scholarly journals Ozone Exerts Cytoprotective and Anti-Inflammatory Effects in Cardiomyocytes and Skin Fibroblasts after Incubation with Doxorubicin

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
V. Simonetti ◽  
V. Quagliariello ◽  
M. Franzini ◽  
R. V. Iaffaioli ◽  
N. Maurea ◽  
...  
Keyword(s):  
Leukotriene B4 ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblast ◽  
Cytoprotective Effect ◽  
Skin Reactions ◽  
Mitochondrial Homeostasis ◽  
Proinflammatory Mediators ◽  
Fetal Cardiomyocytes ◽  
Anti Inflammatory ◽  
Preclinical And Clinical Studies

Introduction. Skin reactions and cardiotoxicity are one of the most common side effects of doxorubicin in cancer patients. The main mechanisms based on the etiopathogenesis of these reactions are mediated by the overproduction of proinflammatory cytokines, metalloproteases, and the disruption of mitochondrial homeostasis. Ozone therapy demonstrated anti-inflammatory effects in several preclinical and clinical studies. The aim of this research is based on the evaluation of cardioprotective and dermatoprotective effects of ozone during incubation with doxorubicin, giving preliminary evidences for further studies in the field of cardio-oncology. Methods. Human skin fibroblast cells and human fetal cardiomyocytes were exposed to doxorubicin at subclinical concentration (100 nM) alone or combined with ozone concentrated from 10 up to 50 μg/mL. Cell viability and multiple anti-inflammatory studies were performed in both cell lines, with particular attention on the quantification of interleukins, leukotriene B4, NF-κB, and Nrf2 expressions during treatments. Results. Ozone decreased significantly the cytotoxicity of doxorubicin in skin fibroblasts and cardiomyocytes after 24 h of incubation. The best cytoprotective effect of ozone was reached to 30 μg/mL with a plateau phase at higher concentration. Ozone also demonstrated anti-inflammatory effects decreasing significantly the interleukins and proinflammatory mediators in both cells. Conclusion. Ozone exerts cardioprotective and dermatoprotective effects during incubation with doxorubicin, and the involved mechanisms are mediated by its anti-inflammatory effects. The overall picture described herein is a pilot study for preclinical studies in oncology.

scholarly journals Fisetin inhibits lipopolysaccharide-induced inflammatory response by activating β-catenin, leading to a decrease in endotoxic shock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilandarage Menu Neelaka Molagoda ◽  
Jayasingha Arachchige Chathuranga C Jayasingha ◽  
Yung Hyun Choi ◽  
Rajapaksha Gedara Prasad Tharanga Jayasooriya ◽  
Chang-Hee Kang ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Endotoxic Shock ◽  
Inflammatory Activity ◽  
Prostaglandin E ◽  
Necrosis Factor Alpha ◽  
Zebrafish Larvae ◽  
Proinflammatory Mediators ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Gsk 3Β

AbstractFisetin is a naturally occurring flavonoid that possesses several pharmacological benefits including anti-inflammatory activity. However, its precise anti-inflammatory mechanism is not clear. In the present study, we found that fisetin significantly inhibited the expression of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Additionally, fisetin attenuated LPS-induced mortality and abnormalities in zebrafish larvae and normalized the heart rate. Fisetin decreased the recruitment of macrophages and neutrophils to the LPS-microinjected inflammatory site in zebrafish larvae, concomitant with a significant downregulation of proinflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase-2a (COX-2a), IL-6, and TNF-α. Fisetin inhibited the nuclear localization of nuclear factor-kappa B (NF-κB), which reduced the expression of pro-inflammatory genes. Further, fisetin inactivated glycogen synthase kinase 3β (GSK-3β) via phosphorylation at Ser9, and inhibited the degradation of β-catenin, which consequently promoted the localization of β-catenin into the nucleus. The pharmacological inhibition of β-catenin with FH535 reversed the fisetin-induced anti-inflammatory activity and restored NF-κB activity, which indicated that fisetin-mediated activation of β-catenin results in the inhibition of LPS-induced NF-κB activity. In LPS-microinjected zebrafish larvae, FH535 promoted the migration of macrophages to the yolk sac and decreased resident neutrophil counts in the posterior blood island and induced high expression of iNOS and COX-2a, which was accompanied by the inhibition of fisetin-induced anti-inflammatory activity. Altogether, the current study confirmed that the dietary flavonoid, fisetin, inhibited LPS-induced inflammation and endotoxic shock through crosstalk between GSK-3β/β-catenin and the NF-κB signaling pathways.

