scholarly journals 1,4-Disubstituted 1H-1,2,3-Triazoles for Renal Diseases: Studies of Viability, Anti-Inflammatory, and Antioxidant Activities

2020 ◽  
Vol 21 (11) ◽  
pp. 3823
Author(s):  
Ching-Yi Cheng ◽  
Ashanul Haque ◽  
Ming-Fa Hsieh ◽  
Syed Imran Hassan ◽  
Md. Serajul Haque Faizi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Metabolic Diseases ◽  
Mesangial Cells ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Renal Diseases ◽  
No Production ◽  
In Silico Studies ◽  
Cox 2 ◽  
Anti Inflammatory

Inflammation is a hallmark of many metabolic diseases. We previously showed that ferrocene-appended 1H-1,2,3-triazole hybrids inhibit nitric oxide (NO) production in in vitro models of lipopolysaccharide-induced inflammation in the BV-2 cell. In the present study, we explored the viability, anti-inflammatory, and antioxidant potential of ferrocene-1H-1,2,3-triazole hybrids using biochemical assays in rat mesangial cells (RMCs). We found that, among all the ferrocene-1H-1,2,3-triazole hybrids, X2–X4 exhibited an antioxidant effect on mitochondrial free radicals. Among all the studied compounds, X4 demonstrated the best anti-inflammatory effect on RMCs. These results were supplemented by in silico studies including molecular docking with human cytosolic phospholipase A2 (cPLA2) and cyclooxygenase 2 (COX-2) enzymes as well as absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. Besides, two new crystal structures of the compounds have also been reported. In addition, combining the results from the inducible nitric oxide synthase (iNOS), cPLA2, COX-2, and matrix metalloproteinase-9 (MMP-9) enzymatic activity analysis and NO production also confirmed this argument. Overall, the results of this study will be a valuable addition to the growing body of work on biological activities of triazole-based compounds.

scholarly journals Anti-Inflammatory and Antioxidant Activities of Medicinal Plants Used by Traditional Healers for Antiulcer Treatment

2019 ◽  
Vol 87 (3) ◽  
pp. 22 ◽  
Author(s):  
Kanokkarn Phromnoi ◽  
Puksiri Sinchaiyakij ◽  
Chakkrit Khanaree ◽  
Piyawan Nuntaboon ◽  
Yupa Chanwikrai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Medicinal Plants ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Traditional Healers ◽  
Gastric Ulcers ◽  
Future Research ◽  
No Production ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory

For centuries, many kinds of native plants and their products have been used for the treatment of gastric ulcers by traditional healers in Phayao province. The current study aimed to investigate the polyphenol content in some of these medicinal plants and to point out the relationship between their antioxidant capacity and anti-inflammatory activities. Six species were selected based on ethnopharmacologic considerations: Punica granatum L., Psidium guajava L., Careya arborea Roxb., Gochnatia decora (Kurz) Cabr., Shorea obtusa Wall. ex Blume, and Ficus hispida L.f. The leaves or bark of these plants were extracted with 70% ethanol and water. Anti-inflammatory and antioxidant activities of the extracts were analyzed based on nitric oxide (NO) and proinflammatory cytokine production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and through the determination of scavenging activity. The results demonstrated that the ethanol extract from P. granatum and P. guajava leaves significantly inhibited NO production by suppressing nitric oxide synthase. The extracts also inhibited tumor necrosis factor-α, interleukin-1, and interleukin-6 in terms of both mRNA and protein levels and possessed high antioxidants. These extracts were shown to contain the highest amount of polyphenols. Our study concluded that among the plants studied, P. granatum and P. guajava have the most significant anti-inflammatory and antioxidant activities and polyphenols. These plants may have the potential for use in gastric ulcer therapy due to their indicated properties. Future research should focus on the isolation of their active compounds and their in vivo biological activities. Their beneficial applications need to be warranted by such evidence.

