Isofraxidin exhibited anti-inflammatory effects in vivo and inhibited TNF-α production in LPS-induced mouse peritoneal macrophages in vitro via the MAPK pathway

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

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In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽

10.3390/biomedicines9060615 ◽

2021 ◽

Vol 9 (6) ◽

pp. 615

Author(s):

Shang-En Huang ◽

Erna Sulistyowati ◽

Yu-Ying Chao ◽

Bin-Nan Wu ◽

Zen-Kong Dai ◽

...

Keyword(s):

Articular Cartilage ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Antioxidant Properties ◽

Serum Levels ◽

Gene Expressions ◽

Tnf Α ◽

Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

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Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

Cellular Physiology and Biochemistry ◽

10.1159/000484192 ◽

2017 ◽

Vol 43 (5) ◽

pp. 2074-2087 ◽

Cited By ~ 19

Author(s):

Liling Yang ◽

Xiangjun Zhou ◽

Weijuan Huang ◽

Qin Fang ◽

Jianlan Hu ◽

...

Keyword(s):

Signalling Pathway ◽

Dependent Manner ◽

Zebrafish Model ◽

Lps Challenge ◽

Cell Counts ◽

Tnf Α ◽

Forsythia Suspensa ◽

Anti Inflammatory

Background/Aims: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF-α expression. Conclusion: This study provides a rationale for the clinical application of PHN as an anti-inflammatory agent.

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Methylprednisolone Protects SAP and Pancreatitis-Associated ALI in Mice by Inhibiting NLRP3 Inflammasome Through NF-κB

10.21203/rs.3.rs-96231/v1 ◽

2020 ◽

Author(s):

Chuan-jiang Liu ◽

Qiang Fu ◽

Wenjing Zhou ◽

Xu Zhang ◽

Rui Chen ◽

...

Keyword(s):

Lung Tissue ◽

Nlrp3 Inflammasome ◽

Antioxidant Properties ◽

Underlying Mechanism ◽

Peritoneal Macrophages ◽

Dependent Manner ◽

Expression Levels ◽

Tnf Α

Abstract Background: Methylprednisolone (MP) is a synthetic corticosteroid with potent anti-inflammatory and antioxidant properties used as therapy for a variety of diseases. The underlying mechanism of MP to reduce acute pancreatitis still needs to be elucidated.Methods: Twenty-four male C57BL/6 mice (6-8 weeks) were used to establish SAP mouse model by administering an intraperitoneal injection of Cae and LPS. Amylase expression levels of serum and PLF were measured with an amylase assay kit. The concentrations of IL-1β and TNF-α in the serum and PLF were detected by ELISA. The level of pancreatic and lung tissue damage and inflammation was assessed by H&E staining and immunofluorescence staining. Western blot and qPCR were used to detect the expression levels of NLRP3, IL-1β and TNF-αin vivo and in vitro.Results: In this study, we found MP, used in the early phase of SAP, decreased the levels of IL-1β and TNF-α in serum and peritoneal lavage fluids (PLF), reduced the level of serum amylase and the expression of MPO in lung tissue, attenuated the pathological injury of the pancreas and lungs in a dose-dependent manner. The expression of NLRP3 and IL-1β in pancreas and lungs was down-regulated significantly depending on the MP concentration. In vitro, MP reduced the levels of IL-1β and TNF-α by down-regulating the expression of NLRP3, IL-1β and p-NF-κB in isolated peritoneal macrophages. Conclusion: MP can attenuate the injury of pancreas and lungs, and the inflammatory response in SAP mice by down-regulating the activation of NF-κB and the NLRP3 inflammasome.

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Protective Effect of Opuntia dillenii Haw Fruit against Lead Acetate-Induced Hepatotoxicity: In Vitro and In Vivo Studies

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6698345 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Reza Shirazinia ◽

Ali Akbar Golabchifar ◽

Vafa Baradaran Rahimi ◽

Abbas Jamshidian ◽

Alireza Samzadeh-Kermani ◽

...