scholarly journals Sargassum fulvellumProtects HaCaT Cells and BALB/c Mice from UVB-Induced Proinflammatory Responses

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Chan Lee ◽  
Gyu Hwan Park ◽  
Eun Mi Ahn ◽  
Chan-Ik Park ◽  
Jung-Hee Jang
Keyword(s):  
Nitric Oxide ◽  
Ethanol Extract ◽  
Prostaglandin E ◽  
Hacat Cells ◽  
Uvb Irradiation ◽  
Proinflammatory Mediators ◽  
Sargassum Fulvellum ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Skin Damages

Ultraviolet (UV) radiation has been reported to induce cutaneous inflammation such as erythema and edema via induction of proinflammatory enzymes and mediators.Sargassum fulvellumis a brown alga of Sargassaceae family which has been demonstrated to exhibit antipyretic, analgesic, antiedema, antioxidant, antitumor, fibrinolytic, and hepatoprotective activities. The purpose of this study is to investigate anti-inflammatory effects of ethylacetate fraction of ethanol extract ofSargassum fulvellum(SFE-EtOAc) in HaCaT keratinocytes and BALB/c mice. In HaCaT cells, SFE-EtOAc effectively inhibited UVB-induced cytotoxicity (60 mJ/cm2) and the expression of proinflammatory proteins such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α(TNF-α), and inducible nitric oxide synthase (iNOS). Furthermore, SFE-EtOAc significantly reduced UVB-induced production of proinflammatory mediators including prostaglandin E2(PGE2) and nitric oxide (NO). In BALB/c mice, topical application of SFE-EtOAc prior to UVB irradiation (200 mJ/cm2) effectively suppressed the UVB-induced protein expression of COX-2, iNOS, and TNF-αand subsequently attenuated generation of PGE2and NO as well. In another experiment, SFE-EtOAc pretreatment suppressed UVB-induced reactive oxygen species production and exhibited an antioxidant potential by upregulation of antioxidant enzymes such as catalase and Cu/Zn-superoxide dismutase in HaCaT cells. These results suggest that SFE-EtOAc could be an effective anti-inflammatory agent protecting against UVB irradiation-induced skin damages.

scholarly journals Therapeutically Targeting Neuroinflammation and Microglia after Acute Ischemic Stroke

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Youngjeon Lee ◽  
Sang-Rae Lee ◽  
Sung S. Choi ◽  
Hyeon-Gu Yeo ◽  
Kyu-Tae Chang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Inflammatory Responses ◽  
Secondary Injury ◽  
Initial Event ◽  
Stroke Models ◽  
Anti Inflammatory ◽  
Preclinical And Clinical Studies ◽  
Multiple Receptor

Inflammation has a pivotal role in the pathogenesis of ischemic stroke, and recent studies posit that inflammation acts as a double-edged sword, not only detrimentally augmenting secondary injury, but also potentially promoting recovery. An initial event of inflammation in ischemic stroke is the activation of microglia, leading to production of both pro- and anti-inflammatory mediators acting through multiple receptor signaling pathways. In this review, we discuss the role of microglial mediators in acute ischemic stroke and elaborate on preclinical and clinical studies focused on microglia in stroke models. Understanding how microglia can lead to both pro- and anti-inflammatory responses may be essential to implement therapeutic strategies using immunomodulatory interventions in ischemic stroke.

