Neo-clerodane diterpenoid, a new metalloprotease snake venom inhibitor from Baccharis trimera (Asteraceae): anti-proteolytic and anti-hemorrhagic properties

Many plants are used in traditional medicine as active agents against various effects induced by snakebite. Few attempts have been made however to identify the nature of plain natural products with anti-ophidian properties. Baccharis trimera (Less) DC (Asteraceae), known in Brazil as carqueja. has been popularly used to treat liver diseases. rheumatism. diabetes, as well as digestive, hepatic and renal disorders. The active component was identified as 7alpha-hydroxy-3,13-clerodadiene-16,15:18,19-diolide, C20H28O5, (clerodane diterpenoid, Bt-CD). We report now the anti-proteolytic and anti-hemorrhagic propenies against snake venoms of a Bt-CD inhibitor from B. trimera. Bt-CD exhibited full inhibition of hemorrhage and proteolytic activity caused by Bothrops snake venoms. The inhibitor was able to neutralize the hemorrhagic, fibrinogenolytic and caseinolytic activities of class P-I and III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. No inhibition of the coagulant activity was observed. Bt-CD also partially inhibited the edema induced by other crude venoms, metallopronteases, basic and acidic phospholipases A(2). To further elucidate the inhibitory specificity of Bt-CD against metalloproteases isolated from snake venoms, a deeper understanding of its Structure and function is necessary. Furthermore, the potential use of these inhibitors to complement anti-venom as an alternative treatment of snakebite envenomations needs to be evaluated in future Studies. (C) 2004 Elsevier B.V.. All rights reserved.

Natural trans-crotonin: the antiulcerogenic effect of another diterpene isolated from the bark of Croton cajucara Benth.

The nor-clerodane diterpene trans-crotonin isolated from the bark of Croton cajucara BENTH. was investigated for its ability to prevent the formation of gastric-mucosa ulceration in different experimental models in mice. The results obtained from crotonin were compared with those obtained with another diterpene, DHC (trans-dehydrocrotonin) in the same models. When previously administered (p.o.) at the dose of 100 mg/kg, crotonin, as well as DHC, significantly reduced (p<0.05) gastric injury induced by stress (72, 67%), indomethacin/bethanechol (78, 29%) and pylorus ligature (35, 30%). In the HCl/ethanol-induced gastric ulcer model, at oral doses of 100 and 250 mg/kg, crotonin significantly prevented (p<0.05) the formation of gastric lesions by 51 and 56%, respectively, when compared to the control group. Gastric injury was also of significantly less magnitude in the DHC treatment group (p<0.05). In the pylorus-ligature model, crotonin (p.o.), like cimetidine, increased the volume of gastric juice when compared to the control group (p<0.05). No significant modifications where found in gastric parameters such as pH or total acid content after oral crotonin treatment. However, systemic alterations were observed when crotonin (100 mg/kg) was previously administered intraduodenally to mice. We observed significant changes (p<0.001) in gastric-juice parameters such as an increase in volume and a decrease in gastric acidity. Those pre-treated with crotonin as well as with DHC did not increase free mucus production (p>0.05). The results suggest that crotonin presents a significant anti-ulcer effect when assessed in these ulcer-induced models. As with DHC, the antiulcerogenic effects of crotonin are probably related to anti-secretory or/and gastroprotective properties of this substance. In light of results obtained with DHC and natural trans-crotonin in the present study, we concluded that the A-ring of both diterpenes is not directly involved in the antiulcerogenic activity.

Investigation of anti-inflammatory and antinociceptive activities of trans-dehydrocrotonin, a 19-nor-clerodane diterpene from Croton cajucara .1.

The anti-inflammatory and antinociceptive effects of trans-dehydrocrotonin, isolated from the bark of Croton cajucara (Euphorbiaceae), were investigated using several animal models. The trans-dehydrocrotonin produced a significant inhibition of carrageenin-induced paw edema and cotton pellet granuloma in rats. It also inhibited the writhings in mice induced by acetic acid, but did not show a significant effect in the hot-plate test in mice. The LD(50) of t-DCTN was 555.0 mg/kg (p.o.) for mice.

A computer-assisted approach for chemotaxonomic studies - Diterpenes in Lamiaceae

This paper describes a new computer approach for chemotaxonomic studies. The methodology employed enables the search for chemical substructures as taxonomic descriptors using all expert system built with plant natural products. The operation of the system was tested with diterpenes as taxonomic markers in Lamiaceae. © 2001 Elsevier Science Ltd.

Ent-labdane and beyerane diterpenes from Erythroxylum betulaceum Mart

•Diterpenes were isolated from wood of Erythroxylum betulaceum Mart.•Two ent-labdanes and one ent-beyrane diterpenes were isolated.•Diterpenes together tropanic alkaloid and may be useful as a chemotaxonomic markers of Erythroxylum. © 2013 Elsevier Ltd.