scholarly journals Anti-inflammatory Activity of Constituents Isolated from Terminalia chebula

2014 ◽  
Vol 9 (7) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Min Hye Yang ◽  
Zulfiqar Ali ◽  
Ikhlas A. Khan ◽  
Shabana I. Khan
Keyword(s):  
Nitric Oxide ◽  
Cellular Level ◽  
Inflammatory Activity ◽  
No Production ◽  
Terminalia Chebula ◽  
Arjunolic Acid ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

This study was aimed at the evaluation of the anti-inflammatory activity of twelve compounds isolated from the methanolic extract of fruits of Terminalia chebula. The activity was determined in terms of their ability to inhibit inducible nitric oxide synthase ( iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated macrophages. Two gallotannins [chebulinic acid (1) and 2,3,6-tri- O-galloyl-β-D-glucose (2)] and two triterpenoids [arjunic acid (3) and arjunolic acid (4)] efficiently reduced nitric oxide (NO) production with IC50 values of 53.4, 55.2, 48.8, and 38.0 μM, respectively. The protein expressions of iNOS and COX-2 were decreased in macrophages by treatment with compounds 1–4 (54–69% and 33–37%, respectively) at 50 μM. This is the first report of anti-inflammatory property of 1–4 mediated by inhibition of iNOS and COX-2 activities at the cellular level.

IGF-I and insulin amplify IL-1β-induced nitric oxide and prostaglandin biosynthesis

1998 ◽  
Vol 274 (4) ◽  
pp. F673-F679 ◽  
Author(s):  
Zhonghong Guan ◽  
Shaavhree Y. Buckman ◽  
Lisa D. Baier ◽  
Aubrey R. Morrison
Keyword(s):  
Nitric Oxide ◽  
Mesangial Cells ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
No Production ◽  
Glomerular Mesangial Cells ◽  
Igf I ◽  
Mitogen Activated Protein ◽  
Transduction Mechanisms ◽  
Cox 2

The inflammatory cytokine interleukin-1β (IL-1β) induces both cyclooxygenase-2 (Cox-2) and the inducible nitric oxide synthase (iNOS) with concomitant release of PGs and nitric oxide (NO) by glomerular mesangial cells. In our current studies, we determine whether insulin and IGF-I are involved in the signal transduction mechanisms resulting in IL-1β-induced NO and PGE2biosynthesis in renal mesangial cells. We demonstrate that both insulin and IGF-I increase IL-1β-induced Cox-2 and iNOS protein expression, which in turn enhance PGE2 and NO production. Our data also indicate that both insulin and IGF-I enhance IL-1β-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation and SAPK activation. These findings implicate the possible role of the MAPK pathway in mediating the effects of insulin and IGF-I on the upregulation of cytokine-stimulated NO and PG biosynthesis. Together, our results indicate that IGF-I and insulin may function to modulate the renal inflammatory process.

scholarly journals Auraptene, a Monoterpene Coumarin, Inhibits LTA-Induced Inflammatory Mediators via Modulating NF-κB/MAPKs Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Chih-Hsuan Hsia ◽  
Thanasekaran Jayakumar ◽  
Wan-Jung Lu ◽  
Joen-Rong Sheu ◽  
Chih-Wei Hsia ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Nuclear Translocation ◽  
Polyacrylamide Gel Electrophoresis ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Objective. Oxidative stress-mediated inflammatory events involve in the progress of several diseases such as asthma, cancers, and multiple sclerosis. Auraptene (AU), a natural prenyloxycoumarin, possesses numerous pharmacological activities. Here, the anti-inflammatory effects of AU were investigated in lipoteichoic acid- (LTA-) induced macrophage cells (RAW 264.7). Methods. The expression of cyclooxygenase (COX-2), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS) and the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38 MAPK, c-Jun N-terminal kinase (JNK), heme oxygenase (HO-1), p65, and IκBα were all identified by western blotting assay. The level of nitric oxide (NO) was measured by spectrometer analysis. The nuclear translocation of p65 nuclear factor kappa B (NF-κB) was assessed by the confocal microscopic staining method. Native polyacrylamide gel electrophoresis was performed to perceive the activity of antioxidant enzyme catalase (CAT). Results. AU expressively reduced NO production and COX-2, TNF-α, IL-1 β, and iNOS expression in LTA-stimulated cells. AU at higher concentration (10 µM) inhibited ERK and JNK, but not p38 phosphorylation induced by LTA. Moreover, AU blocked IκB and p65 phosphorylation, and p65 nuclear translocation. However, AU pretreatment was not effective on antioxidant HO-1 expression, CAT activity, and reduced glutathione (GSH, a nonenzymatic antioxidant), in LTA-induced RAW 264.7 cells. Conclusion. The findings of this study advocate that AU shows anti-inflammatory effects via reducing NF-κB/MAPKs signaling pathways.

