Calystegia soldanella Extract Exerts Anti-oxidative and Anti-inflammatory Effects via the Regulation of the NF-κB/Nrf-2 Pathways in Mouse Macrophages

Plant polyphenols are widely used to treat various inflammatory diseases, owing to their ability to suppress reactive oxygen species production and the expression of inflammatory cytokines. Herein, we investigated phenolic compounds from Calystegia soldanella using UPLC Q-TOF MS/MS and their antioxidative and anti-inflammatory activities were analyzed. The C. soldanella ethyl acetate fraction (CsEF) had the strongest antioxidative activity, given its high polyphenol compound content. It also exhibited anti-inflammatory effects, inhibiting the production of inflammatory cytokines such as NO, PGE2, IL-1β, IL-6, and TNF-α in LPS-stimulated mouse macrophages. CsEF activated the nuclear transcription factor Nrf-2, thereby upregulating antioxidant enzymes such as HO-1 and NQO-1 and inhibiting NF-κB expression, which in turn, suppressed the expression of COX-2, iNOS, and inflammatory cytokines, ultimately exerting anti-inflammatory effects. Further, UPLC-Q-TOF-MS/MS was used to analyze the polyphenol compound contents in CsEF. The quercetin glycosides isoquercitrin and quercitrin were the primary flavonoid compounds, while the caffeic acid derivatives, chlorogenic acid and dicaffeoylquinic acid, were the primary phenolic acids. Thus, C. soldanella, which had only a limited use thus far as a medicinal plant, may serve as a natural medicinal resource for treating inflammatory diseases.

Download Full-text

Sudachinoid- and Ichangensin-Type Limonoids from Citrus junos Downregulate Pro-Inflammatory Cytokines

International Journal of Molecular Sciences ◽

10.3390/ijms21186963 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6963

Author(s):

Jihun Shin ◽

Hwa Young Song ◽

Mina Lee

Keyword(s):

Inflammatory Cytokines ◽

Human Colon ◽

Dominant Group ◽

Citrus Junos ◽

Mouse Macrophages ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

Factor Α ◽

Necrosis Factor ◽

Pro Inflammatory Cytokines

Limonoids, a dominant group of phytochemicals in the Rutaceae family, are known to exhibit several pharmacological activities. To identify natural products having efficacy against inflammatory bowel disease (IBD), we isolated 13 limonoids including a new compound, methyl sudachinoid A, from the seeds of Citrus junos and investigated their anti-inflammatory effects by assessing the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 mouse macrophages and HT-29 human colon epithelial cells. Our findings revealed that limonoids significantly downregulated the pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and nuclear transcription factor κB. In particular, sudachinoid-type compounds, methyl sudachinoid A and sudachinoid B, and ichangensin-type compound, 1-O-methyichangensin downregulated the expression of pro-inflammatory cytokines more potently than other limonoids, nomilin and limonin, which have been previously reported to exhibit anti-inflammatory activities in other cells; nomilin and limonin were therefore employed as positive controls in this study. Herein, we reveal that the anti-inflammatory activities of limonoids including a new compound methyl sudachinoid A from C. junos were mediated via the downregulation of pro-inflammatory cytokines and these limonoids can be employed as potential therapeutic phytochemicals for IBD.

Download Full-text

Anti-Inflammatory and Antinociceptive Activity of Flavonoids Isolated from Viscum album ssp. album

Zeitschrift für Naturforschung C ◽

10.1515/znc-2006-1-205 ◽

2006 ◽

Vol 61 (1-2) ◽

pp. 26-30 ◽

Cited By ~ 34

Author(s):

Didem Deliorman Orhan ◽

Esra Küpeli ◽

Erdem Yesilada ◽

Fatma Ergun

Keyword(s):

