ABSTRACT
PURPOSE: Neurolaena lobata is a Caribbean medicinal plant used for the treatment of several conditions including inflammation. Recent data regarding potent anti-inflammatory activity of the plant and isolated sesquiterpene lactones raised our interest in further pharmacological studies. The present work aimed at providing a mechanistic insight into the anti-inflammatory activity of N. lobata and eight isolated sesquiterpene lactones, as well as a structure-activity relationship and in vivo anti-inflammatory data. METHODS: The effect of the extract and its compounds on the generation of pro-inflammatory proteins was assessed in vitro in endothelial and monocytic cells by enzyme-linked immunosorbent assay. Their potential to modulate the expression of inflammatory genes was further studied at the mRNA level. In vivo anti-inflammatory activity of the chemically characterized extract was evaluated using carrageenan-induced paw edema model in rats. RESULTS: The compounds and extract inhibited LPS- and TNF-α-induced upregulation of the pro-inflammatory molecules E-selectin and interleukin-8 in HUVECtert and THP-1 cells. LPS-induced elevation of mRNA encoding for E-selectin and interleukin-8 was also suppressed. Furthermore, the extract inhibited the development of acute inflammation in rats. CONCLUSIONS: Sesquiterpene lactones from N. lobata interfered with the induction of inflammatory cell adhesion molecules and chemokines in cells stimulated with bacterial products and cytokines. Structure-activity analysis revealed the importance of the double bond at C-4-C-5 and C-2-C-3 and the acetyl group at C-9 for the anti-inflammatory activity. The effect was confirmed in vivo, which raises further interest in the therapeutic potential of the compounds for the treatment of inflammatory diseases.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Asteraceae/chemistry , Lactones/pharmacology , Sesquiterpenes/pharmacology , Animals , E-Selectin/metabolism , Edema/drug therapy , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Interleukin-8/metabolism , Male , Molecular Structure , Monocytes/drug effects , Plant Components, Aerial/chemistry , Rats, Sprague-Dawley , Structure-Activity RelationshipABSTRACT
Several compounds isolated from the plant Carpobrotus edulis were evaluated for their activity against multidrug-resistant (MDR) bacteria and their efflux pump systems. Amongst the compounds isolated, six compounds were tested, namely uvaol, ß-amyrin, oleanolic acid, catechin, epicatechin and monogalactosyldiacylglycerol. Oleanolic acid presented high antibacterial activity against a large number of bacterial strains. The triterpene uvaol was the most active compound for modulation of efflux activity by MDR Gram-positive strains.
Subject(s)
Aizoaceae/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Plant Extracts/pharmacology , Anti-Bacterial Agents/isolation & purification , Humans , Microbial Sensitivity Tests , Oleanolic Acid/isolation & purification , Oleanolic Acid/pharmacology , Plant Extracts/isolation & purification , Triterpenes/isolation & purification , Triterpenes/pharmacologyABSTRACT
A bioassay-guided separation protocol, including the testing of the extracts, fractions and pure compounds for their ability to inhibit P-glycoprotein (the efflux pump responsible for the multidrug resistance of the used cell line) of mouse lymphoma cells containing the human efflux pump gene MDR1, led to the isolation of seven compounds from the chloroform and ethyl acetate soluble fractions of the methanolic extract of Carpobrotus edulis. The compounds were identified by 1D, 2D NMR and MS investigations as triterpens (beta-amyrin, uvaol and oleanolic acid), monogalactosyldiacylglycerol, catechin, epicatechin and procyanidin B5. Uvaol was the most effective and promising compound in the reversal of multidrug resistance in MDR mouse lymphoma cell line.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Aizoaceae/chemistry , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/metabolism , Plant Extracts/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Animals , Galactolipids/pharmacology , Humans , Leukemia L5178/drug therapy , Leukemia L5178/genetics , Leukemia L5178/metabolism , Lymphoma, T-Cell/genetics , Methanol/chemistry , Mice , Oleanolic Acid/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Leaves/chemistry , Rhodamine 123/pharmacokinetics , Transfection , Triterpenes/pharmacologyABSTRACT
Sixteen new diterpene polyesters were isolated and identified from Hungarian Euphorbiaceae species. Two of them (21, 23) are based on formerly unknown diterpene core. The structures of three jatrophane type diterpene heptaester were elucidated (1, 3, 6), which are diterpenoids with the highest degree of esterification identified from this plant family. Some of the isolated compounds have pharmacological effects, others are under testing now.
