scholarly journals Ascidian Tunicate Extracts Attenuate Rheumatoid Arthritis in a Collagen-induced Murine Model

2014 ◽  
Vol 9 (6) ◽  
pp. 1934578X1400900
Author(s):  
Seong-Ho Hong ◽  
Jung-Taek Kwon ◽  
Jae-Ho Lee ◽  
Somin Lee ◽  
Ah Young Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interleukin 10 ◽  
Treated Group ◽  
Pcr Analysis ◽  
Prostaglandin E ◽  
Therapeutic Effects ◽  
Paw Edema ◽  
Mice Model ◽  
The Matrix ◽  
Inflammatory Proteins

Murine rheumatoid arthritis models are often used to investigate the potential therapeutic effects of candidate drugs. The present study has been conducted in order to investigate the therapeutic efficacy of ascidian tunicate extracts in a collagen-induced arthritis DBA1/J mice model. Four types of formulas, ascidian tunicate extracts (ATE), crude ascidian tunicate glycans (ATEC), ascidian tunicate extracts with licorice extracts (ATEL), and crude ascidian tunicate glycans with licorice extracts (ATECL) were orally administered into DBA/1J mice for 3 weeks and paw edema and thickness were evaluated. Changes in inflammatory proteins and cytokines levels were monitored in hind leg tissues by Western blot and quantitative PCR analysis. The oral administration of ascidian tunicate extracts alleviated paw edema and improved the histological hind leg cartilage status. The extracts also reduced the matrix metalloproteinase-9 (MMP-9) protein and prostaglandin E synthase (PGES) levels. In addition, the extracts-treated groups showed increased interleukin-10 (IL-10) levels compared with the non-treated group. These findings suggest that orally administered ascidian tunicate extracts might have potential therapeutic effects for the treatment of rheumatoid arthritis.

scholarly journals Transplantation of bone marrow derived macrophages reduces markers of neuropathology in an APP/PS1 mouse model

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Luís Costa-Marques ◽  
Katrin Arnold ◽  
Marie-Christine Pardon ◽  
Christiane Leovsky ◽  
Samantha Swarbrick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Cell Therapy ◽  
Transgenic Mice ◽  
Amyloid Beta ◽  
Exploratory Study ◽  
Interleukin 10 ◽  
Mechanisms Of Action ◽  
Prostaglandin E ◽  
Therapeutic Effects

Abstract Background We investigated early hallmarks of putative therapeutic effects following systemic transplantation of bone marrow derived macrophages (BM-M) in APP/PS1 transgenic mice. Method BM-M were transplanted into the tail vein and the animals analysed 1 month later. Results BM-M transplantation promoted the reduction of the amyloid beta [37-42] plaque number and size in the cortex and hippocampus of the treated mice, but no change in the more heavily modified pyroglutamate amyloid beta E3 plaques. The number of phenotypically ‘small’ microglia increased in the hippocampus. Astrocyte size decreased overall, indicating a reduction of activated astrocytes. Gene expression of interleukin 6 and 10, interferon-gamma, and prostaglandin E receptor 2 was significantly lower in the hippocampus, while interleukin 10 expression was elevated in the cortex of the treated mice. Conclusions BM-M systemically transplanted, promote a decrease in neuroinflammation and a limited reversion of amyloid pathology. This exploratory study may support the potential of BM-M or microglia-like cell therapy and further illuminates the mechanisms of action associated with such transplants.

scholarly journals Pharmacologic Inhibition of Tpl2 Blocks Inflammatory Responses in Primary Human Monocytes, Synoviocytes, and Blood

2007 ◽  
Vol 282 (46) ◽  
pp. 33295-33304 ◽  
Author(s):  
J. Perry Hall ◽  
Yahya Kurdi ◽  
Sang Hsu ◽  
John Cuozzo ◽  
Julie Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Mediators ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Prostaglandin E ◽  
Human Monocytes ◽  
The Matrix ◽  
Factor Α ◽  
Pharmacologic Inhibition

