Magister Pharmaceuticae - MPharm / Due to the contribution of hypertension to various cardiovascular diseases, many studies are currently focused on identifying efficient bioactive compounds with antihypertensive activity and thus reducing the levels of cardiovascular disease. ACE inhibitors are an important component of the therapeutic regimen for treating hypertension, but due to the increase in the prevalence of side effects of synthetic compounds, alternative and complementary medicines which may consist of pure bioactive compound or a combination of various compounds from natural sources are gaining importance in overcoming hypertension. Hypericum perforatum has been studied for various activities including anti-bacterial, anti-depressant, anti-oxidant properties, but studies on its cardiovascular effects specifically ACE inhibitory activity have not yet been explored. In this study, ACEI assay-guided fractionation of the ethanol extract of Hypericum perforatum was carried out other to isolate a compound with ACE inhibition. A compound – (3-hydroxy 4, 4 dimethyl-4-butyrolactone) was isolated from an active fraction of the plant extract and was tested for ACE inhibition and its chemical structure elucidated using 1HNMR and C13NMR spectrometry and further characterized using mass spectrometry and FTIR.

Thesis (M.S.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains vi, 147 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 128-139).

Tikslas: įvertinti sunkiųjų metalų koncentracijų pasiskirstymą paprastosios jonažolės mineralizate, vandeninėse ir etanolinėse ištraukose bei jų sąveiką su taninais. Uždaviniai: nustatyti ir palyginti cinko ir vario koncentracijas paprastosios jonažolės mineralizatuose bei vandeninėse ištraukose; nustatyti ir palyginti kadmio ir švino koncentraciją paprastosios jonažolės mineralizatuose, vandeninėje bei etanolinėje ištraukose; palyginti sunkiųjų metalų koncentracijų pasiskirstymą skirtingose Lietuvos Respublikos vietovėse, įvertinti paprastosios jonažolės mineralizate esančio sunkiojo metalo (švino) sąveiką su taninais. Buvo vykdoma drėgna mineralizacija Multiwave 3000 mineralizatoriumi (HNO3 + HCl + H2O2). SM koncentracijos mineralizatuose, vandeniniuose ir etanoliniuose tirpaluose buvo nustatytos Perkin Elmer Zeeman 3030 atominiu spektrofotometru. Cinko koncentracijos vidurkis mineralizatuose – 21,49 µg/g, o vandeninėse ištraukose- 15,92 µg/g (p<0,05). Vario koncentracijos vidurkis mineralizatuose - 11,22 µg/g, o vandeninėse ištraukose ji beveik 2 kartus mažesnė (p<0,05). Kadmio koncentracijos vidurkis mineralizatuose - 0,12 µg/g, vandeninėse ištraukoje jis daugiau nei 5 kartus mažesnis, o etanolinėse ištraukose - 0,003 µg/g, skirtumai yra statistiškai reikšmingi (p<0,05). Švino koncentracijos vidurkis mineralizatuose yra 0,46 µg/g, vandeninėse ištraukose - beveik 7 kartus mažesnis, o etanolinėse ištraukose jis lygus 0,05 µg/g, skirtumai yra statistiškai reikšmingi (p<0... [toliau žr. visą tekstą] / Purpose: To assess concentrations of heavy metals in mineralizates, ethanolic and aqueous extract of St. John's wort and their interactions with tannins. Objectives: to determine and compare the concentrations of zinc and copper in mineralizates and aqueous extracts of St. John's Wort; to determine and compare the concentrations of cadmium and lead in mineralizates, aqueous and ethanolic extracts of St. John's Wort; to compare concentrations of heavy metals in herbal raw material, collected in different areas of the Republic of Lithuania; to evaluate heavy metal (lead), which is in the mineralizate of St. John's wort, interactions with tannins. The wet mineralization using Multiwave 3000 mineralizator (HNO3 + HCl + H2O2) was applied. Heavy metals concentrations i mineralizates, aqueous and ethanolic solutions were determined Perkin Elmer Zeeman 3030 atomic spectrophotometer. The average zinc concentration was 21.49 µg/g in the mineralizates, 15.92 µg/g in the aqueous extracts (p<0,05). The average copper concentration was 11.22 µg/g in the mineralizates and it was almost 2 times lower in the aqueous extracts (p<0,05). Average cadmium concentration was 0.12 µg/g in the mineralizates and more than 5 times lower in the aqueous extracts; 0.003 µg/g average concentration of cadmium was found in the aqueous extracts, these differences are statistically significant (p<0,05). Average lead concentration was 0.46 µg/g in the mineralizates and it was almost 7 times lower in... [to full text]