Ethyl Acetate ◽

Inflammatory Diseases ◽

Ethyl Acetate Fraction ◽

Viscum Album ◽

Antinociceptive Activity ◽

Paw Edema ◽

Writhing Test ◽

Activity Assessment ◽

Edema Model ◽

Anti Inflammatory

Abstract Viscum album L. has been used in the indigenous systems of medicine for treatment of headache and some inflammatory diseases. In order to evaluate this information, antinociceptive and anti-inflammatory activities of the five flavonoids (5,7-dimethoxy naringenin or 4′,6′- dimethoxy chalcononaringenin) derivatives, isolated from the ethyl acetate fraction of the extract from V. album ssp. album, were investigated, namely 5,7-dimethoxy-flavanone-4′-O- β-ᴅ-glucopyranoside (1), 2′-hydroxy-4′,6′-dimethoxy-chalcone-4-O-β-ᴅ-glucopyranoside (2), 5,7-dimethoxy-flavanone-4′-O-[2″-O-(5‴-O-trans-cinnamoyl)-β-ᴅ-apiofuranosyl]-β-ᴅ-glucopyranoside (3), 2′-hydroxy-4′,6′-dimethoxy-chalcone-4-O-[2″-O-(5‴-O-trans-cinnamoyl)-β-ᴅ-apiofuranosyl]- β-ᴅ-glucopyranoside (4), 5,7-dimethoxy-flavanone-4′-O-[β-d-apiofuranosyl- (152)]-β-ᴅ-glucopyranoside (5). For the antinociceptive activity assessment the p-benzoquinone- induced writhing test and for the anti-inflammatory activity the carrageenan-induced hind paw edema model in mice were used. The ethyl acetate fraction in a dose of 250 mg/kg as well as compounds 2 and 5 in a 30 mg/kg dose were shown to possess remarkable antinociceptive and anti-inflammatory activities per os without inducing any apparent acute toxicity as well as gastric damage

Download Full-text

Anti-Inflammatory Effects of 6,7-Dihydroxy-4-Methylcoumarin on LPS-Stimulated Macrophage Phosphorylation in MAPK Signaling Pathways

Natural Product Communications ◽

10.1177/1934578x211020970 ◽

2021 ◽

Vol 16 (5) ◽

pp. 1934578X2110209

Author(s):

Yun Sil Kang ◽

You Chul Chung ◽

Jung No Lee ◽

Bong Seok Kim ◽

Chang-Gu Hyun

Keyword(s):

Signaling Pathways ◽

Inflammatory Cytokines ◽

Inflammatory Diseases ◽

Mapk Signaling ◽

Raw 264.7 Cells ◽

Inflammatory Factors ◽

Raw 264.7 ◽

Dependent Manner ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Coumarin derivatives, such as esculetin, have various physiological functions, including antioxidant, anti-inflammatory, antibacterial, antiviral, and anti-cancer. 6,7-Dihydroxy-4-methylcoumarin (6,7-DH-4MC) is a derivative of esculetin, and its anti-inflammatory effect and mechanism in macrophages have not been studied. In this study, the anti-inflammatory activity of 6,7-DH-4MC was evaluated by measuring the expression of inflammatory factors (NO and PGE2) and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in LPS-stimulated RAW 264.7 macrophages. The results revealed that 6,7-DH-4MC significantly reduced NO levels and PGE2 expression without inducing cytotoxicity; it was confirmed that the inhibition of NO and PGE2 expression was related to iNOS and COX-2 downregulation in response to 6,7-DH-4MC treatment. Moreover, 6,7-DH-4MC decreased the levels of pro-inflammatory cytokines, such as IL-1β and IL-6, in a dose-dependent manner. Mechanistic studies revealed reduced phosphorylation of ERK and p38-MAPK upon 6,7-DH-4MC treatment. Furthermore, the degradation of IκB-α and phosphorylation of NF-κB in cells treated with LPS were interrupted by 6,7-DH-4MC treatment. These results suggest that 6,7-DH-4MC is a potential therapeutic agent for inflammatory diseases. To the best of our knowledge, this is the first report demonstrating the anti-inflammatory effects of 6,7-DH-4MC in RAW 264.7 cells via MAPK and NF-κB signaling pathways.

Download Full-text

Anti-inflammatory activity of diindolylmethane alleviates Riemerella anatipestifer infection in ducks

PLoS ONE ◽

10.1371/journal.pone.0242198 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242198

Author(s):

Cherry P. Fernandez-Colorado ◽

Paula Leona T. Cammayo ◽

Rochelle A. Flores ◽

Binh T. Nguyen ◽

Woo H. Kim ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Inflammatory Diseases ◽