Avaliação das atividades cicatrizante e antiinflamatória de Casearia sylvestris Swartz em animais e identificação dos marcadores químicos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ditregra - An auxiliary program for structural determination of diterpenes

This work describes the creation of heuristics rules based on 13C-NMR spectroscopy that characterize several skeletal types of diterpenes. Using a collection of 2745 spectra we built a database linked to the expert system SISTEMAT. Several programs were applied to the database in order to discover characteristic signals that identify with a good performance, a large diversity of skeletal types. The heuristic approach used was able to differentiate groups of skeletons based firstly on the number of primary, secondary, tertiary and quaternary carbons, and secondly the program searches, for each group, if there are ranges of chemical shifts that identifies specific skeletal type. The program was checked with 100 new structures recently published and was able to identify the correct skeleton in 65 of the studied cases. When the skeleton has several hundreds of compounds, for example, the labdanes, the program employs the concept of subskeletal, and does not classify in the same group labdanes with double bounds at different positions. The chemical shift ranges for each subskeletal types and the structures of all skeletal types are given. The consultation program can be obtained from the authors. © 1997 - IOS Press. All rights reserved.

Labdane dimers from Xylopia aromatica

From the stem bark of Xylopia aromatica (Annonaceae), have been isolated two new labdane dimers as their methyl esters, together with the known compounds ent-labda-8(17),13(16),14-trien-18-oic acid, sitosterol and stigmasterol. The structures of the dimers were elucidated on the basis of detailed spectroscopic analyses. (C) 1999 Elsevier B.V. Ltd. All rights reserved.

Cytotoxic constituents of propolis inducing anticancer effects: a review

Objectives Propolis is a honeybee product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anticancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. In this review, the antitumour effects of propolis extracts and its constituents (e. g. flavonoids, terpenes and caffeic acid phenethyl ester) are discussed.Key findings The effect of propolis on experimental carcinogenesis is discussed, as well as its possible mechanisms of action against tumours, involving apoptosis, cell cycle arrest and interference on metabolic pathways. Propolis seems to be efficient against different tumour cells both in vitro and in vivo, which suggests its potential in the development of new anticancer drugs.Summary Propolis extracts may be important economically and would allow a relatively inexpensive cancer treatment. Preclinical investigations are needed to further elucidate the benefits of propolis and its antitumour properties.

Chemopreventive activity of compounds extracted from Casearia sylvestris (Salicaceae) Sw against DNA damage induced by particulate matter emitted by sugarcane burning near Araraquara, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antiplasmodial Natural Products

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Aristolactams and further constituents from Aristolochia chamissonis

Isolou-se do extrato etanólico de galhos de Aristolochia chamissonis espatulenol, sitosterol, sitosterol-beta-D-glicosídeo, colavelool, 13-epi-2-oxo-colavelool, trans-N-p-coumaroiltiramina, alantoína, ácido aristolóquico I e aristolactama AII. As estruturas da aristolactama AII e da piperolactama A são revisadas com base em análises espectrométricas e derivatizações químicas.

Antiulcer activity and subacute toxicity of trans-dehydrocrotonin from Croton cajucara

The antiulcerogenic activity of trans-dehydrocrotonin (DHC), a nor-clerodane diterpene isolated from Croton cajucara Benth. ( Euphorbiaceae), and its subacute ( 35 days) toxicity were studied in mice and rats, respectively. For the antiulcerogenic tests, models of gastric ulcers induced in mice by ethanol/HCl or stress were used. In both models, an oral dose of DHC ( 100 mg/kg) significantly reduced (P< 0.01) the formation of gastric lesions. DHC was also tested for its ability to scavenge free radicals, but no such action was observed in rat liver mitochondria. To assess the subacute toxicity, rats were treated orally with DHC (25, 50 and 100 mg/kg) for 5 weeks. A significant increase in liver weight was observed in male and female rats at highest doses, whereas a significant reduction in plasma alkaline phosphatase and cholesterol levels and an increase in gamma glutamyl transpeptidase were observed only at the highest dose ( 100 mg/kg) in female rats. DHC caused histopathological alterations in the liver that included a turbid tumefaction, microvacuolar degeneration and nuclear alterations. Despite the beneficial antiulcerogenic activity of DHC, our results suggest that the long-term use of this compound may induce liver damage.

NATURAL PRODUCT SUBSTITUTION PATTERN AND SKELETAL RECOGNITION METHOD

This work describes a methodology for identification of skeletal types of diterpenes based on data base with 1500 compounds isolated from Asteraceae. One program named BOTOCSYS was built with the codification of the compounds and their botanical sources. An example of identification of a new substance is given.

Diterpene esters of aristolochic acids from Aristolochia pubescens

From the acetone and ethanol extracts of the tubercula of Aristolochia pubescens, two diterpene esters of aristolochic acids were isolated, together with 23 known compounds. The structures of the compounds were determined on the basis of spectroscopic analysis. (C) 2003 Elsevier Ltd. All rights reserved.