Tumor necrosis factor α (TNFα) is a pro-inflammatory cytokine that controls the initiation and progression of inflammatory diseases such as rheumatoid arthritis. Tpl2 is a MAPKKK in the MAPK (i.e. ERK) pathway, and the Tpl2-MEK-ERK signaling pathway is activated by the pro-inflammatory mediators TNFα, interleukin (IL)-1β, and bacterial endotoxin (lipopolysaccharide (LPS)). Moreover, Tpl2 is required for TNFα expression. Thus, pharmacologic inhibition of Tpl2 should be a valid approach to therapeutic intervention in the pathogenesis of rheumatoid arthritis and other inflammatory diseases in humans. We have developed a series of highly selective and potent Tpl2 inhibitors, and in the present study we have used these inhibitors to demonstrate that the catalytic activity of Tpl2 is required for the LPS-induced activation of MEK and ERK in primary human monocytes. These inhibitors selectively target Tpl2 in these cells, and they block LPS- and IL-1β-induced TNFα production in both primary human monocytes and human blood. In rheumatoid arthritis fibroblast-like synoviocytes these inhibitors block ERK activation, cyclooxygenase-2 expression, and the production of IL-6, IL-8, and prostaglandin E2, and the matrix metalloproteinases MMP-1 and MMP-3. Taken together, our results show that inhibition of Tpl2 in primary human cell types can decrease the production of TNFα and other pro-inflammatory mediators during inflammatory events, and they further support the notion that Tpl2 is an appropriate therapeutic target for rheumatoid arthritis and other human inflammatory diseases.

scholarly journals Tomorou attenuates progression of rheumatoid arthritis through alteration in ULK-1 independent autophagy pathway in collagen induced arthritis mice model

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Arooma Jannat ◽  
Peter John ◽  
Attya Bhatti ◽  
Muhammad Qasim Hayat
Keyword(s):  
Rheumatoid Arthritis ◽  
Ethyl Acetate ◽  
Ethyl Acetate Extract ◽  
Radical Scavenging ◽  
Treated Group ◽  
Phytochemical Analysis ◽  
Mice Model ◽  
Apoptosis Resistance ◽  
Autophagy Pathway ◽  
Anti Inflammatory

Abstract Rheumatoid arthritis (RA) is a multifactorial disease which is complicated by apoptosis resistance. Autophagy is one of the key mechanisms which are involved in the development of resistance to apoptosis as well as to the standard therapies against RA. Aberration in autophagy and apoptosis homeostasis results in the development of oxidative stress thus complicates the pathogenesis of RA. In the given study, tomorou, an indigenous herb of Hunza-Nagar Valley, has been evaluated for its pro-apoptotic, anti-inflammatory, and anti-rheumatic activity. Several major classes of bioactive phytochemicals including steroids, terpenoids, phenols, flavonoids, and essential oils have been detected in the aqueous and ethyl acetate extracts of tomorou through phytochemical analysis. Plant extracts depicted enhanced free radical scavenging activity through di-phenyl-2-picryl hydrazyl hydrate (DPPH) assay and ameliorated the symptoms of arthritis in collagen induced arthritic (CIA) mice model. Moreover, the 6 week extract treatment resulted in the reduction of IL-6 serum levels thus making it an effective anti-inflammatory agent. Upregulation of microtubule-associated proteins light chain 3b (LC3b) and downregulation of UNC51-like kinase 1 (ULK-1) in arthritic mice proposed a ULK-1 independent non-canonical autophagy pathway. Treatment with extracts upregulated the expression of caspase 3 which in turn inhibited the activity of LC3b thus altering the autophagy pathway. However, ULK-1 expression was restored to normal in aqueous extract treated group whereas it was upregulated in ethyl acetate extract treated group. On the other hand, a novel LC3b-independent autophagy pathway was observed in mice treated with ethyl acetate extract due to ULK-1 upregulation. Despite of significantly high IL-6 levels, the arthritic symptoms waned off which suggested the participation of IL-6 in LC3b-independent autophagy pathway in the extract prepared in ethyl acetate. Conclusively, the study established pro-apoptotic, antioxidant, anti-inflammatory and anti-rheumatic activity of tomorou and suggested an intricate autophagy pathway shift.

scholarly journals Therapeutic effects of Smilax glabra and Bolbostemma paniculatum on rheumatoid arthritis using a rat paw edema model

