scholarly journals Guttiferone K Exerts the Anti-inflammatory Effect on Mycobacterium Tuberculosis- (H37Ra-) Infected Macrophages by Targeting the TLR/IRAK-1 Mediated Akt and NF-κB Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Qingwen Zhang ◽  
Jinxia Sun ◽  
Yan Fu ◽  
Weigang He ◽  
Yinhong Li ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Interleukin 1 ◽  
Active Agent ◽  
Infectious Agent ◽  
Underlying Mechanism ◽  
Peritoneal Macrophages ◽  
Infection Model ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Mycobacterium tuberculosis (Mtb) remains a great threat to global health, killing more people than any other single infectious agent and causing uncontrollable inflammation in the host. Poorly controlled inflammatory processes can be deleterious and result in immune exhaustion. The current tuberculosis (TB) control is facing the challenge of drugs deficiency, especially in the context of increasingly multidrug resistant (MDR) TB. Under this circumstance, alternative host-directed therapy (HDT) emerges timely which can be exploited to improve the efficacy of TB treatment and disease prognosis by targeting the host. Here, we established the in vitro infection model of Mtb macrophages with H37Ra strain to seek effective anti-TB active agent. The present study showed that Guttiferone K, isolated from Garcinia yunnanensis, could significantly inhibit Mtb-induced inflammation in RAW264.7 and primary peritoneal macrophages. It was evidenced by the decreased production of inflammatory mediators, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Further studies with immunoblotting and immunofluorescence revealed that Guttiferone K obviously inhibits the nuclear factor-kappa B (NF-κB) both in RAW264.7 and primary peritoneal macrophages relying on the TLR/IRAK-1 pathway. Guttiferone K could also suppress the NLRP3 inflammasome activity and induce autophagy by inhibiting the protein kinase B (p-Akt) and mammalian target of rapamycin (mTOR) phosphorylation at Ser473 and Ser2448 in both cell lines. Thus, Guttiferone K possesses significant anti-inflammatory effect, alleviating Mtb-induced inflammation with an underlying mechanism that targeting on the TLR/IRAK-1 pathway and inhibiting the downstream NF-κB and Akt/mTOR signaling pathways. Together, Guttiferone K can be an anti-inflammatory agent candidate for the design of new adjunct HDT drugs fighting against tuberculosis.

Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats

2005 ◽  
Vol 288 (3) ◽  
pp. E486-E492 ◽  
Author(s):  
Miriam Granado ◽  
Teresa Priego ◽  
Ana I. Martín ◽  
M. Ángeles Villanúa ◽  
Asunción López-Calderón
Keyword(s):  
Growth Hormone ◽  
Immune Cells ◽  
Peritoneal Macrophages ◽  
Chronic Arthritis ◽  
Gastrointestinal Hormone ◽  
Serum Concentrations ◽  
Anti Inflammatory ◽  
Nitrite Nitrate ◽  
Inflammatory Effect

Chronic arthritis induces hypermetabolism and cachexia. Ghrelin is a gastrointestinal hormone that has been proposed as a treatment to prevent cachexia. The aim of this work was to examine the effect of administration of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) to arthritic rats. Male Wistar rats were injected with Freund’s adjuvant, and 15 days later arthritic and control rats were daily injected with GHRP-2 (100 μg/kg) or with saline for 8 days. Arthritis induced an increase in serum ghrelin ( P < 0.01) and a decrease in serum concentrations of leptin ( P < 0.01), whereas GHRP-2 administration increased serum concentrations of leptin. GHRP-2 increased food intake in control rats but not in arthritic rats. However, in arthritic rats GHRP-2 administration ameliorated the external symptoms of arthritis, as it decreased the arthritis score (10.4 ± 0.8 vs. 13.42 ± 0.47, P < 0.01) and the paw volume. In addition, circulating IL-6 and nitrites/nitrates were increased by arthritis, and GHRP-2 treatment decreased the serum IL-6 levels ( P < 0.01). To elucidate whether GHRP-2 is able to modulate IL-6 release directly on immune cells, peritoneal macrophage cultures were incubated with GHRP-2 or ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor. Both GHRP-2 (10−7 M) and ghrelin (10−7 M) prevented endotoxin-induced IL-6 and decreased nitrite/nitrate release from peritoneal macrophages in vitro. These data suggest that GHRP-2 administration has an anti-inflammatory effect in arthritic rats that seems to be mediated by ghrelin receptors directly on immune cells.