scholarly journals Antioxidant and Anti-inflammatory Mechanisms of Astaxanthin in Cardiovascular Diseases

2020 ◽  
Author(s):  
Carolina Parga Martins Pereira ◽  
Ana Carolina Remondi Souza ◽  
Andrea Rodrigues Vasconcelos ◽  
Pietra Sacramento Prado ◽  
José João Name
Keyword(s):  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Cardiovascular Health ◽  
Redox Balance ◽  
Cellular Mechanisms ◽  
Positive Effects ◽  
Antioxidant Agents ◽  
Therapeutic Properties ◽  
Anti Inflammatory ◽  
Preclinical And Clinical Studies

Cardiovascular disease is the most common cause of death. Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular diseases, so anti-inflammatory and antioxidant agents that modulate redox balance have become the targets of research to evaluate their molecular mechanisms and therapeutic properties. Astaxanthin, a carotenoid of the xanthophyll group, has potent antioxidant effects due to its molecular structure and its arrangement in the plasma membrane, factors that favor the neutralization of reactive oxygen and nitrogen species. This carotenoid also stands out for its anti-inflammatory activity, possibly interrelated with its antioxidant effect, as well as for its modulation of lipid and glucose metabolism. Considering the potential positive effects of astaxanthin on cardiovascular health evidenced by preclinical and clinical studies, this paper describes the molecular and cellular mechanisms related to the antioxidant and anti-inflammatory properties of this carotenoid in cardiovascular diseases, especially atherosclerosis.

scholarly journals Regulation by Interleukin-10 and Interleukin-4 of Cyclooxygenase-2 Expression in Human Neutrophils

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1621-1628 ◽  
Author(s):  
Hiroaki Niiro ◽  
Takeshi Otsuka ◽  
Kenji Izuhara ◽  
Kunihiro Yamaoka ◽  
Koichi Ohshima ◽  
...  
Keyword(s):  
Early Stage ◽  
Interleukin 10 ◽  
Pge2 Production ◽  
Interleukin 4 ◽  
Human Neutrophils ◽  
Effector Cells ◽  
Proinflammatory Mediators ◽  
Healthy Donors ◽  
Cox 2 ◽  
Anti Inflammatory

Neutrophils are important effector cells of acute inflammation because of their potential capacity to synthesize various proinflammatory mediators, and inhibition of their production is expected to result in anti-inflammatory effects. In this study, we investigate the effects of the anti-inflammatory cytokines, interleukin-10 (IL-10) and IL-4, on prostanoid synthesis in human neutrophils. Neutrophils isolated from healthy donors constitutively produced a small amount of prostaglandin E2 (PGE2 ) without any stimulations, whereas they produced a large amount of PGE2 after lipopolysaccharide (LPS) stimulation. IL-10 and IL-4 selectively inhibited their LPS-induced PGE2 production. Inhibition by both cytokines occurred at an early stage of LPS stimulation. Anti–IL-10 treatment of LPS-stimulated neutrophils resulted in enhanced PGE2 production. LPS-induced PGE2 and thromboxane B2 (TXB2 ) production in aspirin-treated neutrophils was significantly inhibited by IL-10, IL-4, and NS-398. Moreover, IL-10 and IL-4 inhibited LPS-induced cyclooxygenase (COX) activity in neutrophils. Western blot and immunocytochemical analysis showed that COX-2 protein was clearly induced in LPS-stimulated neutrophils and that its induction was inhibited by both IL-10 and IL-4. Moreover, both of these cytokines inhibited COX-2 mRNA expression in LPS-stimulated neutrophils. These results raise the possibility that these two cytokines may both offer potent clinical utility as anti-inflammatory agents in the future.

