Aqueous Extract from Leaves of Citrus unshiu Attenuates Lipopolysaccharide-Induced Inflammatory Responses in a Mouse Model of Systemic Inflammation

Inflammation is related to various life-threatening diseases including cancer, neurodegenerative diseases, and metabolic syndrome. Because macrophages are prominent inflammatory cells, regulation of macrophage activation is a key issue to control the onset of inflammation-associated diseases. In this study, we aimed to evaluate the potential anti-inflammatory activity of Citrus unshiu leaf extract (CLE) and to elucidate the mechanism underlying its anti-inflammatory effect. We found the inhibitory activity of CLE on the secretion of proinflammatory cytokines and a chemokine from mouse macrophage-like RAW 264.7 cells and mouse peritoneal macrophages. The inhibitory activity of CLE was attributed to downregulated JNK, p38 MAPK, and NF-κB signaling pathways, leading to suppressed gene expression of inflammation-associated proteins. Oral administration of CLE significantly decreased the serum level of proinflammatory cytokines IL-6 and TNFα and increased that of anti-inflammatory cytokine IL-10 in lipopolysaccharide-induced systemic inflammation mice. In addition, oral administration of CLE decreased secretion and gene expression of several proinflammatory proteins in the liver and spleen of the model mice. Overall results revealed that C. unshiu leaf is effective to attenuate inflammatory responses in vitro and in vivo.

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Stevioside Activates AMPK to Suppress Inflammation in Macrophages and Protects Mice from LPS-Induced Lethal Shock

Molecules ◽

10.3390/molecules26040858 ◽

2021 ◽

Vol 26 (4) ◽

pp. 858

Author(s):

Fuyao Wei ◽

Hong Zhu ◽

Na Li ◽

Chunlei Yu ◽

Zhenbo Song ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Mononuclear Cells ◽

Inflammatory Responses ◽

Raw 264.7 Cells ◽

Inflammatory Factors ◽

Enhanced Production ◽

Lethal Shock ◽

Anti Inflammatory

Stevioside, a diterpenoid glycoside, is widely used as a natural sweetener; meanwhile, it has been proven to possess various pharmacological properties as well. However, until now there were no comprehensive evaluations focused on the anti-inflammatory activity of stevioside. Thus, the anti-inflammatory activities of stevioside, both in macrophages (RAW 264.7 cells, THP-1 cells, and mouse peritoneal macrophages) and in mice, were extensively investigated for the potential application of stevioside as a novel anti-inflammatory agent. The results showed that stevioside was capable of down-regulating lipopolysaccharide (LPS)-induced expression and production of pro-inflammatory cytokines and mediators in macrophages from different sources, such as IL-6, TNF-α, IL-1β, iNOS/NO, COX2, and HMGB1, whereas it up-regulated the anti-inflammatory cytokines IL-10 and TGF-β1. Further investigation showed that stevioside could activate the AMPK -mediated inhibition of IRF5 and NF-κB pathways. Similarly, in mice with LPS-induced lethal shock, stevioside inhibited release of pro-inflammatory factors, enhanced production of IL-10, and increased the survival rate of mice. More importantly, stevioside was also shown to activate AMPK in the periphery blood mononuclear cells of mice. Together, these results indicated that stevioside could significantly attenuate LPS-induced inflammatory responses both in vitro and in vivo through regulating several signaling pathways. These findings further strengthened the evidence that stevioside may be developed into a therapeutic agent against inflammatory diseases.

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Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.

Scientific Reports ◽

10.1038/s41598-021-86040-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Isaac J. Morrison ◽

Jianan Zhang ◽

Jingwen Lin ◽

JeAnn E. Murray ◽

Roy Porter ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Responses ◽

Nuclear Antigen ◽

Artocarpus Heterophyllus ◽

Dss Colitis ◽

Treatment And Prevention ◽

Human Cytochrome ◽

Anti Inflammatory ◽

Proliferating Cell

AbstractColorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multiple others, and an enriched extract containing 84% (w/v) artocarpin (determined by HPLC–MS–DAD) was prepared. The enriched extract irreversibly inhibited the activity of human cytochrome P450 CYP2C9, an enzyme previously shown to be overexpressed in CRC models. In vitro evaluations on heterologously expressed microsomes, revealed irreversible inhibitory kinetics with an IC50 value of 0.46 µg/mL. Time- and concentration-dependent cytotoxicity was observed on human cancerous HCT116 cells with an IC50 value of 4.23 mg/L in 72 h. We then employed the azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-induced model in C57BL/6 mice, which revealed that the enriched extract suppressed tumor multiplicity, reduced the protein expression of proliferating cell nuclear antigen, and attenuated the gene expression of proinflammatory cytokines (Il-6 and Ifn-γ) and protumorigenic markers (Pcna, Axin2, Vegf, and Myc). The extract significantly (p = 0.03) attenuated (threefold) the gene expression of murine Cyp2c37, an enzyme homologous to the human CYP2C9 enzyme. These promising chemopreventive, cytotoxic, anticancer and anti-inflammatory responses, combined with an absence of toxicity, validate further evaluation of A. heterophyllus extract as a therapeutic agent.

