Flavonoids from Litsea coreana Decreases TNF-α Secretion from Peritoneal Macrophages in Adjuvant-Induced Arthritis Rats via UPR Pathway

2014 ◽  
Vol 42 (04) ◽  
pp. 905-919 ◽  
Author(s):  
Jian Zhong ◽  
Taotao Ma ◽  
Cheng Huang ◽  
Huanzhong Liu ◽  
Zhaolin Chen ◽  
...  
Keyword(s):  
Initial Step ◽  
Serum Levels ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Adjuvant Induced Arthritis ◽  
Tnf Α ◽  
Mtor Complex 1 ◽  
Dose Dependent ◽  
Upr Pathway

Macrophages play a crucial role in rheumatoid arthritis (RA). Their activation is the initial step of RA. This study was designed to detect the effects of total flavonoids from Litsea coreana Levl. (TFLC) on the complete Freund's adjuvant-induced (CFA-induced) arthritis (AA) in rats and to explore whether inflammatory cytokines were induced by the IRE1/mTORC1/TNF-α-dependant mechanism in peritoneal macrophages. In vivo, our data indicated that TFLC (100, 200 mg/kg, i.g. × 10 days) could significantly suppress secondary paw swelling and serum levels of TNF-α and IL-1β. Histopathological figures showed that TFLC treatment improved the morphologic changes of articular cartilages and synovium. Results of RT-PCR and western blotting demonstrated that TFLC suppressed expression of 78-KD glucose regulated protein (GRP78), X-box binding protein 1 (XBP1), mTOR complex 1 (mTORC1) and TNF-α in peritoneal macrophages of AA rats. Collectively, these results indicate that TFLC is able to ameliorate adjuvant-induced arthritis in a dose-dependent manner by suppressing the IRE1/mTORC1/TNF-α-regulated inflammatory response initiated in peritoneal macrophages.

scholarly journals Methylprednisolone Protects SAP and Pancreatitis-Associated ALI in Mice by Inhibiting NLRP3 Inflammasome Through NF-κB

2020 ◽  
Author(s):  
Chuan-jiang Liu ◽  
Qiang Fu ◽  
Wenjing Zhou ◽  
Xu Zhang ◽  
Rui Chen ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Nlrp3 Inflammasome ◽  
Antioxidant Properties ◽  
Underlying Mechanism ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Expression Levels ◽  
Tnf Α

Abstract Background: Methylprednisolone (MP) is a synthetic corticosteroid with potent anti-inflammatory and antioxidant properties used as therapy for a variety of diseases. The underlying mechanism of MP to reduce acute pancreatitis still needs to be elucidated.Methods: Twenty-four male C57BL/6 mice (6-8 weeks) were used to establish SAP mouse model by administering an intraperitoneal injection of Cae and LPS. Amylase expression levels of serum and PLF were measured with an amylase assay kit. The concentrations of IL-1β and TNF-α in the serum and PLF were detected by ELISA. The level of pancreatic and lung tissue damage and inflammation was assessed by H&E staining and immunofluorescence staining. Western blot and qPCR were used to detect the expression levels of NLRP3, IL-1β and TNF-αin vivo and in vitro.Results: In this study, we found MP, used in the early phase of SAP, decreased the levels of IL-1β and TNF-α in serum and peritoneal lavage fluids (PLF), reduced the level of serum amylase and the expression of MPO in lung tissue, attenuated the pathological injury of the pancreas and lungs in a dose-dependent manner. The expression of NLRP3 and IL-1β in pancreas and lungs was down-regulated significantly depending on the MP concentration. In vitro, MP reduced the levels of IL-1β and TNF-α by down-regulating the expression of NLRP3, IL-1β and p-NF-κB in isolated peritoneal macrophages. Conclusion: MP can attenuate the injury of pancreas and lungs, and the inflammatory response in SAP mice by down-regulating the activation of NF-κB and the NLRP3 inflammasome.

