Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Iridal-Type Triterpenoids Displaying Human Neutrophil Elastase Inhibition and Anti-Inflammatory Effects from Belamcanda chinensis

ABSTRACT: The aim of this study is to explore anti-inflammatory phytochemicals from B. chinensis based on the inhibition of pro-inflammatory enzyme, human neutrophil elastase (HNE) and anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage. Three stereoisomers of iridal-type triterpenoids (1–3) were isolated from the roots of B. chinensis and their stereochemistries were completely identified by NOESY spectra. These compounds were confirmed as reversible noncompetitive inhibitors against HNE with IC50 values of 6.8–27.0 µM. The binding affinity experiment proved that iridal-type triterpenoids had only a single binding site to the HNE enzyme. Among them, isoiridogermanal (1) and iridobelamal A (2) displayed significant anti-inflammatory effects by suppressing the expressions of pro-inflammatory cytokines, such as iNOS, IL-1β, and TNF-α through the NF-κB pathway in LPS-stimulated RAW264.7 cells. This is the first report that iridal-type triterpenoids are considered responsible phytochemicals for anti-inflammatory effects of B. chinensis.

SUBMITTER: Kim J

PROVIDER: S-EPMC8588536 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Phenolic Compounds from Belamcanda chinensis Seeds.

Project description:Two new sucrose derivatives, namely, belamcanosides A (1) and B (2), together with five other known compounds (3-7), were isolated from the seeds of Belamcanda chinensis (L.) DC. Their structures were identified based on spectroscopic data. Especially, the absolute configurations of fructose and glucose residues in 1 and 2 were assigned by acid hydrolysis, followed by derivatization and gas chromatography (GC) analysis. Among the known compounds, (-)-hopeaphenol (3), (+)-syringaresinol (4), and quercetin (5), were isolated from B. chinensis for the first time. In addition, biological evaluation of 1 and 2 against cholesterol synthesis and metabolism at the gene level was carried out. The results showed that compounds 1 and 2 could regulate the expression of cholesterol synthesis and metabolism-associated genes, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), squalene epoxidase (SQLE), low density lipoprotein receptor (LDLR), and sortilin (SORT1) genes in HepG2 cells.

| S-EPMC6017503 | biostudies-other

Neutrophil elastase inhibitory effects of pentacyclic triterpenoids from Eriobotrya japonica (loquat leaves).

Project description:Ethnopharmacological relevanceEriobotrya japonica, a traditional herbal medicine in China and Japan, has long been used to treat chronic bronchitis and coughs.Aim of the studyPentacyclic triterpenoids (PTs), especially ursolic acid (UA), have been found as reversibly and competitively human neutrophil elastase (HNE) inhibitors. However, the limited solubility and poor bioavailability of PTs hinder their clinical use. Crude plant extracts may have a greater activity than isolated constituents of the equivalent dosage. In this study, an Eriobotrya japonica (loquat leaves) extract (triterpenoid composition of loquat leaves, TCLL) with enriched PTs such as UA was prepared. The study aims to compare the HNE inhibitory (HNEI) effect in vitro and the therapeutic effect on acute lung injury (ALI) in vivo between TCLL and UA.Materials and methodsAn HNEI activity bioassay was performed with Sivelestat sodium hydrate as a positive control. A lipopolysaccharide (LPS)-induced lung inflammatory model was established to evaluate TCLL's therapeutic effect on ALI in vivo. The absorption of UA in TCLL and in UA alone was determined using a Caco-2 cell uptake model and LC-MS.ResultsThe IC50 values of TCLL and UA for the HNEI effect were 3.26?±?0.56??g/mL and 8.49?±?0.42??g/mL (P?<?0.01), respectively. TCLL significantly improved the inflammatory cells and inflammatory cytokine production in mice compared with the LPS group (P?<?0.05). Additionally, it performed better than the UA alone group (P?<?0.05). Moreover, the uptake by Caco-2 cells of UA in TCLL was higher than that in UA alone (P?<?0.05).ConclusionTCLL has a significant HNEI effect in vitro and a therapeutic effect on LPS-induced inflammation in a mouse model. Both the effects are more efficient than UA. Improved absorption of PTs in TCLL may be one explanation for these results.

| S-EPMC7127461 | biostudies-literature

Tectorigenin monohydrate: an isoflavone from Belamcanda chinensis.

Project description:THE TITLE COMPOUND [SYSTEMATIC NAME: 5,7-dihydr-oxy-3-(4-hydroxy-phen-yl)-6-meth-oxy-4H-chromen-4-one monohydrate], C(16)H(12)O(6)·H(2)O, is isolated from Belamcanda chinensis and is said to have anti-microbiotic and anti-inflammatory effects. The chromen-4-one system and the benzene ring are inclined at a dihedral angle of 36.79 (6)°. Molecules are linked by inter- and intramolecular O-H⋯O hydrogen bonds.

| S-EPMC2959614 | biostudies-literature

Neutrophil Elastase-mediated proteolysis activates the anti-inflammatory cytokine IL-36 Receptor antagonist.

