Sidastrum paniculatum (L.) Fryxell (Malvaceae): A Promising Source of Bioactive Sulfated Flavonoids Against Aedes aegypti L.

Aedes aegypti L. is known as the most relevant vector mosquito for viruses such as yellow fever, chikungunya, dengue, and Zika, especially in places with unplanned urbanization, and erratic water supply. Plants used in folk medicine have become a useful source of active compounds with the potential to control the dissemination of Ae. aegypti. Compounds isolated from Malvaceae sensu lato have been previously reported as larvicides, repellents, and insecticides. Recent studies have demonstrated the anti Ae. aegypti activity of sulfated flavonoids, an uncommon type of flavonoid derivatives. This research reports the phytochemical investigation of Sidastrum paniculatum (L.) Fryxell, a Malvaceae species with the potential against Ae. aegypti. Chromatographic procedures resulted in the isolation of the compounds: stearic acid (1), N-trans-feruloyltyramine (2), acacetin (3), apigenin (4), tiliroside (5), along with the sulfated flavonoids: wissadulin (6), 7,4'-di-O-methyl-8-O-sulfate flavone (7), yannin (8), beltraonin (9a), 7-O-sulfate isoscutellarein (paniculatumin) (9b), and condadin (10). This is the first report of compound 7-O-sulfate isoscutellarein (9b). The structures were elucidated by spectroscopic analysis (NMR, LC-HRMS and FT-IR). The sulfated flavonoids identified were submitted to a ligand-based and structure-based virtual screening against two targets: 1YIY (from adult Ae. aegypti) and 1PZ4 (from Ae. aegypti larvae). The results indicated that when the O-sulfate group is bearing the position 7, the structures are potentially active in 1PZ4 protein. On the other hand, flavonoids with the O-sulfate group bearing position 8 were showed to be more likely to bind to the 1YIY protein. Our findings indicated that S. paniculatum is a promising source of sulfated flavonoids with potential against Ae. aegypti.

Vasorelaxant action of the total alkaloid fraction obtained from Solanum paludosum Moric. (Solanaceae) involves NO/cGMP/PKG pathway and potassium channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum paludosum Moric. (jurubeba-roxa) is commonly used to treat hypertension as a substitute for Solanum paniculatum L. (jurubeba verdadeira). The total ethanolic extract from the root bark of Solanum paludosum have been found to cause hypotension in rats. AIM OF THE STUDY: To investigate the mechanism by which the total alkaloid fraction obtained from the root bark of Solanum paludosum (FAT-SP) acts as a vasorelaxant agent on rat thoracic aorta. MATERIALS AND METHODS: Rings of rat aorta were suspended in organ bath containing Krebs solution at 37°C, bubbled with carbogen mixture (95% O(2) and 5% CO(2)) under a resting tension of 1 g. Isometric contractions were measured using a force transducer coupled to an amplifier and a microcomputer. RESULTS: FAT-SP has been found cause relaxation of the aortic rings pre-contracted with phenylephrine (Phe) in a concentration-dependent manner, in the presence and absence of endothelium. This effect was more potent on the endothelium-intact aorta. In the presence of endothelium, neither indomethacin (non-selective cyclooxygenase inhibitor) nor atropine (non-selective muscarinic receptor antagonist), produced significant changes on the relaxation response. On the other hand, in the presence of calmidazolium (a calmodulin inhibitor), N-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), hydroxocobalamin (HDX) (scavenger of free-radical nitric oxide), 1-H-[1,2,4]-oxadiazolo-[4,3a]-quinoxalin-1-one (ODQ, selective blocker of soluble guanylate cyclase), Rp-8-bromo-ß-phenyl-1,N(2)-ethenoguanosine 3':5'-cyclic monophosphorothioate sodium salt hydrate (Rp-8-Br-PET-cGMPS, competitive inhibitor of cGMP-dependent protein kinase G) or TEA(+) (tetraethylammonium, nonselective potassium channel blocker), the vasorelaxant effect was significantly reduced, suggesting the involvement of NO/sCG/PKG pathway and potassium channel opening in vasorelaxant action of the FAT-SP. CONCLUSION: The mechanism of vasorelaxant activity of the FAT-SP on rat aorta involves both NO/sCG/PKG pathway and potassium channels.

