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Investigation of the elemental profiles of Hypericum perforatum as used in herbal remediesOwen, Jade Denise January 2014 (has links)
The work presented in this thesis has demonstrated that the use of elemental profiles for the quality control of herbal medicines can be applied to multiple stages of processing. A single method was developed for the elemental analysis of a variety of St John’s Wort (Hypericum perforatum) preparations using Inductively Coupled Plasma – Optical Emission Spectroscopy (ICP-OES). The optimised method consisted of using 5 ml of nitric acid and microwave digestion reaching temperatures of 185⁰C. Using NIST Polish tea (NIST INCT-TL- 1) the method was found to be accurate and the matrix effect from selected St John’s Wort (SJW) preparations was found to be ≤22%. The optimised method was then used to determine the elemental profiles for a larger number of SJW preparations (raw herbs=22, tablets=20 and capsules=12). Specifically, the method was used to determine the typical concentrations of 25 elements (Al, As, B, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, Hg, In, Mg, Mn, Mo, Ni, Pb, Pt, Sb, Se, Sr, V, Y and Zn) for each form of SJW which ranged from not detected to 200 mg/g. To further interpret the element profiles, Principal Component Analysis (PCA) was carried out. This showed that different forms of SJW could be differentiated based on their elemental profile and the SJW ingredient used (i.e. extract or raw herb) identified. The differences in the profiles were likely due to two factors: (1) the addition of bulking agents and (2) solvent extraction. In order to further understand how the elemental profile changes when producing the extract from the raw plant, eight SJW herb samples were extracted with four solvents (100% water, 60% ethanol, 80% ethanol and 100% ethanol) and analysed for their element content. The results showed that the transfer of elements from the raw herb to an extract was solvent and metal dependent. Generally the highest concentrations of an element were extracted with 100% water, which decreased as the concentration of ethanol increased. However, the transfer efficiency for the element Cu was highest with 60% ethanol. The solvents utilised in industry (60% and 80% ethanol) were found to preconcentrate some elements; Cu (+119%), Mg (+93%), Ni (+183%) and Zn (+12%) were found to preconcentrate in 60 %v/v ethanol extracts and Cu (+5%) and Ni (+30%). PCA of the elemental profiles of the four types of extract showed that differentiation was observed between the different solvents and as the ethanol concentration increased, the extracts became more standardised. Analysis of the bioactive compounds rutin, hyperoside, quercetin, hyperforin and adhyperforin followed by subsequent Correlation Analysis (CA) displayed relationships between the elemental profiles and the molecular profiles. For example strong correlations were seen between hyperoside and Cr as well as Quercetin and Fe. This shows potential for tuning elemental extractions for metal-bioactive compounds for increased bioactivity and bioavailability; however further work in needed in this area.
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Bioassay guided fractionation of Angiotensin converting enzyme inhibitor compound from Hypericum perforatumMokwelu, Onyinye Vivian January 2019 (has links)
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.
