Development and characterization of liposomal formulations containing sesquiterpene lactones for the treatment of chronic gout.

Gout and hyperuricemia are characterized by high uric acid levels, and their treatment involves medications that have adverse effects. In this study, we evaluated oral liposomal formulations with eremantholide C and goyazensolide as a novel approach to reduce the toxicity associated with these substances while maintaining their anti-hyperuricemic activity. We characterized the formulations and evaluated them based on encapsulation efficiency and stability over 12 months and under simulated physiological environments. We determined the toxicity of the liposomal formulations in Caco-2 cells and the anti-hyperuricemic activity in rats. The formulations exhibited nanometric size, a narrow size distribution, and a negative zeta potential, indicating their stability and uniformity. The efficient encapsulation of the sesquiterpene lactones within the liposomes emphasizes their potential for sustained release and therapeutic efficacy. Stability evaluation revealed a small decrease in the eremantholide C concentration and a remarkable stability in the goyazensolide concentration. In Caco-2 cells, the liposomes did not exert toxicity, but did exhibit an antiproliferative effect. In vivo assays demonstrated that the liposomes reduced serum uric acid levels. Our study represents an advancement in gout and hyperuricemia treatment. The liposomal formulations effectively reduced the toxicity associated with the sesquiterpene lactones while maintaining their therapeutic effects.

Cytotoxic activity of extracts from Tecoma species and isolated lignans

Abstract A phytochemical study of Tecoma genus (Bignoniaceae) was accomplished by antitumor activity of ethanolic extracts. Species of this genus are composed of small shrubs often used as ornamental plants. The Tecoma stans species is used in folk medicine for different purposes. Recent work shows in vitro anticancer activity against human breast cancer. The ethanolic extracts from leaves and trunks of Tecoma casneifolia, T. garrocha, T. stans var. angustata and T. stans var. stans were tested in vitro. The assays used were against line tumor cells by the MTT method and the most active extracts were further studied. In this way, the ethanolic extract from T. stans var. stans trunks presented the higher cytotoxicity against the tumor cell lines studied (CC50 0.02 to 0.55 µg/ml) when compared to the other extracts tested (CC50 0.08 to 200.0 µg/ml). Accordingly, this extract was selected for chromatographic fractionation from which five known lignans were isolated. Further, paulownin, paulownin acetate, sesamin, olivil and cycloolivil were identified using 13C and 1H NMR, IR, UV and spectroscopy and spectrometric MS techniques. These isolated compounds were tested and exhibited CC50 ranging from 13.01 to100.0 µg/ml which is superior to the ethanolic extract of trunk of T. stans

Esterification of trans-aconitic acid improves its anti-inflammatory activity in LPS-induced acute arthritis.

trans-Aconitic acid (TAA) is an abundant constituent in the leaves of Echinodorus grandiflorus, a medicinal plant used to treat rheumatoid arthritis in Brazil. Esterification was explored as a strategy to increase lipophilicity and biopharmaceutical properties of TAA, a highly polar tricarboxylic acid. We herein report the synthesis of TAA esters via Fischer esterification with ethanol, n-butanol and n-octanol. The reaction kinetics was investigated to produce mono-, di- and tri- derivatives. Mono- and diesters of TAA were obtained as a mixture of positional isomers, whereas the triesters were recovered as pure compounds. The obtained esters were screened in a model of acute arthritis induced by the injection of LPS in the knee joint of Swiss mice. The diesters were the most active compounds, regardless of the alcohol employed in the reaction, whereas bioactivity of the derivatives improved by increasing the length of the aliphatic chain of the alcohol employed in esterification. In general, the esters showed higher potency than TAA. When administered orally to mice at doses of 0.017-172.3 µmol/Kg, the diethyl, di-n-butyl and di-n-octyl esters of TAA reduced the cellular infiltration into the knee joint, especially of neutrophils. The study identified diesters of TAA as potential useful derivatives for the management of rheumatoid arthritis and other inflammatory diseases.

Nematicidal activity of Annona crassiflora leaf extract on Caenorhabditis elegans.

BACKGROUND: The aim of this work was to investigate the potential nematicidal activity of Annona crassiflora leaf extract against Caenorhabditis elegans. METHODS: The hydroalcoholic leaf extract and its fractions (dichloromethane, ethyl acetate, methanol and water) were submitted to mobility assay against the roundworm Caenorhabditis elegans. GC-MS and NMR analysis were performed in order to identify metabolites. RESULTS: The dichloromethane and ethyl acetate fractions showed to be the most active among the hydroalcoholic leaf extracts and its four fractions. The percentages of C. elegans larvae immobility were 98.13 and 89.66%, respectively, at a concentration of 1000 µg.mL(-1). Besides some amino acids, palmitic acid methyl ester, 2-isopropyl-5-methylcyclohexanol, oleic acid methyl esther, stearic acid methyl ester, quercetin and kaempferol were also identified in these fractions. CONCLUSION: The results indicated that of A. crassiflora leaf ethanolic extract has a good potential as a source for natural nematicide.

Pharmacological basis for use of Lychnophora trichocarpha in gouty arthritis: anti-hyperuricemic and anti-inflammatory effects of its extract, fraction and constituents.

