in CHME3 and SVG cell lines corresponding to human microglia and astrocytes, respectively, using various in silico, in vitro, and in situ techniques. Results: The results showed that D5 significantly reduced the level of pro-inflammatory cytokines byup-regulating PPAR-γ expression and suppressing IKK-β, iNOS, NO production, and NF-κB activation in inflamed astrocytes (SVG) and microglia (CHME3) after 24 h of incubation. The data demonstrated remarkably higher efficacy of D5 compared to ASA (Aspirin) in reducing NF-κB-dependent neuroinflammation. Conclusions: We observed that the functional-group alteration had an extreme influence on the levels of druggability and the immunomodulatory properties of two analogs of piperamide, D5, and D4 ((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-N-(4-(hydroxymethyl)phenyl)penta-2,4-dienamide)). The present study suggested D5 as a potential anti-neuroinflammatory agent for further in vitro, in vivo, and clinical investigations.

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Therapeutic potential of IKK-β inhibitors from natural phenolics for inflammation in cardiovascular diseases

Cited by 25 publications

References 177 publications

Liquiritin from Radix Glycyrrhizae Protects Cardiac Mitochondria from Hypoxia/Reoxygenation Damage

Liquiritin from Radix Glycyrrhizae Protects Cardiac Mitochondria from Hypoxia/Reoxygenation Damage

miR‑9 alleviated the inflammatory response and apoptosis in caerulein‑induced acute pancreatitis by regulating FGF10 and the NF‑κB signaling pathway

Methylenedioxy Piperamide-Derived Compound D5 Regulates Inflammatory Cytokine Secretion in a Culture of Human Glial Cells

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