scholarly journals Diterpenoids from the Brown Alga Rugulopteryx okamurae and Their Anti-Inflammatory Activity

Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 677
Author(s):  
Belén Cuevas ◽  
Ana I. Arroba ◽  
Carolina de los Reyes ◽  
Laura Gómez-Jaramillo ◽  
M. Carmen González-Montelongo ◽  
...  

Brown algae of the Family Dictyotaceae produce an array of structurally diverse terpenoids, whose biomedical potential in the anti-inflammatory area has been scarcely explored. Herein, the chemical study of the alga Rugulopteryx okamurae has led to the isolation of ten new diterpenoids: rugukadiol A (1), rugukamurals A–C (2–4), and ruguloptones A–F (6–10). The structures of the new compounds were established by spectroscopic means. Compound 1 exhibits an unprecedented diterpenoid skeleton featuring a bridged tricyclic undecane system. Compounds 2–10 belong to the secospatane class of diterpenoids and differ by the oxygenated functions that they contain. In anti-inflammatory assays, the new diterpenoid 1 and the secospatanes 5 and 10 significantly inhibited the production of the inflammatory mediator NO in LPS-stimulated microglial cells Bv.2 and macrophage cells RAW 264.7. Moreover, compounds 1 and 5 were found to strongly inhibit the expression of Nos2 and the pro-inflammatory cytokine Il1b in both immune cell lines.

2010 ◽  
Vol 48 (8-9) ◽  
pp. 2045-2051 ◽  
Author(s):  
Soo-Jin Heo ◽  
Weon-Jong Yoon ◽  
Kil-Nam Kim ◽  
Gin-Nae Ahn ◽  
Sung-Myung Kang ◽  
...  

2016 ◽  
Vol 15 (4) ◽  
pp. NP13-NP25 ◽  
Author(s):  
Hsiao-Chien Lin ◽  
Jin-Yuarn Lin

Five different crude polysaccharides from guava seed (GSPS), bitter buckwheat (BBPS), common buckwheat (CBPS), red Formosa lambsquarters (RFLPS), and yellow Formosa lambsquarters (YFLPS) were isolated to treat human prostate cancer PC-3 cells via direct action or tumor immunotherapy. The splenocyte- and macrophage-conditioned media (SCM and MCM) were prepared using individual selected polysaccharides, and then SCM or MCM was further collected to treat PC-3 cells. The relationship between PC-3 cell growth and Th1/Th2 cytokines in SCM as well as proinflammatory/anti-inflammatory cytokine secretion profiles in MCM were delineated. The results showed that all 5 selected polysaccharides did not significantly inhibit PC-3 cell growth via direct action. However, SCM or MCM cultured in the absence or presence of 5 selected polysaccharides significantly ( P < .05) inhibited PC-3 cell growth. MCM cultured with 5 polysaccharides dose dependently enhanced their inhibitory effects on the viabilities of PC-3 cells than those cultured without polysaccharides. There was a significant ( P < .05) negative correlation between PC-3 cell viabilities and (interleukin [IL]-6 + tumor necrosis factor [TNF]-α)/IL-10 level ratios in the corresponding MCM, implying that macrophages suppress PC-3 cell growth through decreasing secretion ratios of proinflammatory/anti-inflammatory cytokines in a tumor microenvironment.


2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Cathal McCarthy ◽  
Michelle Duffy ◽  
Declan Mooney ◽  
William James ◽  
Desmond J Fitzgerald ◽  
...  

