A review on anti-infl ammation activity of phenol compound paeonol

Paeonol is a bioactive phenol present in Dioscorea japonica,Paeonia suff ruticosa and Paeonia lactifl ora.It is the main active ingredient in the traditional Chinese medicines Mudanpi and Xu Changqing.Clinical applications of paeonol are mainly focused on anti-infl ammatory eff ects due to its ability to act as an antioxidant,a regulator of infl ammatory enzyme activities,a modulator of infl ammatory signaling pathways and a regulator of adhesion molecules to modulate infl ammation through molecular mechanisms of action.In addition,paeonol also regulates infl ammation by regulating the metabolism of gut microbes.In this review,we searched PubMed,Web of Science,ESI and other websites using“paeonol”“infl ammation”“oxidative stress”“signaling pathways”and“gut microbiota”as keywords.We mainly referred to the relevant literature in the last decade and systematically summarized the studies on the anti-infl ammatory eff ects of paeonol to provide a reference for new drug development and clinical application of paeonol.

NF-κB and STAT3 signaling pathways collaboratively link infl ammation to cancer

Although links between cancer and inflammation were fi rstly proposed in the nineteenth century,the molecular mechanism has not yet been clearly understood.Epidemiological studies have identified chronic infections and infl ammation as major risk factors for various types of cancer.NF-κB transcription factors and the signaling pathways are central coordinators in innate and adaptive immune responses.STAT3 regulates the expression of a variety of genes in response to cellular stimuli,and thus plays a key role in cell growth and apoptosis.Recently,roles of NF-κB and STAT3 in colon,gastric and liver cancers have been extensively investigated.The activation and interaction between STAT3 and NF-κB play vital roles in control of the communication between cancer cells and infl ammatory cells.NF-κB and STAT3 are two major factors controlling the ability of pre-neoplastic and malignant cells to resist apoptosis-based tumor-surveillance and regulating tumor angiogenesis and invasiveness.Understanding the molecular mechanisms of NF-κB and STAT3 cooperation in cancer will offer opportunities for the design of new chemo-preventive and chemotherapeutic approaches.

Moringa oleifera Lam. leaf extract mitigates carbon tetrachloride-mediated hepatic inflammation and apoptosis via targeting oxidative stress and toll-like receptor 4/nuclear factor kappa B pathway in mice

Carbon tetrachloride(CCl4)is a hepatotoxin that triggers liver damage.This study aimed to evaluate the protective effect of phytochemicals detected in Moringa oleifera Lam.leaf extract(MOLE)on CCl4-induced hepatotoxicity in mice.Phytochemicals,total phenolics,and total fl avonoids were detected in MOLE.MOLE markedly decreased the elevation of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in consistence with the ameliorating effect on CCl4-induced histopathological abnormalities.Moreover,MOLE significantly alleviated the decrease in the antioxidant defense mechanism induced by CCl4.The suppressing effect of MOLE on the boosted inflammatory pathway triggered by CCl4 was detected by measuring the protein levels of nuclear factor kappa-light-chain-enhancer of activated B-cells(NF-κB-p65),toll-like receptor 4(TLR4),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,and IL-8 as well as the relative expressions of nuclear factor kappa B(NF-κB),TNF-α,IL-1β,and TLR4 genes.Apoptosis and genotoxicity induced by CCl4 were signifi cantly alleviated by MOLE.MOLE co-administration modulated TLR4/NF-κB pathway as presented by the suppressed gene expression of TLR4 and NF-κB as well as by the reduced protein expression of TLR4 and NF-κB-p65.In conclusion,MOLE has a multifarious protective role against hepatotoxicity through control of oxidative stress and modulation of TLR4/NF-κB.

Chronic infl ammation and gastrointestinal cancer

Chronic inflammation has been identified as an important risk factor in the development of the gastrointestinal(GI)tract cancers,and the underlying molecular mechanisms have been studied extensively.Chronic infl ammation is able to trigger cellular events to promote malignant transformation of normal epithelial cells in the GI tract to cancer.Host inflammation responses in carcinogenesis are through multiple mechanisms such as reactive oxygen and nitration species from mononuclear phagocytes and leukocytes,immune response and pro-inflammatory cytokines.Nuclear factor-κB(NF-κB)has been considered as the central mediator of the immune response.Activation of NF-κB by phosphorylation leads to translocation of NF-κB protein to the nucleus,and in turn regulates the transcription of several pro-infl ammatory cytokines and chemokines.Furthermore,chronic inflammation creates an environment for genomic and epigenetic changes.In this review,we summarize the important molecular mechanisms that link chronic infl ammation and GI tract cancer,including esophageal,gastric and colonic cancers,focusing on infective and noninfective agents such as gastroesophageal reflux disease,Helicobacter pylori gastritis and infl ammatory bowel disease.