Antioxidant, antinociceptive, and anti-inflammatory properties of the ethanolic extract of Combretum duarteanum in rodents.

The antioxidant, antinociceptive, and anti-inflammatory activities of the ethanolic extract from leaves of Combretum duarteanum (EEC) were assessed in rodents through in vitro tests. The antioxidant activity was investigated by using thiobarbituric acid reactive species (TBARS), hydroxyl radical-scavenging, and scavenging activity of nitric oxide assays. The antinociceptive activity was investigated by using acetic acid-induced writhing, formalin, and hot-plate tests in mice. The anti-inflammatory activity was assessed in rats by using the carrageenan-induced hind-paw edema test and arachidonic acid-induced paw edema test. EEC possesses a strong antioxidant potential according to the TBARS, nitric oxide, and hydroxyl radical-scavenging assays; it also presented scavenger activity in all in vitro tests. After intraperitoneal injection, EEC (100, 200, and 400 mg/kg) significantly reduced the number of writhes (38.1%, 90.6%, and 97.8%, respectively) in a writhing test and the number of paw licks during phase 1 (30.5% and 69.5%, higher doses) and phase 2 (38.1%, 90.6%, and 97.8%, all doses) of a formalin test when compared with the control group. Naloxone (1.5 mg/kg, intraperitoneally) antagonized the antinociceptive action of EEC (400 mg/kg), and this finding suggests participation of the opioid system. Administration of 200 and 400 mg/kg (intraperitoneally) of EEC exhibited an anti-inflammatory activity in the carrageenin test, which was based on interference with prostaglandin synthesis. This finding was confirmed by the arachidonic acid test. Together, these results indicate that properties of EEC might be further explored in the search for newer tools to treat painful inflammatory conditions, including those related to pro-oxidant states.

Effects of umbelliferone in a murine model of allergic airway inflammation.

The therapeutic effects of umbelliferone (30, 60 and 90 mg/kg), a coumarin isolated from Typha domingensis (Typhaceae) were investigated in a mouse model of bronchial asthma. BALB/c mice were immunized and challenged by nasal administration of ovalbumin. Treatment with umbelliferone (60 and 90 mg/kg) caused a marked reduction of cellularity and eosinophil numbers in bronchoalveolar lavage fluids from asthmatic mice. In addition, a decrease in mucus production and lung inflammation were observed in mice treated with umbelliferone. A reduction of IL-4, IL-5, and IL-13, but not of IFN-gamma, was found in bronchoalveolar lavage fluids of mice treated with umbelliferone, similar to that observed with dexamethasone. The levels of ovalbumin-specific IgE were not significantly altered after treatment with umbelliferone. In conclusion, our results demonstrate that umbelliferone attenuates the alteration characteristics of allergic airway inflammation. The investigation of the mechanisms of action of this molecule may contribute for the development of new drugs for the treatment of asthma.

Composição química e modulação da resistência bacteriana a drogas do óleo essencial das folhas de Rollinia leptopetala R. E. Fries / Chemical composition and modulation of bacterial drug resistance of the essential oil from the leaves of Rollinia leptopetala R. E. Fries

O óleo essencial das folhasde Rollinia leptopetala foi obtido por hidrodestilação em aparelho de Clevenger e a sua composição química foi analisada através de CG-EM. Com essa técnica, foi possível identificar 22 constituintes em uma mistura complexa demonoterpenos (54,5 por cento) e sesquiterpenos (45,5 por cento). O principal componente encontradonas folhas foi o biciclogermacreno (22,47 por cento). O óleo essencial foi avaliado numa linhagem de Staphylococcus aureus portadora de bomba de efluxo responsável pela resistência norfloxacino. Embora o óleo essencial não tenha apresentado atividade antibacteriana relevante in vitro, ele apresentou atividade moduladora da resistência, ou seja, em combinação com o norfloxacino observou-se uma redução de 4x na concentração inibitória mínima do antibiótico, indicando inibição de bomba de efluxo.