Immunomodulating capacity of kefir

2005 ◽  
Vol 72 (2) ◽  
pp. 195-202 ◽  
Author(s):  
Celso G Vinderola ◽  
Jairo Duarte ◽  
Deepa Thangavel ◽  
Gabriela Perdigón ◽  
Edward Farnworth ◽  
...  
Keyword(s):  
Acetic Acid Bacteria ◽  
Fermented Milk ◽  
Mucosal Immune Response ◽  
Dependent Manner ◽  
Tnf Α ◽  
Translocation Assay ◽  
Feeding Trials ◽  
Dose Dependent ◽  
Different Doses

Kefir is a fermented milk produced by the action of lactic acid bacteria, yeasts and acetic acid bacteria, trapped in a complex matrix of polysaccharides and proteins. Beyond its inherent high nutritional value as a source of proteins and calcium, kefir has a long tradition of being regarded as good for health in countries where it is a staple in the diet. However, published human or animal feeding trials to substantiate this view are not numerous. The aim of this work was to determine the immunomodulating capacity of kefir on the intestinal mucosal immune response in mice and to demonstrate the importance of dose and cell viability on this response. BALB/c mice were fed with commercial kefir ad libitum (diluted 1/10, 1/50, 1/100 or 1/200) or pasteurized kefir (diluted 1/6, 1/10, 1/50, 1/100) for 2, 5 or 7 consecutive days. At the end of each feeding period, the bacterial translocation assay was performed in the liver. Small intestine structure was studied by haematoxilin-eosin staining and light microscopy. The number of IgA+ and IgG+ cells was also determined. For the functional doses chosen, cytokines (IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α and IFN-γ) were determined. Kefir and pasteurized kefir were able to modulate the mucosal immune system in a dose-dependent manner. Kefir was administred 10-times more diluted than pasteurized kefir, but it induced an immunomodulation of similar magnitude, indicating the importance of cell viabilty. The results suggest that a Th1 response was controlled by Th2 cytokines induced by kefir feeding. Pasteurized kefir would induce both Th2 and Th1 responses. This is the first study in vivo regarding the mechanisms involved in the immunomodulating capacity of the oral administration of kefir containing viable or heat-inactivated bacteria at different doses.

scholarly journals Anti-inflammatory Effect of the Peptide LKEKK

2021 ◽  
Vol 6 (5) ◽  
Keyword(s):  
High Specificity ◽  
Dependent Manner ◽  
Thymosin Α1 ◽  
Tnf Α ◽  
Normal Human ◽  
Anti Inflammatory ◽  
Interferon Α2 ◽  
Dose Dependent

We have established that the peptide LKEKK (Np5) corresponding to the sequence 16-20 of thymosin-α1 and to the sequence 131-135 of interferon-α2, in the concentration range 50 300 µg/ear reduces in a dose-dependent manner phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin edema in mice .Tested in parallel peptide with inverted sequence (iNp5, KKEKL, 150-300 µg/ear) was inactive, indicating high specificity of the Np5 action. In the concentration range of 5 20 µM Np5 significantly decrease the TNF-α-induced production by normal human keranocytes of pro-inflammatory mediators IL-6 and IL-1β. Thus, Np5t has a pronounced anti-inflammatory activity in vivo and in vitro.

New Hydrazone Derivatives of Pyrazole-4-carboxaldehydes Exhibited Anti-inflammatory Properties

2020 ◽  
Vol 17 (4) ◽  
pp. 502-511
Author(s):  
Mingxia Song ◽  
Bing Liu ◽  
Shengwang Yu ◽  
Shihui He ◽  
Yuqiu Liang ◽  
...  
Keyword(s):  
Intraperitoneal Administration ◽  
Dependent Manner ◽  
Reference Drug ◽  
Ear Edema ◽  
Tnf Α ◽  
Ic50 Values ◽  
Dose Dependent ◽  
Derivatives Of

Background: Several series of hydrazone derivatives of pyrazole-4-carboxaldehydes (4- 11) were designed and synthesized to screen their inflammatory activity. Methods: The products were characterized by 1H NMR, 13C NMR and HRMS. In vitro LPS-induced TNF-α model and in vivo xylene-induced ear-edema model were used to evaluate their antiinflammatory activity. Results and Conclusion: Bioassays indicated that most of the compounds markedly inhibited the expression of TNF-α at the concentration of 10 µg/mL. Compounds 7b and 11c, two of the most potent compounds, exhibited TNF-α inhibitory ability in a dose-dependent manner with IC50 values of 5.56 and 3.69 µM, respectively. In vivo, intraperitoneal administration with 7b and 11c markedly inhibited the ear edema at the doses of 20 and 50 mg/kg. Compound 11c, inhibited edema by 49.59 % at the dose of 20 mg/kg, was comparable to the reference drug dexamethasone at the same dose (with an inhibition of 50.49 %). To understand the binding pattern, molecular docking of representative 7b and 11c was performed, which demonstrated that both compounds have a forceful binding with the TNF-α, and that the phenyl and hydrazide moieties of them play a significant role in binding with the target site.