We have previously shown that dietary administration of conjugated linoleic acid (CLA) induces regression of pre-established atherosclerosis in the apoE -/- mouse, via modification of inflammatory cell function. However, the exact mechanism through which this occurs has not been elucidated. Here we describe a functional role for signaling of the anti-inflammatory cytokine, IL-10, in atherosclerosis regression and investigate the consequence of enhanced IL-10 generation on the immune cell population in vivo . Our initial aim was todelineate the atheroprotective mechanisms modulated by CLA. Transcriptomic analysis of aortic tissue in the CLA-induced regression model identified an enrichment of the IL-10 signaling pathway. Further analysis of the network identified increased IL-10 receptor expression (localized to the macrophage cells) and STAT3 phosphorylation; and increased expression of downstream target genes such as the anti-inflammatory cytokine IL-1Ra (by 3.45 ± 0.83 p<0.05 fold) and suppressor of cytokine signaling (SOCS3) (by 2.24± 0.44 p<0.01 fold). Moreover, there was increased circulating IL-10 serum levels in apoE -/- mice fed a CLA supplemented 1% cholesterol diet compared with apoE -/- mice fed a 1% cholesterol diet alone (41.9 ± 8.9 vs 79.8 pg/ml ± 22.4 p<0.01). Interestingly, both IL-10 production and STAT3 phosphorylation was significantly increased in bone marrow derived macrophages from CLA fed mice. We next employed flow cytometry to delineate the phenotype of single cell suspensions of aortae. CLA supplementation regulated immune cell infiltration of the aorta with increased number of the anti-inflammatory Ly6C lo monocytes evident during regression (29±8 vs 77±14cells/mg aorta p<0.05). In addition, CLA-induced regression was associated with increased polarization towards an anti-inflammatory M2 phenotype, confirmed by an enrichment of M2 genes in the aorta, which occurred as a consequence of increased aortic IL-10 production. In summary CLA mediated induction of IL-10 signaling alters the immunoinflammatory response to atherosclerosis, with increased volume of Ly6C lo monocytes infiltrating the regressing lesions and directed polarization of macrophages towards an M2 phenotype in the plaque microenvironment.


Marine Drugs ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. 585
Author(s):  
Hui Lei ◽  
Xiaoxu Bi ◽  
Xiuping Lin ◽  
Jianglian She ◽  
Xiaowei Luo ◽  
...  

One strain-many compounds (OSMAC) manipulation of the sponge-derived fungus Pestalotiopsis heterocornis XWS03F09 resulted in the production of new secondary metabolites. The chemical study of the fermentation, cultivated on 3% artificial sea salt in the rice media, led to the isolation of twelve compounds, including eight new polyketide derivatives, heterocornols Q–X (1–8), one new ceramide (9), and three known analogues (10–12). The structures and absolute configurations of the new compounds were elucidated by spectroscopic data and calculated ECD analysis. Heterocornols Q (1) and R (2) are novel 6/5/7/5 tetracyclic polyketide derivatives featuring dihydroisobenzofuran and benzo-fused dioxabicyclo [4.2.1] nonane system, which might be derived from the acetyl-CoA by epoxidation, polyene cyclization, and rearrangement to form the core skeleton. Compound 12 showed moderate or weak antimicrobial activities against with MIC values ranging from 25 to 100 μg/mL. Heterocornols T and X (7 and 8) could inhibit the production of LPS-induced NO significantly, comparable to dexamethasone. Further Western blotting analysis showed 7 and 8 markedly suppressed the iNOS protein expression in LPS-induced RAW 264.7 cells in a dose-dependent manner. The result showed that 7 and 8 might serve as potential leads for development of anti-inflammatory activity.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2555-2555
Author(s):  
Jalila Chagraoui ◽  
Elisa Tomellini ◽  
Leo Aubert ◽  
Iman Fares ◽  
Jean-Francois Spinella ◽  
...  