The essential oil from the leaves of Rollinia leptopetala was obtained by hydrodistillation in Clevenger's apparatus and its chemical composition was analyzed by GC-MS. With this technique could be identified 22 constituents in a complex mixture of monoterpenes (54.5 percent) and sesquiterpenes (45.5 percent). The main component found in the leaves was the bicyclogermacrene (22.47 percent). The essential oil was assayed against a strain of Staphylococcus aureus possessing efflux mechanism of resistance to norfloxacin. Although the essential oil did not display relevant antibacterial activity in vitro, it modulated the activity of the norfloxacin, i.e. in combination with the antibiotic it was observed a fourfold reduction in the minimum inhibitory concentration for norfloxacin, indicating inhibition of efflux pump.

Brine shrimp bioassay of some species of Solanum from Northestern Brazil

Os extratos metanólicos de 13 espécies de Solanum (Solanaceae) foram testados para verifificação da bioatividade em Artemia salina. As espécies testadas (partes aéreas, raízes e frutos) foram: S. asperum, S. capsicoides, S. palinacantum, S. paludosum, S. paniculatum, S. paraibanum, S. sisymbriifolium, S. crinitum, S. diamantinense, S. megalonyx, S. torvum, S. asterophorum e S. stipulaceum. Das treze espécies testadas, quatro foram inativas. Os extratos dos frutos de S. asperum (CL50 = 420,5 µg/mL) e S. paludosum (CL50 = 548,0 µg/mL), partes aéreas de S. diamantinense (CL50 = 481,0 µg/mL) e S. sisymbrifolium (CL50 = 382,7 µg/mL), e das raízes S. asperum (CL50 = 593,4 µg/mL) e S. stipulaceum (CL50 = 823,1 µg/mL) que mostraram atividade moluscicida contra Biomphalaria glabrata também mostraram atividade tóxica em Artemia salina.

The methanolic extracts of 13 Specieis of the genus Solanum (Solanaceae) have been tested for bioactivity in Artemia salina. The extracts investigated were prepared from various parts (aerial parts, roots and fruits) of S. asperum, S. capsicoides, S. palinacantum, S. paludosum, S. paniculatum, S. paraibanum, S. sisymbriifolium, S. crinitum, S. diamantinense, S. megalonyx, S. torvum, S. asterophorum and S. stipulaceum. The lethal concentrations were determined for the extracts and among thirteen plants tested, four appear to be inactive. The extracts of the fruits of S. asperum (LC50 = 420.5 µg/mL) and S. paludosum (LC50 = 548.0 µg/mL), aerial parts of S. diamantinense (LC50 = 481.0 µg/mL) and S. sisymbrifolium (LC50 = 382.7 µg/mL), and the roots of S. asperum (LC50 = 593.4 µg/mL) and S. stipulaceum (LC50 = 823.1 µg/mL), all of which previously showed molluscicidal activity against Biomphalaria glabrata were also found to be active in the present study with brine shrimp.

Morphoanatomical study of the leaves of Ocotea duckei Vattimo (Lauraceae-Lauroideae)

Ocotea duckei Vattimo is a plant native of Northeastern Brazil and popularly know as "Louro-de-cheiro". It is rich in alkaloids, lignans and essential oils. One of the most important constituents found in Ocotea duckei is yangambin, a furofuran lignan having significant pharmacological activities: as platelet activating factor (PAF) receptor antagonist, protective against cardiovascular collapse and anaphylactic shock, anti-allergic, analgesic, anti-convulsivant and as depressant of central nervous system. A morphoanatomical study of the leaves of O. duckei was carried out in order to contribute to separate its from the other species of the genus Ocotea, which would be helpful in its identification. The morphological study was done with stereomicroscope and by field observations. The anatomical studies were made by paradermic and transversal sections of leaves (blade and petiole), cleared and stained with Astrablue and basic Fuchsine. The leaves are alternate, leathery, elliptic to oblong, glabrous, acute to acuminate at the apex, and acute and lightly attenuate at the base. The main anatomical features are the epidermis unistratified, the hypostomatic leaves with stomata of the paracytic type, mesophyll is dorsiventral with secretories cells in the parenchyma and collateral vascular bundles.