scholarly journals Downregulation of TNF-α/TNF-R1 Signals by AT-Lipoxin A4 May Be a Significant Mechanism of Attenuation in SAP-Associated Lung Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Suhui Yu ◽  
Jianming Xie ◽  
Yukai Xiang ◽  
Shengjie Dai ◽  
Dinglai Yu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Tumor Necrosis Factor Receptor ◽  
Microvascular Endothelial Cell ◽  
Death Domain ◽  
Lipoxin A4 ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory ◽  
Significant Mechanism

Our previous studies verified the potent anti-inflammatory effects against severe acute pancreatitis (SAP) of AT-Lipoxin A4 and their analogues. However, the anti-inflammatory effects of AT-Lipoxin A4 on SAP-associated lung injury are not thoroughly known. We used western blot, polymerase chain reaction (PCR), and immunofluorescence to investigate the downregulation of TNF-α signals in cellular and animal models of SAP-associated lung injury following AT-Lipoxin A4 intervention. In vitro, we found that AT-Lipoxin A4 markedly suppressed protein expression in TNF-α signals in human pulmonary microvascular endothelial cell, such as tumor necrosis factor receptor-associated factor 2 (TRAF2), TNF-R1-associated death domain (TRADD), receptor-interacting protein (RIP), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Moreover, AT-Lipoxin A4 inhibited downstream signals activated by TNF-α, including NF-κB/p65, JNK/MAPK, and ERK/MAPK. In vivo, AT-Lipoxin A4 significantly decreased pathological scores of the pancreas and lungs and the serum levels of IL-6 and TNF-α. Immunofluorescence, western blotting, and real-time PCR assay showed that AT-Lipoxin A4 significantly attenuated the expression of TNF-R1, TRADD, TRAF2, and RIP in the lungs of SAP rats. In addition, the activation of NF-κB was also downregulated by AT-Lipoxin A4 administration as compared with SAP rats. AT-Lipoxin A4 could inhibit the production of proinflammatory mediators and activation of TNF-α downstream signals such as NF-κB and MAPK. Downregulation of TNF-α signals by AT-Lipoxin A4 may be a significant mechanism in the attenuation of SAP-associated lung injury.

scholarly journals Canscora lucidissima, a Chinese folk medicine, exerts anti-inflammatory activities by inhibiting the phosphorylation of ERK1/2 in LPS-activated macrophages

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiao-ling Fei ◽  
Xiao-yu Zhang ◽  
Rui-juan Qi ◽  
Yun-feng Huang ◽  
Yi-xin Han ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Southern China ◽  
Raw 264.7 Cells ◽  
Luciferase Reporter ◽  
Effective Treatment Option ◽  
Proinflammatory Mediators ◽  
Inflammatory Models ◽  
Inflammatory Mechanism ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background Canscora lucidissima (Levl. & Vaniot) Hand.-Mazz. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases. However, the underlying mechanism of its anti-inflammatory effect is not fully understood. Methods In this study, we investigated the anti-inflammatory mechanism of ethanol extract of C. lucidissima (Cl-EE) in lipopolysaccharide (LPS)-induced inflammatory models. ELISA, real-time PCR, Western blot and luciferase reporter assay were used for the experiments in vitro, and ICR mouse endotoxemia model was used for in vivo test. Results Our data showed that Cl-EE reduced the production of NO by down-regulating the mRNA and protein expression of inducible nitric oxide synthase (iNOS) in LPS-activated RAW 264.7 cells. Meanwhile, it potently decreased other proinflammatory mediators, such as TNF-α, IL-6, MCP-1 and IL-1β at the transcriptional and translational levels. Further study indicated that Cl-EE did not affect NF-κB signaling pathway but significantly suppressed the phosphorylation of ERK1/2, rather than JNK or p38. In a LPS-induced endotoxemia mouse model, a single intraperitoneal injection of Cl-EE (75–300 mg/kg) could lower circulatory TNF-α, IL-6 and MCP-1 levels. Conclusions Collectively, our results indicated that Cl-EE suppressed the phosphorylation level of ERK1/2 thus reducing the transcription and translation of inflammatory genes, thereby exerted anti-inflammatory activity. This study reveals the anti-inflammatory mechanism of C. lucidissima and may provide an effective treatment option for a variety of inflammatory diseases.

