Novel Tight-Binding Inhibitory Factor-κB Kinase (IKK-2) Inhibitors Demonstrate Target-Specific Anti-Inflammatory Activities in Cellular Assays and following Oral and Local Delivery in an in Vivo Model of Airway Inflammation

Heart failure is generally characterized by increased fibrosis and inflammation, which leads to functional and contractile defects. We have previously shown that short-term estrogen (E2) treatment can rescue pressure overload-induced decompensated heart failure (HF) in mice. Here, we investigate the anti-inflammatory and anti-fibrotic effects of E2 on reversing the adverse remodeling of the left ventricle which occurs during the progression to heart failure. Trans-aortic constriction procedure was used to induce HF. Once the ejection fraction reached ∼30%, one group of mice was sacrificed and the other group was treated with E2 (30 αg/kg/day) for 10 days. In vitro, co-cultured neonatal rat ventricular myocytes and fibroblasts were treated with Angiotensin II (AngII) to simulate cardiac stress, both in the presence or absence of E2. In vivo RT-PCR showed that the transcript levels of the pro-fibrotic markers Collagen I, TGFβ, Fibrosin 1 (FBRS) and Lysil Oxidase (LOX) were significantly upregulated in HF (from 1.00±0.16 to 1.83±0.11 for Collagen 1, 1±0.86 to 4.33±0.59 for TGFβ, 1±0.52 to 3.61±0.22 for FBRS and 1.00±0.33 to 2.88±0.32 for LOX) and were reduced with E2 treatment to levels similar to CTRL. E2 also restored in vitro AngII-induced upregulation of LOX, TGFβ and Collagen 1 (LOX:1±0.23 in CTRL, 6.87±0.26 in AngII and 2.80±1.5 in AngII+E2; TGFβ: 1±0.08 in CTRL, 3.30±0.25 in AngII and 1.59±0.21 in AngII+E2; Collagen 1: 1±0.05 in CTRL.2±0.01 in AngII and 0.65±0.02 (p<0.05, values normalized to CTRL)). Furthermore, the pro-inflammatory interleukins IL-1β and IL-6 were upregulated from 1±0.19 to 1.90±0.09 and 1±0.30 to 5.29±0.77 in the in vivo model of HF, respectively, and reversed to CTRL levels with E2 therapy. In vitro, IL-1β was also significantly increased ∼ 4 fold from 1±0.63 in CTRL to 3.86±0.14 with AngII treatment and restored to 1.29±0.77 with Ang+E2 treatment. Lastly, the anti-inflammatory interleukin IL-10 was downregulated from 1.00±0.17 to 0.49±0.03 in HF and reversed to 0.67±0.09 in vivo with E2 therapy (all values normalized to CTRL). This data strongly suggests that one of the mechanisms for the beneficial action of estrogen on left ventricular heart failure is through reversal of inflammation and fibrosis.

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Effects of prostaglandin lipid mediators on agonist-induced lung endothelial permeability and inflammation

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00519.2016 ◽

2017 ◽

Vol 313 (4) ◽

pp. L710-L721 ◽

Cited By ~ 12

Author(s):

Yunbo Ke ◽

Olga V. Oskolkova ◽

Nicolene Sarich ◽

Yufeng Tian ◽

Albert Sitikov ◽

...

Keyword(s):

Protective Effect ◽

Vascular Endothelial Cells ◽

Biological Activities ◽

Cell Monolayer ◽

Endothelial Permeability ◽

In Vivo Model ◽

Barrier Dysfunction ◽

Anti Inflammatory

Prostaglandins (PG), the products of cyclooxygenase-mediated conversion of arachidonic acid, become upregulated in many situations including allergic response, inflammation, and injury, and exhibit a variety of biological activities. Previous studies described barrier-enhancing and anti-inflammatory effects of PGE2 and PGI2 on vascular endothelial cells (EC). Yet, the effects of other PG members on EC barrier and inflammatory activation have not been systematically analyzed. This study compared effects of PGE2, PGI2, PGF2α, PGA2, PGJ2, and PGD2 on human pulmonary EC. EC permeability was assessed by measurements of transendothelial electrical resistance and cell monolayer permeability for FITC-labeled tracer. Anti-inflammatory effects of PGs were evaluated by analysis of expression of adhesion molecule ICAM1 and secretion of soluble ICAM1 and cytokines by EC. PGE2, PGI2, and PGA2 exhibited the most potent barrier-enhancing effects and most efficient attenuation of thrombin-induced EC permeability and contractile response, whereas PGI2 effectively suppressed thrombin-induced permeability but was less efficient in the attenuation of prolonged EC hyperpermeability caused by interleukin-6 or bacterial wall lipopolysaccharide, LPS. PGD2 showed a modest protective effect on the EC inflammatory response, whereas PGF2α and PGJ2 were without effect on agonist-induced EC barrier dysfunction. In vivo, PGE2, PGI2, and PGA2 attenuated LPS-induced lung inflammation, whereas PGF2α and PGJ2 were without effect. Interestingly, PGD2 exhibited a protective effect in the in vivo model of LPS-induced lung injury. This study provides a comprehensive analysis of barrier-protective and anti-inflammatory effects of different prostaglandins on lung EC in vitro and in vivo and identifies PGE2, PGI2, and PGA2 as prostaglandins with the most potent protective properties.

