scholarly journals Exosome and Melatonin Additively Attenuates Inflammation by Transferring miR-34a, miR-124, and miR-135b

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
June Seok Heo ◽  
Ja-Yun Lim ◽  
Dae Wui Yoon ◽  
Sangshin Pyo ◽  
Jinkwan Kim
Keyword(s):  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Underlying Mechanism ◽  
M2 Macrophages ◽  
Necrosis Factor Alpha ◽  
Cellular Models ◽  
Positive Effects ◽  
Cell Based Therapy ◽  
Anti Inflammatory ◽  
Inflammatory Modulation

The positive effects of mesenchymal stem cells (MSCs) are primarily activated through molecular secretions known as paracrine activity, which regulates the function of various cell types including immune cells. Accumulating evidence shows that exosomes of soluble factors released from MSCs are potential alternative agents for stem cell-based therapy, although the exact underlying mechanism has not been elucidated. The purpose of this study was to evaluate the potential effects of exosomes produced by adipose-derived MSCs and to examine the changes in anti-inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex vivo. Isolated exosomes were used to investigate the inflammatory modulation in pro-inflammatory cytokine-treated fibroblasts and THP-1 cells. The anti-inflammatory mRNA expression associated with M2 macrophages was significantly upregulated after exosome treatment in an interferon gamma and tumor necrosis factor alpha-treated inflammatory environment. Furthermore, melatonin-stimulated exosomes exerted superior anti-inflammatory modulation via exosomal miRNAs miR-34a, miR-124, and miR-135b, compared with exosomes. Our results indicate that melatonin-stimulated exosomes originating from adipose-derived MSCs are safe and efficient tools for regenerative medicine to treat inflammatory diseases.

Scutellaria baicalensis Ameliorates Acute Lung Injury by Suppressing Inflammation In Vitro and In Vivo

2017 ◽  
Vol 45 (01) ◽  
pp. 137-157 ◽  
Author(s):  
Jian-Jung Chen ◽  
Chung-Chun Huang ◽  
Heng-Yuan Chang ◽  
Pei-Ying Li ◽  
Yu-Chia Liang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Water Extract ◽  
Scutellaria Baicalensis ◽  
Raw 264.7 Cells ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

Scutellaria baicalensis has been widely used as both a dietary ingredient and traditional herbal medicine in Taiwan to treat inflammation, cancer, and bacterial and viral infections of the respiratory tract and gastrointestinal tract. This paper aims to investigate the in vitro and in vivo anti-inflammatory effects of S. baicalensis. In HPLC analysis, the fingerprint chromatogram of the water extract of S. baicalensis (WSB) was established. The anti-inflammatory effects of WSB were inverstigated using lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) in vitro and LPS-induced lung injury in vivo. WSB attenuated the production of LPS-induced nitric oxide (NO), tumor necrosis factor-alpha (TNF-[Formula: see text], interleukin-[Formula: see text] (IL-1[Formula: see text], and IL-6 in vitro and in vivo. Pretreatment with WSB markedly reduced the LPS-induced histological alterations in lung tissues. Furthermore, WSB significantly reduced the number of total cells and the protein concentration levels in the BALF. WSB blocked protein expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylation of I[Formula: see text]B-[Formula: see text] protein and MAPKs in LPS-stimulated RAW 264.7 cells and LPS-induce lung injury was also blocked. This study suggests that WSB possesses anti-inflammatory effects in vitro and in vivo, and the results suggested that WSB may be a potential therapeutic candidate for the treatment of inflammatory diseases.