2018 ◽  
Vol 108 ◽  
pp. 309-315 ◽  
Author(s):  
Yarigui Bao ◽  
Hui Li ◽  
Qi-Yan Li ◽  
Yong Li ◽  
Fei Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Effects ◽  
Paw Edema ◽  
Rat Paw Edema ◽  
Edema Model ◽  
Rat Paw

scholarly journals Anti-Inflammatory Activities of Kukoamine A From the Root Bark of Lycium chinense Miller

2020 ◽  
Vol 15 (3) ◽  
pp. 1934578X2091208
Author(s):  
Lin Wang ◽  
Peipei Wang ◽  
Dandan Wang ◽  
Mengqing Tao ◽  
Wenke Xu ◽  
...  
Keyword(s):  
Protective Role ◽  
Prostaglandin E ◽  
Therapeutic Effects ◽  
Root Bark ◽  
Lycium Chinense ◽  
Paw Edema ◽  
Raw 264.7 Macrophage Cells ◽  
Anti Inflammatory ◽  
Lycium Chinense Miller ◽  
Factor Α

Kukoamine A (Kuk A) is a naturally occurring bioactive spermine alkaloid found in the root bark of Lycium chinense, and it exerts various therapeutic effects including antioxidant, neuroprotective, anti-inflammatory, and antidiabetic effects. This study evaluated the anti-inflammatory properties of Kuk A against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells and carrageenan-induced paw edema in rats. Pretreatment of cells with Kuk A significantly inhibited the production of reactive oxygen species, nitric oxide, prostaglandin E2, cyclooxygenase-2 activity, tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 in LPS-treated cells. In addition, pretreatment of rats with Kuk A significantly decreased inflammatory response to carrageenan-induced paw edema by alleviating proinflammatory cytokines in the serum, malondialdehyde levels in the liver and increasing the activities of liver antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) of carrageenan-treated rats. These results suggest the protective role of Kuk A in acute inflammatory reaction and could be useful in the treatment of inflammatory-related disorders.

scholarly journals Predictive Modeling of MAFLD Based on Hsp90α and the Therapeutic Application of Teprenone in a Diet-Induced Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuan Xie ◽  
Lu Chen ◽  
Zhipeng Xu ◽  
Chen Li ◽  
Yangyue Ni ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mouse Model ◽  
Linear Relationship ◽  
Glycosylated Hemoglobin ◽  
Elevated Serum ◽  
Roc Curves ◽  
Treated Group ◽  
Therapeutic Effects ◽  
Mice Model

Background and AimsThe heat shock protein (Hsp) 90α is induced by stress and regulates inflammation through multiple pathways. Elevated serum Hsp90α had been found in nonalcoholic steatohepatitis (NASH). Geranylgeranylacetone (GGA, also called teprenone) is a terpenoid derivative. It was reported to induce Hsp and alleviate insulin resistance. We aimed to evaluate the Hsp90α as a biomarker in predicting metabolic-associated fatty liver disease (MAFLD) and define the therapeutic effects of geranylgeranylacetone for the disease.MethodsA clinical study was conducted to analyze the elements associated with Hsp90α, and a predictive model of MAFLD was developed based on Hsp90α. The histopathological correlation between Hsp90α and MAFLD was investigated through a diet-induced mouse model. Furthermore, GGA was applied to the mouse model.ResultsSerum Hsp90α was increased in patients with MAFLD. A positive linear relationship was found between age, glycosylated hemoglobin (HbA1c), MAFLD, and serum Hsp90α. Meanwhile, a negative linear relationship with body mass index (BMI) was found. A model using Hsp90α, BMI, HbA1c, and ALT was established for predicting MAFLD. The area under the receiver operating characteristic (ROC) curves was 0.94 (95% CI 0.909–0.971, p = 0.000). The sensitivity was 84.1%, and the specificity was 93.1%. In vitro experiments, GGA induced Hsp90α in steatosis cells. In the mice model, Hsp90α decreased in the GGA treatment group. Hepatic steatosis, inflammation, insulin resistance, and glucose intolerance were improved in the GGA-treated group. Serum Hsp90α was positively correlated with steatohepatitis activity according to hepatic histopathology.ConclusionsSerum Hsp90α was elevated in MAFLD, and a positive correlation between serum Hsp90α and the grade of activity of steatohepatitis was observed. The model using BMI, HbA1c, and alanine aminotransferase (ALT) had a good value to predict MAFLD. The findings also revealed the effectiveness of GGA in the treatment of MAFLD.