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Anti-Diabetic Effects and Anti-Inflammatory Effects of Laminaria japonica and Hizikia fusiforme in Skeletal Muscle: In Vitro and In Vivo Model

Nutrients ◽

10.3390/nu10040491 ◽

2018 ◽

Vol 10 (4) ◽

pp. 491 ◽

Cited By ~ 11

Author(s):

Sae-ym Kang ◽

Eunyoung Kim ◽

Inhae Kang ◽

Myoungsook Lee ◽

Yunkyoung Lee

Keyword(s):

Skeletal Muscle ◽

Laminaria Japonica ◽

In Vivo Model ◽

Hizikia Fusiforme ◽

Anti Inflammatory

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Properties of a New Food Supplement Containing Actinia equina Extract

Antioxidants ◽

10.3390/antiox9100945 ◽

2020 ◽

Vol 9 (10) ◽

pp. 945

Author(s):

Marika Lanza ◽

Giovanna Casili ◽

Giovanna Loredana La Torre ◽

Daniele Giuffrida ◽

Archimede Rotondo ◽

...

Keyword(s):

In Vitro Study ◽

Neutrophil Infiltration ◽

Food Supplement ◽

Biologically Active ◽

In Vivo Model ◽

Related Factor ◽

Nuclear Factor ◽

Anti Inflammatory

Marine species represent a great source of biologically active substances; Actinia equina (AE), an Anthozoa Cnidaria belonging to the Actinidiae family, have been proposed as original food and have already been included in several cooking recipes in local Mediterranean shores, and endowed with excellent nutraceutical potential. The aim of this study was to investigate some unexplored features of AE, through analytical screening and an in-vitro and in-vivo model. An in-vitro study, made on RAW 264.7 stimulated with H2O2, showed that the pre-treatment with AE exerted an antioxidant action, reducing lipid peroxidation and up-regulating antioxidant enzymes. On the other hand, the in-vivo study over murine model demonstrated that the administration of AE extracts is able to reduce the carrageenan (CAR)-induced paw edema. Furthermore, the histological damage due to the neutrophil infiltration is prevented, and this highlights precious anti-inflammatory features of the interesting food-stuff. Moreover, it was assessed that AE extract modulated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and The nuclear factor erythroid 2–related factor 2 (Nrf-2) pathways. In conclusion, our data demonstrated that thanks to the antioxidant and anti-inflammatory properties, AE extract could be used as a new food supplement for inflammatory pathology prevention.

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Evaluation In Vivo and In Vitro of the Antioxidant, Antinociceptive, and Anti-Inflammatory Activities of Biflavonoids From Ouratea hexasperma and O. ferruginea

Natural Product Communications ◽

10.1177/1934578x19856802 ◽

2019 ◽

Vol 14 (6) ◽

pp. 1934578X1985680 ◽

Cited By ~ 1

Author(s):

Poliana de Araujo Oliveira ◽

Queli Cristina Fidelis ◽

Thayane Ferreira da Costa Fernandes ◽

Milene Conceição de Souza ◽

Dayane Magalhães Coutinho ◽

...

Keyword(s):

Type I Collagen ◽

In Vivo Model ◽

Type I ◽

Anti Inflammatory ◽

Vitro Model ◽

Factor Α ◽

Necrosis Factor

Ouratea species are used for the treatment of inflammation-related diseases such as rheumatism and arthritic disorders. The Ouratea genus is a rich source of flavonoids and bioflavonoids and for this reason we evaluated the effects of the biflavonoid fractions from the leaves of O. hexasperma (OHME) and O. ferruginea (OFME) in the in vivo model of complete Freund’s adjuvant (CFA)-induced arthritis and in the in vitro model of oxidative stress and cellular viability. The CFA-induced arthritis model in rats was followed by paw volume, articular incapacitation and Randall-selitto models, as well as quantification of cytokines and serum C-terminal telopeptide of type I collagen levels. OHME and OFME demonstrated antinociceptive and anti-inflammatory activities, as well as improvement in articular incapacity and reduction in levels of interleukin 1β (IL-1β), IL-6, tumor necrosis factor α, and type 1 collagen, and increased cell viability. No adverse effects were observed. The results suggest that OHME and OFME can reduce inflammation and bone resorption besides their antioxidant action.

