scholarly journals A Novel Role of Dapagliflozin in Mitigation of Acetic Acid- Induced Ulcerative Colitis by Modulation of Monocyte  Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18)

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 40
Author(s):  
Mohamed Kh. ElMahdy ◽  
Samar A. Antar ◽  
Ehab Kotb Elmahallawy ◽  
Walied Abdo ◽  
Hayfa Hussin Ali Hijazy ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Body Weight ◽  
Acetic Acid ◽  
Nuclear Factor Kappa B ◽  
Caspase 3 ◽  
Control Group ◽  
Nuclear Factor ◽  
Interleukin 18 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

Colon illnesses, particularly ulcerative colitis, are considered a major cause of death in both men and women around the world. The present study investigated the underlying molecular mechanisms for the potential anti-inflammatory effect of Dapagliflozin (DAPA) against ulcerative colitis (UC) induced by intracolonic instillation of 3% v/v acetic acid (AA). DAPA was administered to rats (1 mg/kg, orally) for two weeks during the treatment regimen. Interestingly, compared to the normal group, a marked increase in the index of colon/body weight, colon weight/colon length ratio, serum lactate dehydrogenase (LDH), and C-reactive protein (CRP), besides decrease in the serum total antioxidant capacity (TAC), were reported in the AA control group (p ˂ 0.05). Elevation in colon monocyte chemoattractant protein (MCP1), Interleukin 18 (IL-18), and inflammasome contents were also reported in the AA control group in comparison with the normal group. In addition, colon-specimen immunohistochemical staining revealed increased expression of nuclear factor-kappa B (NF-κB) and Caspase-3 with histopathological changes. Moreover, DAPA significantly (p ˂ 0.05) reduced the colon/body weight index, colon weight/colon length ratio, clinical evaluation, and macroscopic scoring of UC, and preserved the histopathological architecture of tissues. The inflammatory biomarkers, including colon MCP1, IL-18, inflammasome, Caspase-3, and NF-κB, were suppressed following DAPA treatment and oxidants/antioxidants hemostasis was also restored. Collectively, the present data demonstrate that DAPA represents an attractive approach to ameliorating ulcerative colitis through inhibiting MCP1/NF-κB/IL-18 pathways, thus preserving colon function. Antioxidant, anti-inflammatory, and anti-apoptotic properties of DAPA are implicated in its observed therapeutic benefits.

scholarly journals Protective effects of curcumin against methotrexate-induced testicular damage in rats by suppression of the p38-MAPK and nuclear factor-kappa B pathways

2021 ◽  
Author(s):  
Leyla Kilinc ◽  
Yesim Hulya Uz
Keyword(s):  
Body Weight ◽  
P38 Mapk ◽  
Seminiferous Tubule ◽  
Nuclear Factor Kappa B ◽  
Seminiferous Tubules ◽  
Control Group ◽  
Nuclear Factor ◽  
Testicular Damage ◽  
Space Width ◽  
Tubule Diameter

Objective: Methotrexate (MTX), is a commonly used chemotherapeutic agent. This study aimed to investigate the possibility that curcumin (CMN) protects against MTX-induced testicular damage by affecting the phospho (p)-p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kB) signaling pathways. Methods: Male Wistar albino rats were subdivided into three groups. The control group was given an intragastric (ig) administration of dimethyl sulfoxide (DMSO) daily for 14 days, the MTX group was given a single intraperitoneal (ip) dose of MTX (20 mg/kg) on the 11th day, and the MTX+CMN group was given ig CMN (100 mg/kg/day, dissolved in DMSO) for 14 days and a single ip dose of MTX (20 mg/kg) on the 11th day. Results: The animal weights, the seminiferous tubule diameter, and germinal epithelium height significantly decreased in the MTX group compared to the control group. The testes weight and the ratio of the testes to body weight did not change, whereas the number of seminiferous tubules and the interstitial space width increased significantly in the MTX group. The number of phospho-p38 (p-p38) MAPK immunopositive cells and the immunoreactivity of NF-kB also increased in the MTX group compared to the control group. Conclusion: CMN prevented the MTX-induced decreases in the body weight, seminiferous tubule diameter, and the germinal epithelium height, while significantly reducing the number of histologically damaged seminiferous tubules and the interstitial space width changes due to MTX. CMN also reduced the number of p-p38 MAPK immunopositive cells and the NF-kB immunoreactivity.

scholarly journals Supplement of bamboo extract lowers serum monocyte chemoattractant protein-1 concentration in mice fed a diet containing a high level of saturated fat

2011 ◽  
Vol 106 (12) ◽  
pp. 1810-1813 ◽  
Author(s):  
Jason K. Higa ◽  
Wanyu Liu ◽  
Marla J. Berry ◽  
Jun Panee
Keyword(s):  
Body Weight ◽  
Visceral Fat ◽  
High Fat Diet ◽  
Water Extract ◽  
Control Group ◽  
Standard Diet ◽  
High Fat ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

