Pteryxin is a natural coumarin compound that is found in “Qianhu”, a traditional Chinese medicine, which possesses heat-clearing and detoxifying functions according to the theory of Traditional ...Chinese Medicine. Despite its medicinal effects, its anti-inflammatory and mechanisms of actions have not been established.
This study aims to evaluate the anti-inflammatory property and reveal the possible anti-inflammatory mechanisms of pteryxin.
LPS-induced RAW 264.7 macrophages and LPS-induced zebrafish model were used for the anti-inflammatory activity determination of pteryxin. The level of NO, PEG2, TNF-α and IL-6 were measured by ELISA. The accumulation of NO and ROS was stained and observed by a fluorescence microscopy. The nuclear translocation of NF-κB p65 and formation of NLRP3 inflammasome complex in LPS-induced RAW 264.7 macrophage cells were analyzed by immunofluorescence assay. The expression level of iNOS, IL-6, COX-2, TNF-α, p-p38, p38, ERK, JNK, p-ERK, p-JNK, IKK, IκB-α, p-IKK, p-IκB-α, p65, NLRP3, p-p65, Caspase 1 (p 20), ASC, and GAPDH were determined by Western blotting.
Lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) and nitric oxide (NO) secretions were found to be downregulated by pteryxin. Moreover, pteryxin significantly suppressed inflammatory factor secretion in LPS-treated RAW 264.7 cells. Mechanistically, pteryxin significantly downregulated NF-κB/MAPK activation. Moreover, pteryxin inhibited caspase-1 and NLRP3 activation and formation of ASC specks in RAW 264.7 cells, implying that pteryxin inhibits inflammasome assembly, which is a signal for NLRP3 inflammasome activation. In conclusion, pteryxin blocks NF-κB/MAPK signaling, and suppresses the initiation and activation of NLRP3 thereby preventing inflammation.
Pteryxin is a potential treatment option for inflammatory-related diseases.
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•Pteryxin inhibits LPS-induced inflammatory responses.•Anti-inflammatory effects of pteryxin are associated with inhibited NF-κB and MAPK signaling pathway.•Pteryxin could suppresses the priming and activating steps of NLRP3 inflammasomes.
Six ionone glycosides (1–3 and 5–7), including three new ones, named capitsesqsides A−C (1–3), together with an eudesmane sesquiterpenoid glycoside (4) and three known triterpenoid saponins (8–10) ...were isolated from Rhododendron capitatum. The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS.
Chitosan (CHI) based hydrogels promote wound healing and relieve inflammations and chronic infections. However, in hardly healable ulcers with excessively painful inflammations, anti-inflammatory ...activity of hydrogels can be enhanced by the sustained release of non-steroidal anti-inflammatory drugs or combining them with antibiotics. Thus, CHI was crosslinked with genipin (GP) to obtain biocompatible hydrogels. Moreover, their antibacterial activity was confirmed against Staphylococcus aureus and Escherichia coli with an almost 100% bacteria reduction and a potential antibacterial efficacy (R > 2). Furthermore, hydrogels effective healing of ulcerated wounds was corroborated by a significant improvement in metabolic activity (95.58 ± 4.40%), collagen and elastin quantities (1.48 ± 0.07 μg collagen and 5.82 ± 0.73 μg elastin per mg dermal tissue) and histological analysis. Finally, the sustained release of acetylsalicylic acid (ASA), cefuroxime (CFX), tetracycline (TCN) and amoxicillin (AMX) were studied, as well as their anti-inflammatory activity. Results confirm the synergistic anti-inflammatory activity by the significant reduction in the amount of pro-inflammatory cytokines when ASA was combined with CFX (5.39 ± 0.81 ng·mL−1 TNF-α), TCN (4.70 ± 0.21 ng·mL−1 TNF-α and 49.06 ± 9.64 ng·mL−1 IL-8), and AMX (2.28 ± 0.36 ng·mL−1 TNF-α, 14.84 ± 5.57 ng·mL−1 IL-8, and total IL-6 removal).
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•CHI-GP hydrogel formulations were optimized to achieve long-term biocompatible biomaterials.•Antibacterial and wound healing (ulcerated skin) properties of hydrogels were proved.•Loading and sustained release of ASA, CFX, TCN and AMX from CHI-GP hydrogels was studied.•Hydrogels loaded with ASA-antibiotic combinations had a synergistic anti-inflammatory activity.
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Seven new compounds, pleosporallins A–G (1–7), were isolated from Pleosporales sp., a fungus derived from a marine alga Enteromorpha clathrata. The structures of these compounds were ...elucidated by an extensive analysis of NMR, MS, CD spectra, and single crystal X-ray diffraction. Compounds 4 and 5 showed antimicrobial activity with their MIC values of 9.48μg/ml and 7.44μg/ml against Clavibacter michiganense subsp. Sepedonicus and Candida albicans, respectively. Compounds 1–3 exhibited moderate inhibitory activities against the lipopolysaccharide (LPS)-induced intracellular IL-6 production of murine macrophage cell line RAW264.7.