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Informovanost studentů vybraných škol v oblasti vybraných druhů nutraceutik / Selected schools' students' awareness of selected types of nutraceuticalsHomolková, Zuzana January 2018 (has links)
The main topic of this work is food supplements, their legislation and other theory connected with them, the main focus is on plant nutraceuticals, of which are chosen food supplements marketed to support immunity system - echinacea, sea buckthorn and oyster mushroom, food supplements to support psyche - St. John's wort, ginkgo and valerian and dietary supplements to support body fitness - tribulus, garcinia and psyllium. Subsequently, the topic focuses on the marketing of nutraceuticals, its modern ways and the possibilities of increasing the students' awareness in this field through the principles of media education. In the practical part, 112 students aged 15-19 are presented with a lecture presenting the topic and inviting students to raise their interest in the subject. The feedback of the lecture is provided by a questionnaire whose questions correspond to the hypotheses set by the author. KEYWORDS nutraceuticals, media education, marketing, Echinacea, Garcinia, Pleurotus, Hippophae, Gingko, Plantago, Hypericum, Valeriana, Tribulus
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Efeito de elicitação biótica com o fungo Nomuraea rileyi (Farlow) Samson no metabolismo secundário de plantas aclimatadas de Hypericum polyanthemum Klotzsech ex Reichardt / Effect of biotic stress in secondary metabolism of Hypericum polyanthemum Klotzsech ex ReichardtMeirelles, Gabriela de Carvalho January 2012 (has links)
Hypericum polyanthemum é uma planta nativa do Sul do Brasil que contém compostos como flavonóides, taninos, derivados de floroglucinol (uliginosina B) e benzopiranos: HP1 (6-isobutiril-5,7-dimetóxi-2,2-dimetilbenzopirano), HP2 (7-hidróxi-6-isobutiril-5- metóxi-2,2-dimetilbenzopirano), e HP3 (5-hidróxi-6-isobutiril-7-metóxi-2,2- dimetillbenzopirano). Esses metabólitos são responsáveis por uma série de atividades biológicas como inibidores da monoaminoxidase (IMAO), antiproliferativa e antitumoral. No presente trabalho modificações na biomassa vegetal e no teor de metabólitos bioativos de plantas de H. polyanthemum cultivadas sob condições controladas e após 18 semanas de aclimatação foram investigadas após elicitação com o fungo Nomuraea rileyi através da adição do microrganismo liofilizado e pulverizado (LP), ou liofilizado, autoclavado e pulverizado (LAP) por curtos e longos períodos de tempo. Plantas cultivadas sob condições controladas tratadas com LAP demonstraram aumento na concentração dos benzopiranos HP1, HP2 e HP3 enquanto LP provocou efeito negativo ou ainda, não alterou a síntese destes compostos. Porém, baixos níveis do floroglucinol uliginosina B foram detectados em todos os tratamentos. Tratamentos com LAP por longos períodos de tempo em plantas cultivadas a campo provocaram aumento de biomassa (2x) e a análise química demonstrou elevação do teor de compostos fenólicos totais nas partes vegetativas das plantas submetidas a todos os tratamentos. Ainda, a análise apontou um diferente grau de acúmulo dos metabólitos, com maiores teores de HP1, HP2, HP3 e uliginosina B sendo encontrados nas partes reprodutivas das plantas tratadas com LAP. A elevação dos metabólitos bioativos em resposta ao elicitor fúngico sugere que estes compostos são induzíveis na resposta de defesa de H. polyanthemum. Os resultados obtidos nesse trabalho são relevantes em virtude da planta não sofrer danos. Assim, o sistema descrito representa uma nova abordagem em pesquisas com plantas visando otimizar condições para a produção de biomassa e metabólitos secundários de interesse medicinal. / Hypericum polyanthemum is a native plant of South Brazil that contains compounds such as flavonoids, tannins, phloroglucinol derivatives (uliginosin B) and benzopyrans: HP1 (6-isobutyryl-5,7-dimethoxy-2,2-dimethylbenzopyran), HP2 (7-hydroxy-6-isobutyryl-5- methoxy-2,2-dimethylbenzopyran), and HP3 (5-hydroxy-6-isobutyryl-7-methoxy-2,2- dimethylbenzopyran). These metabolites are responsible for biological activities such as monoamine oxidase inhibitor, antiproliferative and antitumoral. In this work changes in biomass and bioactive metabolites after elicitation with the fungi Nomuraea riley added as freeze dried culture (DC) or as freeze dried autoclaved cell powder (DACP) for short and long periods of time have been investigated in Hypericum polyanthemum plants grown under controlled conditions and after 18 weeks of field acclimatization. Plants treated with DACP showed increased concentrations of the benzopyrans while the DC affected negatively or did not alter the synthesis of these compounds. Nevertheless, low levels of uliginosin B were detected in all treatments. Long time treatment of field grown acclimatized plants with DACP triggered plant growth doubling the biomass and chemical analyses demonstrated increased total phenolic compounds yields in the vegetative parts of plants submitted to the treatments. Furthermore, the analysis showed different pattern of metabolites accumulation, with higher yields of benzopyrans and uliginosin B accumulated in the reproductive parts of the plants treated with DACP during all experiment. The elevation of bioactive metabolites levels in response to the elicitor suggests that these compounds are inducible in plant defense response of H. polyanthemum. The results obtained are relevant since the plant did not suffer injury. Then, the system described represents a new approach in plant research aimed to optimize the conditions for biomass and accumulation of secondary metabolites.
