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

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.

scholarly journals Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2529
Author(s):  
Haeyeop Kim ◽  
Woo Seok Yang ◽  
Khin Myo Htwe ◽  
Mi-Nam Lee ◽  
Young-Dong Kim ◽  
...  
Keyword(s):  
Ethanol Extract ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Related Proteins ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

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.

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

Biomedicines ◽  
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.

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

2017 ◽  
Vol 43 (5) ◽  
pp. 2074-2087 ◽  
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.

scholarly journals Mitoprotective Effects of Centella asiatica (L.) Urb.: Anti-Inflammatory and Neuroprotective Opportunities in Neurodegenerative Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Jia Hui Wong ◽  
Anna M. Barron ◽  
Jafri Malin Abdullah
Keyword(s):  
Neurodegenerative Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Antioxidant Properties ◽  
Centella Asiatica ◽  
Asiatic Acid ◽  
Wide Range ◽  
Anti Inflammatory

Natural products remain a crucial source of drug discovery for accessible and affordable solutions for healthy aging. Centella asiatica (L.) Urb. (CA) is an important medicinal plant with a wide range of ethnomedicinal uses. Past in vivo and in vitro studies have shown that the plant extract and its key components, such as asiatic acid, asiaticoside, madecassic acid and madecassoside, exhibit a range of anti-inflammatory, neuroprotective, and cognitive benefits mechanistically linked to mitoprotective and antioxidant properties of the plant. Mitochondrial dysfunction and oxidative stress are key drivers of aging and neurodegenerative disease, including Alzheimer’s disease and Parkinson’s disease. Here we appraise the growing body of evidence that the mitoprotective and antioxidative effects of CA may potentially be harnessed for the treatment of brain aging and neurodegenerative disease.

scholarly journals Libidibia ferreaFruit Crude Extract and Fractions Show Anti-Inflammatory, Antioxidant, and Antinociceptive EffectIn Vivoand Increase Cell ViabilityIn Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Tamires Rocha Falcão ◽  
Aurigena Antunes de Araújo ◽  
Luiz Alberto Lira Soares ◽  
Iuri Brilhante de Farias ◽  
Wliana Alves Viturino da Silva ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Cell Viability ◽  
Gallic Acid ◽  
Cell Line ◽  
Crude Extract ◽  
Leukocyte Migration ◽  
Total Glutathione ◽  
Anti Inflammatory

Background.Libidibia ferrea(L. ferrea)is found throughout the northeastern region of Brazil, where it has been used in folk medicine with beneficial effects on many inflammatory disorders.Purpose. This study investigated the phytochemical composition of the crude extract and fractions ofL. ferreafruit and evaluated its anti-inflammatory and antinociceptive activitiesin vivoand effect on cell viabilityin vitro.Methods. Characterization of polyphenols present in crude extract (CE), hydroalcoholic fractions of 20-80% ethanol (CE20, CE40, CE60, and CE80), aqueous fraction (AqF), and ethyl acetate (EAF) fractions ofL. ferreafruit was performed by chromatographic analysis.Anti-inflammatory activity was evaluated by using a carrageenan-induced peritonitis model submitted to a leukocyte migration assay and myeloperoxidase activity (MPO) analysis. Total glutathione and malondialdehyde (MDA) levels were assessed to evaluate the oxidative stress level. Antinociceptive activity was evaluated by acetic acid-induced abdominal writhing and hot plate test.In vitrocell viability was determined by using MTT assay in a mouse embryonic fibroblast cell line (3T3 cells).Results. Chromatography revealed the presence of ellagic acid content in EAF (3.06), CE (2.96), and CE40 (2.89). Gallic acid was found in EAF (12.03), CE 20 (4.43), and CE (3.99).L. ferreacrude extract and all fractions significantly reduced leukocyte migration and MPO activity (p<0.001).L. ferreaantioxidant effect was observed through high levels of total glutathione and reduction of MDA levels (p<0.001). Acetic acid-induced nociception was significantly inhibited after administration ofL. ferreacrude extract and all fractions (p<0.001). Crude extract and all fractions significantly increased the viability of the 3T3 cell line (p<0.05).Conclusions. The appropriate extraction procedure preserves the chemical components ofL. ferreafruit, such as gallic acid and ellargic acid. Crude extract and fractions ofL. ferreafruit exhibited anti-inflammatory, antioxidant, antinociceptive activitiesin vivoand enhanced cell viabilityin vitro.