Antrodia Cinnamomea ameliorates neointimal formation by inhibiting infl ammatory cell infi ltration through downregulation of adhesion molecule expression in vitro and in vivo

The increased vascular infl ammation is a key event in the development of atherosclerotic lesions.Antrodia cinnamomea has been shown to promote anticancerogenic activity through decreasing infl ammation.However,the potential role of A.cinnamomea in cardiovascular diseases remains unexplored.Herein,using carotid arterial ligation models,we found that ethanol extract from A.cinnamomea(EEAC)signifi cantly inhibited neointimal hyperplasia in a dose-dependent manner,accompanied with the reduced expression of activated p65 and infl ammatory cytokines.We also show that EEAC ameliorated TNF-α-induced phosphorylation of p65 and pro-infl ammatory cytokine expression in both vascular smooth muscle cells(VSMCs)and macrophages in vitro.Mechanistically,EEAC suppressed expression levels of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule(VCAM-1)in VSMCs,which attenuates the ability of monocytes/macrophages adhesion to VSMCs.Furthermore,the expression level of these adhesion molecules and infi ltration of monocytes/macrophages were also decreased in neointimal VSMCs of arteries pretreated with EEAC.Altogether,our results reveal a novel function of A.cinnamomea in suppressing vascular infl ammation upon ligation injury during neointimal formation,likely through inhibition of infl ammatory cell infi ltration via downregulating the adhesion molecules in VSMCs.Thus,A.cinnamomea may offer a pharmacological therapy to slow down disease progression in patients with vascular injury.

Lunasin protease inhibitor concentrate decreases pro-infl ammatory cytokines and improves histopathological markers in dextran sodium sulfate-induced ulcerative colitis

Lunasin protease inhibitor concentrate(LPIC)is a novel combination of soy bioactive peptide lunasin,Kunitz and Bowman-Birk protease inhibitors.The reported anti-inflammatory and anticancer properties of each one of them suggest LPIC as a promising candidate for the treatment of infl ammatory-related diseases.Our objective was to assess the in vivo anti-infl ammatory properties of LPIC.First,an in vitro test was performed in lipopolysaccharide(LPS)-activated RAW264.7 murine macrophages by measuring the production of nitric oxide(NO),interleukin-6(IL-6),and tumor necrosis factorα(TNF-α)as infl ammatory markers.For the in vivo model,ulcerative colitis(UC)was induced in mice via oral administration of dextran sodium sulfate(DSS).LPIC treatment was performed via daily intraperitoneal injection of 50 mg/kg body weight.Body weight,visible blood in stool and stool consistency were scored daily as macroscopic indicators of disease progression.Occult blood was evaluated by the presence of hemoglobin in stool every third day.Colon length,caecum weight,colonic myeloperoxidase activity(MPO),presence of pro-inflammatory cytokines in blood and colon,changes in the architecture,and expression of inducible nitric oxide synthase(i NOS)in colonic tissue were evaluated.In vitro,LPIC induced production of NO and maintained cytokine levels in comparison to activated untreated macrophages.In vivo,LPIC increased colonic bleeding and did not improve macroscopic markers of the disease,but reduced colonic IL-1βand IL-6,decreased systemic circulation of TNF-α,attenuated neutrophils infi ltration and i NOS expression in colonic tissue,and diminished the damage in colonic architecture.Our results suggest that combinations of peptides in LPIC may counteract the antiinfl ammatory properties in vitro;while in vivo,LPIC can signifi cantly reduce the histopathological damage,hence is a possible therapeutic strategy to attenuate UC.