•Crystal structures of diacetylated 19OH-DHEA and 17α-ethynyl derivatives are reported•DFT computations at the B3LYP/6-31+G(d,p) level of theory were performed•Anti-inflammatory and ...anti-hypercholesterolemic activity was assessed by PASSonline•In silico screening indicate that acetylation improves 19OH-DHEA derivatives activity
The synthesis of 17α-ethynyl-3β,17β,19-trihydroxyandrost-5-en derivatives diacetylated at position 3- and 19- (2a), or monoacetylated at position 3 (2b) or 19 (2c), obtained by Grignard reaction over 3β,19-diacetoxyandrost-5-en-17-one (1a), is described. The characterization (NMR, IR, HRMS) and structural analysis of the target molecules are presented, with support from SXRD diffraction studies for three derivatives and DFT computations at the B3LYP/6-31+G(d,p) level of theory, featuring Hirshfeld surface analyses and ESP computations. The impact of these structural derivatizations was further analyzed employing a theoretical evaluation of the potential biological activity of these molecules through the PASS test, envisioning a potential use of these new steroids as lipid metabolism regulators and anti-inflammatory agents.
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Humboldtia unijuga Bedd., endemic to Agasthyamala in Western Ghats in India, is traditionally used by local Kani tribes for chicken pox, head ache and snake bite. This study reports the isolation of ...erythrodiol-3-acetate (HU-1) and 2,4-di-tert-butylphenol (HU-2) from H. unijuga roots and their anti-inflammatory and anticancer activities in macrophage, skin and breast cancer cell lines. Effects of HU-1 and HU-2 treatments (50, 100 µg/mL) on gene expression profiles of pro-inflammatory cytokines TNFα, IL-6 and IL-1β, and apoptosis genes p53 and caspase 7 were studied. HU-2 exerted a significantly superior anti-inflammatory effect compared to HU-1 in all three pro-inflammatory genes. HU-2 showed a superior dose dependent anticancer effect through activation of p53 gene over HU-1 in MCF-7 cells. HU-1 exhibited a dose dependent effect on caspase 7 gene in both cell lines while HU-2 was more effective in A431. HU-2 has potential for development as a novel anti-inflammatory and anticancer agent.
Six scalemic mixtures of previously undescribed diacetylenic spiroacetal enol ethers (DSEEs) and six scalemic mixtures of known DSEEs were isolated from the flowers of Tanacetum tatsienense. Except ...for E-epidendranthemenol, Z-O-acetyl-epi dendranthemenol, and Z-O-isovaleryl-epidendranthemenol, the remaining scalemic mixtures of DSEEs were resolved by chiral HPLC, and their structures were determined through an analysis of HR-ESI-MS and NMR data. The absolute configurations of seven pairs of enantiomers and one pair of epimers were determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectra. In addition, the inhibitory effects of all of the DSEEs on nitric oxide (NO) production were evaluated in LPS-stimulated RAW264.7 cells. The results showed that (+)-tatsienenol B had a weak inhibitory effect on NO production. The IC50 value of the compound was 19.78 ± 0.78 μM. This study is the first to report that DSEEs are isolable from plants as scalemic mixtures. Moreover, this study is the first to determine the absolute configurations of DSEEs by chiral resolution and ECD calculations.
Six scalemic mixtures of previously undescribed diacetylenic spiroacetal enol ethers (DSEEs) and six scalemic mixtures of known DSEEs were isolated from the flowers of Tanacetum tatsienense. Display omitted
•Diacetylenic spiroacetal enol ethers (DSEEs) were isolated from the flowers of Tanacetum tatsienense.•It is reported for the first time that DSEEs were isolated from plants as scalemic mixtures.•Their absolute configurations were determined by chiral resolution and ECD calculations.
Interleukin 37 expression protects mice from colitis McNamee, Eóin N; Masterson, Joanne C; Jedlicka, Paul ...