scholarly journals Flavonoids Identified from KoreanScutellaria baicalensisGeorgi Inhibit Inflammatory Signaling by Suppressing Activation of NF-κB and MAPK in RAW 264.7 Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Gyeong-Eun Hong ◽  
Jin-A. Kim ◽  
Arulkumar Nagappan ◽  
Silvia Yumnam ◽  
Ho-Jeong Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Mediators ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Two Dimensional Gel Electrophoresis ◽  
Necrosis Factor Alpha ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Scutellaria baicalensisGeorgi has been used as traditional medicine for treating inflammatory diseases, hepatitis, tumors, and diarrhea in Asia. Hence, we investigated the anti-inflammatory effect and determined the molecular mechanism of action of flavonoids isolated from KoreanS. baicalensisG. in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to examine cytotoxicity of the flavonoids at various concentrations of 10, 40, 70, and 100 µg/mL. No cytotoxicity was observed in RAW 264.7 cells at these concentrations. Furthermore, the flavonoids decreased production of inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha and inhibited phosphorylation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in LPS-induced RAW 264.7 cells. Moreover, to identify the differentially expressed proteins in RAW 264.7 cells of the control, LPS-treated, and flavonoid-treated groups, two-dimensional gel electrophoresis and mass spectrometry were conducted. The identified proteins were involved in the inflammatory response and included PRKA anchor protein and heat shock protein 70 kD. These findings suggest that the flavonoids isolated fromS. baicalensisG. might have anti-inflammatory effects that regulate the expression of inflammatory mediators by inhibiting the NF-κB signaling pathway via the MAPK signaling pathway in RAW 264.7 cells.

scholarly journals Polyene Phosphatidylcholine Interacting with TLR-2 Prevents the Synovial Inflammation via Inactivation of MAPK and NF-κB Pathways

2021 ◽  
Author(s):  
Zixuan Xu ◽  
Wenting Hao ◽  
Daxiang Xu ◽  
Yan He ◽  
Ziyi Yan ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Ex Vivo ◽  
Mapk Pathway ◽  
Synovial Fibroblasts ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Synovial Inflammation ◽  
Joint Disease ◽  
Drug Candidate ◽  
Anti Inflammatory

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune joint disease that causes cartilage and bone damage or even disability, seriously endangering human health. Chronic synovial inflammation has been shown to play a vital role in the disease sustainability. Therefore, down-regulation of synovial inflammation is considered to be an effective discipline for RA therapy. Polyene phosphatidylcholine (PPC) is a hepatoprotective agent, which was observed to inhibit inflammation in macrophages and prevent collagen-induced arthritis (CIA) of rats in our previous study. However, the underlying mechanism remains unclear. The present study further reported that PPC can inhibit the synovial inflammation. In lipopolysaccharide (LPS)-stimulated primary synovial fibroblasts (SFs) of mice, PPC significantly decreased pro-inflammatory cytokines production while increasing anti-inflammatory cytokines level. In this process, PPC down-regulated the expression of TLR-2 and their downstream signaling molecules such as MyD88, p-ERK1/2, p-JNK1/2, p-P38 in the MAPK pathway and p-IκBα and NF-κB-p65 in NF-kB pathway. Moreover, the inhibitory effect of PPC on the above molecules and cytokines was weakened after the use of TLR-2 agonist Pam3CSK4. However, PPC lost its anti-inflammatory effect and showed an activation of MAPK and NF-kB pathways in the TLR-2-/- primary SFs after exposure to LPS. Furthermore, these results were confirmed in the SFs from the CIA mouse ex vivo. Collectively, this study demonstrated that PPC can alleviate synovial inflammation through TLR-2 mediated MAPK and NF-κB pathways, which can be proposed to be a potential drug candidate for RA therapy.

scholarly journals IL-12/IL-23p40 identified as a downstream target of apremilast in ex vivo models of arthritis

2019 ◽  
Vol 11 ◽  
pp. 1759720X1982866 ◽  
Author(s):  
Tue W. Kragstrup ◽  
Mary Adams ◽  
Søren Lomholt ◽  
Morten A. Nielsen ◽  
Line D. Heftdal ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
In Vitro Models ◽  
Pde4 Inhibitor ◽  
Necrosis Factor Alpha ◽  
Downstream Effects ◽  
Immune Mediated