Over-expression of programmed death-ligand 1 and programmed death-1 on antigen-presenting cells as a predictor of organ dysfunction and mortality during early sepsis: a prospective cohort study

BACKGROUND:This study aimed to explore the changes of programmed death-ligand 1(PDL1)and programmed death-1(PD-1)expression on antigen-presenting cells(APCs)and evaluate their association with organ failure and mortality during early sepsis.METHODS:In total,40 healthy controls and 198 patients with sepsis were included in this study.Peripheral blood was collected within the first 24 h after the diagnosis of sepsis.The expression of PDL1 and PD-1 was determined on APCs,such as B cells,monocytes,and dendritic cells(DCs),by flow cytometry.Cytokines in plasma,such as interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-4(IL-4),IL-6,IL-10,and IL-17A were determined by Luminex assay.RESULTS:PD-1 expression decreased significantly on B cells,monocytes,myeloid DCs(mDCs),and plasmacytoid DCs(pDCs)as the severity of sepsis increased.PD-1 expression was also markedly decreased in non-survivors compared with survivors.In contrast,PD-L1 expression was markedly higher on mDCs,pDCs,and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors.The PD-L1 expression on APCs(monocytes and DCs)was weakly related to organ dysfunction and infl ammation.The area under the receiver operating characteristic curve(AUC)of the PD-1 percentage of monocytes(monocyte PD-1%)+APACHE II model(0.823)and monocyte PD-1%+SOFA model(0.816)had higher prognostic value than other parameters alone.Monocyte PD-1%was an independent risk factor for 28-day mortality.CONCLUSION:The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs.PD-L1 in monocytes and DCs was weakly correlated with infl ammation and organ dysfunction during early sepsis.The combination of SOFA or APACHE II scores with monocyte PD-1%could improve the prediction ability for mortality.

Association of Serum Chemerin Levels with Coronary Artery Disease: Pathogenesis and Clinical Research

Recent studies have revealed that chemerin plays an essential role in the development of cardiovascular diseases.Autopsy studies found a strong correlation between the secretion of chemerin in peripheral tissues and aortic and coronary atherosclerosis.Plasma chemerin is a marker of systemic infl ammation and is associated with metabolic syndrome.Chemerin plays a vital role in vascular infl ammation and atherogenesis.Plasma chemerin levels are increased in patients with dilated cardiomyopathy,and chemerin is associated with left ventricular dysfunction.In this review,we focus on chemerin expression,chemerin processing,its biological function,and its role in the diagnosis of cardiovascular diseases.

Glycyrrhizic Acid Attenuates Balloon-Induced Vascular Injury Through Inactivation of RAGE Signaling Pathways

Percutaneous coronary intervention is a well-established technique used to treat coronary artery disease,but the risk of coronary artery in-stent restenosis following percutaneous coronary intervention is still high.Previous studies revealed that high mobility group protein B1(HMGB1)plays a critical role in neointima formation.In this study,we aimed to investigate the role of glycyrrhizic acid(GA),an HMGB1 inhibitor,in the process of neointima formation and the potential mechanisms.We investigated the role of GA in neointima formation through an iliac artery balloon injury model in rabbits.Proliferation,migration,and phenotype transformation of human vascular smooth muscle cells(VSMCs)were observed.Besides,infl ammation and receptor for advanced glycosylation end products(RAGE)signaling pathways were studied.The results indicate that GA attenuated neointima formation and downregulated HMGB1 expression in injured artery in rabbits.HMGB1 promoted proliferation,migration,and phenotype transformation through the activation of RAGE signaling pathways in VSMCs,and blockade of HMGB1 by GA(1,10,and 100μM)could attenuate those processes and reduce proliferation of human VSMCs.In conclusion,the HMGB1 inhibitor GA might be useful to treat proliferative vascular diseases by downregulating RAGE signaling pathways.Our results indicate a new and promising therapeutic agent for restenosis.

Negative regulation of NLRP3 infl ammasome signaling

Infl ammasomes are multiprotein complexes that serve as a platform for caspase-1 activation and interleukin-1β(IL-1β)maturation as well as pyroptosis.Though a number of infl ammasomes have been described,the NLRP3 inflammasome is the most extensively studied.NLRP3 inflammasome is triggered by a variety of stimuli,including infection,tissue damage and metabolic dysregulation,and then activated through an integrated cellular signal.Many regulatory mechanisms have been identifi ed to attenuate NLRP3 infl ammasome signaling at multiple steps.Here,we review the developments in the negative regulation of NLRP3 inflammasome that protect host from inflammatory damage.