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

Nutrients ◽  
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.

scholarly journals Identification of a Kavain Analog with Efficient Anti-inflammatory Effects

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Olivier Huck ◽  
Xiaxian Han ◽  
Hannah Mulhall ◽  
Iryna Gumenchuk ◽  
Bin Cai ◽  
...  
Keyword(s):  
Joint Destruction ◽  
Cell Types ◽  
Interferon Γ ◽  
Piper Methysticum ◽  
Tnf Α ◽  
Osteoclast Activation ◽  
Anti Inflammatory ◽  
Soft Tissue Inflammation

Abstract Kavain, a compound derived from Piper methysticum, has demonstrated anti-inflammatory properties. To optimize its drug properties, identification and development of new kavain-derived compounds was undertaken. A focused library of analogs was synthesized and their effects on Porphyromonas gingivalis (P. gingivalis) elicited inflammation were evaluated in vitro and in vivo. The library contained cyclohexenones (5,5-dimethyl substituted cyclohexenones) substituted with a benzoate derivative at the 3-position of the cyclohexanone. The most promising analog identifed was a methylated derivative of kavain, Kava-205Me (5,5-dimethyl-3-oxocyclohex-1-en-1-yl 4-methylbenzoate.) In an in vitro assay of anti-inflammatory effects, murine macrophages (BMM) and THP-1 cells were infected with P. gingivalis (MOI = 20:1) and a panel of cytokines were measured. Both cell types treated with Kava-205Me (10 to 200 μg/ml) showed significantly and dose-dependently reduced TNF-α secretion induced by P. gingivalis. In BMM, Kava-205Me also reduced secretion of other cytokines involved in the early phase of inflammation, including IL-12, eotaxin, RANTES, IL-10 and interferon-γ (p < 0.05). In vivo, in an acute model of P. gingivalis-induced calvarial destruction, administration of Kava-205Me significantly improved the rate of healing associated with reduced soft tissue inflammation and osteoclast activation. In an infective arthritis murine model induced by injection of collagen-antibody (ArthriomAb) + P. gingivalis, administration of Kava-205Me was able to reduce efficiently paw swelling and joint destruction. These results highlight the strong anti-inflammatory properties of Kava-205Me and strengthen the interest of testing such compounds in the management of P. gingivalis elicited inflammation, especially in the management of periodontitis.

scholarly journals A Novel Lactic Acid Bacteria Mixture: Macrophage-Targeted Prophylactic Intervention in Colorectal Cancer Management

2020 ◽  
Vol 8 (3) ◽  
pp. 387
Author(s):  
Petra Hradicka ◽  
Jane Beal ◽  
Monika Kassayova ◽  
Andrew Foey ◽  
Vlasta Demeckova
Keyword(s):  
Colorectal Cancer ◽  
Male Rats ◽  
Cancer Management ◽  
Immune Parameters ◽  
Chemically Induced ◽  
Tnf Α ◽  
Vitro Model ◽  
Macrophage Subsets

Colorectal cancer (CRC) is one of the most common forms of cancer. Its onset from chronic inflammation is widely accepted. Moreover, dysbiosis plays an undeniable role, thus the use of probiotics in CRC has been suggested. They exhibit both anti- and pro-inflammatory properties and restore balance in the microbiota. The aim of this study was to investigate the immunomodulatory properties of six lactobacilli with probiotic features in an in vitro model of macrophage-like cells and to test these pooled probiotics for their anti-tumour properties in a chemically induced CRC model using Wistar male rats. Upon co-culture of M1- and M2-like macrophages with lactobacilli, cytokine release (TNF-α, IL-1β, IL-18, IL-23) and phagocytic activity using fluorescent-labelled bacteria were tested. The effects of orally administered probiotics on basic cancer and immune parameters and cytokine concentration (TNF-α, IL-1β, IL-18) in colon tumours were studied. Tested lactobacilli exhibited both pro- and anti-inflammatory properties in in vitro conditions. In vivo study showed that the administration of probiotics was able to decrease multiplicity, volume and total tumour numbers, restore colon length (p < 0.05) and increase IL-18 production (p < 0.05) in tumour tissue. These data indicate both an immunomodulatory effect of probiotics on distinct macrophage subsets and a protective effect against chemically-induced CRC.

