scholarly journals Antioxidant and immunomodulatory effect of AKSS16-LIV01 – a multi herbal formulation against ethanol induced liver dysfunction in mice

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

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.


2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.


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.


Author(s):  
Tae-Young Gil ◽  
Bo-Ram Jin ◽  
Chul-Hee Hong ◽  
Jong Hyuk Park ◽  
Hyo-Jin An

Abstract Background Macrophages play a crucial role in inflammation. Astilbe chinensis is one of perennial herbs belonging to the genus Astilbe. Plants in the genus have been used for pain, headaches, arthralgia, and chronic bronchitis. However, the effect of A.chinensis on inflammation remains unclear. To study the anti-inflammatory action of A.chinensis ethanol extract (ACE), we investigated the effect of ACE on the production of pro-inflammatory mediators and cytokines in macrophages. Methods We evaluated the effectiveness of ACE in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and thioglycollate (TG)-elicited peritoneal macrophages from male C57BL/6 mice. We measured the levels of pro-inflammatory mediators and cytokines, and examined the anti-inflammatory actions of ACE on nuclear factor κB (NF-κB) pathway in the macrophages. Western blot analysis and immunofluorescence microscopy were used to determine protein level and translocation, respectively. Results ACE suppressed the output of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines in stimulated macrophages via inhibiting the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. ACE suppressed mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α). We examined the efficacies of ACE on NF-κB activation by measuring the expressions including IκB kinase (IKK), inhibitor of κB (IκB), and nuclear p65 proteins. In addition, the inhibition of NF-κB p65’s translocation was determined with immunofluorescence assay. Conclusion Our findings manifested that ACE inhibited LPS or TG-induced inflammation by blocking the NF-κB signaling pathway in macrophages. It indicated that ACE is a potential therapeutic mean for inflammation and related diseases.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jhy Jhu Lin ◽  
Jeanne O'Connell ◽  
Steve Sinclair

Abstract Objectives Development of a probiotic P. acidilactici NRRL B-50517 that resists to high temperature (up to 85°C), stomach acids, and air. Clinic evaluation of P. acidilactici NRRL B-50517 as a safe probiotic for regulation of weight related pro-inflammatory cytokines. Methods Survival studies were conducted by incubating P. acidilactici NRRL B-50517 in either liquid MRS broth, pH1.5 at 85°C overnight, or in dried powder at 85°C for 5–10 minutes. Healthy volunters were randomly assigned two capsules of placebo or Pediococcus probiotics (4 billion CFU) daily for three months. Biweekly phone interviews with 30 participants were performed to ensure daily dosage administration, and to collect the results of the questionnaire related to 6 categories of gut functions. Percent body fat measurements and serum were collected upon study initiation and completion. Serum was processed for cytokine analysis by multiplex ELISA assays. Results P. acidilactici NRRL B-50,517 survived at 85°C and pH 1.5 in MRS broth and dried powder forms. No statistical significantly changes of gut functions between the placebo group and the probiotic group in appetite: t-value 1.6808, p-value 0.1313; energy level: t-value 0.7508. p-value 0.5003; bowel movement: t-value 0.3348. p-value 0.7464; stool quality: t-value 0.6929, p-value 0.5080; bloating: t-value 2.0583. p-value 0.0736; gas t-value: 1.9560, p-value 0.0875. On average, the probiotic lost 0.86% ± 0.42% body fat whereas the control group gained 0.28% ± 0.19, P = 0.0264. Pro-inflammaroty IL-6 ratios differed by 0.61 ± 0.22 and 3.06 ± 0.87 in the probiotic and control groups, respectively (P = 0.0295); pro-inflammatory IL23 ratio was 0.65 ± 0.14 in the probiotic and 1.71 ± 0.38 in the control group, P = 0.0068. Conclusions Novel P. acidilactici NRRL B-50,517 is safe for human consumption and may be useful in reducing body fat and pro-inflammatory markers. Funding Sources TEDCO, Maryland.


1997 ◽  
Vol 15 (6) ◽  
pp. 2312-2321 ◽  
Author(s):  
A M Gianni ◽  
S Siena ◽  
M Bregni ◽  
M Di Nicola ◽  
S Orefice ◽  
...  

PURPOSE To assess the efficacy, toxicity, and applicability of high-dose therapy administered as adjuvant initial treatment to women with breast cancer with extensive nodal involvement. PATIENTS AND METHODS Sixty-seven patients with stage II to III breast cancer involving > or = 10 axillary nodes received a novel high-dose sequential (HDS) regimen, including the high-dose administration of three non-cross-resistant drugs (cyclophosphamide, methotrexate, and melphalan) given within the shortest interval of time as possible with hematologic and nonhematologic toxicity. RESULTS Sixty-three patients completed the program as planned, one patient died of acute toxicity, and three patients were switched to standard-dose adjuvant therapy. After a median follow-up duration of 48.5 months and a lead follow-up of 78 months, actuarial relapse-free survival for all 67 registered patients is 57% and overall survival is 70%, respectively. Comparison with a historical control group of 58 consecutive patients showed a significantly superior rate of freedom from relapse for the HDS-treated group (57% v 41%, respectively), in particular when two subgroups of patients, more homogeneous for their number of involved nodes, were compared (65% v 42%). Overall, treatment was of short duration (median, 70 days), required a median of 32 days of hospital stay, and was associated with only a few severe side effects (the most distressing being oral mucositis after melphalan therapy). CONCLUSION HDS therapy emerges as an effective and applicable regimen, whose major toxicity was occasional. Final assessment of its value in a randomized, multicenter trial is presently underway.


2005 ◽  
Vol 385 (3) ◽  
pp. 815-821 ◽  
Author(s):  
Stephen R. CLARK ◽  
Peter B. ANNING ◽  
Marcus J. COFFEY ◽  
Andrew G. ROBERTS ◽  
Lawrence J. MARNETT ◽  
...  

PGHS-2 (prostaglandin H synthase-2) is induced in mammalian cells by pro-inflammatory cytokines in tandem with iNOS [high-output (‘inducible’) nitric oxide synthase], and is co-localized with iNOS and nitrotyrosine in human atheroma macrophages. Herein, murine J774.2 macrophages incubated with lipopolysaccharide and interferon γ showed induction of PGHS-2 and generated NO using iNOS that could be completely depleted by 12(S)-HPETE [12(S)-hydroperoxyeicosatetraenoic acid; 2.4 μM] or hydrogen peroxide (500 μM) (0.42±0.084 and 0.38±0.02 nmol·min−1·106 cells−1 for HPETE and H2O2 respectively). COS-7 cells transiently transfected with human PGHS-2 also showed HPETE- or H2O2-dependent NO decay (0.44±0.016 and 0.20±0.04 nmol·min−1·106 cells−1 for 2.4 μM HPETE and 500 μM H2O2 respectively). Finally, purified PGHS-2 consumed NO in the presence of HPETE or H2O2 (168 and 140 μM·min−1·μM enzyme−1 for HPETE and H2O2 respectively), in a haem-dependent manner, with 20 nM enzyme consuming up to 4 μM NO. Km (app) values for NO and 15(S)-HPETE were 1.7±0.2 and 0.45±0.16 μM respectively. These data indicate that PGHS-2 catalytically consumes NO during peroxidase turnover and that pro-inflammatory cytokines simultaneously upregulate NO synthesis and degradation pathways in murine macrophages. Catalytic NO consumption by PGHS-2 represents a novel interaction between NO and PGHS-2 that may impact on the biological effects of NO in vascular signalling and inflammation.


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