scholarly journals Volatile Composition, Toxicity, Analgesic, and Anti-Inflammatory Activities of Mucuna pruriens

2020 ◽  
Vol 15 (7) ◽  
pp. 1934578X2093232
Author(s):  
Opeyemi N. Avoseh ◽  
Isiaka A. Ogunwande ◽  
Gbenga O. Ojenike ◽  
Fanyana M. Mtunzi
Keyword(s):  
Essential Oil ◽  
Essential Oils ◽  
Opioid Analgesic ◽  
Dry Weight ◽  
Mucuna Pruriens ◽  
Opioid Antagonist ◽  
Flame Ionization ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory ◽  
Anti Inflammation

The volatile constituents, toxicity, antinociception, and anti-inflammatory activities of the essential oil obtained from the leaf of Mucuna pruriens utilis collected from Nigeria are reported. The essential oil was analyzed comprehensively utilizing gas chromatography (GC)-flame ionization detector and GC coupled with mass spectrometry (MS) using the HP-5 column. The antinociceptive and anti-inflammatory assays were analyzed by a hot plate, formalin, and carrageenan-induced edema assays, respectively. The essential oil was obtained in a yield of 0.2% (v/w) calculated on a dry weight basis. A total of 36 compounds representing 94.8% of the oil contents were identified. The oil contained a high content of ( E)-2-hexenal (19.0%), linalool (8.9%), 1-hexanol (6.6%), and trans-dehydroxylinalool oxide (5.2%). The analgesic property of the essential oil was slightly significant ( P < 0.5) only at the third hour for the 400 mg/kg while other doses are less active. The rate of inhibition was moderate (24.1%-54%) during the analgesic phase of the formalin assay. The rate of inhibition at the anti-inflammatory phases of both formalin and carrageenan were significantly high (100%) and P < 0.001 for all the doses during the reaction duration. The potential proinflammatory mechanism might be due to effects on several proinflammatory mediators, including, histamine, serotonin, and bradykinin, and the ability of the essential oils to act as centrally mediated opioid analgesic. Mucuna pruriens essential oils displayed a high anti-inflammation potential and can be used as a potential centrally mediated opioid antagonist against analgesia.

scholarly journals Anti-Inflammatory Effects of Essential Oils of Amomum aromaticum Fruits in Lipopolysaccharide-Stimulated RAW264.7 Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Nguyen Hai Dang ◽  
Le Thi Van Anh ◽  
Nguyen Tien Dat
Keyword(s):  
Essential Oils ◽  
Chronic Inflammation ◽  
Raw264.7 Cells ◽  
Phytochemical Analysis ◽  
Cellular Injury ◽  
Volatile Oils ◽  
Physiologic Response ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory ◽  
First Time

Inflammation is a vital physiologic response of cellular injury, infection, or autoimmune activation. Overproduction of proinflammatory mediators may result in the chronic inflammation that leads to many diseases such as rheumatoid arthritis, asthma, multiple sclerosis, and atherosclerosis. In this study, we assessed for the first time the anti-inflammatory effects of the essential oils of Amomum aromaticum fruits (AAE) in RAW264.7 murine macrophage model. As a result, AAE potently inhibited the production of nitric oxide in LPS-induced RAW264.7 cells with the IC50 value of 0.45 ± 0.11 μg/ml. AAE also dose-dependently reduced the expression of two proinflammatory proteins iNOS and COX-2 in the stimulated cells. Phytochemical analysis revealed that major compositions of the volatile oils including 1,8 cineole (48.22%), geranial (9.24%), neral (6.72%), α-pinene (2.43%), and α-terpineol (2.28%) may contribute greatly to the inhibition effects due to their anti-inflammatory properties. The results suggest for the potential uses of AAE in chronic inflammation prevention.

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