Medicinal plants which have been widely used in folk medicine are known to contain important biologically active compounds. Most of today&rsquo / s synthetic drug raw materials are to be prepared by using plant originated compounds as the starting material. Hypericum Perforatum is one of the medicinal plants that grows in Europe, Western Asia and Northern Africa and is distinguished by its golden yellow flowers. The common name of the plant is St. John&rsquo / s wort. From the time of the ancient Greeks down through the middle Ages, the plant was considered to be imbued with magical powers and was used to ward off evil and protect against disease. As a practical folk-remedy, it has been used widely to heal wounds, remedy kidney troubles, and alleviate nervous disorders, even insanity. In the last thirty years, Hypericum perforatum has undergone extensive clinical and laboratory testing. The extract of the flower is a red liquid that contains many biologically active compounds such as: naphtodianthrones (hypericin, pseudohypericin), phloroglucinols (hyperforin, adhyperforin), flavonoids (quercetin, hyperoside, quercitrin, isoquercitrin, rutin, campferol, myricetin, amentofloavone), procyanidins (procyanidin, catechin, epicatechin polymers) , tannins (tannic acid), essential oils (terpenes, alcohols), amino acids (GABA, Cysteine, glutamine, leucine, lysine, ornithine, praline, threonine), phenyl propanes (caffeic acid, chlorogenic acid), xanthones (keilcorin, norathriol), organic acids peptides and polysaccharides (other water soluble compounds). These compounds have previously been isolated using HPLC method. The aim of this study is to isolate the main biologically active compound groups of Hypericum Perforatum and simply characterize the compounds with TLC, UV-VIS spectroscopy, NMR spectroscopy using standard compounds as references.

Tez (Yüksek Lisans) - Süleyman Demirel Üniversitesi, Sağlık Bilimleri Enstitüsü, Tıbbi Biyoloji Anabilim Dalı, 2006. / Kaynakça var.

Thesis (M.Tech.: Homoeopathy)-Dept. of Homoeopathy, Durban University of Technology, 2006 xxxiii, 112 leaves : ill. / The purpose of this double-blind placebo-controlled study was to evaluate the relative and combined efficacy of the homoeopathic similimum, taken orally, and the topical application of a lotion made from the homoeopathic mother tinctures of Hypericum perforatum and Calendula officinalis in the treatment of venous leg ulcers. Venous hypertension in the lower limb, occurring from a variety of causes, leads to microcirculatory abnormalities which may permit the formation of a chronic ulcer (Zimmet, 1998). Venous leg ulcers are a cause of much debility, social isolation, depression, fears of loss of employment and income (Royal College of Nursing Institute, 1998). The mainstay of treatment at present is compression bandaging to reduce the venous pressure in the lower limb. Eighty percent of venous leg ulcers will heal within eight to twelve weeks with compression bandaging (Thomas, 1997). Homoeopathy is a system of medicine based on natural laws of healing, and recognizes the biophysical energy of an individual (also known as the vital force) as that which provides the normal protective defence mechanisms of the body, and is disturbed in disease, producing symptoms on the physical, mental and emotional levels (Vithoulkas, 1980). Many plants are known to have wound-healing properties (Curtis and Fraser, 2003). Calendula officinalis and Hypericum perforatum were considered the best plants in a homoeopathic lotion to be used on chronic venous leg ulcers, as they cover all the common problems associated with this type of wound, providing pain relief and anti-microbial activity (Lawless, 1995). In this study, homoeopathic mother tinctures of the herbs were used to make the lotion for topical application to the wounds.

