Essential Oils Downregulate Pro-Inflammatory Cytokines and Nitric Oxide-mediated Oxidative Stress in Alloxan-induced Diabetogenic Rats.

Author(s):  
Muhammad Ejaz ul Haq ◽  
Muhammad Sajid Hamid Akash ◽  
Kanwal Rehman ◽  
Malik Hassan Mahmood

Introduction: Hyperglycemia is associated with elevated level of reactive nitrogen species (RNS) that leads to nitrosative stress and exacerbates progression of diabetic complications. Method: Present study was aimed to evaluate therapeutic effects of essential oils (EOs) on increased serum level of nitric oxide (NO) in diabetogenic rats. Diabetogenic rats were treated with EOs separately and/or in combination at the dose of 100 mg/kg, orally for one month. Blood sampling was done at 1st, 15th and 30th day of treatment period to investigate the effect of treatment on biomarkers of diabetic complications. Results: In diabetogenic rats, serum levels of NO, malondialdehyde (MDA) and pro-inflammatory cytokines were significantly increased when compared with that of control group. Whereas, diabetogenic rats treated with EOs decreased serum levels of NO, MDA and pro-inflammatory cytokines up to significant extent when compared with that diabetogenic rats treated with standard antidiabetic drug. Moreover, EOs also increased insulin sensitivity in peripheral tissues and insulin secretion from β-cells of pancreatic islets more efficiently when compared with that of diabetogenic rats. Additionally, it was also found that EOs improved lipid profile and normal functions of kidney and liver as compared to that of diabetogenic rats. Conclusion: Findings of this study indicate that EOs may reduce pro-inflammatory cytokine level by modulating the expression of NO. EOs may also ameliorate the nitrosative stress and maintain glucose homeostasis that are major culprits of diabetic complications.

2018 ◽  
Vol 52 (10) ◽  
pp. 924-948 ◽  
Author(s):  
Gerwyn Morris ◽  
Brisa S Fernandes ◽  
Basant K Puri ◽  
Adam J Walker ◽  
Andre F Carvalho ◽  
...  

Background: The blood–brain barrier acts as a highly regulated interface; its dysfunction may exacerbate, and perhaps initiate, neurological and neuropsychiatric disorders. Methods: In this narrative review, focussing on redox, inflammatory and mitochondrial pathways and their effects on the blood–brain barrier, a model is proposed detailing mechanisms which might explain how increases in blood–brain barrier permeability occur and can be maintained with increasing inflammatory and oxidative and nitrosative stress being the initial drivers. Results: Peripheral inflammation, which is causatively implicated in the pathogenesis of major psychiatric disorders, is associated with elevated peripheral pro-inflammatory cytokines, which in turn cause increased blood–brain barrier permeability. Reactive oxygen species, such as superoxide radicals and hydrogen peroxide, and reactive nitrogen species, such as nitric oxide and peroxynitrite, play essential roles in normal brain capillary endothelial cell functioning; however, chronically elevated oxidative and nitrosative stress can lead to mitochondrial dysfunction and damage to the blood–brain barrier. Activated microglia, redox control of which is mediated by nitric oxide synthases and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, secrete neurotoxic molecules such as reactive oxygen species, nitric oxide, prostaglandin, cyclooxygenase-2, quinolinic acid, several chemokines (including monocyte chemoattractant protein-1 [MCP-1], C-X-C motif chemokine ligand 1 [CXCL-1] and macrophage inflammatory protein 1α [MIP-1α]) and the pro-inflammatory cytokines interleukin-6, tumour necrosis factor-α and interleukin-1β, which can exert a detrimental effect on blood–brain barrier integrity and function. Similarly, reactive astrocytes produce neurotoxic molecules such as prostaglandin E2 and pro-inflammatory cytokines, which can cause a ‘leaky brain’. Conclusion: Chronic inflammatory and oxidative and nitrosative stress is associated with the development of a ‘leaky gut’. The following evidence-based approaches, which address the leaky gut and blood–brain barrier dysfunction, are suggested as potential therapeutic interventions for neurological and neuropsychiatric disorders: melatonin, statins, probiotics containing Bifidobacteria and Lactobacilli, N-acetylcysteine, and prebiotics containing fructo-oligosaccharides and galacto-oligosaccharides.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Soumendra Darbar ◽  
Srimoyee Saha ◽  
Kausikisankar Pramanik ◽  
Atiskumar Chattopadhyay

