Marcos José Salvador

Essential oils from neotropical Myrtaceae: chemical diversity and biological properties.

Myrtaceae family (121 genera, 3800–5800 spp.) is one of the most important families in tropical forests. They are aromatic trees or shrubs, which frequently produce edible fruits. In the neotropics, ca. 1000 species were found. Several members of this family are used in folk medicine, mainly as an antidiarrheal, antimicrobial, antioxidant, cleanser, antirheumatic, and anti‐inflammatory agent and to decrease the blood cholesterol. In addition, some fruits are eaten fresh or used to make juices, liqueurs, and sweets very much appreciated by people. The flavor composition of some fruits belonging to the Myrtaceae family has been extensively studied due to their pleasant and intense aromas. Most of the essential oils of neotropical Myrtaceae analyzed so far are characterized by predominance of sesquiterpenes, some with important biological properties. In the present work, chemical and pharmacological studies carried out on neotropical Myrtaceae species are reviewed, based on original articles published since 1980. The uses in folk medicine and chemotaxonomic importance of secondary metabolites are also briefly discussed.

Antihypertensive effects of isoquercitrin and extracts from Tropaeolum majus L.: Evidence for the inhibition of angiotensin converting enzyme

AIM OF THE STUDY Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic properties. In the present study, we assessed whether the hypotensive and/or antihypertensive mechanism of hydroethanolic extract (HETM), semi-purified fraction (TMLR) obtained from T. majus and the flavonoids isoquercitrin (ISQ) and kaempferol (KPF) can be mediated by their interaction with angiotensin converting enzyme (ACE). METHODS AND METHODS Firstly, to evaluate changes in mean arterial pressure (MAP), different groups of normotensive and spontaneously hypertensive rats (SHR) were orally and intraduodenally treated with HETM (10-300 mg/kg) and TMLR (12.5-100mg/kg) and intravenously treated with ISQ and KPF being later anesthetized with ketamine (100mg/kg) and xylazine (20mg/kg). The left femoral vein and the right carotid artery were isolated, and polyethylene catheters were inserted for ISQ and KPF (0.5-4 mg/kg) administration and blood pressure recording, respectively. The plasmatic ACE activity was evaluated to indirect fluorimetry, in serum samples after orally treatment with HETM, TMLR, ISQ and KPF. RESULTS The oral administration of the HETM and its TMLR significantly reduced, in a dose-dependent manner, the MAP in both normotensive and SHR. In addition, these preparations significantly decreased the MAP for up to 3h after the administration of the extract. Additionally, the intravenous administration of ISQ, but not KPF, decreased MAP in rats. Otherwise, neither the extracts nor ISQ affected the heart rate. The oral administration of the HETM, TMLR or ISQ reduced ACE activity in serum samples at 90 min after administration. Finally, the intravenous administration of ISQ caused a significant reduction in the hypertensive response to angiotensin I, but not angiotensin II in normotensive rats. CONCLUSION Our results show that the hypotensive effects caused by the HETM, as well as by its TMLR, may be associated with the high levels of the flavonoid ISQ found in this plant. In addition, ISQ-induced hypotension in rats is an event dependent on the inhibition of angiotensin II generation by ACE.

Gastroprotective and ulcer healing effects of essential oil from Hyptis spicigera Lam. (Lamiaceae)

ETHNOPHARMACOLOGICAL RELEVANCE Hyptis Jacq. (Lamiaceae) is being used in traditional medicine to treat fever, inflammation and gastric disturbances. Hyptis spicigera Lam. is a native plant distributed across the central region of Brazil. The essential oil extracted from this plant is used in folk medicine as antipyretic. AIM OF THE STUDY The effects of the essential oil obtained from the aerial parts of Hyptis spicigera (OEH) were evaluated for their gastroprotective and healing activities. MATERIALS AND METHODS OEH chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). The gastroprotective action of the OEH was evaluated in rodent experimental models (ethanol and NSAID). To elucidate mechanisms of action, the antisecretory action and involvements of NO, SH, mucus and PGE2 were evaluated. The acetic acid-induced gastric ulcer model and Western Blot assay (COX-2 and EGF) were also used to evaluate the OEH healing capacity. RESULTS GC-MS analysis of OEH indicated three monoterpenes as major compounds: alpha-pinene (50.8%), cineole (20.3%) and beta-pinene (18.3%) and, at the dose of 100 mg/Kg, p.o., OEH provided effective gastroprotection against lesions induced by absolute ethanol (97%) and NSAID (84%) in rats. OEH do not interfere with H+ secretion in gastric mucosa and its gastric protection does not depend on nitric oxide (NO) and sulfhydryl compounds (SH). The gastroprotective action of OEH occurs due to an increase in the gastric mucus production (28%) induced by PGE2 levels. Furthermore, OEH demonstrated a great healing capacity with 87% of reduction in ulcerative lesion area. It accelerated the healing of acetic acid-induced gastric lesions due to an increase in COX-2 (75%) and EGF (115%) expression in gastric mucosa. No sign of toxicity was observed in this study, considering the analyzed parameters. CONCLUSIONS All these results suggest the efficacy and safety of Hyptis spicigera in combating and healing gastric ulcer. Considering the results, it is suggested that the OEH could probably be a good therapeutic agent for the development of new phytotherapeutic medicine for the treatment of gastric ulcer.

