scholarly journals Biphasic Effect ofPhyllanthus emblicaL. Extract on NSAID-Induced Ulcer: An Antioxidative Trail Weaved with Immunomodulatory Effect

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Ananya Chatterjee ◽  
Subrata Chattopadhyay ◽  
Sandip K. Bandyopadhyay
Keyword(s):  
Inflammatory Cytokine ◽  
Ethanolic Extract ◽  
Protein Carbonyl ◽  
Protein Carbonyl Content ◽  
Biphasic Effect ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Antioxidative Property

Amla (Phyllanthus emblicaL.), apart from its food value, can be used as a gastroprotective agent in non steroidal anti-inflammatory drug (NSAID)-induced gastropathy. It has been suggested that the antioxidative property of amla is the key to its therapeutic effect. Hence, on the basis ofin vitroantioxidative potential, the ethanolic extract of amla (eAE) was selected forin vivostudy in NSAID-induced ulcer. Intriguingly, eAE showed biphasic activity in ulcerated mice, with healing effect observed at 60 mg/kg and an adverse effect at 120 mg/kg.The dose-dependent study revealed that switching from anti-oxidant to pro-oxidant shift and immunomodulatory property could be the major cause for its biphasic effect, as evident from the total antioxidant status, thiol concentration, lipid peroxidation, protein carbonyl content followed by mucin content, synthesis and cytokine status. Further, Buthionine sulfoxamine (BSO) pretreatment established the potential impact of antioxidative property in the healing action of eAE. However, eAE efficiently reduced pro-inflammatory cytokine (TNF- and IL-1) levels and appreciably upregulate anti-inflammatory cytokine (IL-10) concentration. In conclusion, gastric ulcer healing induced by eAE was driven in a dose-specific manner through the harmonization of the antioxidative property and modulation of anti-inflammatory cytokine level.

scholarly journals P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tnf Α ◽  
Public Dataset ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

scholarly journals Rationally synthesized coumarin based pyrazolines ameliorate carrageenan induced inflammation through COX-2/pro-inflammatory cytokine inhibition

MedChemComm ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 421-430 ◽  
Author(s):  
Priyanka Chandel ◽  
Anoop Kumar ◽  
Nishu Singla ◽  
Anshul Kumar ◽  
Gagandeep Singh ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cytokine Inhibition ◽  
Cox 2 ◽  
Anti Inflammatory

In the present work, coumarin based pyrazolines (7a–g) have been synthesized and investigated for their in vitro and in vivo anti-inflammatory potential.

scholarly journals Extract from Bougainvillea xbuttiana (Variety Orange) Inhibits Production of LPS-Induced Inflammatory Mediators in Macrophages and Exerts a Protective Effect In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Rodolfo Abarca-Vargas ◽  
Vera L. Petricevich
Keyword(s):  
Inflammatory Mediators ◽  
Ethanolic Extract ◽  
Peritoneal Macrophages ◽  
Experimental Models ◽  
Nitric Oxide Release ◽  
Lps Challenge ◽  
Secretion Of Mediators ◽  
Anti Inflammatory

Background. Different pharmacological properties, such as antioxidant, antiproliferative, and anti-inflammatory properties, have been described among natural products. We previously described that the Bougainvillea xbuttiana (Variety Orange) ethanolic extract (BxbO) has an anti-inflammatory effect; however, this action is not fully understood. In this study, the action of the BxbO extract on the secretion of inflammatory mediators in two experimental models, in vitro and in vivo, after LPS challenge was evaluated. Methods. Peritoneal macrophages were obtained from female BALB/c mice and LPS-challenged with or without the BxbO extract. For the evaluation of mediators, the supernatants at 0, 12, 24, 36, and 48 hours were collected. For in vivo estimation, groups of female BALB/c mice were first intraperitoneously injected with different amounts of LPS and later administered the oral BxbO extract (v.o.) for 144 hours. To understand the mechanism of action, sera obtained from mice were collected at 0, 2, 4, 8, 12, and 24 hours after LPS challenge (with or without BxbO) for the detection of mediators. Results. The results showed that, in both peritoneal macrophages and sera of mice treated with the BxbO extract 1 hour before or together with LPS challenge, proinflammatory cytokines and nitric oxide release were unquestionably repressed. In contrast, in both systems studied here, the IL-10 levels were elevated to 5 to 9 times. At lethal doses of LPS, the BxbO extract treatment was found to protect animals from death. Conclusions. The results revealed that the inhibitory, protective, and benign effects of the BxbO extract were due to its capacity to balance the secretion of mediators.

scholarly journals Production of some cytokines in patients with autoimmune thyroid disease

2004 ◽  
Vol 50 (3) ◽  
pp. 29-32 ◽  
Author(s):  
T. V. Glazanova ◽  
L. N. Bubnova ◽  
E. M. Trunin ◽  
A. S. Kuzmichev ◽  
I. E. Pavlova
Keyword(s):  
Inflammatory Cytokines ◽  
Cell Activation ◽  
Autoimmune Thyroid ◽  
Diminished Capacity ◽  
Anti Inflammatory ◽  
Toxic Goiter ◽  
Anti Inflammatory Cytokine ◽  
Active Formation