Background: Apremilast (Otezla®) is a phosphodiesterase 4 (PDE4) inhibitor approved for the treatment of psoriasis and psoriatic arthritis (PsA), but the reason why apremilast shows clinical effect is not fully understood. The objective of this study was to study the downstream effects of apremilast on cells of inflamed joints in immune-mediated inflammatory arthritis. Methods: Synovial fluid was obtained from patients with active rheumatoid arthritis (RA), PsA or peripheral spondyloarthritis (SpA; n = 18). The in vitro models consisted of synovial fluid mononuclear cells (SFMCs) or fibroblast-like synovial cells (FLSs) cultured for 48 h, SFMCs cultured for 21 days, an osteoclast pit formation assay, and a mineralization assay. Results: In SFMCs cultured for 48 h, apremilast decreased the production of interleukin (IL)-12/IL-23p40 (the shared subunit of IL-12 and IL-23), colony-stimulating factor 1, CD6, and CD40 and increased the production of C-X-C motif chemokine 5 dose-dependently. Apremilast had a very different response signature compared with the tumor necrosis factor alpha inhibitor adalimumab with a substantially greater inhibition of IL-12/IL-23p40. In SFMCs cultured for 21 days, apremilast increased the secretion of IL-10. In FLS cultures, apremilast decreased matrix metalloproteinase-3 production. Apremilast decreased osteoclastogenesis but did not affect mineralization by human osteoblasts. Conclusion: This study reveals the downstream effects of apremilast in ex vivo models of arthritis with a strong inhibition of IL-12/IL-23p40 by SFMCs. Our findings could explain some of the efficacy of apremilast seen in IL-12/IL-23-driven immune-mediated inflammatory diseases such as psoriasis and PsA.

The effect of total flavonoids from Saussurea involucrata on the secretion of pro-inflammatory mediators in lipopolysaccharide stimulated RAW264.7 macrophages

2020 ◽  
Author(s):  
Li-Shan Yan ◽  
Li Wang ◽  
Brian Chi-Yan Cheng ◽  
Yu Ding ◽  
Jing Kong ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Nuclear Translocation ◽  
Cell Model ◽  
Inflammatory Diseases ◽  
Underlying Mechanism ◽  
Total Flavonoids ◽  
Saussurea Involucrata ◽  
Cytokines And Chemokines ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory

Abstract Background Saussurea involucrate (SI) has long been used to treat inflammatory diseases, such as rheumatoid arthritis. The main active constituents of SI are flavonoids, which are a class of polyphenolic compounds. However, few studies have investigated the anti-inflammatory activity of the total flavonoids of SI (FSI). The mechanism underlying this action is still not fully understood. In the present study, we employed RAW264.7 cell line as an inflammatory cell model to investigate the anti-inflammatory effects of FSI and explore the corresponding molecular mechanisms.Methods We extracted FSI using chromatographic column method. The cell viability was determined by MTT assay. The production of nitric oxide (NO) was detected by Griess assay. The release of cytokines and chemokines were determined by ELISA assays. The nuclear translocation of p65, c-Jun, and IRF3 was detected by immunofluorescence microscopy. Western blotting analysis was performed to determine the related protein expression.Results The results showed that the amount of FSI extracted from SI was 751.5 mg/g. The production of inflammatory mediators was effectively inhibited by FSI. Meanwhile, FSI also suppressed the nuclear translocation of p65, c-Jun, and IRF3. The elevated expression of iNOS, COX-2, p-IKKα/β, p-TBK1, p-IκBα, p-ERK, p-p38, p-JNK, p-p65, p-c-Jun, p-IRF3 induced by LPS was remarkably reduced by FSI treatment.Conclusion These findings indicated that FSI has a potential ability to inhibit the secretion of pro-inflammatory mediators and the underlying mechanism may be related to block the p65, c-Jun, and IRF3 signaling pathways. This study provided evidence for the anti-inflammatory mode and the underlying mechanism of FSI.

cis-Aconitic Acid, a Constituent of Echinodorus grandiflorus Leaves, Inhibits Antigen-Induced Arthritis and Gout in Mice

Planta Medica ◽  
2021 ◽  
Author(s):  
Diego Pinto de Oliveira ◽  
Eliana de Faria Garcia ◽  
Mariana Assíria de Oliveira ◽  
Luiza C. M. Candido ◽  
Fernanda M. Coelho ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Oral Treatment ◽  
Joint Inflammation ◽  
Underlying Mechanism ◽  
Monosodium Urate ◽  
Joint Cavity ◽  
Leukocyte Accumulation ◽  
Aconitic Acid ◽  
Anti Inflammatory