Diuretic and potassium-sparing effect of isoquercitrin-an active flavonoid of Tropaeolum majus L.

AIM OF THE STUDY Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic effects supporting the ethnopharmacological use of this plant as diuretic. In the present work, phytochemical investigation, guided by bio-assay in spontaneously hypertensive rats (SHR), was carried out in order to identify the compounds responsible for diuretic action. MATERIAL AND METHODS Chromatographic fractionation of the hydroethanolic extract yielded an active fraction (TMLR) rich in isoquercitrin. TMLR (25-100mg/kg) and isoquercitrin (5-10mg/kg), as well the reference drug hydrochlorothiazide (10mg/kg) were orally administered in a single dose or daily for 7 days to SHR. The urine excretion rate, pH, density, conductivity and content of sodium (Na(+)) and potassium (K(+)) electrolytes were measured in the urine of saline-loaded animals. RESULTS The urinary excretion rate was dose-dependently increased in both TMLR and isoquercitrin groups, as well as Na(+). Despite the changes in urinary excretion of electrolytes, the plasmatic levels of Na(+) and K(+) had not been changed. In addition, we did not find any evidence of renal toxicity or other adverse effects in these animals, even after prolonged treatment with TMLR or isoquercitrin. CONCLUSION This research supports and extends the ethnomedicinal use of T. majus as diuretic. This activity seems to be associated to the presence of the flavonol isoquercitrin.

Evaluation of immunomodulatory and anti-inflammatory effects and phytochemical screening of Alternanthera tenella Colla (Amaranthaceae) aqueous extracts

Alternanthera tenella Colla extracts are used in Brazilian traditional folk medicine to treat a variety of infectious diseases as well as inflammation and fever. In this work, the immunomodulatory, anti-inflammatory and potential toxic effects of cold (CAE) and hot (HAE) aqueous extracts of A. tenella were investigated in vivo. In addition, we analyzed the phytochemical properties of both extracts. BALB/c mice were immunized in vivo with sheep red blood cells and concomitantly inoculated intraperitoneally (i.p.) with each extract (50, 100 or 200 mg/kg). Specific antibody-producing cells were enumerated using plaque-forming cell assays (PFC) and anti-SRBC IgG and IgM serum levels were measured via enzyme-linked immunosorbent assay. Body and lymphoid organ weights were determined after treatments in order to evaluate toxic effects. Carrageenan-induced paw edema was employed to investigate anti-inflammatory activity in mice inoculated i.p. with CAE or HAE (200 or 400 mg/kg). Phytochemical screening was performed using spectrometric and chromatographic approaches and revealed that CAE possessed higher tannin and flavonoid levels than HAE. PFC numbers were increased after treatment with CAE (100 mg/kg) four days after immunization, as were the serum antibody titers after four and seven days, suggesting immunostimulatory activity through modulation of B lymphocyte functions. Body and organ weights did not show major changes, suggesting that extracts administered to mice did not induce significant toxicity. Both extracts had significant anti-inflammatory activity in the paw edema assay. These results suggested that aqueous extracts from A. tenella contained several chemical compounds that possess positive and/or negative modulator effects on the immune system, which appeared to correlate with tannin and flavonoid levels in those extracts. In summary, these studies provide important insight into the biological activities of A. tenella.

