scholarly journals Immunomodulatory Effects of Diterpene Quinone Derivatives from the Roots ofHorminum pyrenaicumin Human PBMC

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
K. Becker ◽  
S. Schwaiger ◽  
B. Waltenberger ◽  
D. Fuchs ◽  
C. K. Pezzei ◽  
...  

Several phytochemicals were shown to interfere with redox biology in the human system. Moreover, redox biochemistry is crucially involved in the orchestration of immunological cascades. When screening for immunomodulatory compounds, the two interferon gamma- (IFN-γ-) dependent immunometabolic pathways of tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) and neopterin formation by GTP-cyclohydrolase 1 (GTP-CH-I) represent prominent targets, as IFN-γ-related signaling is strongly sensitive to oxidative triggers. Herein, the analysis of these pathway activities in human peripheral mononuclear cells was successfully applied in a bioactivity-guided fractionation strategy to screen for anti-inflammatory substances contained in the root ofHorminum (H.) pyrenaicumL. (syn. Dragon’s mouth), the only representative of the monophyletic genusHorminum. Four abietane diterpene quinone derivatives (horminone, 7-O-acetylhorminone, inuroyleanol and its 15,16-dehydro-derivative, a novel natural product), two nor-abietane diterpene quinones (agastaquinone and 3-deoxyagastaquinone) and twoabeo18 (4 → 3) abietane diterpene quinones (agastol and its 15,16-dehydro-derivative) could be identified. These compounds were able to dose-dependently suppress the above mentioned pathways with different potency. Beside the description of new active compounds, this study demonstrates the feasibility of integrating IDO-1 and GTP-CH-I activity in the search for novel anti-inflammatory compounds, which can then be directed towards a more detailed mode of action analysis.

1997 ◽  
Vol 48 (1) ◽  
pp. 11-15 ◽  
Author(s):  
A. Mustafa ◽  
A. Mustafa ◽  
F. Nyberg ◽  
F. Nyberg ◽  
M. Mustafa ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7363
Author(s):  
Xavier Capó ◽  
Miquel Martorell ◽  
Josep A. Tur ◽  
Antoni Sureda ◽  
Antoni Pons

Background: Pork lard (PL) is traditionally used as an anti-inflammatory agent. We propose to demonstrate the anti-inflammatory properties of PL, and elucidate which compounds could be responsible for the anti-inflammatory effects. Methods: The anti-inflammatory effects of PL were tested in a rat model of zymosan-induced hind paw inflammation. Further, the hydroalcoholic extract from PL was obtained, the composition analyzed, and the anti-inflammatory activity of the extracts and isolated components assayed using immune cells stimulated with lipopolysaccharide (LPS). Results: Applying the ointment on the inflamed rat feet reduced the foot diameter, foot weight, and activities of antioxidant enzymes and inflammatory markers of circulating neutrophils. The main components of the hydroalcoholic extract were 5-dodecanolide, oleamide, hexadecanoic acid, 9-octadecenoic acid, hexadecanamide, and resolvin D1. Conclusions: PL reduces the immune response in an animal model stimulated with zymosan. Hydroalcoholic PL extract and its components (5-Dodecanolide, Oleamide, and Resolvin D1) exerted an anti-inflammatory effect on LPS-stimulated neutrophils and peripheral mononuclear cells reducing the capability to produce TNFα, as well as the activities of antioxidant and pro-inflammatory enzymes. These effects are attributable to 5-dodecanolide, although the effects of this compound alone do not reach the magnitude of the anti-inflammatory effects observed by the complete hydroalcoholic extract.


2021 ◽  
Author(s):  
Alireza Karimollah ◽  
Anahid Hemmatpur ◽  
Taha Vahid

Abstract There are accumulating reports regarding poor response to the common antidepressant therapy. Antidepressant resistance has often been associated with activation of the inflammatory system. Accordingly, major depressive disorder (MDD) patients displaying inflammation prior to the treatment are less responsive to antidepressants. We hypothesized that the inefficacy of antidepressant therapy in some patients could be due to the drugs’ inflammatory mode of action that remained overshadowed by their substantial therapeutic value. Bupropion is a common-used antidepressant that is prescribed for seasonal affective disorders and smoking cessation as well. Nevertheless, there are some reports regarding inflammation induction and depressive behavior exacerbation in response to bupropion. Here, we put a spot on bupropion and investigate the alterations of innate and adaptive immunity cytokines and the influence on immune signaling pathways. Therefore, we treated LPS-stimulated human peripheral mononuclear cells (PBMCs) with different doses of bupropion. Pro-/ anti-inflammatory cytokines (TNF-ɑ, IL-1ß, IL-17, and IL-10) on both transcriptional and translational levels are assessed as well as the involvement of the JAK2 /STAT3, TLR2, and TLR4 signaling in this process. Bupropion decreased IL-17A, TNF-ɑ, and IL-1ß protein levels in the cultures. Nonetheless, the results regarding the target genes expression were controversial. Surprisingly, TNF-ɑ and IL-17A genes expression increased following bupropion treatment. TLR2, TLR4, JAK2, and STAT3 gene expression also rose in response to bupropion. Our findings suggest that bupropion possesses pro-inflammatory properties especially at concentrations of 50 and 100 and would rather be co-administrated with anti-inflammatory agents at least in patients with inflammatory conditions.


Author(s):  
Kimberley E. Freedman ◽  
Jessica L. Hill ◽  
Yuren Wei ◽  
Allegra R. Vazquez ◽  
Diana Grubb ◽  
...  

Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-treatment as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an anti-inflammatory effect of B. subtilis, manifested as a decrease in immune cell populations within the basal state along with an increase in anti-inflammatory immune cells in response to LPS stimulation. Overall gastrointestinal health, microbiota, and circulating and fecal markers of inflammation and gut barrier function were largely unaffected by DE111 treatment. These data suggest that the novel probiotic B. subtilis DE111 may have clinical applications in modulating immune homeostasis via anti-inflammatory mechanisms.


2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Panayoula C. Tsiotra ◽  
Constantine Tsigos ◽  
Eleni Anastasiou ◽  
Eleni Yfanti ◽  
Eleni Boutati ◽  
...  

Resistin has been shown to cause insulin resistance and to impair glucose tolerance in rodents, but in humans its physiological role still remains elusive. The aim of this study was to examine whether resistin mRNA expression in human peripheral mononuclear cells (PBMCs) and its corresponding plasma levels are altered in type 2 diabetes. Resistin mRNA levels were easily detectable in human PBMC, and found to be higher in DM2 compared to healthy women(P=.05). Similarly, mononuclear mRNA levels of the proinflammatory cytokines IL-1β, TNF-α, and IL-6 were all significantly higher in DM2 compared to control women(P<.001). The corresponding plasma resistin levels were slightly, but not significantly, increased in DM2 women(P=.051), and overall, they correlated significantly with BMI (r=0.406,P=.010) and waist circumference (r=0.516,P=.003), but not with fasting insulin levels or HOMA-IR. Resistin mRNA expression is increased in PBMC from DM2 women, together with increased expression of the inflammatory cytokines IL-1β, TNF-α, and IL-6, independent of obesity. These results suggest that resistin and cytokines might contribute to the low-grade inflammation and the increased atherogenic risk observed in these patients.


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