scholarly journals Aldosterone directly affects apelin expression and secretion in adipocytes

2013 ◽  
Vol 51 (1) ◽  
pp. 37-48 ◽  
Author(s):  
He Jiang ◽  
Xiao-Ping Ye ◽  
Zhong-Yin Yang ◽  
Ming Zhan ◽  
Hai-Ning Wang ◽  
...  
Keyword(s):  
Target Genes ◽  
Direct Interaction ◽  
Serum Levels ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Plasma Apelin ◽  
Dose Dependent

There is a high incidence of metabolic syndrome among patients with primary aldosteronism (PA), which has recently been associated with an unfavorable cardiometabolic profile. However, the underlying mechanisms have not been clarified in detail. Characterizing aldosterone (Ald) target genes in adipocytes will help us to elucidate the deleterious effects associated with excess Ald. Apelin, a novel adipokine, exerts beneficial effects on obesity-associated disorders and cardiovascular homeostasis. The objective of this study was to investigate the effects of high Ald levels on apelin expression and secretion and the underlying mechanisms involved in adipocytes. In vivo, a single-dose Ald injection acutely decreased apelin serum levels and adipose tissue apelin production, which demonstrates a clear inverse relationship between the levels of plasma Ald and plasma apelin. Experiments using 3T3-L1 adipocytes showed that Ald decreased apelin expression and secretion in a time- and dose-dependent manner. This effect was reversed by glucocorticoid receptor (GR) antagonists or GR (NR3C1) knockdown; furthermore, putative HREs were identified in the apelin promoter. Subsequently, we verified that both glucocorticoids and mineralocorticoids regulated apelin expression through GR activation, although no synergistic effect was observed. Additionally, detailed potential mechanisms involved a p38 MAPK signaling pathway. In conclusion, our findings strengthen the fact that there is a direct interaction between Ald and apelin in adipocytes, which has important implications for hyperaldosteronism or PA-associated cardiometabolic syndrome and hoists apelin on the list of potent therapeutic targets for PA.

scholarly journals Anti-inflammatory Effect of the Peptide LKEKK

2021 ◽  
Vol 6 (5) ◽  
Keyword(s):  
High Specificity ◽  
Dependent Manner ◽  
Thymosin Α1 ◽  
Tnf Α ◽  
Normal Human ◽  
Anti Inflammatory ◽  
Interferon Α2 ◽  
Dose Dependent

We have established that the peptide LKEKK (Np5) corresponding to the sequence 16-20 of thymosin-α1 and to the sequence 131-135 of interferon-α2, in the concentration range 50 300 µg/ear reduces in a dose-dependent manner phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin edema in mice .Tested in parallel peptide with inverted sequence (iNp5, KKEKL, 150-300 µg/ear) was inactive, indicating high specificity of the Np5 action. In the concentration range of 5 20 µM Np5 significantly decrease the TNF-α-induced production by normal human keranocytes of pro-inflammatory mediators IL-6 and IL-1β. Thus, Np5t has a pronounced anti-inflammatory activity in vivo and in vitro.

Synthesis, Antioxidant and Anticancer Activities of Efficient Glutathione Peroxidase Mimic

2011 ◽  
Vol 282-283 ◽  
pp. 317-321
Author(s):  
Ting Ting Lin ◽  
Jun Qiu Liu
Keyword(s):  
Glutathione Peroxidase ◽  
Oxidative Damage ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Peroxidase Mimic ◽  
Age Related ◽  
Tnf Α ◽  
Dose Dependent

Glutathione peroxidase (GPX) is a well-known selenoenzyme that can protect cells against oxidative damage. A novel dicyclodextrinyl ditelluride (2-TeCD) compound was devised as a functional mimic of the GPX. The antioxidant effect of 2-TeCD was evaluated by its ability to protect mitochondria from oxidative damage. 2-TeCD could also suppress the TNF-α induced inflammatory effect on HUVECs surface in a dose-dependent manner. Meanwhile, 2-TeCD exhibited anti-proliferative property both in vitro and in vivo. These results indicate that 2-TeCD may be useful for developing medical agents in many pathological conditions such as cataract­, age-related diseases­, atherosclerosis, cancer and so on.