The effect of dexamethasone on mucosal immunity of uterine tissue during pregnancy in rat

2019 ◽  
Vol 20 (1) ◽  
pp. 75-84
Keyword(s):  
Early Pregnancy ◽  
Histopathological Examination ◽  
Early Period ◽  
Interleukin 10 ◽  
Treated Group ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Uterine Tissue ◽  
Leukocytic Infiltration

Disturbances in early pregnancy immunity affect embryo development, endometrial receptivity, placental development, fetal growth and lead to subfertility, dexamethasone is a synthetic glucocorticoid used for treatment of various complications. Immune cells and cytokines were examined during the early pregnancy in twenty-four female rats and six male rats for mating. Rats were grouped into two group control and dexamethasone treated by a dose of 50µgm/kgm body weight daily starting from one week before mating and persisted for one week after pregnancy. Blood samples were collected from each rat at 5hrs and at 1,3,7 day of pregnancy. Extracted RNA was subjected to real time PCR to determine mRNA levels for immune related genes interleukin1a(IL1A) and interleukin 10(IL10). Histopathological examination was done to uterus in order to detect leukocyte infiltration in uterine tissue. Results showed that significant increase in white blood cell count mainly eosinophil at 5hrs and lymphocyte at three and seven day of pregnancy of dexamethasone treated group. Moreover, TNF, C-reactive protein and progesterone were increased mainly at seven day of pregnancy of dexamethasone treated group. Similarly, interleukin 1alpha and interleukin 10 significantly increased at 5hrs and one day of pregnancy of dexamethasone treated group. In contrast, serum levels of total antioxidant capacity and estrogen were decreased significantly at 5hrs and seven day in dexamethasone treated group. Histopathological examination of uterus revealed leukocytic infiltration especially neutrophil and few eosinophils at five hours and one day of gestation then eosinophil become absent at 3day and seven day of dexamethasone group. Epithelial height and uterine gland diameter significantly increased at 5hrs, three day and seven days of gestation of dexamethasone treated group. The present investigation demonstrated that using of dexamethasone by dose of 50µgm/kgm during early pregnancy had a conflicting impact on some immune cytokines and parameters and may reflect a harmful response of immune system toward early period of pregnancy

scholarly journals TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 716
Author(s):  
Oksana Sintsova ◽  
Irina Gladkikh ◽  
Anna Klimovich ◽  
Yulia Palikova ◽  
Viktor Palikov ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Control Group ◽  
Transient Receptor Potential Vanilloid ◽  
Paw Edema ◽  
Mice Model ◽  
Edema Formation ◽  
Sensitivity Experiment ◽  
Tnf Α ◽  
Anti Inflammatory

Currently the TRPV1 (transient receptor potential vanilloid type 1) channel is considered to be one of the main targets for pro-inflammatory mediators including TNF-α. Similarly, the inhibition of TRPV1 activity in the peripheral nervous system affects pro-inflammatory mediator production and enhances analgesia in total. In this study, the analgesic and anti-inflammatory effects of HCRG21, the first peptide blocker of TRPV1, were demonstrated in a mice model of carrageenan-induced paw edema. HCRG21 in doses of 0.1 and 1 mg/kg inhibited edema formation compared to the control, demonstrated complete edema disappearance in 24 h in a dose of 1 mg/kg, and effectively reduced the productionof TNF-α in both doses examined. ELISA analysis of blood taken 24 h after carrageenan administration showed a dramatic cytokine value decrease to 25 pg/mL by HCRG21 versus 100 pg/mL in the negative control group, which was less than the TNF-α level in the intact group (40 pg/mL). The HCRG21 demonstrated potent analgesic effects on the models of mechanical and thermal hyperalgesia in carrageenan-induced paw edema. The HCRG21 relief effect was comparable to that of indomethacin taken orally in a dose of 5 mg/kg, but was superior to this nonsteroidal anti-inflammatory drug (NSAID) in duration (which lasted 24 h) in the mechanical sensitivity experiment. The results confirm the existence of a close relationship between TRPV1 activity and TNF-α production once again, and prove the superior pharmacological potential of TRPV1 blockers and the HCRG21 peptide in particular.

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