Subject(s)
Diterpenes/chemistry , Phytotherapy , Polyesters/chemistry , Rosales/chemistry , Diterpenes/isolation & purification , Hungary , Polyesters/isolation & purificationABSTRACT
From the pro-inflammatory active extract of Euphorbia peplus, a new diterpene polyester (1) based on the jatrophane skeleton was isolated together with the known compounds 2-5. The irritant activities of some jatrophane diterpenes (2, 3 and 6-9) were also investigated: only compound 2 was found to exert a weak pro-inflammatory activity on mouse ear.
Subject(s)
Diterpenes/chemistry , Irritants/chemistry , Plant Extracts/chemistry , Animals , Diterpenes/isolation & purification , Diterpenes/toxicity , Ear , Irritants/isolation & purification , Irritants/toxicity , Mice , Molecular Structure , Plant Extracts/toxicityABSTRACT
A new pepluane diterpene polyester (2) was isolated from a CH2Cl2 extract of the whole, undried plant of Euphorbia peplus, together with the known compound 1. The structures were established by high-field spectroscopic methods, including 2D NMR techniques, and by X-ray crystallography, and the stereostructure of the first member of the pepluane diterpenoids (1) was revised.
ABSTRACT
A new lathyrane diterpene (1) has been isolated and characterized from a CH2Cl2 extract of the roots of Euphorbia lathyris. Detailed spectral analysis revealed that the structure of 1, including relative stereochemistry, is that of a diester of a hitherto unknown, polyfunctional diterpene parent alcohol.
ABSTRACT
BACKGROUND: Streptococcus pneumoniae is an important pathogen for both children and adults. Although there is an effective vaccine, it is not protective under 2 years of age and common serotypes differ from one location to another. METHODS: A total of 44 Streptococcus pneumoniae isolates were recovered from clinical specimens of children in various hospitals in Ankara, Turkey. All isolates were serotyped and evaluated for vaccine coverage and tested for antibacterial susceptibility. RESULTS: There were 23 different serotypes with a predominance of serotypes 6A, 14, 19F and 23F. The nine-valent conjugate vaccine, which has been proposed for use in young children, covers 90.4% of isolations in children < 2 years of age. This coverage decreases to 43.4% after 2 years of age. The coverage of 23-valent vaccine is better than that of the conjugate vaccine (60.8% vs 43.4%, P < 0.05). Two relatively common and resistant types in our isolates (10A and 21) are not included in either vaccines and adding these serotypes into the 23-valent vaccine was suggested. Although the rate of intermediately penicillin resistant strains was 31.8%, highly penicillin resistant strains were not found in the present study. CONCLUSIONS: The usefulness of conjugate vaccine before 2 years of age and appropriate choice of vaccine strains to include all resistant serotypes for older children in our region, is discussed. It is shown that conjugated vaccine is protective in children less than 2 years of age, but a booster with 23-valent vaccine will be needed once they are older than 2.
Subject(s)
Bacterial Vaccines/immunology , Pneumococcal Infections/microbiology , Streptococcus pneumoniae/classification , Vaccines, Conjugate/immunology , Child , Child, Preschool , Developing Countries , Drug Resistance, Microbial , Humans , Infant , Microbial Sensitivity Tests , Pneumococcal Infections/prevention & control , Serotyping , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/immunology , TurkeyABSTRACT
Three new jatrophane diterpenes, esulatin A, B and C (1-3) were isolated and characterized from the whole, undried plant of Euphorbia esula. By means of spectral analysis, the structures were established as penta- and heptaesters of hitherto unknown, polyfunctional diterpene parent alcohols. Esulatin A (1) and C (3) are the diterpenoids with the highest degree of esterification identified to date from the family Euphorbiaceae.