Tese apresentada ao Programa de Pós-Graduação em Ciências da Saúde, da Universidade do Extremo Sul Catarinense - UNESC, para a obtenção do título de Doutora em Ciências da Saúde. / A Proteína quinase C (PKC) está intimamente envolvida em processos celulares de armazenamento de informações, formação de memória, plasticidade sináptica e sobrevivência e manutenção neuronal. Tendo em vista os efeitos inibidores da PKC de algumas substâncias usadas no tratamento de alguns transtornos psiquiátricos e outras patologias, neste estudo, foram avaliados os efeitos farmacológicos e a segurança da administração crônica de inibidores da PKC, tamoxifeno (TMX), Hypericum perforatum (HP) e lítio (Li), sobre alterações comportamentais, parâmetros de danos oxidativos e níveis de fatores neurotróficos no cérebro de ratos Wistar. Os animais receberam TMX (1mg / kg), HP (5mg / kg), Li (47,5 mg / kg) e água (grupo controle) durante um período de 28 dias, via gavagem. Os animais foram então submetidos aos testes comportamentais: campo aberto, labirinto em cruz elevado, nado forçado, reconhecimento de objetos e esquiva inibitória. Além disso, os níveis de NGF, BDNF e GDNF foram avaliados no hipocampo e córtex frontal de ratos. As substâncias reativas ao ácido tiobarbitúrico (TBARS) e a formação de proteínas carboniladas foram avaliadas no córtex frontal, hipocampo, núcleo accumbens e estriado. Não foram observadas diferenças significativas nos testes do campo aberto, labirinto em cruz elevado e nado forçado, quando administrados os inibidores da PKC em ratos machos ou fêmeas. No teste de esquiva inibitória, o tratamento com HP induziu dano na aquisição de memória em ratos machos e fêmeas. A administração de TMX ou HP, mas não de Li, diminuíram o índice de reconhecimento de objeto em ratos machos e fêmeas, no teste de reconhecimento de objetos. A administração crônica de HP e TMX diminuiu, e o Li aumentou, os níveis de BDNF no hipocampo de ratos machos e fêmeas. TMX e HP diminuíram os níveis de NGF somente no hipocampo de fêmeas. O TMX protegeu o dano lipídico no núcleo accumbens e estriado, enquanto HP diminuiu os níveis de TBARS no hipocampo, núcleo accumbens e estriado em ratos fêmeas. No córtex frontal, o tratamento com TMX e HP induziu o dano a proteína, enquanto que apenas o HP diminuiu os níveis de proteínas carboniladas no estriado. O TMX reduziu o dano lipídico no núcleo accumbens e estriado, enquanto HP diminuiu os níveis de TBARS no hipocampo, núcleo accumbens e estriado em ratos fêmeas. No córtex frontal, o tratamento com TMX e HP diminuiu o dano protéico, enquanto que apenas o HP diminuiu os níveis de proteínas carboniladas no estriado. Os resultados do presente estudo sugerem que o tratamento a longo prazo com TMX ou HP pode conduzir a um déficit cognitivo significativo, pela diminuição dos níveis de fatores neurotróficos no cérebro de ratos machos e fêmeas quando comparado com o Li. Desta forma, sugere-se que a PKC está intimamente envolvida com a formação da memória. É importante ressaltar, que apesar do Li, TMX e HP, per se, mostrarem redução de dano oxidativo, o uso crônico de TMX e HP deve-se ter cautela quanto ao dano cognitivo.

Abstract Hypericum perforatum L. (St. John’s wort) is a medicinal plant widely utilized for the treatment of depression. The antidepressant activity is mainly attributed to the phenolic compounds hypericins and hyperforins, which also have a wide range of other pharmacologically interesting properties. The biosynthetic routes leading to hypericins and hyperforins are poorly understood, although a polyketide pathway including type III polyketide synthases (PKSs) has been suggested to be involved. Furthermore, a gene called hyp-1 is assumed to attend to the final stages of the hypericin biosynthesis. In the present work, the biosynthesis of hypericins and hyperforins in H. perforatum was further studied by focusing on the elucidation of the precursors and genes involved. The incorporation of isotopically labelled branched-chain amino acids into hyperforins was investigated as well as the possibilities to enhance the production of hyperforins in H. perforatum in vitro cultures by feeding them with amino acid precursors. Furthermore, two novel cDNAs encoding for type III PKSs were isolated from H. perforatum. The functions of these new genes, designated HpPKS1 and HpPKS2, as well as the role of hyp-1 were elucidated by comparing their expression with the levels of hypericins and hyperforins in H. perforatum tissues. The enzymatic activity of the recombinant HpPKS2 protein was also analyzed. To study Hyp-1 at a protein level, a protein extraction method was optimized for tissues of Hypericum species. The results show the incorporation of valine and isoleucine into the acyl side chain of hyperforin and adhyperforin, respectively. Through the biotransformation of the amino acid precursors, it is possible to enhance the levels of adhyperforin, but not hyperforin, in H. perforatum shoot cultures, which demonstrates the tight regulation of the hyperforin biosynthesis. A correlation between HpPKS1 expression and hyperforins was detected in H. perforatum tissues. The localization of HpPKS2 mRNA in dark glands in which hypericins accumulate as well as the octaketide synthase activity of the recombinant HpPKS2 suggest that HpPKS2 is associated with possible co-operating tailoring enzymes in the biosynthesis of hypericins. The presence of both hyp-1 mRNA and Hyp-1 protein in distinct places compared with hypericins in H. perforatum tissues does not support the idea that Hyp-1 would be involved in the biosynthesis of hypericins in dark glands, although mobility of the Hyp-1 protein was shown to be possible. The present thesis extends knowledge about the biosynthesis of hypericins and hyperforins in H. perforatum by providing new candidate genes for their biosynthesis and by identifying precursors for hyperforins. Moreover, new information was obtained about the role of hyp-1 in H. perforatum.

