Ulva pertusa, a Marine Green Alga, Attenuates DNBS-Induced Colitis Damage via NF-κB/Nrf2/SIRT1 Signaling Pathways.
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ABSTRACT:
SUBMITTER: Ardizzone A
PROVIDER: S-EPMC9331369 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Three new sterols, (24R)-5,28-stigmastadiene-3β,24-diol-7-one (1), (24S)-5,28-stigmastadiene-3β,24-diol-7-one (2), and 24R and 24S-vinylcholesta-3β,5α,6β,24-tetraol (3), together with three known sterols (4-6) were isolated from the green alga Ulva australis. The structures of the new compounds (1-3) were elucidated through 1D and 2D nuclear magnetic resonance spectroscopy as well as mass spectrometry. Compounds 4-6 were identified as isofucoterol (4), 24R,28S and 24S,28R-epoxy-24-ethylcholesterol (5), and (24S)-stigmastadiene-3β,24-diol (6) on the basis of spectroscopic data analyses and comparison with those reported in the literature. Compounds 4-6 were isolated from U. australis for the first time. These compounds, together with the previously isolated secondary metabolites of this alga, were investigated for their inhibitory effects on human recombinant aldose reductase in vitro. Of the compounds, 24R,28S and 24S,28R-epoxy-24-ethylcholesterol (5), 1-O-palmitoyl-3-O-(6'-sulfo-α-d-quinovopyranosyl) glycerol, (2S)-1-O-palmitoyl-3-O-[α-d-galactopyranosyl(1→2)β-d-galactopyranosyl] glycerol, 4-hydroxybenzoic acid, 4-hydroxyphenylacetic acid, and 8-hydroxy-(6E)-octenoic acid weakly inhibited the enzyme, while the three new sterols, 1-3, were almost inactive.
| S-EPMC5666407 | biostudies-literature
Project description:Increased amounts of reactive oxygen species (ROS) have been implicated in many pathological conditions, including cancer. The major machinery that the cell employs to neutralize excess ROS is through the activation of the antioxidant-response element (ARE) that controls the activation of many phase II detoxification enzymes. The transcription factor that recognizes the ARE, Nrf2, can be activated by a variety of small molecules, most of which contain an α,β-unsaturated carbonyl system. In the pursuit of chemopreventive agents from marine organisms, we built, fractionated, and screened a library of 30 field-collected eukaryotic algae from Florida. An edible green alga, Ulva lactuca, yielded multiple active fractions by ARE-luciferase reporter assay. We isolated three monounsaturated fatty acid (MUFA) derivatives as active components, including a new keto-type C18 fatty acid (1), the corresponding shorter chain C16 acid (2), and an amide derivative (3) of the C18 acid. Their chemical structures were elucidated by NMR and mass spectrometry. All three contain the conjugated enone motif between C7 and C9, which is thought to be responsible for the ARE activity. Subsequent biological studies focused on 1, the most active and abundant ARE activator isolated. C18 acid 1 induced the expression of ARE-regulated cytoprotective genes, including NAD(P)H:quinone oxidoreductase 1, heme oxygenase 1, thioredoxin reductase 1, both subunits of the glutamate-cysteine ligase (catalytic subunit and modifier subunit), and the cystine/glutamate exchange transporter, in IMR-32 human neuroblastoma cells. Its cellular activity requires the presence of Nrf2 and PI3K function, based on RNA interference and pharmacological inhibitor studies, respectively. Treatment with 1 led only to Nrf2 activation, and not the increase in production of NRF2 mRNA. To test its ARE activity and cytoprotective potential in vivo, we treated mice with a single dose of a U. lactuca fraction that was enriched with 1, which showed ARE-activating effects similar to those observed in vitro. This could be owing to this fraction's ability to stabilize Nrf2 through inhibition of Keap1-mediated Nrf2 ubiquitination and the subsequent accumulation and nuclear translocation of Nrf2. The induction of many ARE-driven antioxidant genes in vivo and most prominently in the heart agreed with the commonly recognized cardioprotective properties of MUFAs. A significant increase in Nqo1 transcript levels was also found in other mouse tissues such as the brain, lung, and stomach. Collectively, this study provides new insight into why consumption of dietary seaweed may have health benefits, and the identified compounds add to the list of chemopreventive dietary unsaturated fatty acids.