Abstract Recently, we have identified a small molecule, UM171 that enables the expansion of human HSC with both short- and long-term repopulating capacity. Ongoing clinical trials further confirm the beneficial effects of this molecule in patients. Transcriptome analysis of cord blood-derived CD34+ cells and AML cell lines exposed to UM171 revealed unsuspected and strong inflammatory signatures pointing to simultaneous activation of pro-inflammatory (including NFKB and IFN signaling) and anti-inflammatory (including detoxification responses) programs. Moreover, characterisation of cell subsets expanded differentially in presence of UM171, showed a significant and preferential expansion of functional dendritic cell progenitors (CD34+CD86+CD45RA+) and mast cells (FCER1A+c-kit+). In line with this result, immuno-suppressors such as glucocorticoids (dexamethasone) or cAMP elevating agents (IBMX, forskolin) suppressed UM171-mediated pro-inflammatory signaling. These drugs also compromise the ability of UM171 to expand HSCs with long-term repopulating activity and generate dendritic and mast cell progenitors ex vivo. Moreover, knockdown of glucocorticoid receptor (NR3C1) reverts the antagonistic effect of glucocorticoids on UM171 inflammatory properties. Importantly, detrimental effects of glucocorticoid on HSC function was also observed in absence of UM171, thus indicating that inflammation is critical to HSC expansion, independently of the culture conditions. We also found that UM171 induces the expression of the inflammatory mediator CD86 on HSC subsets and knockdown of this receptor leads to a loss of long-term HSCs and substantial depletion of lymphoid compartment. Previously, we have shown that EPCR, a well known anti-inflammatory mediator, is induced by UM171 on CD34+ cord blood cells and defines a cell population with sustained short- and long-term repopulating activity (Fares et al., Blood 2017). We now show that disruption of EPCR function markedly skews UM171 effects towards pro-inflammatory response, thus exacerbating inflammation. Importantly, this uncontrolled inflammation impairs both immune cells generation and HSC activity suggesting that EPCR-driven anti-inflammatory signals provide a critical negative feedback constraining excessive inflammation in HSC and dendritic cell progenitors. Altogether our results strongly suggest that UM171-mediated positive regulation of HSC function occurs through a coordinated and biphasic mechanism allowing a controlled and adequate pro- and anti-inflammatory status, thus creating a permissive environment for stem and immune cell survival and expansion. Most importantly, our data indicate that integration of pro- and anti-inflammatory signals is essential for human HSC self-renewal in the presence or in the absence of UM171, thus revealing a critical balance of pro- and anti-inflammatory activities in human HSC. Disclosures Sauvageau: ExCellThera: Employment, Equity Ownership.


Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 84 ◽  
Author(s):  
Marcelino Gutiérrez ◽  
Ricardo Santamaría ◽  
José Félix Gómez-Reyes ◽  
Héctor M. Guzmán ◽  
Javier Ávila-Román ◽  
...  

Gorgonian octocorals are considered a prolific source of secondary metabolites with a wide range of biological activities, including anti-inflammatory activity. In particular, the genus Briareum is known for producing a wealth of diterpenes with complex chemical structures. The chemical study of the methanolic extract of Briareum asbestinum collected in Bocas del Toro, on the Caribbean side of Panama, led to the isolation of three new eunicellin-type diterpenes: briarellin T (1), asbestinin 27 (2), asbestinin 28 (3) and the previously described asbestinin 17 (4). The structures of the new compounds were determined by extensive NMR analyses and HRMS. Anti-inflammatory activity assays showed a significant reduction of the pro-inflammatory cytokines TNF-α, IL-6, IL-1β and IL-8 as well as a downregulation of COX-2 expression in LPS-stimulated THP-1 macrophages. These findings support the potential use of these marine compounds as therapeutic agents in the treatment of inflammatory diseases.


Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2393 ◽  
Author(s):  
Jian Ma ◽  
Bixuan Cao ◽  
Chengbin Liu ◽  
Peipei Guan ◽  
Yu Mu ◽  
...  

Six new metabolites, actinofuranones D-I (compounds 1–6), were isolated together with three known compounds—JBIR-108 (7), E-975 (8), and E-492 (9)—from a fermentation broth of Streptomyces gramineus derived from the lichen Leptogium trichophorum. The structures of the new compounds 1–6 were established using comprehensive NMR spectroscopic data analysis, as well as UV, IR, and MS data. The anti-inflammatory activity of these isolated compounds were evaluated by examining their ability to inhibit nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 4, 5, 8, and 9 attenuated the production of NO due to the suppression of the expression of nitric oxide synthase (iNOS) in LPS-induced RAW 264.7 cells. Moreover, 4, 5, 8, and 9 also inhibited LPS-induced release of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α).