Abstract cis-Aconitic acid is a constituent from the leaves of Echinodorus grandiflorus, a medicinal plant traditionally used in Brazil to treat inflammatory conditions, including arthritic diseases. The present study aimed to investigate the anti-arthritic effect of cis-aconitic acid in murine models of antigen-induced arthritis and monosodium urate-induced gout. The possible underlying mechanisms of action was evaluated in THP-1 macrophages. Oral treatment with cis-aconitic acid (10, 30, and 90 mg/kg) reduced leukocyte accumulation in the joint cavity and C-X-C motif chemokine ligand 1 and IL-1β levels in periarticular tissue. cis-Aconitic acid treatment reduced joint inflammation in tissue sections of antigen-induced arthritis mice and these effects were associated with decreased mechanical hypernociception. Administration of cis-aconitic acid (30 mg/kg p. o.) also reduced leukocyte accumulation in the joint cavity after the injection of monosodium urate crystals. cis-Aconitic acid reduced in vitro the release of TNF-α and phosphorylation of IκBα in lipopolysaccharide-stimulated THP-1 macrophages, suggesting that inhibition of nuclear factor kappa B activation was an underlying mechanism of cis-aconitic acid-induced anti-inflammatory effects. In conclusion, cis-aconitic acid has significant anti-inflammatory effects in antigen-induced arthritis and monosodium urate-induced arthritis in mice, suggesting its potential for the treatment of inflammatory diseases of the joint in humans. Additionally, our findings suggest that this compound may contribute to the anti-inflammatory effect previously reported for E. grandiflorus extracts.

scholarly journals Bile acid bio-nanoencapsulation improved drug targeted-delivery and pharmacological effects via cellular flux: 6-months diabetes preclinical study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Armin Mooranian ◽  
Susbin Raj Wagle ◽  
Bozica Kovacevic ◽  
Ryu Takechi ◽  
John Mamo ◽  
...  
Keyword(s):  
Bile Acid ◽  
Targeted Delivery ◽  
Oral Delivery ◽  
Ex Vivo ◽  
Biological Effects ◽  
Protective Effects ◽  
Β Cells ◽  
Positive Effects ◽  
Anti Inflammatory

AbstractThe antilipidemic drug, probucol (PB), has demonstrated potential applications in Type 2 diabetes (T2D) through its protective effects on pancreatic β-cells. PB has poor solubility and bioavailability, and despite attempts to improve its oral delivery, none has shown dramatic improvements in absorption or antidiabetic effects. Preliminary data has shown potential benefits from bile acid co-encapsulation with PB. One bile acid has shown best potential improvement of PB oral delivery (ursodeoxycholic acid, UDCA). This study aimed to examine PB and UDCA microcapsules (with UDCA microcapsules serving as control) in terms of the microcapsules’ morphology, biological effects ex vivo, and their hypoglycemic and antilipidemic and anti-inflammatory effects in vivo. PBUDCA and UDCA microcapsules were examined in vitro (formulation studies), ex vivo and in vivo. PBUDCA microcapsules exerted positive effects on β-cells viability at hyperglycemic state, and brought about hypoglycemic and anti-inflammatory effects on the prediabetic mice. In conclusion, PBUDCA co-encapsulation have showed beneficial therapeutic impact of dual antioxidant-bile acid effects in diabetes treatment.

Eucommiae Cortex Inhibits TNF-α and IL-6 Through the Suppression of Caspase-1 in Lipopolysaccharide-Stimulated Mouse Peritoneal Macrophages

2012 ◽  
Vol 40 (01) ◽  
pp. 135-149 ◽  
Author(s):  
Min-Cheol Kim ◽  
Dae-Seung Kim ◽  
Su-Jin Kim ◽  
Jinbong Park ◽  
Hye-Lin Kim ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Pharmacological Action ◽  
Underlying Mechanism ◽  
Peritoneal Macrophages ◽  
Prostaglandin E ◽  
Necrosis Factor Alpha ◽  
Caspase 1 ◽  
Factor Alpha ◽  
Mouse Peritoneal Macrophages

Eucommiae cortex (EC) is used in various traditional Korean medicines in the form of tonics, analgesics, and sedatives. However, the underlying mechanism of its anti-inflammatory effect remains unclear. This study attempts to determine the effects of EC on lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. The findings of the study show that EC inhibits the LPS-induced production of tumor necrosis factor-alpha and interleukin-6. Exposure to EC also reduces an inflammation-induced increase in the levels of cyclooxigenase-2 and the production of prostaglandin E 2 and nitric oxide in mouse peritoneal macrophages. Furthermore, EC suppresses the activation of nuclear factor-kappa B and caspase-1. These results provide novel insights into the pharmacological action of EC and indicate that EC has a potential in the treatment of inflammatory diseases.