Chemopreventive and hepatoprotective roles of adiponectin (SULF2 inhibitor) in hepatocelluar carcinoma

2016 ◽  
Vol 397 (3) ◽  
pp. 257-267 ◽  
Author(s):  
Mohammed M.H. Al-Gayyar ◽  
Ahmed Abbas ◽  
Ahmed M. Hamdan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Extracellular Enzyme ◽  
Dependent Manner ◽  
Hepg2 Cell Line ◽  
Tnf Α ◽  
Dose Dependent

Abstract Sulfatase 2 (SULF2) is an extracellular enzyme that catalyzes the removal of 6-O-sulfate groups from the heparan sulfate (HS). As elevated SULF2 activity has been correlated with hepatocellular carcinoma (HCC), this study was conducted to evaluate the chemoprotective and the hepatoprotective roles of adiponectin, as a SULF2 inhibitor, against hepatocellular carcinoma both in vivo and in vitro. HCC was induced in rats using thioacetamide (200 mg/kg). Treated rats received adiponectin (5 μg/kg) once a week. Moreover, human hepatocellular carcinoma (HepG2) cell line was used as an in-vitro model. In both in-vivo and in-vitro models, adiponectin completely blocked HCC-induced SULF2 elevation. The antitumor activity of adiponectin was confirmed by 80% increased the survival rate, 73% reduction in the average number of nodules per nodule-bearing liver and 46% reduction in serum AFP. In addition, adiponectin ameliorated HCC-induced expression of tumor invasion markers, MMP9, syndecan-1 and FGF-2. Moreover, adiponectin attenuated HCC-induced elevation of nfκb and TNF-α levels. Moreover, treatment of HepG2 cell line with adiponectin showed dose-dependent reduction of HepG2 cell viability and elevation of cellular cytotoxicity. Besides, Adiponectin yielded the same results in HepG2 cells in a dose-dependent manner. Adiponectin achieved both hepatoprotective and chemoprotective effects against HCC through blocking of SULF2.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

Changes in growth rate and thyroid- and sex-hormones blood levels in rats under sub-chronic lithium treatment

2006 ◽  
Vol 25 (5) ◽  
pp. 243-250 ◽  
Author(s):  
M S Allagui ◽  
N Hfaiedh ◽  
C Vincent ◽  
F Guermazi ◽  
J-C Murat ◽  
...  
Keyword(s):  
Growth Rate ◽  
Lithium Treatment ◽  
Lithium Carbonate ◽  
Serum Levels ◽  
Antagonistic Effect ◽  
Blood Levels ◽  
Vaginal Mucosa ◽  
Dependent Manner ◽  
Serum Concentrations ◽  
Dose Dependent

Lithium therapy, mainly used in curing some psychiatric diseases, is responsible for numerous undesirable side effects. The present study is a contribution to the understanding of the pathophysiological mechanisms underlying lithium toxicity. Male and female mature rats were divided into three batches and fed commercial pellets: one batch was the control and the second and third batches were given 2 g (Li1) and 4 g (Li2) of lithium carbonate/kg of food/day, respectively. After 7, 14, 21 and 28 days, serum levels of free tri-iodothyronine (FT3), thyroxine (FT4), testosterone and estradiol were measured. Attention was also paid to growth rate and a histological examination of testes or vaginal mucosa was carried out. In treated rats, a dose-dependent loss of appetite and a decrease in growth rate were observed, together with symptoms of polydypsia, polyuria and diarrhea. Lithium serum concentrations increased from 0.44 mM (day 7) to 1.34 mM (day 28) in Li1 rats and from 0.66 to 1.45 mM (day 14) in Li2 rats. Li2 treatment induced a high mortality after 14 days, reaching 50-60% in female and male animals. From these data, the LD50 (14 days Li2 chronic treatment) was calculated to be about 0.3 g/day per kilogram of animal, leading to Li serum concentrations of about 1.4 mM. A significant decrease of FT3 and FT4 was observed in treated rats. This effect appeared immediately for the highest dose and was more pronounced for FT3, resulting in an increase of the FT4/FT3 ratio. In males, testosterone decreased and spermatogenesis was stopped. Conversely, in females, estradiol increased in a dose-dependent manner as the animals were blocked in the diestrus phase at day 28. This finding supports a possible antagonistic effect of lithium on the estradiol receptors.

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