Imbalance ofproinflammatory and anti-inflammatory cytokines makes a considerable contribution to the pathogenesis of autoimmune diseases, including those of the thyroid. The specific features ofperipheral mononuclear cell production of anti-inflammatory cytokines (TNF-a, IL-1(3, and IL-6), the level of the anti-inflammatory cytokine IL-10 in the serum and the serum level of autoantibodies to thyroglobulin were studied by enzyme immunoassay in 20 patients with histologically verified diffuse toxic goiter (DTG) and in 18 patients with autoimmune thyroiditis (AIT). Both in DTG and AIT, there was a significant enhancement of the capacity of peripheral blood cells to the spontaneous production of proinflammatory cytokines (TNF-a, IL-1(3, and IL-6), which is indicative of preexisting cell activation; their diminished capacity to respond to an inductor in vitro, which reflects an in vivo potential response to antigenic stimulation; as well as increased IL-10 synthesis. More pronounced impairments of cytokine-producing capacity were observed along with the more active formation of autoantibodies to thyroglobulin in patients with AIT.

scholarly journals Modulation of inflammatory responses by Sutherlandia frutescens

2015 ◽  
Author(s):  
◽  
Wei Lei
Keyword(s):  
Aqueous Extract ◽  
Inflammatory Responses ◽  
Ethanolic Extract ◽  
Microbial Activities ◽  
Murine Macrophages ◽  
Oral Consumption ◽  
Anti Inflammatory ◽  
The Impact

Sutherlandia frutescens (L.) R. Br (Lessertia frutescens) is a medicinal plant traditionally used in southern Africa. It has been used for patients suffering from numerous types of cancer, infectious diseases, and various inflammatory conditions. This study was designed to determine the impact of S. frutescens on the inflammatory response and anti-microbial activities on cell and/or animal models. Aqueous and ethanolic extracts of S. frutescens were made and verified using HPLC. These extracts were used to treat murine macrophages (e.g., RAW 264.7 cells and primary macrophages isolated from mice) to evaluate the impact of S. frutescens on in vitro inflammatory responses. This study found that the aqueous extract and a polysaccharide-enriched fraction from the aqueous extract exhibited an immuno-stimulatory activity on murine macrophages. Treatment with aqueous extract or polysaccharides increased the production of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines/chemokines via activating the toll-like receptor 4 signaling pathway. On the other hand, the ethanolic extract of S. frutescens dose-dependently decreased the production of ROS, NO, inducible nitric oxide synthase (iNOS), and various inflammatory cytokines and chemokines in murine macrophages co-stimulated with lipopolysaccharide (LPS) and interferon gamma (IFNy). Follow up experiments demonstrated that the anti-inflammatory activity of the ethanolic extract was mediated via reductions in the activation of NF-kB, extracellular-signal-regulated kinase 1/2 (ERK1/2), and signal transducers and activators of transcription 1 (STAT1). RNA sequencing provided more evidences to support the anti-inflammatory activity of the ethanolic extract of S. frutescens. To our surprise, chlorophylls isolated from S. frutescens had a greater effect on the anti-inflammatory of S. frutescens than that of unique compounds (i.e., sutherlandiosides and sutherlandins). To investigate the impact of oral consumption of S. frutescens on in vivo inflammatory responses and anti-microbial activities, mice were fed with AIN-93G based diet with/without containing ground S. frutescens powder or were gavaged with S. frutescens extracts followed by challenge with E. coli or LPS. These experiments found that oral consumption of S. frutescens had limited or no impact on the in vivo inflammatory responses and anti-microbial activities. Overall, this study provide a better understanding on the beneficial therapeutic properties of S. frutescens using in vitro models, however these studies in a laboratory mouse model suggest that consumption of S. frutescens had only a modest impact on host anti-microbial and inflammatory responses to a gram-negative microbial challenge whether intact microbes or bacterial endotoxin (i.e., LPS) was used.

The Histone Deacetylase (HDAC) Inhibitor PCI-24781 Decreases Pro-Inflammatory Cytokine Secretion In Vitro and In Vivo and Protects Against Endotoxemia In a Sepsis Model

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3914-3914
Author(s):  
Sriram Balasubramanian ◽  
Mint Sirisawad ◽  
Susanne Steggerda ◽  
Wangsen Cao ◽  
Charles Lowenstein ◽  
...  
Keyword(s):  
Hdac Inhibitor ◽  
Research Funding ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Employment Equity ◽  
Inflammatory Disorders ◽  
Equity Ownership ◽  
Anti Inflammatory

