Maria de Fátima Vanderlei de Souza

Bioactivities from Marine Algae of the Genus Gracilaria

Seaweeds are an important source of bioactive metabolites for the pharmaceutical industry in drug development. Many of these compounds are used to treat diseases like cancer, acquired immune-deficiency syndrome (AIDS), inflammation, pain, arthritis, as well as viral, bacterial, and fungal infections. This paper offers a survey of the literature for Gracilaria algae extracts with biological activity, and identifies avenues for future research. Nineteen species of this genus that were tested for antibacterial, antiviral, antifungal, antihypertensive, cytotoxic, spermicidal, embriotoxic, and anti-inflammatory activities are cited from the 121 references consulted.

Sources of alpha-, beta-, gamma-, delta- and epsilon-carotenes: a twentieth century review

Since humans cannot synthesize carotenoids, they depend upon the diet exclusively for the source of these micronutrients. It has claimed that they may alleviate chronic diseases such as cancers. The present communication constitutes a global review of the scientific literature on plants and others organisms that biosynthesize carotenoids, which include the series alpha-, beta-, gamma-, delta- and epsilon-carotenes. The results of the literature survey lists more than five hundred sources.

Natural products with antileprotic activity

Leprosy is a chronic infectious disease caused by Mycobacterium leprae bacillus. It was considered to be an incurable disease for ages. Nowadays leprosy is a vanishing disease although we can meet it principally in the tropical zone countries. Brazil has the second greatest number of leprosy cases around the world with almost 30,000 new cases diagnosed in 2005. The present work constitutes a literature review on plant extracts and chemically defined molecules of natural origin showing antileprotic activity. The review refers to 11 plants, their families, and geographical distribution, the utilized parts, the type of extract and the tested organism. It also includes 17 compounds isolated from higher plants and microorganisms, classified into appropriate chemical groups. Some aspects of recent antileprotic-activity-directed research on natural products are discussed. For this purpose 63 references were consulted.

N-salicyloyltryptamine, a new anticonvulsant drug, acts on voltage-dependent Na+, Ca2+, and K+ ion channels.

The aim of this work was to study the effects of N‐salicyloyltryptamine (STP), a novel anticonvulsant agent, on voltage‐gated ion channels in GH3 cells. In this study, we show that STP at 17 μM inhibited up to 59.2±10.4% of the Ito and 73.1±8.56% of the IKD K+ currents in GH3 cells. Moreover, the inhibitory activity of the drug STP on K+ currents was dose‐dependent (IC50=34.6±8.14 μM for Ito) and partially reversible after washing off. Repeated stimulation at 1 Hz (STP at 17 μM) led to the total disappearance of Ito current, and an enhancement of IKD. In the cell‐attached configuration, application of STP to the bath increased the open probability of large‐conductance Ca2+‐activated K+ channels. STP at 17 μM inhibited the L‐type Ca2+ current by 54.9±7.50% without any significant changes in the voltage dependence. STP at 170 μM inhibited the TTX‐sensitive Na+ current by 22.1±2.41%. At a lower concentration (17 μM), no effect on INa was observed. The pharmacological profile described here might contribute to the neuroprotective effect exerted by this compound in experimental ‘in vivo’ models.

Triterpenes and phenolic compounds isolated from the aerial parts of Herissantia tiubae and evaluation of 5,4′,-dihydroxy-3,6,7,8,3′-pentamethoxyflavone as a modulator of bacterial drug resistance

In our continuous study of the Malvaceae family, we describe here the isolation of four triterpenes (frideline, lupeol, cycloartenol, and cycloeucalenol), a steroid (β-sitosterol), and four phenolic compounds from the aerial parts of Herissantia tiubae (K. Schum.) Brizicky (i.e., a benzoic acid derivative, a coumarin and two flavonoids, kaempferol 7-O-α-l-rhamnopyranoside and 4′,5-dihydroxy-3,6,7,8,3′-pentamethoxyflavone). The structural identification of the compounds was made by comparison with literature data and spectral analysis, including two-dimensional NMR techniques. These compounds are reported here for the first time in genus Herissantia. The pentamethoxyflavone was assayed against strains of Staphylococcus aureus possessing efflux mechanisms of resistance to norfloxacin, tetracycline, and erythromycin. Although the compound did not display relevant antibacterial activity (MIC ≥ 512 μg/mL), it modulated the activity of antibiotics, i.e., in combination with antibiotics (at 128 μg/mL), a two-fold reduction in the MIC values for tetracycline and erythromycin, a 32-fold reduction in the MIC for norfloxacin were observed.

New Sulphated Flavonoids from Wissadula periplocifolia (L.) C. Presl (Malvaceae)

Wissadula periplocifolia (L.) C. Presl (Malvaceae) is commonly used in Brazil to treat bee stings and as an antiseptic. The antioxidant properties of its extracts have been previously demonstrated, thus justifying a phytochemical investigation for its bioactive phenolic constituents. This has yielded five new sulphated flavonoids: 8-O-sulphate isoscutellarein (yannin) (1a); 4′-O-methyl-7-O-sulphate isoscutellarein (beltraonin) (1b); 7-O-sulphate acacetin (wissadulin) (2a); 4′-O-methyl-8-O-sulphate isoscutellarein (caicoine) (2b) and 3′-O-methyl-8-O-sulphate hypolaetin (pedroin) (3b) along with the known flavonoids 7,4′-di-O-methyl-8-O-sulphate isoscutellarein (4), acacetin, apigenin, isoscutellarein, 4′-O-methyl isoscutellarein, 7,4′-di-O-methylisoscutellarein, astragalin and tiliroside. The compounds were isolated by column chromatography and identified by NMR (1H, 13C, HMQC, HMBC and COSY) and LC-HRMS. A cell based assay was carried out to evaluate the preliminary cytotoxic properties of the flavonoids against UVW glioma and PC-3M prostate cancer cells as well as non-tumour cell lines. The obtained results showed that acacetin, tiliroside, a mixture of acacetin + apigenin and the sulphated flavonoids 2a + 2b exhibited inhibitory activity against at least one of the cell lines tested. Among the tested flavonoids acacetin and tiliroside showed lower IC50 values, presenting promising antitumor effects.