Regulation of STIM1, store-operated Ca2+ influx, and nitric oxide generation by retinoic acid in rat mesangial cells

2007 ◽  
Vol 292 (3) ◽  
pp. F1054-F1064 ◽  
Author(s):  
Wanke Zhang ◽  
Hua Meng ◽  
Zhen-Hua Li ◽  
Zhenju Shu ◽  
Xiuye Ma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mesangial Cells ◽  
26S Proteasome ◽  
Renal Diseases ◽  
No Production ◽  
Beneficial Effects ◽  
Retinoic Acids ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Endothelial Nitric Oxide

It has been shown that store-operated Ca2+ influx (SOC) plays critical roles in the activation of endothelial nitric oxide (NO) synthase (eNOS) and generation of NO in endothelial cells. Recent studies indicate stromal interaction molecule 1 (STIM1) is the molecule responsible for SOC activation following Ca2+ depletion in the ER. Retinoic acids (RA) have beneficial effects in the treatment of renal diseases. The mechanism of the RA action is still largely unknown. In the current study, we used primary cultured rat mesangial cells to examine the effect of RA on SOC and STIM1. In these cells, BK caused concentration-dependent [Ca2+]i mobilization. Treatment of the cells with RA, while it had no effect on the initial peak, reduced the plateau phase of BK-mediated [Ca2+]i response, indicating the inhibition of SOC by RA. The level of STIM1 protein but not mRNA in RA-treated cells was significantly reduced. RA treatment did not affect TGF-β-mediated gradual Ca2+ influx which occurred by superoxide anion-mediated mechanism, indicating RA treatment specifically inhibited SOC in mesangial cells. RT-PCR and Western blot analysis demonstrated that eNOS was expressed in rat mesangial cells grown in media containing 11 and 30 but not 5.5 mM glucose. Downregulation of STIM1 protein and BK-induced SOC by RA treatment or STIM1 dsRNA were associated with abolished NO production. The 26S proteasome inhibitor lactacystin blocked the RA-mediated downregulation of BK-induced SOC, suggesting that ubiquitin-proteasome pathway may be involved in RA-mediated STIM1 protein downregulation in rat mesangial cells. Our data suggest that glucose-induced eNOS expression and NO production in mesangial cells may contribute to hyperfiltration in diabetes and RA may exert beneficial effects by downregulation of STIM1 and SOC in mesangial cells.

scholarly journals Discovery of Phenolic Glycoside from Hyssopus cuspidatus Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation

2021 ◽  
Vol 22 (22) ◽  
pp. 12128
Author(s):  
Xingyu Liu ◽  
Jie Su ◽  
Geng Wang ◽  
Lihua Zheng ◽  
Guannan Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Peritoneal Macrophages ◽  
Mitogen Activated Protein Kinase ◽  
Raw 264.7 Cells ◽  
Phenolic Glycoside ◽  
No Production ◽  
Cox 2 ◽  
Anti Inflammatory