scholarly journals S-Layer Protein Mediates the Stimulatory Effect of Lactobacillus helveticus MIMLh5 on Innate Immunity

2012 ◽  
Vol 79 (4) ◽  
pp. 1221-1231 ◽  
Author(s):  
Valentina Taverniti ◽  
Milda Stuknyte ◽  
Mario Minuzzo ◽  
Stefania Arioli ◽  
Ivano De Noni ◽  
...  
Keyword(s):  
Cell Line ◽  
Ex Vivo ◽  
Lactobacillus Helveticus ◽  
Human Macrophage ◽  
Mouse Bone Marrow ◽  
Similar Response ◽  
Bacterial Cells ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

ABSTRACTThe ability to positively affect host health through the modulation of the immune response is a feature of increasing importance in measuring the probiotic potential of a bacterial strain. However, the identities of the bacterial cell components involved in cross talk with immune cells remain elusive. In this study, we characterized the dairy strainLactobacillus helveticusMIMLh5 and its surface-layer protein (SlpA) usingin vitroandex vivoanalyses. We found that MIMLh5 and SlpA exert anti-inflammatory effects by reducing the activation of NF-κB on the intestinal epithelial Caco-2 cell line. On the contrary, MIMLh5 and SlpA act as stimulators of the innate immune system by triggering the expression of proinflammatory factors tumor necrosis factor alpha and COX-2 in the human macrophage cell line U937 via recognition through Toll-like receptor 2. In the same experiments, SlpA protein did not affect the expression of the anti-inflammatory cytokine interleukin-10. A similar response was observed following stimulation of macrophages isolated from mouse bone marrow or the peritoneal cavity. These results suggest that SlpA plays a major role in mediating bacterial immune-stimulating activity, which could help to induce the host's defenses against and responses toward infections. This study supports the concept that the viability of bacterial cells is not always essential to exert immunomodulatory effects, thus permitting the development of safer therapies for the treatment of specific diseases according to a paraprobiotic intervention.

Antiangiogenic Properties of a Novel Shark Cartilage Extract: Potential Role in the Treatment of Psoriasis

1998 ◽  
Vol 2 (3) ◽  
pp. 146-152 ◽  
Author(s):  
Éric Dupont ◽  
Pierre E. Savard ◽  
Camille Jourdain ◽  
Christina Juneau ◽  
Alain Thibodeau ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Active Agent ◽  
Histological Change ◽  
Vascular Changes ◽  
Collagenase Activity ◽  
Dependent Inhibition ◽  
Inhibition Of Angiogenesis ◽  
Shark Cartilage ◽  
Anti Inflammatory

Background: A number of inflammatory and immune diseases are associated with vascular changes. Psoriasis, as an example, is a common inflammatory skin disease with dilation of capillaries as an early histological change. In more developed psoriatic lesions there is proliferation of blood vessels and neovascularization. The use of agents that target these vascular changes represents a novel therapeutic strategy in the treatment of inflammatory diseases. Since cartilage is an avascular tissue, it has been hypothesized that there may be factors found in cartilage that inhibit blood vessel formation. Objective: The objectives of this study were 1) to determine whether extracts of cartilage could inhibit angiogenesis, and 2) since altered angiogenesis is associated with certain diseases, including psoriasis, to examine whether inhibition of angiogenesis could potentially contribute to the treatment of psoriasis. Methods: Extracts of shark cartilage were prepared by homogenization and ultrafiltration to derive the active agent termed Æ-941. This agent was tested for antiangiogenesis activity using the embryonic vascularization test, which is a modification of the ex vivo chick embryo culture (CAM). Since one of the first steps in angiogenesis is degradation by metalloproteinases of the basement membrane of capillaries, Æ-941 was tested for collagenase activity using a fluorogenic peptide substrate. Anti-inflammatory properties were tested using a cutaneous irritation model in humans. Results: A dose dependent inhibition in embryonic neovascularization as well as in collagenase activity by Æ-941 was demonstrated. When test compounds were applied on the forearms of test subjects, Æ-941 was shown to have anti-inflammatory properties. Anecdotal data suggested that topical Æ-941 had a beneficial effect in psoriasis. Conclusion: Our results show that Æ-941 has anti-angiogenic and anti-inflammatory properties. Antiangiogenesis agents such as Æ-941 provide an entirely new class of agents to treat cutaneous and systemic diseases associated with altered vascularity.

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