Proceedings of the National Academy of Sciences - PNAS,
10/2011, Volume:
108, Issue:
40
Journal Article
Peer reviewed
Open access
IL-37, a newly described member of the IL-1 family, functions as a fundamental inhibitor of innate inflammation and immunity. In the present study, we examined a role for IL-37 during experimental ...colitis. A transgenic mouse strain was generated to express human IL-37 (hIL-37tg), and these mice were subjected to dextran sulfate sodium (DSS)-induced colitis. Despite the presence of a CMV promoter to drive expression of IL-37, mRNA transcripts were not present in colons at the resting state. Expression was observed only upon disruption of the epithelial barrier, with a six- to sevenfold increase (P = 0.02) on days 3 and 5 after continuous exposure to DSS. During the development of colitis, clinical disease scores were reduced by 50% (P < 0.001), and histological indices of colitis were one-third less in hIL-37tg mice compared with WT counterparts (P < 0.001). Reduced inflammation was associated with decreased leukocyte recruitment into the colonic lamina propria. In addition, release of IL-1β and TNFα from ex vivo colonic explant tissue was decreased 5- and 13-fold, respectively, compared with WT (P ≤ 0.005), whereas IL-10 was increased sixfold (P < 0.001). However, IL-10 was not required for the anti-inflammatory effects of IL-37 because IL-10-receptor antibody blockade did not reverse IL-37-mediated protection. Mechanistically, IL-37 originating from hematopoietic cells was sufficient to exert anti-inflammatory effects because WT mice reconstituted with hIL-37tg bone marrow were protected from colitis. Thus, IL-37 emerges as key modulator of intestinal inflammation.
Green propolis ethanol extract (GPEE) is one of the most used compounds in folk medicine. Alternative dosage forms, such as orally disintegrating films (ODFs) and forms of incorporation of active ...principles, such as the printing technique, are arousing interest due to the possibility of producing personalized dosages and possible reduction of the degradation of compounds. The aim of this study was to evaluate the effect of green propolis standardized ethanol extract EPP-AF® (GPEE) incorporation on hydroxypropyl methylcellulose (HPMC) using the printing technique (1–4 print layers). GPEE was characterized by propolis dry matter, total phenolics and flavonoids, HPLC chemical fingerprint, apparent viscosity, density, and surface tension. The ODFs with different numbers of printed layers were characterized in relation to color, moisture content, mechanical properties, structure, disintegration time, surface pH, stability, cytotoxicity, and anti-inflammatory activity tests. GPEE showed properties similar to those observed for commercial inks. The number of printed layers affected film properties. ODFs demonstrated stability considering the chemical propolis biomarker selected for this evaluation. ODFs with GPEE showed anti-inflammatory activity, where a reduction of about 40% NO2− concentration against macrophage cells was found after adding one GPEE layer. As such, printing on hydroxypropyl methylcellulose oral films as a vehicle for green propolis ethanolic extract represents an interesting alternative to produce materials with controlled anti-inflammatory activity.
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•Viscosity, density and surface tension values of GPEE are similar to commercial inks.•Oral films of HPMC-based printed are a promising way to deliver active compounds.•HPMS-based printed films maintain the stability of phenolic compounds.•Films printed with green propolis ethanol extract have anti-inflammatory activity.
The regular consumption of fish and its products has been associated with decreased incidence of inflammatory conditions. Indeed, fish present several antioxidants and anti-inflammatory compounds ...(e.g., high levels of ω3 polyunsaturated fatty acids – PUFA). Therefore, this work explored fish roe derived from three different species, namely sardine, horse mackerel and sea bass, to produce new delivery devices. Aqueous and lipidic extracts were obtained using the Matyash method. Despite, the three aqueous extracts showed ability to scavenge peroxyl, hydroxyl and nitric oxide radicals, the ones derived from sardine roe were the most efficient. Thus, they were combined with sardine roe-derived lipidic extracts to prepare large unilamellar liposomes, designated as fishroesomes. The aqueous extracts, at non-cytotoxic concentrations, decreased the levels of pro-inflammatory mediators produced by stimulated macrophages, being these effects enhanced by its combination with liposomes. Consequently, the developed formulations could be promising natural options for the treatment of inflammatory diseases.
Fish roe has been increasingly included in the human diet due to its nutritional value (e.g., high levels of ω3 polyunsaturated fatty acids – PUFA) and health benefits. Therefore, this work used aqueous and lipidic extracts derived from roes of different fish, namely sardine, horse mackerel and sea bass, to produce novel, natural and safer formulations for the treatment of inflammatory conditions. The roes-derived aqueous extracts obtained using the Matyash method demonstrated significant antioxidant activity in comparison with the negative control (without compounds). Due to the overall higher antioxidant activity of sardine roe-derived aqueous extracts, they were used in combination with the lipidic extracts to produce large unilamellar liposomes. These sardine roe-derived formulations presented notable antioxidant and anti-inflammatory activities, at non-cytotoxic levels. Moreover, a complementary action between the two extracts was observed. Thus, this study provides important insights about the value of roe-derived aqueous and lipidic extracts that can be used to prepare new pharmaceutical formulations with bioactivity levels compatible with their medical use for the treatment of inflammatory diseases.
•Aqueous extracts of sardine, horse mackerel and sea bass roes had antioxidant action.•Sardine roe-derived aqueous and lipidic extracts were able to produce fishroesomes.•Fishroesomes had antioxidant and anti-inflammatory effects at non-cytotoxic levels.•A synergistic action between the two extracts was observed.•These formulations are promising therapeutic options for inflammatory diseases.
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