scholarly journals PPAR-γ Activation Exerts an Anti-inflammatory Effect by Suppressing the NLRP3 Inflammasome in Spinal Cord-Derived Neurons

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Qing-Qi Meng ◽  
Zhen-Cheng Feng ◽  
Xing-Liang Zhang ◽  
Li-Qiong Hu ◽  
Min Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Functional Recovery ◽  
Nlrp3 Inflammasome ◽  
Interleukin 1 ◽  
Peroxisome Proliferator ◽  
Caspase 1 ◽  
Cord Injury ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Persistent inflammation disrupts functional recovery after spinal cord injury (SCI). Peroxisome proliferator-activated receptor gamma (PPAR-γ) activation promotes functional recovery in SCI rats by inhibiting inflammatory cascades and increasing neuronal survival. We sought to clarify the relationship between PPAR-γ activation and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome suppression, and the role of NF-κB in activating the NLRP3 inflammasome in neurons. In SCI rats, we found that rosiglitazone (PPAR-γ agonist) inhibited the expression of caspase-1. In in vitro neurons, G3335 (PPAR-γ antagonist) reversed the rosiglitazone-induced inhibition of caspase-1, interleukin 1 (IL-1β), and interleukin 6 (IL-6). Rosiglitazone inhibited the expression of NLRP3, caspase-1, IL-1β, and IL-6. However, the activator of NLRP3 could counteract this inhibition induced by PPAR-γ activation. NF-κB did not participate in the process of rosiglitazone-induced inhibition of NLRP3. Consistent with our in vitro results, we verified that locomotor recovery of SCI rats in vivo was regulated via PPAR-γ, NLRP3, and NF-κB. These results suggest that PPAR-γ activation exerts an anti-inflammatory effect by suppressing the NLRP3 inflammasome—but not NF-κB—in neurons and that PPAR-γ activation is a promising therapeutic target for SCI.

In vitro immunoregulatory activity and anti-inflammatory effect of Echinococcus granulosus laminated layer

Acta Tropica ◽  
2021 ◽  
Vol 218 ◽  
pp. 105886
Author(s):  
Sara Benazzouz ◽  
Manel Amri ◽  
Junhua Wang ◽  
Samia Bouaziz ◽  
Fahima Ameur ◽  
...  
Keyword(s):  
Echinococcus Granulosus ◽  
Anti Inflammatory ◽  
Laminated Layer ◽  
Inflammatory Effect

scholarly journals Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2529
Author(s):  
Haeyeop Kim ◽  
Woo Seok Yang ◽  
Khin Myo Htwe ◽  
Mi-Nam Lee ◽  
Young-Dong Kim ◽  
...  
Keyword(s):  
Ethanol Extract ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Related Proteins ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

scholarly journals In vitro evidence for the involvement of H2S pathway in the effect of clodronate during inflammatory response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rosangela Montanaro ◽  
Alessio D’Addona ◽  
Andrea Izzo ◽  
Carlo Ruosi ◽  
Vincenzo Brancaleone
Keyword(s):  
Inflammatory Markers ◽  
In Vitro Study ◽  
Inos Expression ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Inflammatory Effect

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.

scholarly journals Development and Evaluation of a Topical Anti-Inflammatory Preparation Containing Dodonaea polyandra Extract