Abstract Background Liver complication arises commonly due to high alcohol consumption rate. Majority of the people residing in both developed and under developed countries consuming alcohol face various liver complications such as liver fibrosis, fatty liver, liver cirrhosis and even hepatocellular carcinoma. Invention of safe and symptomatic medication to overcome this situation is a new challenge worldwide. The main objective of the study is to deliver a safe and symptomatic medication to reduce the ethanol induced liver dysfunction. Methods In this study we have developed a multi herbal formulation (AKSS-16-LIV01) which minimised liver damage against various toxicants. Swiss albino mice were divided into seven groups where ethanol induced damage was observed for weeks followed by sanative response observation by our herbal formulation. The groups are normal control group, ethanol treated group (50% v/v), AKSS16-LIV01 low dose (75 mg/kg/day) pre-treated group, AKSS16-LIV01 middle dose (150 mg/kg/day) pre-treated group, AKSS16-LIV01 high dose (300 mg/kg/day) pre-treated group, Sylimarin pre-treated group (100 mg/kg/day) and only AKSS16-LIV01 (300 mg/kg/day) treated group. Results The results potrayed significant elevation of various biochemical parameters, lipid profile parameters, lipid peroxidation, nitric oxide (NO) concentration, nitric oxide synthase level and pro inflammatory cytokines level i.e. tumor necrosis factor (TNF-α) and transforming growth factor (TGF-β1) in the ethanol induced mice. On the other hand serum total protein, total albumin, albumin globulin ratio and level of tissue antioxidant enzymes activity (SOD, CAT, GSH and GPx) were significantly reduced by ethanol. Dose depended therapeutic application of the formulation (AKSS16-LIV01) significantly suppressed all the relevant above parameters and protected the liver from ethanol induced fibrogenesis. Apart from this gross morphology of the liver, H&E liver histology and massontrichrome&serius red examination of the liver section strongly supported the hepatoprotive effect of the formulation as compared with standard drug Sylimarin. Result of the study implies that developed multi herbal formulation (AKSS16-LIV01) at a dose of 300 mg/kg/day gave the best optimum response to reduce the ethanol intoxication. Conclusion Result clearly depict that AKSS16-LIV01 may be a safe and nontoxic medication which protect the liver against ethanol induced oxidative injury and maintained pro inflammatory cytokines level in the future. Graphical Abstract


2021 ◽  
Vol 23 (4) ◽  
pp. 536-540
Author(s):  
O. M. Bilyi ◽  
N. A. Mitriaieva ◽  
M. V. Krasnoselskyi ◽  
L. V. Hrebinyk

Secondary edematous breast cancer (SEBC), T4b, has a poor prognosis. The aim of this study is to examine the balance in serum levels of pro-inflammatory (TNFά, IL-8) and anti-inflammatory (IL-4) cytokines in patients with SEBC before special treatment. Materials and methods. A total of 87 patients with breast cancer (BC) were examined before treatment: 42 patients with SEBC in T4bN0-3M0 stage and 45 BC patients in T3-4N1-3M0 stage without edema. The control group consisted of 15 patients with fibroadenomas. The serum levels of cytokines (IL-4, IL-8, TNFά) in the patients was determined using the enzyme-linked immunosorbent assay. Results. In the SEBC patients as compared to the patients without cancer, the serum pro-inflammatory cytokine (IL-8, TNFά) levels were significantly increased and the anti-inflammatory cytokine (IL-4) level was slightly increased in 22 %. In BC without edema, an imbalance was noted in favor of pro-inflammatory cytokines, but in SEBC it was more pronounced (31.6 versus 12.4 and 5.6 versus 3.2, respectively). Conclusions. In the majority of SEBC patients, there is an imbalance in the cytokine profile in favor of the pro-inflammatory cytokines (IL-8, TNFά). SEBC patients with elevated levels of both pro- and anti-inflammatory cytokines before treatment are the highest risk group of tumor progression and metastasis. Inhibition of the IL-8 effects or related CXC chemokines, TNFά, and others may have important consequences for the systemic treatment of SEBC.


2016 ◽  
Vol 10 (10) ◽  
pp. 1093-1098 ◽  
Author(s):  
Abdulkarim Alhetheel ◽  
Ahmed Albarrag ◽  
Zahid Shakoor ◽  
Khalid Alswat ◽  
Ayman Abdo ◽  
...  