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Beneficial Effect of Herbal Formulation KM1608 on Inflammatory Bowl Diseases: A Preliminary Experimental Study

Molecules ◽

10.3390/molecules23082068 ◽

2018 ◽

Vol 23 (8) ◽

pp. 2068 ◽

Cited By ~ 2

Author(s):

Myoung-Sook Shin ◽

Sang-Back Kim ◽

Jaemin Lee ◽

Han-Seok Choi ◽

Jimin Park ◽

...

Keyword(s):

Mouse Model ◽

Oral Administration ◽

Inflammatory Responses ◽

Activity Index ◽

Inflammatory Activity ◽

Raw264.7 Cells ◽

Tnf Α ◽

Anti Inflammatory

Aucklandia lappa DC., Terminalia chebula Retz and Zingiber officinale Roscoe have been traditionally used in east Asia to treat chronic diarrhea and abdominal pain. This study aimed to evaluated the anti-inflammatory activity of KM1608, which is composed of three natural herbs in a mouse model of dextran sodium sulfate (DSS)-induced ulcerative colitis. The anti-inflammatory activity and underlying mechanism were assessed in vitro using LPS-treated RAW264.7 cells. The in vivo effect of KM1608 on DSS-induced colitis was examined after oral administration in mice. KM1608 significantly inhibited the inflammatory mediators such as nitric oxide, interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor (TNF)-α in LPS-treated RAW264.7 cells. The inhibitory effect of KM1608 was attributed to the reduction of Akt phosphorylation in the LPS-treated cells. In the mouse model, oral administration of KM1608 significantly improved DSS-induced colitis symptoms, such as disease activity index (DAI), colon length, and colon weight, as well as suppressed the expression of IL-6, TNF-α, and myeloperoxidase (MPO) in the DSS-induced colitis tissues. Taken together, KM1608 improved colitis through the regulation of inflammatory responses, suggesting that KM1608 has potential therapeutic use in the treatment of inflammatory diseases.

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Effect of Benzoylsalicylic Acid on IKK-Beta Kinase and NF-κB Pathway in Murine Macrophage raw 264.7 Cells

10.21203/rs.3.rs-941317/v1 ◽

2021 ◽

Author(s):

Samuel Kamatham ◽

Naresh Babu V. Sepuri ◽

Naresh Kumar

Keyword(s):

Inflammatory Responses ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Dual Inhibitor ◽

Inflammatory Agent ◽

Iκb Kinase ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Abstract The transcription factor NF-κB regulates a large array of genes of immune and inflammatory responses. Deregulated NF-κB signalling is implicated in the pathogenesis and broad spectrum of human inflammatory disorders and malignancies. The mechanism for NF-κB activation is the inducible degradation of IκB, triggered through its site-specific phosphorylation by a multi-subunit IκB kinase (IKK) complex. Aspirin (acetylsalicylic acid) a well-known anti-inflammatory agent that binds to ATP binding pocket of IKKβ and inhibits its kinase activity. However, several side effects of aspirin due to the inactivation of COX-1 limits the therapeutic usage of ASA. Here we have demonstrate the effect of a plant phenolic compound benzoylsalicylic acid (BzSA) isolated first time in plants a potent anti-viral compound inhibits Tobacco mosaic virus (TMV) and enhance the plant defense response (Samuel et all 2016&2017) inhibit the IKKβ mediated NF-κB pathway higher than aspirin. Our In-vitro COX enzymatic assays with BzSA have shown less COX-1 and high COX-2 inhibition as compared to ASA. Western blotting analysis of Raw 264.7 cells that were pre-treated with BzSA down-regulated LPS stimulated pIKK-β, pIκB, NF-κBp65, TNF-α, COX-1, COX-2, 5-LOX, IL-1β, and IL-6 higher than ASA. Therefore, our observations suggested that the potencial therapeutic value of BzSA an upcoming new inhibitor of NF-KB pathway and the dual inhibitor of COX2/5-LOX without effecting the usefull COX-1. Hence useful as an anti-inflammatory agent like ASA.

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Luteolin-3′-O-Phosphate Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Regulating NF-κB/MAPK Cascade Signaling in RAW 264.7 Cells

Molecules ◽

10.3390/molecules26237393 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7393

Author(s):

Jung-Hwan Kim ◽

Tae-Jin Park ◽

Jin-Soo Park ◽

Min-Seon Kim ◽

Won-Jae Chi ◽

...