Splenic Lymphocytes ◽

Expression Levels ◽

Riemerella Anatipestifer ◽

Qrt Pcr ◽

Reverse Transcription Pcr ◽

Anti Inflammatory

3,3’-Diindolylmethane (DIM) is found in cruciferous vegetables and is used to treat various inflammatory diseases because of its potential anti-inflammatory effects. To investigate effects of DIM in Riemerella anatipestifer-infected ducks which induce upregulation of inflammatory cytokines, ducks were treated orally with DIM at dose of 200 mg/kg/day and infected the following day with R. anatipestifer. Infected and DIM-treated ducks exhibited 14% increased survival rate and significantly decreased bacterial burden compared to infected untreated ducks. Next, the effect on the expression level of inflammatory cytokines (interleukin [IL]-17A, IL-17F, IL-6, IL-1β) of both in vitro and in vivo DIM-treated groups was monitored by quantitative reverse-transcription PCR (qRT-PCR). Generally, the expression levels of the cytokines were significantly reduced in DIM-treated splenic lymphocytes stimulated with killed R. anatipestifer compared to stimulated untreated splenic lymphocytes. Similarly, the expression levels of the cytokines were significantly reduced in the spleens and livers of DIM-treated R. anatipestifer–infected ducks compared to infected untreated ducks. This study demonstrated the ameliorative effects of DIM in ducks infected with R. anatipestifer. Thus, DIM can potentially be used to prevent and/or treat R. anatipestifer infection via inhibition of inflammatory cytokine expression.

Download Full-text

Pro-Inflammatory Cytokines at Ultra-Low Dose Exert Anti-Inflammatory Effect In Vitro: A Possible Mode of Action Involving Sub-Micron Particles?

Dose-Response ◽

10.1177/1559325820961723 ◽

2020 ◽

Vol 18 (4) ◽

pp. 155932582096172

Author(s):

Ilaria Floris ◽

Thorsten Rose ◽

Juan Antonio Collado Rojas ◽

Kurt Appel ◽

Camille Roesch ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Mode Of Action ◽

Inflammatory Diseases ◽

Resistive Pulse ◽

Tnf Α ◽

Anti Inflammatory ◽

Factor Α ◽

Pro Inflammatory Cytokines ◽

Inflammatory Effect

Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are pro-inflammatory cytokines involved in acute and chronic inflammatory diseases. Indeed, immunotherapy blocking these 2 cytokines has been developed. Micro-immunotherapy (MI) also uses ultra-low doses (ULD) of pro-inflammatory cytokines, impregnated on lactose-sucrose pillules, to counteract their overexpression. The study has been conducted with 2 objectives: examine the anti-inflammatory effect in vitro and the capacity of 2 unitary medicines, TNF-α (27 CH) and IL-1β (27 CH), to reduce the secretion of TNF-α in human primary monocytes and THP-1 cells differentiated with phorbol-12-myristate-13-acetate, after lipopolysaccharide (LPS) exposure; then, investigate the presence of particles possibly containing starting materials using tunable resistive pulse sensing technique. The results show that the unitary medicines, tested at 3 pillules concentrations (5.5, 11 and 22 mM), have reduced the secretion of TNF-α in both models by about 10−20% vs. vehicle control, depending on concentration. In this exploratory study, particles (150−1000 nm) have been detected in MI ULD-impregnated pillules and a hypothesis for MI medicines mode of action has been proposed. Conscious that more evaluations are necessary, authors are cautious in the conclusions because the findings described in the study are still limited, and future investigations may lead to different hypothesis.

Download Full-text

TMIC-52. REACTIVE ASTROCYTES AID THE EVOLUTION OF IMMUNOSUPPRESSIVE ENVIRONMENT AND DRIVE ONCOGENIC SIGNALING IN GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noz175.1086 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi259-vi259

Author(s):

Dieter Heiland ◽

Vidhya Ravi ◽

Simon P Behringer ◽

Julian Wurm ◽

Juergen Beck ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Inflammatory Diseases ◽

Mapk Signaling ◽

Reactive Astrocytes ◽

Marker Genes ◽

Loss Of Function ◽

Oncogenic Signaling ◽

Tumor Environment ◽

The Central Nervous System ◽

Anti Inflammatory

Abstract Reactive astrocytes are caused by multiple pathologies of the central nervous system, whereby they undergo distinct transcriptomic re-programming. Although the role of reactive astrocytes in some inflammatory diseases has been investigated, many central questions regarding the immunoregulatory functions of tumor-associated astrocytes and their crosstalk to microglia remain poorly understood. In our presented study, we purified astrocytes from various pathologies and different brain tumors to map the transcriptional landscape of reactive astrocytes. We identified the marker genes CHI3L1 and CD274 highly enriched in reactive astrocytes of the marginal astrogliosis scar at the tumor boarder. Human neocortical slices along with a microglia loss-of-function model were used to explore the crosstalk of microglia and reactive astrocytes within the tumor environment. Our results revealed that the reactive phenotype mutually arises from both, microglia and tumor cells. This interaction caused JAK/STAT signalling in reactive astrocytes along with a large release of anti-inflammatory cytokines such as TGFß and IL10. Additionally, inhibition of the JAK/STAT pathway recovered the release of anti-inflammatory cytokines and resulted in a pro-inflammatory environment. Besides the immunosuppressive properties, we found evidence that reactive astrocytes drove AKT and MAPK signaling in the tumor through astrocytic released CHI3L1 and consequential binding to IL13RA2. Our findings revealed increased malignant properties arising from astrocytic-tumor interaction, which were rescued by IL13RA2 inhibition. In a nutshell, reactive astrocytes have decisive regulatory tasks in the microenvironment of CNS tumors. Along with microglia, reactive astrocytes cause the evolution of an immunosuppressive environment and support malignant properties of the tumor.