Project description:The interleukin-36 receptor antagonist (IL-36Ra) which regulates IL-36?, -? and -? is linked to psoriatic inflammation, especially loss-of-function mutations in pustular psoriasis subtypes. As observed with other IL-1 superfamily proteins, the IL-36 members require N-terminal cleavage for full biological activity but the mechanisms of IL-36Ra activation remain poorly defined. Using different blood leukocyte and skin resident cell preparations, and recombinant proteins, we have identified that neutrophil elastase, but not other neutrophil derived proteases, cleaves IL-36Ra into its highly active antagonistic form. The activity of this processed form of IL-36Ra was confirmed in human primary dermal fibroblasts and keratinocytes and in skin equivalents. A significant dose dependent reduction of IL-36? induced IL-8 and chemokine ligand 20 (CCL20) levels were detected following addition of the cleaved IL-36Ra compared to full length IL-36Ra. By activating IL-36Ra, the neutrophil derived protease can inhibit IL-36 induced chemokine production, including IL-8 and CCL20, and reduce further inflammatory cell infiltration. These findings strongly indicate neutrophil elastase to be a key enzyme in the biological function of IL-36Ra and that neutrophils can play a regulatory role in psoriatic inflammation with regard to balancing the pro-inflammatory activity of IL-36.

| S-EPMC4840362 | biostudies-literature

Anti-inflammatory and immunomodulatory properties of ?1-antitrypsin without inhibition of elastase.

Project description:The rationale of ?1-antitrypsin (AAT) augmentation therapy to treat progressive emphysema in AAT-deficient patients is based on inhibition of neutrophil elastase; however, the benefit of this treatment remains unclear. Here we show that clinical grade AAT (with elastase inhibitory activity) and a recombinant form of AAT (rAAT) without anti-elastase activity reduces lung inflammatory responses to LPS in elastase-deficient mice. WT and elastase-deficient mice treated with either native AAT or rAAT exhibited significant reductions in infiltrating neutrophils (23% and 68%), lavage fluid levels of TNF-? (70% and 80%), and the neutrophil chemokine KC (CXCL1) (64% and 90%), respectively. Lung parenchyma TNF-?, DNA damage-inducible transcript 3 and X-box binding protein-1 mRNA levels were reduced in both mouse strains treated with AAT; significantly lower levels of these genes, as well as IL-1? gene expression, were observed in lungs of AAT-deficient patients treated with AAT therapy compared with untreated patients. In vitro, LPS-induced cytokines from WT and elastase-deficient mouse neutrophils, as well as neutrophils of healthy humans, were similarly reduced by AAT or rAAT; human neutrophils adhering to endothelial cells were decreased by 60-80% (P < 0.001) with either AAT or rAAT. In mouse pancreatic islet macrophages, LPS-induced surface expression of MHC II, Toll-like receptor-2 and -4 were markedly lower (80%, P < 0.001) when exposed to either AAT or rAAT. Consistently, in vivo and in vitro, rAAT reduced inflammatory responses at concentrations 40- to 100-fold lower than native plasma-derived AAT. These data provide evidence that the anti-inflammatory and immunomodulatory properties of AAT can be independent of elastase inhibition.

| S-EPMC3773761 | biostudies-literature

Inhibition of human neutrophil elastase by pentacyclic triterpenes.

Project description:ScopeInhibiting human neutrophil elastase (HNE) is a promising strategy for treating inflammatory lung diseases, such as H1N1 and SARS virus infections. The use of sivelestat, the only clinically registered synthesized HNE inhibitor, is largely limited by its risk of organ toxicity because it irreversibly inhibits HNE. Therefore, potent reversible HNE inhibitors are promising alternatives to sivelestat.Methods and resultsAn in vitro HNE inhibition assay was employed to screen a series of triterpenes. Six pentacyclic triterpenes, but not tetracyclic triterpenes, significantly inhibited HNE. Of these pentacyclic triterpenes, ursolic acid exhibited the highest inhibitory potency (IC50 = 5.51 µM). The HNE inhibitory activity of ursolic acid was further verified using a mouse model of acute smoke-induced lung inflammation. The results of nuclear magnetic resonance and HNE inhibition kinetic analysis showed that the pentacyclic triterpenes competitively and reversibly inhibited HNE. Molecular docking experiments indicated that the molecular scaffold, 28-COOH, and a double bond at an appropriate location in the pentacyclic triterpenes are important for their inhibitory activity.ConclusionOur results provide insights into the effects of pentacyclic triterpenes on lung inflammatory actions through reversible inhibition of HNE activity.

| S-EPMC3869726 | biostudies-literature

Triterpenoids from Euphorbia maculata and Their Anti-Inflammatory Effects.