It seems quite necessary to obtain effective substances from natural products against inflammatory response (IR) as there are presently clinical problems regarding accompanying side effects and lowered quality of life. This work aimed to investigate the abilities of hyssopuside (HY), a novel phenolic glycoside isolated from Hyssopus cuspidatus (H. cuspidatus), against IR in lipopolysaccharide (LPS)-induced RAW 264.7 cells and mouse peritoneal macrophages. The results indicated that HY could reduce nitric oxide (NO) production and inhibit the production and secretion of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in LPS-stimulated macrophages. Moreover, data from the immunofluorescence study showed that HY suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. The Western blot results suggested that HY reversed the LPS-induced degradation of IκB (inhibitor of NF-κB), which is normally required for the activation of NF-κB. Meanwhile, the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) diminished significantly with the presence of HY in response to LPS stimulation. On the other hand, HY had a negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Moreover, an in silico study of HY against four essential proteins/enzymes revealed that COX-2 was the most efficient enzyme for the interaction, and binding of residues Phe179, Asn351, and Ser424 with HY played crucial roles in the observed activity. The structure analysis indicated the typical characterizations with phenylethanoid glycoside contributed to the anti-inflammatory effects of HY. These results indicated that HY manipulated its anti-inflammatory effects mainly through blocking the NF-κB signal transduction pathways. Collectively, we believe that HY could be a potential alternative phenolic agent for alleviating excessive inflammation in many inflammation-associated diseases.

scholarly journals Anti-Inflammatory Effect of Liverwort (Marchantia polymorpha L.) and Racomitrium Moss (Racomitrium canescens (Hedw.) Brid.) Growing in Korea

Plants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2075
Author(s):  
So-Yeon Kim ◽  
Minji Hong ◽  
Tae-Hee Kim ◽  
Ki Yeon Lee ◽  
Se Jin Park ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Activity ◽  
Methanol Extract ◽  
Marchantia Polymorpha ◽  
No Production ◽  
Hacat Cells ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Bryophytes contain a variety of bioactive metabolites, but studies about the anti-inflammatory effect of bryophytes are meager. Therefore, the present study aimed to compare the anti-inflammatory effect of methanol extract of Marchantia polymorpha L. (liverwort) and Racomitrium canescens (Racomitrium moss) in lipopolysaccharide (LPS)-induced HaCaT cells. To evaluate the anti-inflammatory effect of liverwort and Racomitrium moss, the levels of nitric oxide (NO) production and the mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 and IL-1β in LPS-induced HaCaT cells were measured. The methanol extract of liverwort and Racomitrium moss significantly decreased LPS-induced NO production in HaCaT cells. When compared with Racomitrium moss extract, pre-treatment with methanol extract of liverwort markedly inhibited the expression of iNOS, COX-2, IL-6, and IL-1β at the concentration of 100 µg/mL with the exception of TNF-α. Further, liverwort extract markedly attenuated the production of TNF-α, IL-6, and IL-1β in the culture medium. In addition, ethyl acetate and butanol fractions obtained from the methanol extract of liverwort showed remarkable inhibitory activity against the production of NO in LPS-stimulated HaCaT cells. The LC-MS data revealed the presence of bisbibenzyl types of bioactive components in the methanol extract of liverwort. These data demonstrate that liverwort extract exhibits effective inhibitory activity against the production of inflammatory mediators in LPS-induced HaCaT cells and may be useful for the treatment of inflammation-mediated diseases.

scholarly journals (3β,16α)-3,16-Dihydroxypregn-5-en-20-one from the Twigs of Euonymus alatus (Thunb.) Sieb. Exerts Anti-Inflammatory Effects in LPS-Stimulated RAW-264.7 Macrophages