Chemical composition of the essential oils of Annona pickelii and Annona salzmannii (Annonaceae), and their antitumour and trypanocidal activities

The essential oils from the leaves of Annona pickelii and Annona salzmannii (Annonaceae) were obtained by hydrodistillation using a Clevenger apparatus, and analysed by GC-MS and GC-FID. A total of 21 compounds were identified in the essential oil of A. pickelii and 23 in that of A. salzmannii; sesquiterpenes predominated in both essential oils. Bicyclogermacrene (38.0%), (E)-caryophyllene (27.8%), α-copaene (6.9%) and α-humulene (4.0%) were the main components of A. pickelii, while δ-cadinene (22.6%), (E)-caryophyllene (21.4%), α-copaene (13.3%), bicyclogermacrene (11.3%) and germacrene D (6.9%) were the main components of A. salzmannii. The biological activities of the essential oils against Trypanosoma cruzi epimastigote forms and cytotoxicity against tumour cell lines (antitumour) were investigated. The essential oils showed potent trypanocidal and antitumour activities with values of IC50 lower than 100 µg mL−1.

Comprehensive characterization of lipids from Amazonian vegetable oils by mass spectrometry techniques

An integrative approach in mass spectrometry (MS) comprising gas chromatography coupled to MS (GC-MS), ultra-efficiency liquid chromatography coupled to MS (UPLC-MS) and easy ambient sonic-spray ionization MS (EASI-MS) is proposed for the comprehensive characterization of Amazonian oils. Coconut, andiroba and castor seed oils, which are vastly sold in markets of the Amazonian region of Brazil, were selected as a representative test set. These oils were found to contain several lipids such as triacylglycerides (TAGs), fatty acids (FAs), phytosterols and limonoids. In the analyzed samples 30 different TAGs, 11 FAs, 6 phytosterols and 7 limonoids were identified. The antioxidant capacity (AOC) of the oils, as measured by their oxygen radical absorbance capacity (ORAC), was also used to evaluate their potential biological properties as well as their possible consumption as food. Edible virgin coconut oil was the most active (0.720±0.001 Trolox eq./mmol), whereas considerable lower activity was observed for andiroba and castor seed oils. The antimicrobial activities of the oils were also recorded against a panel of pathogenic bacteria and fungi in which andiroba oil was the only one that was active, solely against Enterococcus aeruginosa.

Antioxidant and antimicrobial activities of aporphinoids and other alkaloids from the bark of Annona salzmannii A. DC. (Annonaceae)

The antioxidant capacity by oxygen radical absorbance capacity (ORAC)-FL method and antimicrobial activity using the broth microdilution method of aporphinoids (liriodenine 1, anonaine 2 and asimilobine 3) and other alkaloids (reticuline 4 and cleistopholine 5) isolated from the bark of Annona salzmannii A. DC. (Annonaceae) were evaluated. For antioxidant activity, the most active alkaloid was asimilobine with ORAC value of 2.09 relative trolox equivalents. For antimicrobial activity, some alkaloids showed significant minimal inhibitory concentration (MIC) values in the range of 25–100 µg mL−1. The most active compounds were the aporphinoids liriodenine, anonaine and asimilobine, some of them more active than the positive control.

Antioxidant Action of Mangrove Polyphenols against Gastric Damage Induced by Absolute Ethanol and Ischemia-Reperfusion in the Rat

Rhizophora mangle, the red mangrove, has long been known as a traditional medicine. Its bark has been used as astringent, antiseptic, hemostatic, with antifungic and antiulcerogenic properties. In this paper, we aimed to evaluate the antioxidant properties of a buthanolic fraction of the R. mangle bark extract (RM) against experimental gastric ulcer in rats. Unib-Wh rats received pretreatment of R. mangle after the induction of gastric injury with absolute ethanol and ischemia-reperfusion. Gastric tissues from both methods were prepared to the enzymatic assays, the levels of sulfhydril compounds (GSH), lipid peroxides (LPO), and the activities of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The RM protected the gastric mucosa in both methods used, ethanol-induced gastric ulcer and ischemia-reperfusion, probably, by modulating the activities of the enzymes SOD, GPx, and GR and increasing or maintaining the levels of GSH; in adittion, LPO levels were reduced. The results suggest that the RM antioxidant activity leads to tissue protection; thus one of the antiulcer mechanisms present on the pharmacological effects of R. mangle is the antioxidant property.

Constituents of the leaves of Magnolia ovata.

Two new lignans, magnovatins A (1) and B (2), along with nine known compounds, were isolated from the leaves of Magnolia ovata. The known compounds were identified as acuminatin (3), licarin A (4), kadsurenin M, 4-O-demethylkadsurenin M, oleiferin A, oleiferin C, spathulenol, parthenolide, and 11,13-dehydrocompressanolide. In addition, compounds 1 and 2 yielded four new derivatives (1a, 1b, 2a, and 2b). The structures of the new compounds were established on the basis of spectrometric data evaluation. Free-radical scavenging and antimicrobial activities of the major compunds 1, 3, and 4 were investigated.