Made available in DSpace on 2015-05-14T12:59:47Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1405299 bytes, checksum: d51bdd6014b151dd17656e41664c6342 (MD5) Previous issue date: 2009-10-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Foeniculum vulgare Mill. is a plant that has been known and used by mankind since antiquity because of its antimicrobial, analgesic, antiinflammatory, antispasmodic and anxiolytic properties. It is also widely used in the food and cosmetics industries. The objective of the present study was to investigate the chronic preclinical toxicity of the lyophilized crude hydroalcoholic extract (LCHAE) of the fruit of F. vulgare commercialized in sachet form in order to demonstrate the safety of its use by the population, based on Resolution 90/2004 of the Brazilian Regulatory Authorities. In this study, Wistar rats (Rattus norvegicus albinus) were treated orally with 8.5, 25.5 and 76.5 mg/kg of LCHAE for 13 weeks (n=10 per dose and sex). General signs of toxicity, lethality and food and water consumption were evaluated daily, while weight was evaluated weekly and body temperature, glucose levels and behavioral parameters using open-field and rota-rod tests were assessed every two weeks. At the end of treatment, 50% of the animals in each group were sacrificed for blood analysis and 30% were submitted to histopathology. The remaining animals then formed the satellite group that remained under observation for 21 days following treatment to evaluate the reversal and/or appearance of possible toxic effects. During the 13 weeks of treatment, no signs of toxicity were noted and none of the animals died. In the females, there was a reduction in weight and food consumption and an increase in water intake. LCHAE reduced the time both males and females spent on the rotating bar, and reduced ambulation in the females and defecation and rearing in both sexes. In both males and females, a hypoglycemic effect occurred and there was an increase in aspartate aminotransferase (AST) and alkaline phosphatase (ALP), as well as a reduction in platelet count. In the females, there was an increase in alanine transaminase (ALT), leukocytes and neutrophils and a decrease in cholesterol. In the males, a reduction in lymphocytes occurred and there was an increase in monocytes. Histopathology revealed signs of hepatotoxicity including mild portal inflammation with the presence of mononuclear exudate, hepatic lobular necrosis associated with lymphocytic/histiocytic infiltration and mild sinusoidal inflammation. In addition, there were signs of toxicity in the lungs: focal pneumonitis with alveolar septal thickening consisting of mononuclear exudate. In the satellite groups, the majority of the biochemical, hematological and histopathological alterations in the liver were found to persist, suggesting irreversibility. Further studies should be developed to confirm these findings; nevertheless, these results indicate that LCHAE is toxic particularly to the liver and lungs, in both sexes and at the three doses used. / Foeniculum vulgare Mill. é uma planta usada pelos humanos desde a antiguidade, devido às suas atividades antimicrobiana, analgésica, anti-inflamatória, antiespasmódica e ansiolítica, além de ser uma espécie utilizada na indústria de alimentos e cosméticos. O presente trabalho objetivou investigar a toxicidade préclínica crônica do extrato hidroalcoólico bruto liofilizado do fruto de F. vulgare (saches), na perspectiva de avaliar a segurança de seu uso pela população, com base na Resolução nº 90/2004 da Agência Nacional de Vigilância Sanitária e algumas modificações. Neste estudo, ratos Wistar (Rattus norvegicus albinus) foram tratados por via oral (v.o.) com as doses 8,5; 25,5 e 76,5 mg/kg do EHABL durante 13 semanas (n=10 por dose e sexo). Foram avaliados diariamente sinais gerais de toxicidade, letalidade, consumo de alimentos e água; semanalmente, variação da evolução ponderal; e, quinzenalmente, temperatura corporal, glicemia e parâmetros comportamentais através dos testes de campo aberto e da barra giratória. Ao final do tratamento, 50 % dos animais de cada grupo foram sacrificados para análises sanguíneas, dos quais 30 % passaram por investigação histopatológica. O restante dos animais passou a fazer parte do grupo satélite, os quais permaneceram em observação 21 dias após o tratamento, para a verificação da reversão e/ou aparecimento de possíveis efeitos tóxicos. Na triagem farmacológica comportamental, não se observaram características de toxicidade e mortes durante as 13 semanas de tratamento. Em fêmeas, houve uma diminuição no peso corpóreo e no consumo de alimentos, com um aumento no consumo de água. O EHABL reduziu o tempo de permanência na barra giratória em ambos os sexos; diminuiu a ambulação em fêmeas; e reduziu os parâmetros defecação e levantar em ambos os sexos. Em machos e fêmeas, houve um efeito hipoglicemiante, aumento da aspartato aminotransferase (AST) e fosfatase alcalina (FAL), com redução das plaquetas. Em fêmeas, ocorreu um aumento da alanina aminotransferase (ALT), leucócitos, neutrófilos e diminuição do colesterol. Nos machos, ocorreu diminuição do número de linfócitos e aumento do número de monócitos. A análise histopatológica mostrou indícios de hepatotoxicidade, como portite discreta com a presença de exsudação mononuclear, necrose lobular hepática associada a afluxo linfoistiocitário e inflamação sinusoidal discreta. Adicionalmente, o pulmão apresentou sinais de toxicidade: pneumonite focal com espessamento de septo alveolar por exsudação mononuclear. Nos grupos satélites, observou-se que a maioria das alterações bioquímicas, hematológicas e histopatológicas, no fígado, persistiram, mostrando a necessidade de maiores investigações. Portanto, de acordo com os resultados obtidos, o EHABL apresentou uma toxicidade significativa, especialmente no fígado e pulmão, em ambos os sexos e nas três doses utilizadas.