Introduction: A number of cytokines have been implicated in hepatitis C virus (HCV)-related liver disease. This study aimed to assess the serum levels of pro-inflammatory cytokines in patients with HCV infection before (naïve) and after successful treatment (sustained responders) with Pegylated interferon and ribavirin. Methodology: The present study included 19 naïve HCV patients and 8 sustained responders. Additionally, 20 healthy individuals were included as a control group. The serum levels of the pro-inflammatory cytokines interleukin-8 (IL-8), IL-6, IL-10, IL-1β, and IL-12p70 were measured using flow cytometry. Results: The serum IL-8 levels were significantly higher in the naïve group (21.5±10.7 pg/mL; p = 0.02) than in the control group (14.1±1.7 pg/mL) and the sustained responder group (10.4±6.2 pg/mL; p = 0.002). The serum IL-6 levels were significantly higher in the naïve group (7.3±2.06 pg/mL; p = 0.02) than in the control group (5.9±1.01 pg/mL) whereas IL-6 in sustained responder group (6.4±1.5 pg/mL) was no different than naïve HCV patients or the controls. The serum IL-10 levels were significantly higher in the naïve group (4.42±0.64 pg/mL) than in the control group (3.6±0.34 pg/mL; p =0.0002) and not the sustained responder group (4.1±0.86 pg/mL). Moreover, the serum IL-12p70 levels were higher in the sustained responder group (3.43±0.84 pg/mL; p =0.05) than in the control group (2.76±0.83 pg/mL). There were no differences in the serum IL-1β levels among the groups. Conclusion: Successful anti-viral therapy against HCV was associated with significant reductions in the serum IL-8 levels and skewing of the pretreatment Th2 dominant immune response to the Th1 response.


Biomolecules ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 261 ◽  
Author(s):  
Gadah Albasher ◽  
Rafa Almeer ◽  
Fatimah O. Al-Otibi ◽  
Noorah Al-Kubaisi ◽  
Ayman M. Mahmoud

Exposure to organophosphorus insecticides causes several health problems to animals and humans. Red beetroot (RBR) is rich in antioxidant ingredients and possesses a promising hepatoprotective activity. This study evaluated the potential of RBR extract to prevent chlorpyrifos (CPF)-induced liver injury, with an emphasis on oxidative stress, inflammation and apoptosis. Rats received 10 mg/kg CPF and were treated with 300 mg/kg RBR extract for 28 days. CPF caused liver injury evidenced by elevated serum levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and bilirubin, along with several histological alterations. Hepatic lipid peroxidation (LPO) and nitric oxide (NO) levels, as well as inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines were increased in CPF-intoxicated rats. RBR prevented CPF-induced histological alterations, and ameliorated liver function, LPO, NO, iNOS and pro-inflammatory cytokines. RBR boosted glutathione and antioxidant enzymes, and increased Nrf2 expression. In addition, RBR diminished Bax and caspase-3, and increased Bcl-2 expression. In conclusion, RBR prevented CPF-induced liver injury via attenuation of oxidative stress, inflammation and apoptosis. RBR enhanced antioxidant defenses, suggesting that it could be used as a potential therapeutic intervention to minimize CPF hepatotoxicity.


Author(s):  
Bhagirath Ramawat ◽  
Alvee Saluja ◽  
Jayashree Bhatacharjee ◽  
Anshuman Srivastava ◽  
Rajinder K. Dhamija

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samira Ahmadvand Koohsari ◽  
Abdorrahim Absalan ◽  
Davood Azadi

AbstractThe therapeutic effects of mesenchymal stem cells-extracellular vesicles have been proved in many inflammatory animal models. In the current study, we aimed to investigate the effect of extracellular vesicles (EVs) derived from human umbilical cord-MSC (hUCSC-EV) on the clinical score and inflammatory/anti-inflammatory cytokines on the EAE mouse model. After induction of EAE in C57Bl/6 mice, they were treated intravenously with hUCSC-EV or vehicle. The clinical score and body weight of all mice was registered every day. On day 30, mice were sacrificed and splenocytes were isolated for cytokine assay by ELISA. Cytokine expression of pro-/anti-inflammatory cytokine by real-time PCR, leukocyte infiltration by hematoxylin and eosin (H&E) staining, and the percent of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) positive cells by immunohistochemistry were assessed in the spinal cord. Our results showed that hUCSC-EV-treated mice have lower maximum mean clinical score (MMCS), pro-inflammatory cytokines, and inflammatory score in comparison to the control mice. We also showed that hUCSC-EV administration significantly improved body weight and increased the anti-inflammatory cytokines and the frequency of Treg cells in the spleen. There was no significant difference in the percent of GFAP and MBP positive cells in the spinal cord of experimental groups. Finally, we suggest that intravenous administration of hUCSC-EV alleviate induce-EAE by reducing the pro-inflammatory cytokines, such as IL-17a, TNF-α, and IFN-γ, and increasing the anti-inflammatory cytokines, IL-4 and IL-10, and also decrease the leukocyte infiltration in a model of MS. It seems that EVs from hUC-MSCs have the same therapeutic effects similar to EVs from other sources of MSCs, such as adipose or bone marrow MSCs.