Abstract Abstract 3914 Inhibitors of histone deacetylases (HDACs) are currently in clinical testing for treating various cancers, and two have been recently approved by the US FDA for treating cutaneous T-cell lymphoma. Here we describe novel anti-inflammatory properties of the HDAC inhibitor PCI-24781 which is in clinical trials for multiple indications including lymphoma (Evens et al., Blood 114: 2726, ASH 2009 Annual Meeting Abstracts). Cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) have been shown to be involved in human inflammatory disorders, and an anti-IL-6 treatment was recently approved for rheumatoid arthritis (RA). Therefore, the effect of PCI-24781 on cytokine production by lipopolysaccharide (LPS)-stimulated human peripheral mononuclear blood cells (PBMC) as well as isolated monocytes was studied at the RNA expression level by microarrays and Taqman, and at the protein level by ELISA. PCI-24781 potently inhibits the production and secretion of several pro-inflammatory cytokines, including IL-6, TNF-a and interleukin-1beta (IL-1b), at both RNA and protein levels. In murine RAW macrophages as well, PCI-24781 inhibited LPS-stimulated IL-6 secretion at 20nM. PCI-24781 was most effective when given with or before LPS, but was still effective when given an hour after LPS. Similarly, PCI-24781 greatly attenuated in vivo pro-inflammatory cytokine production in LPS-treated Balb/c mice; the IC50 for IL-6 inhibition was < 5 mg/kg. Both the in vitro and in vivo IC50s for IL-6 inhibition are considerably less than the concentrations required to inhibit growth and induce apoptosis in tumor cells (0.2-0.5mM) and in xenograft models (60-80 mg/kg). The mechanism by which these cytokines are controlled involves attenuation of the LPS receptor TLR4 signaling at multiple levels, including acetylation of targets such as MKP-1 and NF-kB subunit p65 in the downstream MAPK and NF-kB pathways; other factors include reduced expression of proteasome, IKK and other NF-kB subunits. Interestingly, we observed a large reduction in levels of NOS2, which causes hypotension during sepsis by producing the inflammatory mediator nitric oxide (NO). Therefore the activity of PCI-24781 was tested in a model of sepsis where mice were treated with a lethal dose of 100 mg/kg LPS, an endotoxin known to be a major mediator of sepsis in humans. PCI-24781 was injected twice, first 16 h before LPS and then 2 h before LPS, in groups of 10 mice each. Control mice that did not receive any PCI-24781 all died within 2 days after LPS (mortality 100%). Pretreatment with PCI-24781 led to dose-dependent increase in survival with 60% of the mice surviving past 6 days with 2 doses of 50mg/kg PCI-24781. These data show that the HDAC inhibitor PCI-24781 protects mice from lethal endotoxemia. Thus, taken together, our data suggest that PCI-24781 has potent anti-inflammatory activities and may be useful to treat inflammatory disorders including RA and sepsis in humans. Disclosures: Balasubramanian: Pharmacyclics: Employment, Equity Ownership. Sirisawad:Pharmacyclics: Employment, Equity Ownership. Steggerda:Pharmacyclics: Employment, Equity Ownership. Cao:Pharmacyclics: Research Funding. Lowenstein:Pharmacyclics: Research Funding. Buggy:Pharmacyclics: Employment, Equity Ownership.

Maydis Stigma Elicits Analgesia and Blocks Edema in Mice and Inhibits Inflammation in Macrophages

2017 ◽  
Vol 45 (07) ◽  
pp. 1477-1496 ◽  
Author(s):  
Yun Hee Jeong ◽  
You-Chang Oh ◽  
Won-Kyung Cho ◽  
Hye Jin Yang ◽  
Jin Yeul Ma
Keyword(s):  
Acetic Acid ◽  
Target Genes ◽  
Biological Activities ◽  
Scientific Evidence ◽  
Ethanolic Extract ◽  
Anticancer Activities ◽  
Ear Edema ◽  
Anti Inflammatory

Maydis Stigma (MS) is an herb traditionally used in many parts of the world. Previous studies have reported that MS plays a role in several biological activities, including antidiabetic and anticancer activities. However, the effects of a MS ethanolic extract (MSE) on the anti-inflammatory cellular mechanism remain unclear. Here, we investigated the anti-inflammatory properties of MSE and its molecular mechanism both in vitro and in vivo. The effects of MSE on the production of inflammatory mediators, cytokines, and related proteins and the identification of target genes were determined using LPS-stimulated macrophages. We also determined the analgesic and anti-inflammatory effects of MSE by examining acetic acid-induced writhing responses and xylene-induced ear edema in mice. Our results indicated that MSE markedly decreased iNOS and COX-2 levels without causing cytotoxicity and suppressed the secretion of NO in LPS-stimulated macrophages. MSE also inhibited the production of proinflammatory cytokines, such as TNF-[Formula: see text], IL-6, and IL-1[Formula: see text], and induced the expression of HO-1. Moreover, MSE treatment significantly reduced the LPS-stimulated activation of MAPK, NF-[Formula: see text]B, and AP-1. Furthermore, MSE exerted an analgesic effect on the acetic acid-induced abdominal writhing response test and an anti-inflammatory effect on xylene-induced ear edema in ICR mice. Finally, we investigated the components of MSE using UPLC-ESI-MS and found that it contains the maysin as a marker component. Overall, these observations demonstrate that MSE has anti-inflammatory and antinociceptive effects both in vitro and in vivo, which may provide new scientific evidence for its use as a potential therapeutic agent for the treatment of inflammation.

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