ETHNOPHARMACOLOGICAL RELEVANCE: The ethanolic extract of Lychnophora trichocarpha Spreng. is used in Brazilian folk medicine to treat bruise, pain and inflammatory diseases. AIM OF THE STUDY: The present study aimed at investigating whether ethanolic extract of L. trichocarpha, its ethyl acetate fraction and its main bioactive compounds could be useful to treat gouty arthritis by countering hyperuricemia and inflammation. MATERIALS AND METHODS: L. trichocarpha ethanolic extract (LTE), ethyl acetate fraction from ethanolic extract (LTA) and isolated compounds were evaluated for urate-lowering activity and liver xanthine oxidase (XOD) inhibition in oxonate-induced hyperuricemic mice. Anti-inflammatory activity in monosodium urate crystal-induced paw oedema, an experimental model of gouty arthritis, was also investigated. RESULTS: Crude ethanolic extract and its ethyl acetate fraction showed significant urate-lowering effects. LTE was also able to significantly inhibit liver xantine oxidase (XOD) activity in vivo at the dose of 250mg/kg. Luteolin, apigenin, lupeol, lychnopholide and eremantholide C showed the anti-hyperuricemic activities among tested compounds. Apigenin also showed XOD inhibitory activity in vivo. Luteolin, lychnopholide, lupeol and eremantholide C, in turn, did not shown significant inhibitory activity towards this enzyme, indicating that this mechanism is not likely to be involved in urate-lowering effects of those compounds. LTE, LTA, lupeol, ß-sitosterol, lychnopholide, eremantholide, luteolin and apigenin were also found to inhibit monosodium urate crystals-induced paw oedema in mice. CONCLUSIONS: Ethanolic extract of Lychnophora trichocarpha and some of its bioactive compounds may be promising agents for the treatment of gouty arthritis since they possesses both anti-hiperuricemic and anti-inflammatory properties.

Chemical composition and vasodilatation induced by Cuphea carthagenensis preparations.

The aerial parts of Cuphea carthagenensis (Jacq.) J.F. Macbride (Lythraceae) are traditionally employed in Brazil to treat cardiovascular diseases. The aim of this study was to compare preparations of C. carthagenensis aerial parts (aqueous and ethanol extracts, together with derived fractions) with regard to their total phenolic contents and in vitro vasodilating activity. The main flavonoids found in the extracts were isolated and identified as quercetin derivatives. The extracts and fractions showed similar HPLC profiles with the presence of quercetin-5-O-ß-glucopyranoside, quercetin-3-O-α-arabinofuranoside and quercetin-3-sulfate in all of them, but marked differences in the contents of flavonoids, proanthocyanidins, tannis and total phenolics. Excepting the aqueous extract, all assayed preparations elicited vasodilatation on pre-contracted rat aortic rings in the range of pIC(50) 4.53±0.03 to 4.98±0.06. Polynomial regression analysis demonstrated the relationship between vasodilating activity and the contents of flavonoids (r(2)=0.5190), proanthocyanidins (r(2)=0.8016), tannins (r(2)=0.8041) and total phenolics (r(2)=0.6226), suggesting the participation of these compounds in the pharmacological effect and their potential use as chemical markers for the species.

Antimicrobial, antiviral and cytotoxic activity of extracts and constituents from Polygonum spectabile Mart.

Polygonum spectabile is used in Brazil for treatment of several infection diseases. Extracts and constituents isolated from this species were evaluated for cytotoxicity and effects on 15 bacterias and yeasts as well on 4 viruses strains (HHV-1, VACV-WR, EMCV, DEN-2). Less polar extracts were effective against Staphylococcus aureus, Bacillus subtillis, Micrococcus luteus, M. canis and Tricophyton mentagrophytes and T. rubrum. Two known chalcones and 3-O-ß-D-glucosyl-ß-sitosterol were isolated. The ethanol extract was the only one to show antiviral activity (CE50 < 30 µg/ml). One chalcone has inhibited the growth of several bacteria and was significantly active against dermathophytes. The 3 compounds isolated have shown moderate cytotoxicity against Vero and LLCMK(2) cells (CC(50) < 50 µg/ml). These results support the use of P. spectabile as antimicrobial agent.

Antifungal constituents of Clytostoma ramentaceum and Mansoa hirsuta.

Ethanol extracts of Clytostoma ramentaceum Bur. & K. Schum and Mansoa hirsuta DC. (Bignoniaceae) inhibited the growth of standardized cultures of Aspergillus niger and Fusarium oxysporum, at concentrations of 400 microg and 500 microg, in bioautographic assays. The activity-guided fractionation of C. ramentaceum extract afforded ursolic acid and 2-(3',4'-dihydroxyphenyl) ethanol, both active against the test fungi (100 microg). These compounds are reported for the first time in C. ramentaceum and were not detected in M. hirsuta extract, according to HPLC analysis. The bioguided study of M. hirsuta resulted in five active fractions (100 to 200 microg), whose GC-MS analysis allowed us to identify 11 compounds, mostly alkanols and alkanodiols, that may be regarded as the antifungal constituents of M. hirsuta.

Antimicrobial activity and constituents of Coccoloba acrostichoides.

The ethanol extract and fractions from Coccoloba acrostichoides aerial parts were assayed for in vitro antimicrobial activity. The extract was active against the assayed bacteria while most of the fractions also inhibited fungal growth, especially the n-hexane and EtOAc fractions. The isolated beta-sitosterol and betulin were tested, being the last one active against Fusarium oxysporum.

In vitro evaluation of the activity of aromatic nitrocompounds against Trypanosoma cruzi.

Fourteen compounds were evaluated for their activity against Trypanosoma cruzi blood stream forms at the concentration of 500 g/ml. Six compounds were active and re-tested at lower concentrations.

In vitro evaluation of the activity of aromatic nitrocompounds against Trypanosoma cruzi

Fourteen compounds were evaluated for their activity against Trypanosoma cruzi blood stream forms at the concentration of 500 æg/ml. Six compounds were active and re-tested at lower concentrations