Keyword(s):

Cell Viability ◽

Lead Acetate ◽

Male Rats ◽

Tnf Α ◽

Wide Range ◽

Hepatoprotective Effects ◽

Anti Inflammatory ◽

Opuntia Dillenii

Lead is one of the most common environmental contaminants in the Earth’s crust, which induces a wide range of humans biochemical changes. Previous studies showed that Opuntia dillenii (OD) fruit possesses several antioxidant and anti-inflammatory properties. The present study evaluates OD fruit hydroalcoholic extract (OHAE) hepatoprotective effects against lead acetate- (Pb-) induced toxicity in both animal and cellular models. Male rats were grouped as follows: control, Pb (25 mg/kg/d i.p.), and groups 3 and 4 received OHAE at 100 and 200 mg/kg/d + Pb (25 mg/kg/d i.p.), for ten days of the experiment. Thereafter, we evaluated the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), catalase (CAT) activity and malondialdehyde (MDA) in serum, and liver histopathology. Additionally, the cell study was also done using the HepG2 cell line for measuring the direct effects of the extract on cell viability, oxidative stress MDA, and glutathione (GSH) and inflammation tumor necrosis factor-α (TNF-α) following the Pb-induced cytotoxicity. Pb significantly increased the serum levels of ALT, AST, ALP, and MDA and liver histopathological scores but notably decreased CAT activity compared to the control group ( p < 0.001 for all cases). OHAE (100 and 200 mg/kg) significantly reduced the levels of serum liver enzyme activities and MDA as well as histopathological scores while it significantly increased CAT activity compared to the Pb group ( p < 0.001 –0.05 for all cases). OHAE (20, 40, and 80 μg/ml) concentration dependently and significantly reduced the levels of MDA and TNF-α, while it increased the levels of GSH and cell viability in comparison to the Pb group ( p < 0.001 –0.05 for all cases). These data suggest that OHAE may have hepatoprotective effects against Pb-induced liver toxicity both in vitro and in vivo by its antioxidant and anti-inflammatory activities.

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A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo

Cellular and Molecular Immunology ◽

10.1038/cmi.2009.50 ◽

2009 ◽

Vol 6 (5) ◽

pp. 387-392 ◽

Cited By ~ 27

Author(s):

Yinan Wang ◽

Xueling Cui ◽

Guixiang Tai ◽

Jingyan Ge ◽

Nan Li ◽

...

Keyword(s):

Critical Role ◽

Peritoneal Macrophages ◽

Activin A ◽

Mouse Peritoneal Macrophages

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Phenolic Derivatives from Radix Astragali and their Anti-inflammatory Activities

Natural Product Communications ◽

10.1177/1934578x1400901112 ◽

2014 ◽

Vol 9 (11) ◽

pp. 1934578X1400901

Author(s):

Wei Chen ◽

Ying-Ying Zhang ◽

Zhuo Wang ◽

Xiao-Hua Luo ◽

Wan-Chun Sun ◽

...

Keyword(s):

Spectroscopic Analysis ◽

Peritoneal Macrophages ◽

Inos Mrna ◽

Radix Astragali ◽

Inhibitory Effects ◽

Tnf Α ◽

Cox 2 ◽

Phenolic Derivatives ◽

Anti Inflammatory ◽

Mouse Peritoneal Macrophages

Two new (3, 4) and two known phenolic derivatives (1, 2) were isolated from Radix Astragali. The structures of 1–4 were elucidated by extensive spectroscopic analysis. The anti-inflammatory activities of the isolated compounds were evaluated in LPS-induced mouse peritoneal macrophages. All four compounds exhibited potent inhibitory effects on TNF-α production and TNF-α, COX-2, IL-1β, IL-6 and iNOS mRNA expression at 50 μM.

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Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models

Nutrients ◽

10.3390/nu12072032 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2032

Author(s):

Vishnu Raj ◽

Balaji Venkataraman ◽

Saeeda Almarzooqi ◽

Sanjana Chandran ◽

Shreesh K. Ojha ◽

...

Keyword(s):

Nuclear Translocation ◽

In Vitro Models ◽

Mrna Levels ◽

Colonic Inflammation ◽

Tnf Α ◽

Cox 2 ◽

Anti Inflammatory ◽

Ht 29

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-α-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 µM and 50 µM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1β, IL-6, and TNF-α) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-α-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.

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