The main purpose of the theses was to find if the abiotic elicitor 2,4,6-trimethyl-N-(pyrazine- 2-yl)benzenesulfonamide has any influence on the secondary metabolites production in callus and suspension cultures of Hypericum perforatum L. The cultivation was taking place in the Murashige a Skoog (MS) nutrient medium enriched by the growth regulator - alpha-naphthyl acetic acid at the concentration of 1 mg.L-1 . The elicitor was added to the cultures at the three levels of concentration: c1= 100.0 mg/100 ml; c2= 10.0 mg/100 ml; c3= 1.00 mg/100 ml. The individual samples were taken after 6, 24, 48, 72 and 168 hours of the elicitor application. The control samples without the elicitor were taken after 6, 48 and 168 hours. The collected samples were dried and subsequently transformed into methanol extracts in order to determine secondary metabolites content (rutin, hyperoside and quercetin) by HPLC method. Release of these metabolites into nutrient media was also subject of this observation. The elicitation has influenced production of the secondary metabolites, particularly in callus cultures, wherein several statistically significant values, characterizing increase in their production, were measured. The highest content of rutin (0.169 mg.g-1 DW) was determined in callus culture after 168 hours when...

This was a chemical laboratory study. The main focus was to evaluate the chemical stability of Hypericum perforatum (St John's wort), Ginkgo biloba and Piper methysticum (Kava Kava) under unfavourable environmental conditions. Different dosage forms representing the same amount of active ingredients for each were used. Some of the dosage forms were self manufactured according to Good Manufacturing Practice. Samples of the dried powder of each plant was also exposed to a series of gamma¬radiation. Acetone was used as an extractant for all three plants, after evaluating and discarding the extraction method stipulated in the British Herbal Pharmacopoeia. Identification of the different plants were carried out by means of Thin Layer Chromatography. The in-house developed mobile phases EMW, BEA and CEF, showed better separation and visibility compared to the mobile phases used in the British Herbal Pharmacopoeia. The plates were sprayed with either vanillin or p-anisaldehide for optimal visualization of the separated compounds. After the specified period of 6-months, comparative TLC was performed on all samples. This was achieved for each plant by applying all samples stored at a specific condition i.e.25°C, on the same plate. The samples were stored at low temperature after exposure to the specific time interval. Quantitative analysis was performed by spectrophotometry, and high pressure liquid chromatography. The data obtained from these analytical methods, were used to evaluate the relative chemical stability of each dosage form. The relationship between the quantitative data and the qualitative changes in the TLC fingerprints, were compared, hoping to achieve a common pattern relating to the stability. The order of the reaction as well as the reaction rate constant (k) for each dosage form was calculated, except for kava kava. The shelf-life (too) was calculated using the analyzed data obtained by spectrophotometry or HPLC. The relevance of conventional pharmaceutical calculations in the prediction of shelf-life, by means of accelerated stability tests, was investigated for the possible application to herbal products. The effects of gamma radiation on the degradation of the chemical compounds present in each plant, was evaluated. After an evaluation of all the relevant data, it seemed that the tablet-dosage forms were equally effective regarding stability, compared to the capsules. Liquid extracts appeared to be less stable than the extract capsules. The extract capsules seemed to degrade more rapidly than the herbal tablets or herbal capsules. Exposure to low dose radiation (4.4 kGy) did not seem to have an influence on the stability. It was evident that some herbs were more sensitive to sunlight or heat than others. In general, all three of the chosen plants seemed to be relatively stable if stored in the specified conditions. It seemed valid for the shelf-life to be expressed as two years. / Dissertation (MSc (Pharmacology))--University of Pretoria, 2001. / Pharmacology / unrestricted