| S-EPMC3663146 | biostudies-literature
Project description:Rebamipide is a quinolone derivative that has been commonly used for the treatment of gastric and duodenal ulcers. However, the molecular mechanisms of rebamipide against acetic acid-evoked colitis have not been adequately examined. Hence, the current study aimed to investigate the ameliorative effect of rebamipide in a rat model of acetic acid-evoked ulcerative colitis and the linked mechanisms pertaining to SIRT1/FoxO3a/Nrf2 and PI3K/AKT pathways. Herein, colitis was induced by the intrarectal administration of 3% acetic acid solution in saline (v/v) while rebamipide was administered by oral gavage (100 mg/kg/day) for seven days before the colonic insult. The colonic injury was examined by macroscopical and microscopical examination. The current findings demonstrated that rebamipide significantly improved the colonic injury by lowering the colonic disease activity index and macroscopic mucosal injury score. Moreover, it mitigated the histopathological aberrations and microscopical damage score. The favorable outcomes of rebamipide were driven by combating inflammation evidenced by dampening the colonic expression of NF-κBp65 and the pro-inflammatory markers CRP, TNF-α, and IL-6. In the same context, rebamipide curtailed the colonic pro-inflammatory PI3K/AKT pathway as seen by downregulating the immunostaining of PI3K and p-AKT(Ser473) signals. In tandem, rebamipide combated the colonic pro-oxidant events and augmented the antioxidant milieu by significantly diminishing the colonic TBARS and replenishing GSH, SOD, GST, GPx, and CAT. In the same regard, rebamipide stimulated the colonic upstream SIRT1/FoxO3a/Nrf2 axis by upregulating the expression of SIRT1, FoxO3a, and Nrf2, alongside downregulating Keap-1 gene expression. These antioxidant actions were accompanied by upregulation of the protein expression of the cytoprotective signal PPAR-γ in the colons of rats. In conclusion, the present findings suggest that the promising ameliorative features of rebamipide against experimental colitis were driven by combating the colonic inflammatory and oxidative responses. In perspective, augmentation of colonic SIRT1/FoxO3a/Nrf2 and inhibition of PI3K/AKT pathways were engaged in the observed favorable outcomes.
| S-EPMC10142103 | biostudies-literature
Project description:Allisartan isoproxil is a new nonpeptide angiotensin II receptor blocker (ARB) precursor drug that is used to treat hypertension and reduce the risk of heart disease. The present study explored the effects of allisartan isoproxil on diabetic cardiomyopathy (DCM) and revealed the roles of hyperglycaemia‑induced oxidative stress and inflammation. A rat DCM model was established by high‑fat diet feeding in combination with intraperitoneal injection of streptozocin. Echocardiographs showed that diabetic rats exhibited significantly decreased cardiac function. Troponin T (cTnT) and B‑type natriuretic peptide (BNP) were significantly increased in DCM rats as obtained by ELISA. Allisartan isoproxil significantly improved the EF% and E'/A' ratio. Histopathologic staining showed that allisartan isoproxil prevented histological alterations, attenuated the accumulation of collagen, and ameliorated cTnT and BNP levels. Western blot and immunohistochemical results indicated that the expression levels of silent information regulator 2 homologue 1 (SIRT1) and nuclear factor erythroid 2‑related factor 2 (Nrf2) were decreased in the hearts of diabetic rats, and antioxidant defences were also decreased. In addition, allisartan isoproxil decreased the expression of NF‑κB p65 and the inflammatory cytokines TNF‑α and IL‑1β which were determined by reverse transcription‑quantitative PCR in the diabetic heart. Western blotting and TUNEL staining results also showed that cardiac Bax and cleaved caspase‑3 and the number of apoptotic myocardial cells were increased in the diabetic heart and decreased following treatment with allisartan isoproxil. In conclusion, the present results indicated that allisartan isoproxil alleviated DCM by attenuating diabetes‑induced oxidative stress and inflammation through the SIRT1/Nrf2/NF‑κB signalling pathway.
| S-EPMC7845586 | biostudies-literature
Project description:Liver fibrosis, which means a sort of the excessive accumulation of extracellular matrices (ECMs) components through the liver tissue, is considered as tissue repair or wound-healing status. This pathological stage potentially leads to cirrhosis, if not controlled, it progressively results in hepatocellular carcinoma. Herein, we investigated the pharmacological properties and underlying mechanisms of Gardeniae Fructus (GF) against thioacetamide (TAA)-induced liver fibrosis of mice model. GF not only attenuated hepatic tissue oxidation but also improved hepatic inflammation. We further confirmed that GF led to ameliorating liver fibrosis by ECMs degradations. Regarding the possible underlying mechanism of GF, we observed GF regulated epigenetic regulator, Sirtuin 1 (SIRT1), in TAA-injected liver tissue. These alterations were well supported by SIRT1 related signaling pathways through regulations of its downstream proteins including, AMP-activated protein kinase (AMPK), p47phox, NADPH oxidase 2, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1, respectively. To validate the possible mechanism of GF, we used HepG2 cells with hydrogen peroxide treated oxidative stress and chronic exposure conditions via deteriorations of cellular SIRT1. Moreover, GF remarkably attenuated ECMs accumulations in transforming growth factor-β1-induced LX-2 cells relying on the SIRT1 existence. Taken together, GF attenuated liver fibrosis through AMPK/SIRT1 pathway as well as Nrf2 signaling cascades. Therefore, GF could be a clinical remedy for liver fibrosis patients in the future.