Keyword(s):

Molecular Mechanisms ◽

Inflammatory Responses ◽

Mitogen Activated Protein Kinase ◽

Inflammatory Activity ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Mitogen Activated Protein ◽

Anti Inflammatory

Luteolin (LT), present in most plants, has potent anti-inflammatory properties both in vitro and in vivo. Furthermore, some of its derivatives, such as luteolin-7-O-glucoside, also exhibit anti-inflammatory activity. However, the molecular mechanisms underlying luteolin-3′-O-phosphate (LTP)-mediated immune regulation are not fully understood. In this paper, we compared the anti-inflammatory properties of LT and LTP and analyzed their molecular mechanisms of action; we obtained LTP via the biorenovation of LT. We investigated the anti-inflammatory activities of LT and LTP in macrophage RAW 264.7 cells. We confirmed from previously reported literature that LT inhibits the production of nitric oxide and prostaglandin E2, as well as the expression of inducible NO synthetase and cyclooxygenase-2. In addition, expressions of inflammatory genes and mediators, such as tumor necrosis factor-α, interleukin-6, and interleukin-1β, were suppressed. LTP showed anti-inflammatory activity similar to LT, but better anti-inflammatory activity in all the experiments, while also inhibiting mitogen-activated protein kinase and nuclear factor-kappa B more effectively than LT. At a concentration of 10 μM, LTP showed differences of 2.1 to 44.5% in the activity compared to LT; it also showed higher anti-inflammatory activity. Our findings suggest that LTP has stronger anti-inflammatory activity than LT.

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Anti-Inflammatory Effect of Ethanol Extract from Grateloupia elliptica Holmes on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells and Mice Ears

Journal of the Korean Society of Food Science and Nutrition ◽

10.3746/jkfn.2015.44.8.1128 ◽

2015 ◽

Vol 44 (8) ◽

pp. 1128-1136 ◽

Cited By ~ 6

Author(s):

Nan-Young Bae ◽

Min-Ji Kim ◽

Koth-Bong-Woo-Ri Kim ◽

Na-Kyung Ahn ◽

Yeon-Uk Choi ◽

...

Keyword(s):

Inflammatory Responses ◽

Ethanol Extract ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Anti Inflammatory ◽

Inflammatory Effect

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Anti-Inflammatory Effects of Novel Standardized Platelet Rich Plasma Releasates on Knee Osteoarthritic Chondrocytes and Cartilage in vitro

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190619111118 ◽

2019 ◽

Vol 20 (11) ◽

pp. 920-933 ◽

Cited By ~ 3

Author(s):

Lucía Gato-Calvo ◽

Tamara Hermida-Gómez ◽

Cristina R. Romero ◽

Elena F. Burguera ◽

Francisco J. Blanco

Keyword(s):

Gene Expression ◽

Ex Vivo ◽

Platelet Rich Plasma ◽

Cartilage Explants ◽

Ex Vivo Model ◽

Chondrocyte Viability ◽

Platelet Concentration ◽

The Absolute ◽

Anti Inflammatory

Background: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. Objective: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. Methods: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/µl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1β (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1β (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/µl or PRP-R with 1.5·105 platelets/µl for 21 days to assess matrix inflammatory degradation. Results: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1β and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. Conclusion: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.

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Red Grape Polyphenol Oral Administration improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200313152648 ◽

2020 ◽

Vol 20 ◽

Author(s):

Thea Magrone ◽

Emilio Jirillo ◽

Manrico Magrone ◽

Matteo Antonio Russo ◽

Paolo Romita ◽

...

Keyword(s):

Contact Dermatitis ◽

Oral Administration ◽

Allergic Contact Dermatitis ◽

Laboratory Data ◽

Anti Oxidant ◽

Anti Inflammatory ◽

Red Grape ◽

Allergic Contact ◽

Drop Outs

Background: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce release of pro-inflammatory cytokines and nitric oxide (NO), while increasing levels of interleukin (IL)-10, an anti-inflammatory cytokine. Objective: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients. Method: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). Other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups seven drop outs were recorded. Result: At T1 in comparison to T0, in treated patients, values of IFN-γ, IL-4, IL-17, PTX3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo-treated patients no modifications of biomarkers were evaluated at T1. Conclusion: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols.

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A New Flavonol From Saussurea involucrata With Anti-Inflammatory Activity

Natural Product Communications ◽

10.1177/1934578x211007638 ◽

2021 ◽

Vol 16 (5) ◽

pp. 1934578X2110076

Author(s):

Sheng Pan ◽

Zi-Guan Zhu

Keyword(s):

Nitric Oxide ◽

Aerial Part ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Spectroscopic Methods ◽

Soluble Extract ◽

Saussurea Involucrata ◽

Tnf Α ◽

Anti Inflammatory

A new flavonol named 6-(2'',3''-epoxy-3''-methylbutyl)-resokaempferol (1), together with five known compounds (2-6) were isolated from the EtOAc-soluble extract of the aerial part of Saussurea involucrata. Their structures were elucidated on the basis of spectroscopic methods. All compounds were evaluated for their anti-inflammatory effects by measuring the production of nitric oxide (NO) and TNF-α in vitro. Among them, compound 1 showed potential inhibitory activity on the production of NO and TNF-α in LPS-induced RAW 264.7 cells with IC50 values of 48.0 ± 1.5 and 41.4 ± 1.7 µM, respectively.

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