Download Full-text

The Screening Research of NF-κB Inhibitors from Moutan Cortex Based on Bioactivity-Integrated UPLC-Q/TOF-MS

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/6150357 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7

Author(s):

Yujie Lu ◽

Wenjuan Liu ◽

Man Zhang ◽

Yanfang Deng ◽

Min Jiang ◽

...

Keyword(s):

Inflammatory Diseases ◽

Ultra Performance Liquid Chromatography ◽

Cellular Level ◽

Pathological Process ◽

Root Cortex ◽

Flight Mass Spectrometry ◽

Moutan Cortex ◽

Anti Inflammatory ◽

Systematic Identification ◽

Tof Ms

Inflammation is a common and important pathological process, and nuclear factor-κB (NF-κB) is a key mediator of it. Moutan Cortex (MC), the dried root cortex of Paeonia suffruticosa Andr., is widely used as a remedy for the treatment of inflammatory diseases in Asian region. However, there are few studies on the systematic identification of NF-κB inhibitors of MC. In this study, the effect of inhibiting NF-κB activation of MC was assessed at the cellular level using a tumor necrosis factor-α (TNF-α) induced inflammatory model. Subsequently, ultra-performance liquid chromatography-quadrupole/time of flight-mass spectrometry (UPLC-Q/TOF-MS) combined with biological activity assay was established to screen and identify potential anti-inflammatory ingredients in MC. The results revealed that MC significantly inhibited the activation of NF-κB. Seven potential NF-κB inhibitors were screened from MC, including oxypaeoniflorin, paeoniflorin, galloylpaeoniflorin, benzoyloxypaeoniflorin, mudanpioside C, gallic acid, and paeonol. Among them, the NF-κB inhibitor activity of galloylpaeoniflorin, benzoyloxypaeoniflorin, and mudanpioside C is first reported here. In conclusion, the anti-inflammatory activity of MC was associated with the seven components mentioned above. And the bioactivity-integrated UPLC-Q/TOF which contains both chemical and bioactive details is suitable for screening active ingredients from natural medicines.

Download Full-text

Capsaicin affects macrophage anti-inflammatory activity via the MAPK and NF-κB signaling pathways

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000721 ◽

2021 ◽

Author(s):

Jingshuang Li ◽

Hui Wang ◽

Lili Zhang ◽

Ni An ◽

Wan Ni ◽

...

Keyword(s):

Signaling Pathways ◽

Inflammatory Cytokines ◽

Inflammatory Diseases ◽

Underlying Mechanism ◽

Peritoneal Macrophages ◽

The Body ◽

Inflammatory Activity ◽

Inflammatory Factors ◽

Tnf Α ◽

Anti Inflammatory

Abstract. Capsaicin, the main constituent in chili, is an extremely spicy vanillin alkaloid and is found in several Capsicum species in China. Traditionally, it has been used to treat inflammatory diseases such as allergic rhinitis, neuralgia after shingles, refractory female urethral syndrome, spontaneous recalcitrant anal pruritus, and solid tumors. Constant stimulation of the body by inflammatory factors can lead to chronic inflammation. Capsaicin possesses anti-inflammatory activity; however, the underlying mechanism is unknown. We investigated the effect of capsaicin on the secretion of macrophage inflammatory factors in a lipopolysaccharide-induced inflammation model using 56 healthy, SPF grade, BALB/c mice. To this end, mice peritoneal macrophages were isolated and stimulated with lipopolysaccharide (1 μg/mL) and capsaicin (25, 50, 75, or 100 μg/mL) for 24 h. At all concentrations tested, capsaicin significantly promoted the phagocytosis of neutral red dye by macrophages. Furthermore, the gene expression and secretion of inflammatory cytokines significantly increased after induction with lipopolysaccharide (P<0.01); the interleukin (IL)-6 level was 204 μg/mL, tumor necrosis factor (TNF)-α level was 860 μg/mL, and nitric oxide (NO) level was 19.8 μg/mL. However, the treatment with capsaicin reduced their levels (P<0.01) and protein expression of lipopolysaccharide-induced extracellular signal-related kinase 1/2 and p65 (P<0.05). Overall, capsaicin reduced the secretion of inflammatory cytokines (P<0.01), interleukins, TNF-α (P<0.01), and NO by inhibiting the nuclear factor-kappa B and microtubule-associated protein kinase signaling pathways, and thereby reduced lipopolysaccharide-induced inflammatory response in macrophages.