Ocotea duckei Vattimo é uma espécie nativa do nordeste brasileiro, conhecida popularmente como "Louro-de-cheiro". É rica em alcalóides, lignanas e óleos essenciais. Um dos constituintes mais importantes obtidos de Ocotea duckei é iangambina, uma lignana furorânica, que têm demonstrado várias atividades farmacológicas como: antagonista do receptor do fator de agregação plaquetária (PAF), efeito protetor contra colapso cardiovascular e choque anafilático, antialérgica, analgésica, anticonvulsivante e depressora do sistema nervosos central. O estudo morfo-anatômico das folhas de O. duckei foi realizado com o objetivo de contribuir com a sua identificação. O estudo morfológico foi realizado com auxílio de estereomicroscópio e através de observações de campo. O estudo anatômico foi feito a partir de cortes paradérmicos e transversais da folha (lâmina e pecíolo), descorados e corados com azul de astra e fucsina básica. As folha desta espécie são alternas, elípticas a oblongas, glabras, ápice agudo a acuminado e base aguda a ligeiramente atenuada. As características anatômicas principais são: epiderme uniestratificada, folha hipoestomática, com estômatos do tipo paracítico, mesofilo dorsiventral, presença de células secretoras no parênquima e feixes vasculares colaterias.

Use of cabbage leaves (Brassica oleracea var. acephala) in the stabilization of bone mass after menopause / Uso do suco das folhas da couve (Brassica oleracea var acephala), na estabilização da massa óssea pós-menopausa

This work evaluates the use of cabbage leaves, Brassica oleracea var acephala (Cruciferae family) to stabilize bone mass in 13 menopausal women. The mature leaves were used after removal of the midrib and petiole and taken as a juice and given to the patient once a day for 24 months. Densitometric exams were performed every six months. The measurement points were the Trocanter and Ward's triangle. According to the results found, the use of cabbage leaf juice results in bone mass stabilization at the points studied, with perspectives for its use as an important option in disease prevention.

Neste trabalho foi avaliado a utilização da folha da couve Brassica oleracea variedade acephala, pertencente à família Cruciferae, para estabilizar a massa óssea em 13 mulheres após a menopausa. As folhas da couve foram usadas após retirar a nervura principal e o peciolo, na forma de suco de uma folha ao dia, durante 24 meses. Foi realizado a cada seis meses o exame de densitometria óssea para avaliar os resultados. Os locais de medição foram o trocanter e o triângulo de Ward. De acordo com os resultados encontrados, podemos concluir que o uso da folha da couve foi capaz de estabilizar a massa óssea nos sítios estudados, com perspectivas do seu uso também como opção importante para prevenção da doença.

Cytotoxic pyranonaphthoquinones from Melloa quadrival vis (Bignoniaceae).

Three new pyranonaphthoquinones: 5-hydroxy-6-methoxy-alpha-lapachone, 5,6-dihydroxy-a-lapachone and 4',5-dihydroxy-6-methoxy-alpha-lapachone, and two known compounds: lapachol and 5,5'-dihydroxy-3',4',7-trimethoxyflavanone, were isolated from the stem bark of Melloa quadrivalvis. Their structures were established by spectrometric data, mainly 1D- and 2D-NMR and mass spectra. The methylazoetetrazolium (MTT) method using viable cells of the strain Hep2 and the strain NCIH-292 demonstrated cytotoxic activity. The CI50 was also calculated. The chloroform extract and 5-hydroxy-6-methoxy-alpha-lapachone inhibited cell growth.