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Wai-Rong Zhao ◽  
Wen-Ting Shi ◽  
Jing Zhang ◽  
Kai-Yu Zhang ◽  
Ye Qing ◽  
...  

Inflammation response is a regulated cellular process and excessive inflammation has been recognized in numerous diseases, such as cardiovascular disease, neurodegenerative disease, inflammatory bowel disease, and cancer. Tribulus terrestris L. (TT), also known as Bai Jili in Chinese, has been applied in traditional Chinese medicine for thousands of years while its anti-inflammatory activity and underlying mechanism are not fully elucidated. Here, we hypothesize Tribulus terrestris L. extract (BJL) which presents anti-inflammatory effect, and the action mechanism was also investigated. We employed the transgenic zebrafish line Tg(MPO:GFP), which expresses green fluorescence protein (GFP) in neutrophils, and mice macrophage RAW 264.7 cells as the in vivo and in vitro model to evaluate the anti-inflammatory effect of BJL, respectively. The production of nitric oxide (NO) was measured by Griess reagent. The mRNA expression levels of inflammatory cytokines and inducible nitric oxide synthase (iNOS) were measured by real-time PCR, and the intracellular total or phosphorylated protein levels of NF-κB, Akt, and MAPKs including MEK, ERK, p38, and JNK were detected by western blot. We found that BJL significantly inhibited fin transection or lipopolysaccharide- (LPS-) induced neutrophil migration and aggregation in zebrafish in vivo. In mice macrophage RAW 264.7 cells, BJL ameliorated LPS-triggered excessive release of NO and transcription of inflammatory cytokine genes including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). BJL also reduced the LPS-induced elevations of intracellular iNOS and nuclear factor kappa B (NF-κB) which mediate the cellular NO and inflammatory cytokine productions, respectively. Moreover, LPS dramatically increased the phosphorylation of Akt and MAPKs including MEK, ERK, p38, and JNK in RAW 264.7 cells, while cotreatment BJL with LPS suppressed their phosphorylation. Taken together, our data suggested that BJL presented potent anti-inflammatory effect and the underlying mechanism was closely related to the inhibition of Akt/MAPKs and NF-κB/iNOS-NO signaling pathways.


Author(s):  
Natalia Voloshyna ◽  
Tetiana Negreba ◽  
Tatiana Koliada ◽  
Tetiana Pohuliaieva

The relationships between the nature of the prognosis, normal and elevated levels of pro-inflammatory (INF-γ, IL-1β) and anti-inflammatory cytokines (IL-10, IL-12), the prevalence of haplotypes AA and AG in 105 patients with sporadic form (recurrent course (RС) — 72, progressive types of course (PTС) — 33) and in 33 patients with family form (RС — 15, PTС — 18) of multiple sclerosis. Studies have shown that with RС, a favorable and uncertain prognosis in patients with a sporadic form of MS was significantly more likely to occur with a normal level of anti-inflammatory cytokines (IL-10, IL-12), while in a familial form, a normal level of IL-10 was associated with a favorable and IL-12 — with an uncertain forecast. With PTС in patients with a sporadic form, the normal INF-γ content was more likely to occur with an unfavorable prognosis, while its increased content was characteristic of an uncertain prognosis. In the family form, an unfavorable prognosis was more common with an elevated level of the pro-inflammatory cytokine INF-γ and a normal level of anti-inflammatory cytokine IL-10. This suggests that a complex and differentiated interaction of pro- and anti-inflammatory cytokines occurs with the participation of various pathogenetic mechanisms for different forms and types of course. Uncertain prognosis in familial form of RT, unlike sporadic, was more common in patients with AA haplotype. A comparative assessment of the relationship between AA and AG haplotypes revealed the predominance of AA haplotype with an uncertain prognosis in patients with familial form of RT. Haplotype AG was significantly more common in the family form of PTT and did not depend on the nature of the prognosis. Thus, the prevalence of AA and AG haplotypes in both sporadic and familial forms revealed a close relationship with the nature of the prognosis and the type of course. Key words: multiple sclerosis, sporadic and familial form, prognosis, type of course, cytokines, haplotype


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