2015 ◽  
Vol 18 (4) ◽  
pp. 578 ◽  
Author(s):  
Bradley S Simpson ◽  
Xianling Luo ◽  
Jiping Wang ◽  
Yunmei Song ◽  
David Claudie ◽  
...  
Keyword(s):  
Phase Separation ◽  
Human Skin ◽  
Dosage Form ◽  
Interleukin 1 ◽  
In Vitro Release ◽  
Skin Inflammation ◽  
Skin Model ◽  
Inflammation Model ◽  
Anti Inflammatory

Purpose: We have previously reported that the Australian Northern Kaanju (Kuuku I’yu) medicinal plant Dodonaea polyandra has anti-inflammatory activity. This is attributed largely to the presence of clerodane diterpenoids contained within the leaf resin. We envisaged developing a topical preparation to treat indications relating to skin inflammation. However, it was unknown whether the resin could be incorporated into a suitable dosage form while retaining the therapeutic value demonstrated in previous work. Therefore, the following study was undertaken to assess parameters of safety and efficacy for a prototype formulation containing the leaf resin extracted from D. polyandra. Methods: Using the assessment criteria of optimum appearance, tactile feeling, spreadability and odour, 78 different formulations were developed. Formulation stability was assessed using a centrifugal test with preparations displaying phase separation further modified or re-formulated. A prototype formulation containing 5% w/w plant resin was selected and subjected to in vitro release studies. This was quantified through HPLC analysis using two major bioactive diterpenoids as reference. The prototype formulation was tested for efficacy in a TPA-induced acute murine skin inflammation model as well as a 3D human skin model for irritancy/toxicity (Epiderm™). Results: The prototype resin cream was a chartreuse-coloured homogenous semisolid preparation that was readily spreadable upon contact with skin with no sensation of tackiness, residual greasiness, or irritation. The optimized cream showed no phase separation after 30 min centrifugation at 825 g. In the TPA-induced inflammation model, the resin formulation significantly reduced ear thickness and interleukin-1 beta levels in mouse ear tissue. The 5% w/w resin cream formulation showed no irritancy in a 3D human skin model. Conclusions: Our results demonstrate that bioactive resin from D. polyandra can be formulated into a stable and non-irritant semi-solid dosage form and reduce parameters of acute skin inflammation in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Effects of esculentoside A on turnour necrosis factor production by mice peritoneal macrophages

1992 ◽  
Vol 1 (6) ◽  
pp. 375-377 ◽  
Author(s):  
Fang Jun ◽  
Zheng Qin Yue ◽  
Wang Hong Bin ◽  
Ju Dian Wen ◽  
Yi Yang Hua
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Inflammatory Mediator ◽  
Platelet Activating Factor ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Necrosis Factor ◽  
Inflammatory Effect

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous experiments showed that it had strong anti-inflammatory effects. Tumour necrosis factor (TNF) is an important inflammatory mediator. In order to study the mechanism of the anti-inflammatory effect of EsA, it was determined whether TNF production from macrophages was altered by EsA under lipopolysaccharide (LPS) stimulated conditions. EsA was found to decrease both extracellular and cell associated TNF production in a dose dependent manner at concentrations higher than 1 μmol/l EsA. Previous studies have showed that EsA reduced the releasing of platelet activating factor (PAF) from rat macrophages. The reducing effects of EsA on the release of TNF and PAF may explain its anti-inflammatory effect.

scholarly journals Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

2018 ◽  
Vol 51 (6) ◽  
pp. 2575-2590 ◽  
Author(s):  
Gang Zhong ◽  
Ruiming Liang ◽  
Jun Yao ◽  
Jia Li ◽  
Tongmeng Jiang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cruciate Ligament ◽  
Interleukin 1 ◽  
Cartilage Degradation ◽  
Chondrocyte Apoptosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Viability Assay ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

Background/Aims: Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA. Methods: The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation. Conclusion: In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA.

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