Maria de Fátima V. Souza

Natural products inhibitors of the angiotensin converting enzyme (ACE): a review between 1980 - 2000

Inhibition of Angiotensin Converting Enzyme (ACE) is a modern therapeutic target in the treatment of hypertension. Within the enzyme cascade of the renin-angiotensin system, ACE removes histidyl-leucine from angiotensin I to form the physiologically active octapeptide angiotensin II, one of the most potent known vasoconstrictors. Therefore, a rationale for treating hypertension would be to administer drugs or natural compounds which selectively inhibit ACE. The present work constitutes a review of the literature of plants and chemically defined molecules from natural sources with in vitro anti-hypertensive potential based on the inhibition of ACE. The review refers to 321 plants, the parts utilized, type of extract and whether they are active or not. It includes also the names of 158 compounds isolated from higher plants, marine sponges and algae, fungi and snake venom. Some aspects of recent research with natural products directed to produce anti-hypertensive drugs are discussed. In this review, 148 references were cited.

Modulation of drug resistance in Staphylococcus aureus by a kaempferol glycoside from Herissantia tiubae (Malvaceae).

In an ongoing project to evaluate natural compounds isolated from plants from the Brazilian biodiversity as modulators of antibiotic resistance, kaempferol‐3‐O‐β‐d‐(6″‐E‐p‐coumaroyl) glucopyranoside (tiliroside), isolated from Herissantia tiubae (Malvaceae) was investigated using the strain SA‐1199B of Staphylococcus aureus, which overexpresses the norA gene encoding the NorA efflux protein which extrudes hydrophilic fluorquinolones and some biocides, such as benzalkonium chloride, cetrimide, acriflavine and ethidium bromide. The minimum inhibitory concentrations (MICs) of the antibiotics and biocides were determined by the microdilution assay in the absence and in the presence of sub‐inhibitory concentration of tiliroside. Although tiliroside did not display relevant antibacterial activity (MIC = 256 µg/mL), it modulated the activity of antibiotics, i.e. in combination with antibiotics a reduction in the MIC was observed for norfloxacin (16‐fold), ciprofloxacin (16‐fold), lomefloxacin (four‐fold) and ofloxacin (two‐fold), and an impressive reduction in the MICs for the biocides (up to 128‐fold). The results presented here represent the first report of a kaempferol glycoside as a putative efflux pump inhibitor in bacteria. The present finding indicates that H. tiubae (and broadly Malvaceae) could serve as a source of plant‐derived natural products that modulate bacterial resistance, i.e. a source of potential adjuvants of antibiotics. Copyright

Bioassay-guided evaluation of antinociceptive effect of N-salicyloyltryptamine: a behavioral and electrophysiological approach.

We investigated the antinociceptive and nerve excitability effects of the N-salicyloyltryptamine (NST) NST-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg (i.p.) were administered (i.p.). This effect was not antagonized by naloxone (1.5 mg/kg, i.p.). NST inhibited the licking response of the injected paw when 100 and 200 mg/kg were administered (i.p.) to mice in the first and second phases of the formalin test. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and showed that NST (3.57 mM) significantly reduced (29.2%) amplitude of the compound action potential (CAP) suggesting a sodium channel effect induced by NST. Our results demonstrated an antinociceptive activity of the NST that could be, at least in part, associated to the reduction of the action potential amplitude. NST might represent an important tool for pain management.

Biological activity of Herissantia crispa (L.) Brizicky

The crude methanol extract (EMeOH) of the aerial parts of Herissantia crispa (L.) Brizicky, plant riches in flavonoids and without pharmacological studies, was tested to value its activity under the behaviour parameters and to determine the lethal dose (LD50) in mice; antimicrobial and antiulcerogenic activities. The EMeOH (5,000 mg/kg, v.o. or 2,000 mg/kg i.p.) did not alter the behaviour parameters and there were not mice deaths. The extract inhibited the bacterial growth. The EMeOH (750 mg/kg) showed anti-diarroeal activity. The EMeOH (250, 500 and 750 mg/kg) decreased the gastric lesions induced by 0.3 M HCl/ethanol 60% in mice. In conclusion, the EMeOH presents anti-ulcerogenic activity;, however it is necessary to value the antiulcerogenic activity in more specific models and to study the action mechanism by which the vegetable sample protects the gastric mucosa.

Anticonvulsant evaluation of Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, in rodents

O presente estudo buscou avaliar os efeitos do extrato etanolico das raizes de Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, (EER) e sua possivel atividade anticonvulsivante em roedores. No teste das convulsoes induzidas pelo pentilenotetrazol (PTZ) os animais tratados com EER, 250 mg/kg (i.p.), apresentaram aumento significativo (p<0,05) da latencia para o aparecimento das convulsoes (328,9±47,5) quando comparado aos do grupo controle (103,5±21,8) e reduziu o numero de obitos. Esse efeito foi bloqueado pela administracao do flumazenil. O EER produziu aumento significativo (p<0,05) na latencia nos testes da picrotoxina (PIC) e da estricnina (EST), nas maiores doses. No modelo do eletrochoque auricular o EER nao produziu alteracoes significativas em nenhum dos parâmetros avaliados. Entretanto, no modelo do abrasamento induzido pelo PTZ, a administracao com o EER produziu um efeito protetor, atenuando de forma significativa (p<0,05) o desenvolvimento e a severidade das crises convulsivas. Os resultados, sugerem que o EER induziu efeito anticonvulsivante em roedores e que o sistema GABAergico pode estar envolvido nessa resposta.

Anticonvulsant property of N-salicyloyltryptamine: evidence of enhance of central GABAergic neurotransmission

AIM: In the present study we verified the anticonvulsant properties of the new tryptamine analogue, N-salicyloyltryptamine (NST), in rodents. METHODS AND RESULTS: In the evaluation of the anticonvulsant activity, NST protected the animals from the incidence of seizures induced by pentylenetetrazole (PTZ) and picrotoxin (PIC), in doses of 100 and 200 mg/kg. NST (100 and 200 mg/kg, i.p.) significantly eliminated the extensor reflex of maximal electric-induced seizure tests in 40% of the experimental animals. However, in the PTZ model FLU (10 mg/kg, i.p.), an antagonist of the benzodiazepine (BZD) site in the GABAA-BZD receptor complex, inhibited the prolongation of seizure latency induced by NST. CONCLUSION: Our results demonstrated an anticonvulsant activity of the new analogue that could be, at least in part, associated to the involvement of the GABAergic mechanism.

Antiedematogenic activity of the indole derivative N-salicyloyltryptamine in animal models

The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.