Mechanism of the antihypertensive and vasorelaxant effects of the flavonoid tiliroside in resistance arteries

Hypertension is a leading cause of death and disability globally, and its prevalence continues to accelerate. The cardiovascular effects of the flavonoid tiliroside have never been reported. In this work, using complementary in vivo and in vitro approaches, we describe the antihypertensive effect of tiliroside and the underlying mechanisms involved in the reduction of blood pressure. Tiliroside (1, 5 or 10 mg/kg) induced a dose-dependent long-lasting decrease in blood pressure in conscious DOCA-salt hypertensive rats that was accompanied by an increased heart rate. Tiliroside also induced a concentration-dependent vasodilation of mesenteric resistance arteries precontracted with phenylephrine. Removal of the endothelium or pretreatment of the preparation with L-NAME or indomethacin did not modify the vasodilator response for tiliroside. When vessels were precontracted with a high K⁺ (50 mM) solution, tiliroside exhibited a vasodilator effect similar to that observed in vessels precontracted with phenylephrine. Experiments carried out in nominally Ca²⁺-free solution showed that tiliroside antagonized CaCl₂-induced contractions. Moreover, tiliroside reduced the rise in intracellular Ca²⁺ concentration induced by membrane depolarization in vascular smooth muscle cells. Finally, tiliroside decreased the voltage-activated peak amplitude of the L-type Ca²⁺ channel current in freshly dissociated vascular smooth muscle cells from mesenteric arteries. Altogether, our results point to an antihypertensive effect of tiliroside due to a reduction in peripheral resistance through blockage of voltage-activated peak amplitude of the L-type Ca²⁺ channel in smooth muscle cells.

Phytochemical investigation of Wissadula periplocifolia (L.) C. Presl and evaluation of its antibacterial activity

A phytochemical study on the aerial parts of Wissadula periplocifolia using chromatographic techniques has led to the isolation of sitosterol (1a), stigmasterol (1b), sitosterol 3-O-β-D-glucopyranoside (2a), stigmasterol 3-O-β-D-glucopyranoside (2b), phaeophytin A (3), 132-hydroxy-(132-S)-phaeophytin A (4), phaeophytin B (5), 173-ethoxyphaeophorbide (6), 3,4-seco-urs-4(23),20(30)-dien-3-oic acid (7), 3-oxo-21β-H-hop-22(29)-ene (8), dammaradienone (9a), and taraxastenone (9b). The isolated compounds were characterised by spectroscopic analysis. A preliminary assay to evaluate the antibacterial activity of W. periplocifolia extracts and fractions showed that the dichloromethane, ethyl acetate, and n-butanol fractions were active against Enterococcus faecalis.

Phenolic constituents from Wissadula periplocifolia (L.) C. Presl. and anti-inflammatory activity of 7,4′-di-O-methylisoscutellarein

Abstract This study reports the first phenolics from Wissadula genus (Malvaceae) and the anti-inflammatory activity of 7,4′-di-O-methylisoscutellarein. Using chromatographic methods, five phenolic compounds were isolated from aerial parts of Wissadula periplocifolia (L.) C. Presl. The compounds were identified as 4-hydroxybenzoic acid, 3-hydroxybenzoic acid, trans-cinnamic acid, tamgermanetin and 7,4′-di-O-methylisoscutellarein using spectroscopic methods. The flavone 7,4′-di-O-methylisoscutellarein showed anti-inflammatory activity by inhibiting neutrophils recruitment in a mice model of pleurisy and by decreasing significantly the production of cytokines IL-1β and TNF-α.

Anti-asthmatic and anxiolytic effects of Herissantia tiubae, a Brazilian medicinal plant

Herissantia tiubae (HtE) is a Brazilian plant used in folk medicine to treat inflammatory diseases. Our aim was to determine whether the HtE has anti‐inflammatory and anxiolytic effects in a murine model of asthma. Ovalbumin (OVA)‐sensitized BALB/c mice were treated with HtE (50, 100, or 200 mg/kg) or dexamethasone before each OVA challenge. After the last challenge, animals were subjected to anxiety tests and respiratory measurements. Following euthanasia, we quantified immune cells in the bronchoalveolar lavage (BAL), serum IgE titer and cytokine levels, cellular infiltration and mucus content in the lung tissues, and cellular composition of the mediastinal lymph nodes. OVA challenge in sensitized animals caused: (1) reduction of mean respiratory and dominant respiratory rate (from 398 ± 12 to 286 ± 20 cicles per minute (cpm) and from 320 ± 14 to 162 ± 15 cpm, respectively); (2) increase in behavioral markers of anxiety tests; (3) substantial pro‐inflammatory effects, including rise in OVA‐specific IgE titer (from 0 to 1:2048) and these inflammatory effect diminished the titer to 1:512 after HtE treatment; rise in plasma IL‐13 (from 13 ng/mL in saline to 227 ng/mL in OVA and HtE treatment restored to 1.29 ng/mL; rise in total BAL cell count (from 0.742 cells/mL in saline to 11.77 cells/mL in OVA), with prominent eosinophilia. H. tiubae extract affected respiratory parameters similarly to aminophylline, behavioral changes comparable to diazepam, and inflammation being as efficient as dexamethasone. H. tiubae extract (HtE) possesses both anti‐inflammatory and anxiolytic properties in the murine model of asthma.