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3848 ◽  
Author(s):  
Seulah Lee ◽  
Dahae Lee ◽  
Su Cheol Baek ◽  
Mun Seok Jo ◽  
Ki Sung Kang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Medicinal Plant ◽  
Phytochemical Analysis ◽  
No Production ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Euonymus Alatus ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Pharmacologically Active

To discover new pharmacologically active natural products, here, we performed the phytochemical analysis of a Korean medicinal plant. Euonymus alatus (Thunb.) Sieb. is a traditional medicinal plant that has been used as a remedy for various diseases in Asian countries. In particular, the cork cambium on the twigs of E. alatus has been used to treat dysmenorrhea, tumors, diabetes, and wound. Phytochemical analysis of the methanolic extract of E. alatus twigs led to the isolation of a sterol, which was identified as (3β,16α)-3,16-dihydroxypregn-5-en-20-one (1) by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionization mass spectrometry. The stereochemistry of 1 was established with nuclear Overhauser effect spectroscopy (NOESY) analysis and comparison of electronic circular dichroism (ECD) data. To the best of our knowledge, the isolation of compound 1 from nature is first reported here, as well as the complete and revised NMR data assignment of 1. In lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages, compound 1 significantly inhibited nitric oxide (NO) production at an IC50 value of 12.54 ± 0.05 μM as well as the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, the pre-treatment with compound 1 attenuated the LPS-induced phosphorylation of nuclear factor kappa B (NF-κB) p65 through the inhibition of the phosphorylation of IκB kinase alpha (IKKα), IKKβ, and inhibitor of kappa B alpha (IκBα). Compound 1 also inhibited the LPS-induced phosphorylation of p38, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Taken together, compound 1 may serve as an anti-inflammatory constituent of E. alatus twigs and its anti-inflammatory property is thought to be associated with the inhibition of NO production via suppression of iNOS and COX-2 expression through inhibition of IKKα/β, I-κBα and NF-κB p65 activation and downregulation of p38, JNK, and ERK mitogen-activated protein kinase signal pathways in RAW 264.7 macrophages. These findings also provide experimental evidence that compound 1 identified from E. alatus twigs could be a candidate for an anti-inflammatory agent.

scholarly journals Purification and Structural Characterization of Sulfated Polysaccharides Derived from Brown Algae, Sargassum binderi: Inhibitory Mechanism of iNOS and COX-2 Pathway Interaction

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 822
Author(s):  
Jun-Geon Je ◽  
Hyo-Geun Lee ◽  
Kurukulasuriya H. N. Fernando ◽  
You-Jin Jeon ◽  
Bomi Ryu
Keyword(s):  
Brown Algae ◽  
Biological Activities ◽  
Average Molecular Weight ◽  
Sulfated Polysaccharides ◽  
No Production ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Sargassum Binderi

Among the components derived from brown algae, anionic sulfated polysaccharides, which contain sulfated fucose as the major monosaccharide, exert significant biological activities. In this study, we purified and structurally characterized sulfated polysaccharides from brown algae, Sargassum binderi (S. binderi; SBPs), and evaluated their biological activity in vitro and in vivo. The SBPs were separated based on their charges and their biophysical properties were investigated according to their functional groups, structural features, and molecular weights using FTIR, NMR, and MALS. Among all the SBPs, Fraction 4 (SBP-F4), with an average molecular weight of 2.867 × 105 g/mol, had the highest polysaccharide and sulfate contents (75.15 ± 0.25% and 24.08 ± 0.18%, respectively). The biological activities of SBP-F4 were investigated further in vitro and in vivo. Our results showed that SBP-F4 significantly suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in LPS-activated macrophages. Moreover, in the LPS-treated zebrafish model, a significant decrease in cell death and NO production was observed. Collectively, these results show that SBPs not only exert protective effects against LPS-induced cytotoxicity but also inhibit the activation and anti-inflammatory activity of macrophages. Therefore, polysaccharides derived from S. binderi are potential anti-inflammatory agents for use in clinical settings.

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