Spices are of great importance in the indigenous culinary and traditional medicine systems of the people of Nkonkobe Municipality of the Eastern Cape, South Africa. The present investigation evaluated the ethnopharmacological potentials of two indigenous South African spices- Foeniculum vulgare and Lippia javanica. The pharmacological investigations on these two plant species include ultra-morphology, nutrient and mineral analysis, evaluation of the essential oil, phytochemical and antioxidant assays, antimicrobial, anti-inflammatory as well as anti-urolithiatic assay of the acetone and aqueous extracts of the two plants. The species were selected for study as the most cited plants after an ethnobotanical survey conducted on the indigenous knowledge of plants used as spices and medicine in Nkonkobe Municipality, Eastern Cape of South Africa. Among the plants cited Foeniculum vulgare(Apiaceae) and Lippia javanica (Verbenaceae) stood out as the most commonly used spices. Others were members of the families; Solanaceae, Apiaceae, Amaryllidaceae, Amaranthaceae and Lamiaceae. Ultra-morphological studies conducted on the leaves of the two selected plants using scanning electron microscope revealed the presence of non-glandular and glandular trichomes, stomata and crystals. The leaf surfaces of these herbs may serve as secretory sites where aromatic secondary metabolites are produced. Analyses of the proximate, mineral, vitamin and anti-nutrients contents of these two spices showed that both species are good sources of these phytochemicals and may be used to enrich the human diet. Lippia javanica possesses lower lipid (0.50 percent), fibre (5 percent) and carbohydrate (64.96 percent) contents than Foeniculum vulgare. On the other hand, protein (20.54 percent), ash (11.60 percent) and moisture content (11.69 percent) were higher in Foeniculum vulgare than in Lippia javanica. Foeniculum vulgare showed higher N (3286 mg/100g), Mg (386.7 mg/100g), K (3187 mg/100g) and Na (1383 mg/100g) content while Lippia javanica was higher in Ca (1833 mg/100g), Zn (4.7 mg/100g), Cu (0.9 mg/100g) and Fe (78.4 mg/100g). Vitamins Aand E were also higher in Lippia javanica (1.31 mg/100g; 2.52 mg/100g) while Foeniculum vulgare (0.45 mg/100g) had higher vitamin C content. No significant differences were observed in the phytate, oxalate and tannin contents of the two spices, but saponin and cyanide were significantly lower in Lippia javanica (268.5 mg/100g; 8.45 mg/100g) than in Foeniculum vulgare (1855 mg/100g; 10.5 mg/100g) Evaluation of the essential oil component, cytotoxicity and antimicrobial activities of both fresh and dried leaves of Lippia javanica and Foeniculum vulgare revealed that the dried samples yielded more oil and also contain more chemical than the fresh samples of both plants. The overall antimicrobial activity evaluated using susceptibility and microdilution assays revealed that the oils of F. vulgare and L. javanica exhibited high antifungal and antibacterial activity, compared to the reference drugs. In addition, essential oil from fresh leaves of both spices was less toxic compared to the oil from the dried leaves. Polyphenolic evaluation of the aqueous and acetone extracts of the plants revealed that the acetone extract had higher phenol, flavanol, flavonoid and proanthocyanidin contents than the aqueous extracts. The total phenolic content of acetone and aqueous extracts were 4.49 ± 0.411 mg/g and 3.73 ± 0.498 mg/g tannic acid equivalent (TAE) respectively for Lippia javanica. The same trend was also observed in Foeniculum vulgare with total phenolic content of acetone and aqueous extracts were 4.22 ± 0.325 mg/g and 4.17 ± 0.651 mg/g tannic acid equivalent (TAE) respectively. Further assessment of the antioxidant activity of the solvent extracts revealed that both plants exhibited promising free radical scavenging potentials against 1,1 diphenyl-2-picrylhydrazyl (DPPH), 2, 2’-azino-bis(3- ethylbenzthiazoline-6-sulfonic acid (ABTS), reducing power, lipid peroxidation, nitric oxide, phosphomolybdate and hydrogen peroxide. Antimicrobial activities of the acetone and aqueous extracts of the two plants revealed moderate antibacterial and antifungal activities. They inhibited the growth of Microsporium canis and Trichophyton rubrum that were not susceptible to the standard antifungal drug used as control.