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Antitussive and Anti-inflammatory Dual-active Agents Developed from Natural Product Lead Compound 1-Methylhydantoin

Molecules ◽

10.3390/molecules24132355 ◽

2019 ◽

Vol 24 (13) ◽

pp. 2355 ◽

Cited By ~ 3

Author(s):

Yang Xu ◽

Fang Wang ◽

Hongye Guo ◽

Shihan Wang ◽

Shuling Ni ◽

...

Keyword(s):

Natural Product ◽

Binding Pocket ◽

In Vivo Model ◽

Lead Compound ◽

Pm 2.5 ◽

In Silico Study ◽

Acute Pneumonia ◽

Long Time ◽

Anti Inflammatory

Natural products play an important role in drug discovery. This work employed a natural product 1-methylhydantoin as the lead compound to develop novel dual-active drugs. 1-Methylhydantoin was isolated from Oviductus Ranae, which is a traditional Chinese medicine that has been used for tussive and inflammation treatment for a long time. An in silico study screened the more active 1-methylhydantoin derivatives. Antitussive assessment indicated that the newly synthesized agent had similar bioactivity with the natural product. An anti-inflammatory model used xylene induced ear edema model. At the same dosage (100 mg/Kg), the newly prepared agent had an inhibition rate 53.18% which was much higher than that of the lead compound (22.69%). The results might be ascribed to the cyclooxygenases-1 (COX-1) and cyclooxygenases-2 (COX-2) selectivity, and the fitness of the compound, and the binding pocket. The anti-particulate matter (PM 2.5) acute pneumonia was evaluated through an in vivo model constructed by nasal instillation with PM 2.5 suspension. The results of the above models suggested that this novel agent had remarkable antitussive, anti-inflammatory, and anti-PM 2.5 acute pneumonia activities.

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Evaluation of alpha-lipoic acid anti-inflammatory properties using zebrafish as in vivo model

Fish & Shellfish Immunology ◽

10.1016/j.fsi.2019.04.072 ◽

2019 ◽

Vol 91 ◽

pp. 389-390

Author(s):

G. Camiolo ◽

L. Rodríguez-Ruiz ◽

Irene Pardo-Sanchez ◽

G. Li Volti ◽

R. Avola ◽

...

Keyword(s):

Lipoic Acid ◽

In Vivo Model ◽

Alpha Lipoic Acid ◽

Anti Inflammatory

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Nebulizer Inhalation Exposure To Swine Confinement Facility Dust Mediates Airway Inflammation: An In Vivo Model

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a4807 ◽

2011 ◽

Author(s):

Ruth Pender ◽

Steven Hurley ◽

Radiah C. Minor ◽

Jenora T. Waterman

Keyword(s):

Airway Inflammation ◽

Inhalation Exposure ◽

In Vivo Model ◽

Swine Confinement

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Perilla Leaf Extract (PLE) Attenuates COPD Airway Inflammation via the TLR4/Syk/PKC/NF-κB Pathway In Vivo and In Vitro

Frontiers in Pharmacology ◽

10.3389/fphar.2021.763624 ◽

2022 ◽

Vol 12 ◽

Author(s):

Jiqiao Yuan ◽

Xuyu Li ◽

Nan Fang ◽

Ping Li ◽

Ziqian Zhang ◽

...

Keyword(s):

Airway Inflammation ◽

Airflow Limitation ◽

Interleukin 4 ◽

Inflammatory Factors ◽

Chronic Obstructive ◽

Potential Mechanism ◽

Tnf Α ◽

Anti Inflammatory

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease characterized by persistent airflow limitation but still lacking effective treatments. Perilla frutescens (L.) Britt., an important traditional medicinal plant with excellent antioxidant and anti-inflammatory properties, is widely used for the treatment of respiratory disease in China. However, its protective activity and mechanism against COPD airway inflammation have not been fully studied. Here, the anti-inflammatory effects of the PLE were investigated, and its underlying mechanisms were then elucidated. The presented results suggested a notable effect of the PLE on airway inflammation of COPD, by significantly ameliorating inflammatory cell infiltration in lung tissue, lessening leukocytes (lymphocytes, neutrophils, and macrophages) and inflammatory mediators (interleukin 4 (IL-4), IL-6, IL-17A, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α)) in the bronchoalveolar lavage fluid (BALF) of cigarette smoke (CS)/lipopolysaccharide (LPS)-induced COPD mice in vivo and inhibiting the production of inflammatory factors (nitric oxide (NO), IL-6, and TNF-α) and intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells in vitro. For further extent, PLE treatment significantly suppressed the expression and phosphorylation of TLR4, Syk, PKC, and NF-κB p65 in vivo and their mRNA in vitro. Subsequently, by co-treating with their inhibitors in vitro, its potential mechanism via TLR4/Syk/PKC/NF-κB p65 signals was disclosed. In summary, the obtained results indicated a noteworthy effective activity of the PLE on COPD inflammation, and partly, the TLR4/Syk/PKC/NF-κB p65 axis might be the potential mechanism.

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