Project description:Euphorbia maculata is a medicinal plant of the Euphorbiaceae family, which can produce anti-inflammatory and cancer chemopreventive agents of triterpenoids. The present study reports on the bioactive triterpenoids of this plant. Two new lanostane-type triterpenoids, named (3S,4S,7S,9R)-4-methyl-3,7-dihydroxy-7(8?9) abeo-lanost-24(28)-en-8-one (1) and 24-hydroperoxylanost-7,25-dien-3?-ol (2), together with 15 known triterpene derivatives, were isolated from Euphorbia maculata. The structures of the new compounds were determined on the basis of extensive spectroscopic data (UV, MS, ¹H and 13C-NMR, and 2D NMR) analysis. All tetracyclic triterpenoids (1?11) were evaluated for their anti-inflammatory effects in the test of TPA-induced inflammation (1 ?g/ear) in mice. The triterpenes exhibited significant anti-inflammatory activities.

| S-EPMC6225269 | biostudies-other

Two New 3,4;9,10-seco-Cycloartane Type Triterpenoids from Illicium difengpi and Their Anti-Inflammatory Activities.

Project description:A pair of new 3,4;9,10-seco-cycloartane type triterpenoid stereoisomerides: 24R,25-dihydroxy-3,4;9,10-seco-4(28)-cycloarten-10,3-olide (1) named Illiciumolide A and 24S,25-dihydroxy-3,4;9,10-seco-4(28)-cycloarten-10,3-olide (2) named Illiciumolide B were isolated from the stem bark of Illicium difengpi, as well as five known biogenetically related triterpenoids, including sootepin E (3), betulinic acid (4), lupeol (5), (all-Z)-1,5,9,13,17,21-hexamethyl-1,5,9,13,17,21-cyclotertracosahexaene (6), and (all-E)-2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene (7). The structures of two new compounds were determined on the basis of spectroscopic analysis including 1D-, 2D-NMR, and MS techniques. Two assays were conducted: inhibition of tumor necrosis factor-alpha (TNF-α) and inhibition of nuclear factor kappa B (NF-κB) in RAW264. 7 cells induced by lipopolysaccharide (LPS). It was observed that compounds 1, 2 and 7 showed significant inhibition of TNF-α production and NF-κB release. The molecule docking results showed that compounds 1 and 2 got high fitness scores with dual specificity mitogen-activated protein kinase kinase 1 (MPKK1), whose activation plays a pivotal role between TNF-α and activation of NF-κB. The anti-HIV-1 potency of compounds 1-5 was also discussed, in addition to the results of computer-aided screening for targets.

| S-EPMC3671308 | biostudies-literature

Anti-inflammatory triterpenoids from the stems of Microtropis fokienensis.

Project description:Three new ursane- and four new oleanane- type triterpenoids 1-7 were isolated, along with six known compounds 8-13, from the methanolic extract of Microtropis fokienensis. All structures were elucidated by mass and NMR spectroscopic methods. The isolates 4-10 and known compounds 14-17 that were previously isolated from this material were evaluated for anti-inflammatory activity based on effects against superoxide anion generation and elastase release by neutrophils in response to fMLP/CB. 11α,30-Dihydroxy-2,3-seco-olean-12-en-2,3-dioic anhydride (7) was the first triterpene anhydride from the genus of Microtropis to have the ring A expanded to a seven-membered ring; it showed significant anti-inflammatory activity against superoxide anion generation and elastase release. Unexpectedly, 30-hydroxy-2,3-seco-lup-20(29)-ene-2,3-dioic acid (17) showed the best effect against superoxide anion generation and elastase release with IC50 values of 0.06±0.01 and 1.03±0.35 µg/mL, respectively. Compound 17 had a dioic acid function, and compound 7 had an anhydride function modification in ring A; both showed promising activity in the target assays.

| S-EPMC6271155 | biostudies-literature

Inhibition of neutrophil elastase prevents neutrophil extracellular trap formation and rescues mice from endotoxic shock.

Project description:Neutrophil elastase (NE) is a serine protease stored in the azurophilic granules of neutrophils and released into the extracellular milieu during inflammatory response or formation of neutrophil extracellular traps (NETs). Neutrophils release NETs to entrap pathogens by externalizing their cellular contents in a DNA framework decorated with anti-microbials and proteases, including NE. Importantly, excess NETs in tissues are implicated in numerous pathologies, including sepsis, rheumatoid arthritis, vasculitis, and cancer. However, it remains unknown how to effectively prevent NET formation. Here, we show that NE plays a major role during NET formation and that inhibition of NE is a promising approach for decreasing NET-mediated tissue injury. NE promoted NET formation by human neutrophils. Whereas sivelestat, a small molecule inhibitor of NE, inhibited the formation of NETs in vitro , administration of free sivelestat did not have any efficacy in a murine model of lipopolysaccharide-induced endotoxic shock. To improve the efficacy of sivelestat in vivo, we have developed a nanoparticle system for delivering sivelestat. We demonstrate that nanoparticle-mediated delivery of sivelestat effectively inhibited NET formation, decreased the clinical signs of lung injury, reduced NE and other proinflammatory cytokines in serum, and rescued animals against endotoxic shock. Collectively, our data demonstrates that NE signaling can initiate NET formation and that nanoparticle-mediated inhibition of NE improves drug efficacy for preventing NET formation.

| S-EPMC7075277 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data