| S-EPMC8614944 | biostudies-literature
Project description:Although the use of airborne molecules as infochemicals is common in terrestrial plants, it has not been shown to occur in an ecologically relevant context in marine seaweeds. Like terrestrial plants, intertidal plants spend part of their lives emersed at low tide and release volatile organic compounds (VOCs) into the air when they are grazed or physiologically stressed. We hypothesized seaweeds could use airborne VOCs as infochemicals and respond to them by upregulating a keystone defensive metabolite, dimethylsulfoniopropionate (DMSP). We conducted laboratory and field experiments in which Ulva fenestrata was exposed to airborne dimethyl sulfide (DMS), a volatile antiherbivore and antioxidant metabolite released when the seaweed is grazed or physiologically stressed. In the laboratory, U. fenestrata exposed to DMS had 43-48% higher DMSP concentrations, relative to controls, 6-9 days after exposure. In the field, U. fenestrata 1 m downwind of DMS emitters had 19% higher DMSP concentrations than upwind seaweeds after 11 days. To our knowledge, this is the first demonstration of a marine plant using an airborne molecule released when damaged to elicit defensive responses. Our study suggests that the ability to detect airborne compounds has evolved multiple times or before the divergence of terrestrial plants and green algae.
| S-EPMC10017803 | biostudies-literature
Project description:BACKGROUND:Carotenoids are widely distributed in plants and algae, and their biosynthesis has attracted widespread interest. Carotenoid-related research has mostly focused on model species, and there is a lack of data on the carotenoid biosynthetic pathway in U. prolifera that is the main species leading to green tide, a harmful plague of floating green algae. RESULTS:The carotenoid content of U. prolifera samples, that is the main species leading to green tide, a harmful plague of floating green algae at different temperatures revealed that its terpenoid was highest in the samples subjected to high temperature at 28?°C (H), followed by the samples subjected to low temperature at 12?°C (L). Its terpenoid was lowest in the samples subjected to medium temperature at 20?°C (M). We conducted transcriptome sequencing (148.5 million raw reads and 49,676 unigenes in total) of samples that were subjected to different temperatures to study the carotenoid biosynthesis of U. prolifera. There were 1125-3164 significant differentially expressed genes between L, M and H incubation temperatures, of which 11-672 genes were upregulated and 453-3102 genes were downregulated. A total of 3164 genes were significantly differentially expressed between H and M, of which 62 genes were upregulated and 3102 genes were downregulated. A total of 2669 significant differentially expressed genes were observed between L and H, of which 11 genes were upregulated and 2658 genes were downregulated. A total of 13 genes were identified to be involved in carotenoid biosynthesis in U. prolifera, and the expression levels of the majority were highest at H and lowest at M of incubation temperature. Both the carotenoid concentrations and the expression of the analysed genes were lowest in the normal temperature group, while low temperature and high temperature seemed to activate the biosynthesis of carotenoids in U. prolifera. CONCLUSIONS:In this study, transcriptome sequencing provided critical information for understanding the accumulation of carotenoids and will serve as an important reference for the study of other metabolic pathways in U. prolifera.
| S-EPMC6293516 | biostudies-literature
Project description:We present here the draft genome sequences of four marine bacterial strains which can use ulvan as their sole carbon source. We used ulvan extracted from the green alga Ulva ohnoi Each bacterium contains a polysaccharide-utilizing locus, which is necessary for the complete degradation of ulvan.
| S-EPMC6965591 | biostudies-literature
Project description:Comparative genomic analysis of a photosymbiont evolution
| PRJNA832740 | ENA
Project description:MAIN CONCLUSION:Desiccation leads to structural changes of the inner pectic cell wall layers in Ulva compressa. This contributes to protection against mechanical damage due to desiccation-rehydration cycles. Ulva compressa, characterized by rbcL phylogeny, is a common species in the Mediterranean Sea. Ulva as an intertidal species tolerates repeated desiccation-rehydration cycles in nature; the physiological and structural basis were investigated under experimental conditions here. Desiccation to 73% relative water content (RWC) led to a significant decrease of the maximum quantum yield of photosystem II (F v/F m) to about half of the initial value. A reduction to 48 or 27% RWC caused a more drastic effect and thalli were only able to recover fully from desiccation to 73% RWC. Relative electron transport rates were stimulated at 73% RWC, but decreased significantly at 48 and 27% RWC, respectively. Imaging-PAM analysis demonstrated a homogenous desiccation process within individual thallus discs. The different cell wall layers of U. compressa were characterized by standard staining procedures, i.e. calcofluor white and aniline blue for structural components (cellulose, callose), ruthenium red for pectins and toluidine blue for acidic polysaccharides. Already a reduction to 73% RWC caused severe changes of the cell walls. The inner pectin-rich layers followed the shrinkage process of the cytoplasm, while the outer denser fibrillar layers maintained their shape. In this way, the thalli were not plasmolyzed during water loss, and upon recovery not negatively influenced by any mechanical damage. Transmission electron microscopy corroborated the arrangement of the different layers clearly distinguishable by their texture and electron density. We suggest the flexibility of the pectin-rich cell wall layers as a major contribution to desiccation tolerance in Ulva.
| S-EPMC4498240 | biostudies-literature