2018 ◽  
Vol 17 (4) ◽  
pp. 1285-1296
Author(s):  
Jae-Woo Park ◽  
Jayoung Oh ◽  
Seok-Jae Ko ◽  
Mun Seog Chang ◽  
Jinsung Kim

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.


2012 ◽  
Vol 27 (3) ◽  
pp. 223-230 ◽  
Author(s):  
Renata Cristiane Gennari Bianchi ◽  
Eduardo Rochete Ropelle ◽  
Carlos Kiyoshi Katashima ◽  
José Barreto Campello Carvalheira ◽  
Luiz Roberto Lopes ◽  
...  

PURPOSE: To study if the pre-radiotherapy physical activity has radio-protective elements, by measuring the radio-induced activation of pro-inflammatory cytokines as interleukin-6 (il-6), transforming growth factor -β (tgf -β), tumor necrosis factor -α (tnf-α) and protein beta kinase β (ikkβ), through western blotting analysis. METHODS: A randomized study with 28 Wistar hannover rats, males, with a mean age of 90 days and weighing about 200 grams. The animals were divided into three groups: (GI, GII and GIII). GIII group were submitted to swimming for eight weeks (zero load, three times a week, about 30 minutes). Then, the groups (except the control group) were submitted to irradiation by cobalt therapy, single dose of 3.5 gray in the whole body. All animals were sacrificed by overdose of pentobarbital, according to the time for analysis of cytokines, and then a fragment of the lower lobe of the right lung went to western blotting analysis. RESULTS: The cytokines IKK β, TNF-α and IL-6 induced by radiation in the lung were lower in the exercised animals. However, exercise did not alter the radiation-induced increase in tgf-β. CONCLUSION: The results show a lower response in relation to inflammatory cytokines in the group that practiced the exercise pre-radiotherapy, showing that exercise can protect tissues from tissue damage due to irradiation.


Author(s):  
Anita Aminoshariae ◽  
Mohammed Bakkar ◽  
Tracey Bonfield ◽  
Santosh Ghosh ◽  
Thomas A Montagnese ◽  
...  

Objective: The aim of this study was to investigate the levels of Human Beta Defensin (hBD) 2 and 3, chemokine and cytokine expressions between teeth endodontically diagnosed with symptomatic irreversible pulpitis (SIP), asymptomatic irreversible pulpitis (ASIP) and normal pulps. We hypothesized that there would be a correlation between hBD’s and the immunoregulatory response. Design: Pulpal samples were collected with paper points. Six samples were obtained from normal teeth, 21 from SIP, 18 from ASIP. Levels of cytokines and betadefensins were measured by Luminex technology and ELISA, respectively. Data were statistically analyzed using Kruskal-Wallis, Wilcoxon Mann-Whitney test and Spearman correlation test. Differences were considered significant at p<0.05. Results: hBD-2 levels correlated with samples obtained from patients in the ASIP group, but not in the samples obtained from patients with SIP or the control group. HBD-3 concentrations associated with all of the cytokines and chemokines in both SIP and ASIP groups. However, in the normal group, hBD-3 correlated with only TNFα, IL-8, MCP-1, IL-1β, MIP-1a, RANTES, IL-17 in normal group. When comparing control levels of hBD-2 and hBD-3 with patients samples from either the ASIP or the SIP groups, hBD-2 and hBD-3 concentrations were highest in the ASIP group. Conclusions: The hBD-2 and-3 were highly associated with the levels of the chemokines and cytokines in ASIP group. HBD-3 concentrations correlate with the levels of the chemokines and the cytokines in the SIP and ASIP groups.


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