Download Full-text

Effects of Carrageenans on Biological Properties of Echinochrome

Marine Drugs ◽

10.3390/md16110419 ◽

2018 ◽

Vol 16 (11) ◽

pp. 419 ◽

Cited By ~ 4

Author(s):

Ekaterina Sokolova ◽

Natalia Menzorova ◽

Victoria Davydova ◽

Alexandra Kuz’mich ◽

Anna Kravchenko ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Sea Urchin ◽

Protective Action ◽

Biological Properties ◽

Early Embryos ◽

Ros Formation ◽

Anti Inflammatory ◽

Species Production ◽

Anti Inflammatory Cytokine ◽

Pro Inflammatory Cytokines

Sea urchin pigment echinochrome A (Ech), a water-insoluble compound, is the active substance in the cardioprotective and antioxidant drug Histochrome® (PIBOC FEB RAS, Moscow, Russia). It has been established that Ech dissolves in aqueous solutions of carrageenans (CRGs). Herein, we describe the effects of different types of CRGs on some properties of Ech. Our results showed that CRGs significantly decreased the spermotoxicity of Ech, against the sea urchin S. intermedius sperm. Ech, as well as its complex with CRG, did not affect the division and development of early embryos of the sea urchin. Ech reduced reactive oxygen species production (ROS) in neutrophils, caused by CRG. The obtained complexes of these substances with pro- and anti-activating ROS formation properties illustrate the possibility of modulating the ROS induction, using these compounds. The CRGs stimulate the induction of anti-inflammatory IL-10 synthesis, whereas Ech inhibits this synthesis and increases the production of the pro-inflammatory cytokines IL-6 and TNFα. The inclusion of Ech, in the complex with the CRGs, decreases Ech’s ability to induce the expression of pro-inflammatory cytokines, especially TNFα, and increases the induction of anti-inflammatory cytokine IL-10. Thus, CRGs modify the action of Ech, by decreasing its pro-inflammatory effect. Whereas, the Ech’s protective action towards human epithelial HT-29 cells remains to be unaltered in the complex, with κ/β-CRG, under stress conditions.

Download Full-text

Columbianadin Suppresses Lipopolysaccharide (LPS)-Induced Inflammation and Apoptosis through the NOD1 Pathway

Molecules ◽

10.3390/molecules24030549 ◽

2019 ◽

Vol 24 (3) ◽

pp. 549 ◽

Cited By ~ 3

Author(s):

Chao Zhang ◽

Alan Hsu ◽

He Pan ◽

Yinuo Gu ◽

Xu Zuo ◽

...

Keyword(s):

Inflammatory Response ◽

Inflammatory Cytokines ◽

Molecular Mechanisms ◽

Therapeutic Agent ◽

Inflammatory Diseases ◽

Mechanisms Of Action ◽

Bioactive Constituents ◽

Cellular Apoptosis ◽

Anti Inflammatory ◽

Inflammatory Effect

Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Although the anti-inflammatory activity of CBN has been reported, the underpinning mechanism of this remains unclear. In this study, we investigated the anti-inflammatory effect of CBN on lipopolysaccharide (LPS)-stimulated THP-1 cells and explored the possible underlying molecular mechanisms. The results showed that CBN suppressed LPS-mediated inflammatory response mainly through the inactivation of the NOD1 and NF- κ B p65 signaling pathways. Knockdown of NOD1 reduced the degree to which inflammatory cytokines decreased following CBN treatment, whereas forced expression of NOD1 and CBN treatment reduced NF- κ B p65 activation and the secretion of inflammatory cytokines. Furthermore, CBN significantly reduced cellular apoptosis by inhibiting the NOD1 pathway. Collectively, our results indicate that CBN suppressed the LPS-mediated inflammatory response by inhibiting NOD1/NF- κ B activation. Further investigations are required to determine the mechanisms of action of CBN in the inhibition of NOD signaling: However, CBN may be employed as a therapeutic agent for multiple inflammatory diseases.

Download Full-text