Monocyte chemoattractant protein-1 (MCP-1) is an inflammatory chemokine up-regulated in obese subjects, contributing to the development of type 2 diabetes. The present study investigated the inhibitory effect of an ethanol–water extract from bamboo (BEX,Phyllostachys edulis) on the blood concentration of MCP-1. C57BL/6J mice were fed a standard diet or a high-fat diet with or without the BEX supplement (11 g dry mass/17 000 kJ) for 6 months. A total of ten mice were used in each group. Body weight and food consumption were measured weekly. After euthanisation, the weight of visceral fat and circulating MCP-1 concentration were measured. In comparison with the standard control group, the high-fat control group had increased body weight, abdominal fat storage and serum MCP-1 concentration by 60 % (P < 0·001), 266 % (P < 0·001) and 180 % (P < 0·01), respectively. In comparison with the high-fat control group, the high-fat BEX group showed a 3 % decrease in body weight (P < 0·01), 24 % decrease in mesenteric fat depot (P < 0·01) and 49 % decrease in serum MCP-1 concentration (P < 0·05). The present study suggests that the BEX supplement in the high-fat diet ameliorates elevated MCP-1 concentrations in the blood, and whether this is related to modulated endocrine properties of the visceral fat is to be studied.

scholarly journals Effects of Onchung-eum, an Herbal Prescription, on 5-Fluorouracil–Induced Oral Mucositis

2018 ◽  
Vol 17 (4) ◽  
pp. 1285-1296
Author(s):  
Jae-Woo Park ◽  
Jayoung Oh ◽  
Seok-Jae Ko ◽  
Mun Seog Chang ◽  
Jinsung Kim
Keyword(s):  
Inflammatory Cytokines ◽  
Oral Mucositis ◽  
Caspase 3 ◽  
Skin Diseases ◽  
Nuclear Factor Κb ◽  
Control Group ◽  
Nuclear Factor ◽  
Cheek Pouches ◽  
Herbal Prescription ◽  
Pro Inflammatory Cytokines

In most cancer patients, chemotherapy-induced oral mucositis (OM) is a frequent side effect, leading to low quality of life and delay in therapy. The aim of this study was to evaluate the effects of Onchung-eum, a well-known herbal prescription in traditional medicine comprising 8 herbs that has long been used for skin diseases, on 5-fluorouracil (5-FU)–induced OM in human pharyngeal cells and golden Syrian hamsters. DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and reactive oxygen species production were measured in vitro. The effects of Onchung-eum on OM of hamster cheek pouches induced by 5-FU were evaluated histologically and using TUNEL assay. In addition, the expression of nuclear factor-κB, caspase-3, and pro-inflammatory cytokines were measured by immunoblotting and immunohistochemistry. Significantly increased cell viability was observed in the Onchung-eum–treated groups compared with the 5-FU–treated control group. In 500 and 1000 mg/kg Onchung-eum–treated groups, the damaged epithelial layers in the cheek pouches of hamsters were significantly recovered. Moreover, at all concentrations, cell death in the cheek pouches of hamsters in the Onchung-eum–treated groups significantly decreased. The expression of pro-inflammatory cytokines, nuclear factor-κB, and caspase-3 also significantly decreased in Onchung-eum–treated groups at 500 and 1000 mg/kg. In conclusion, this study revealed that Onchung-eum can be used to treat chemotherapy-induced OM. However, further studies are required to understand the underlying mechanisms.

scholarly journals Isolation and characterization of cytotoxic and anti-inflammatory constituents from Scoparia dulcis L

2020 ◽  
Vol 44 (7-8) ◽  
pp. 381-387
Author(s):  
Mohammad Nur-e-Alam ◽  
Sarfaraz Ahmed ◽  
Muhammad Yousaf ◽  
Shabana I Khan ◽  
Ramzi A Mothana ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acetic Acid ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Scoparia Dulcis ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Scoparia dulcis L. is one of the edible widely distributed Scropholariaceae species in Asia, Africa and America. It is used in the treatment of respiratory and inflammatory diseases, diabetes, hypertension, cancer, hepatitis and tuberculosis. A phytochemical investigation on S. dulcis led to the isolation of two new acyclic diterpenes Acetic acid 6-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-4,8-dimethyl-undeca-4,8-dienyl ester (1) and Acetic acid 8-hydroxy-2-(6-hydroxy-4-methyl-hex-4-enylidene)-6,10-dimethyl-undeca-5,9-dienyl ester (2) in addition to eight known compounds (3–10), namely scopadulciol (3), 4- epi-scopadulcic acid B (4), dulcidiol (5), scopadulcic acid B (6), hymenoxin (7), glutinol (8), eupatilin (9) and 5-demethylnobiletin (10). The structures elucidation was performed using spectroscopic means, including 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrum spectrometric analysis. Furthermore, the isolated compounds were investigated for their anti-inflammatory activity through the determination of inhibition of nuclear factor-kappa B activity in human chondrosarcoma (SW1353) cells, the inhibition of inducible nitric oxide synthase mouse macrophages (RAW264.7) and the decrease in cellular oxidative stress in HepG2 cells. Moreover, the cytotoxic activity was investigated against four cancer and two kidney cell lines. Among the isolates, 3, 5 and 10 showed anti-inflammatory activity in terms of inhibiting nuclear factor-kappa B and inducible nitric oxide synthase. Compounds 3–5 were the most cytotoxic towards cancer cell lines (IC50: 3.8 µM to 42.3 µM) followed by 10 (IC50: 30.9- > 64.4 µM). Cytotoxicity of compounds 3–5 was comparable to the activity of doxorubicin.

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