A novel fluorinated stilbene exerts hepatoprotective properties in CCl4-induced acute liver damage

2011 ◽  
Vol 89 (10) ◽  
pp. 759-766 ◽  
Author(s):  
Horacio Rivera ◽  
Martha S. Morales-Ríos ◽  
Wendy Bautista ◽  
Mineko Shibayama ◽  
Víctor Tsutsumi ◽  
...  
Keyword(s):  
Liver Damage ◽  
Inflammatory Responses ◽  
Acute Liver Damage ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Glutamyl Transpeptidase

There has been a recently increase in the development of novel stilbene-based compounds with in vitro anti-inflamatory properties. For this study, we synthesized and evaluated the anti-inflammatory properties of 2 fluorinated stilbenes on carbon tetrachloride (CCl4)-induced acute liver damage. To achieve this, CCl4 (4 g·kg–1, per os) was administered to male Wistar rats, followed by either 2-fluoro-4′-methoxystilbene (FME) or 2,3-difluoro-4′-methoxystilbene (DFME) (10 mg·kg–1, per os). We found that although both of the latter compounds prevented cholestatic damage (γ-glutamyl transpeptidase activity), only DFME showed partial but consistent results in the prevention of necrosis, as assessed by both alanine aminotransferase activity and histological analysis. Since inflammatory responses are mediated by cytokines, mainly tumour necrosis factor α (TNF-α), we used the Western blot technique to determine the action of FME and DFME on the expression level of this cytokine. The observed increase in the level of TNF-α caused by CCl4 administration was only prevented by treatment with DFME, in agreement with our biochemical findings. This result was confirmed by measuring interleukin-6 (IL-6) levels, since the expression of this protein depends on the level of TNF-α. In this case, DFME completely blocked the CCl4-induced increase of IL-6. Our results suggest that DFME possesses greater anti-inflammatory properties in vivo than FME. DFME constitutes a possible therapeutic agent for liver disease and could serve as a template for structure optimization.

scholarly journals Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Zengjie Zheng ◽  
Hailong Jiang ◽  
Yan Huang ◽  
Jie Wang ◽  
Lei Qiu ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Activity Index ◽  
Tumor Necrosis Factor Receptor ◽  
Disease Activity Index ◽  
Acute Colitis ◽  
Surface Plasmon Resonance Analysis ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Snake has been used for centuries as a traditional Chinese medicine, especially for therapeutic treatment for inflammatory diseases; however, its mechanisms of action and active constituents remain controversial. In our study, a tumor necrosis factor receptor 1 (TNFR1) selective binding peptide, Hydrostatin-SN1 (H-SN1), which was screened from a Hydrophis cyanocinctus venom gland T7 phage display library, was shown to exhibit significant anti-inflammatory activity in vitro and in vivo. As a TNFR1 antagonist, it reduced cytotoxicity mediated by TNF-α in L929 fibroblasts and effectively inhibited the combination between TNF-α with TNFR1 in surface plasmon resonance analysis. H-SN1 was also shown to suppress TNFR1–associated signaling pathways as it minimized TNF-α-induced NF-кB and MAPK activation in HEK293 embryonic kidney and HT29 adenocarcinoma cell lines. We next determined the effect of H-SN1 in vivo using a murine model of acute colitis induced by dextran sodium sulfate, demonstrating that H-SN1 lowered the clinical parameters of acute colitis including the disease activity index and histologic scores. H-SN1 also inhibited TNF/TNFR1 downstream targets at both mRNA and protein levels. These results indicate that H-SN1 might represent a suitable candidate for use in the treatment of TNF-α-associated inflammatory diseases such as inflammatory bowel diseases.

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