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Sunkiųjų metalų koncentracijų įvertinimas skirtingais būdais paruoštoje Paprastosios jonažolės (Hypericum perforatum L.) vaistinėje augalinėje žaliavoje / Determination of heavy metals concentrations in different ways prepared herbal raw material of St. John's Wort (Hypericum perforatum L.)Foktas, Povilas 18 June 2014 (has links)
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]
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Isolation Of A Bioactive Compound Hypericin From A Medicinal Plant Hyppericum Perforatum L. Using Basic Chromatography MethodsDuru, Betul 01 December 2003 (has links) (PDF)
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.
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Kantaron otundan (Hypericum perforatum L.) elde edilen hyperisin maddesinin insan lenfosit kültürlerinde kardeş kromatid değişimi (KKD) üzerine etkisi /Yücel, Nezahat Kaştan. Yılmaz, Hacı Ramazan. January 2006 (has links) (PDF)
Tez (Yüksek Lisans) - Süleyman Demirel Üniversitesi, Sağlık Bilimleri Enstitüsü, Tıbbi Biyoloji Anabilim Dalı, 2006. / Kaynakça var.
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The relative and combined efficacy of the homoeopathic similimum (taken orally) and the topical application of a lotion (prepared from the homoeopathic mother tinctures of Hypericum perforatum and Calendula officinalis) in the treatment of venous leg ulcersHoffmann, Delia January 2006 (has links)
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.
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Efeito de elicitação biótica com o fungo Nomuraea rileyi (Farlow) Samson no metabolismo secundário de plantas aclimatadas de Hypericum polyanthemum Klotzsech ex Reichardt / Effect of biotic stress in secondary metabolism of Hypericum polyanthemum Klotzsech ex ReichardtMeirelles, Gabriela de Carvalho January 2012 (has links)
Hypericum polyanthemum é uma planta nativa do Sul do Brasil que contém compostos como flavonóides, taninos, derivados de floroglucinol (uliginosina B) e benzopiranos: HP1 (6-isobutiril-5,7-dimetóxi-2,2-dimetilbenzopirano), HP2 (7-hidróxi-6-isobutiril-5- metóxi-2,2-dimetilbenzopirano), e HP3 (5-hidróxi-6-isobutiril-7-metóxi-2,2- dimetillbenzopirano). Esses metabólitos são responsáveis por uma série de atividades biológicas como inibidores da monoaminoxidase (IMAO), antiproliferativa e antitumoral. No presente trabalho modificações na biomassa vegetal e no teor de metabólitos bioativos de plantas de H. polyanthemum cultivadas sob condições controladas e após 18 semanas de aclimatação foram investigadas após elicitação com o fungo Nomuraea rileyi através da adição do microrganismo liofilizado e pulverizado (LP), ou liofilizado, autoclavado e pulverizado (LAP) por curtos e longos períodos de tempo. Plantas cultivadas sob condições controladas tratadas com LAP demonstraram aumento na concentração dos benzopiranos HP1, HP2 e HP3 enquanto LP provocou efeito negativo ou ainda, não alterou a síntese destes compostos. Porém, baixos níveis do floroglucinol uliginosina B foram detectados em todos os tratamentos. Tratamentos com LAP por longos períodos de tempo em plantas cultivadas a campo provocaram aumento de biomassa (2x) e a análise química demonstrou elevação do teor de compostos fenólicos totais nas partes vegetativas das plantas submetidas a todos os tratamentos. Ainda, a análise apontou um diferente grau de acúmulo dos metabólitos, com maiores teores de HP1, HP2, HP3 e uliginosina B sendo encontrados nas partes reprodutivas das plantas tratadas com LAP. A elevação dos metabólitos bioativos em resposta ao elicitor fúngico sugere que estes compostos são induzíveis na resposta de defesa de H. polyanthemum. Os resultados obtidos nesse trabalho são relevantes em virtude da planta não sofrer danos. Assim, o sistema descrito representa uma nova abordagem em pesquisas com plantas visando otimizar condições para a produção de biomassa e metabólitos secundários de interesse medicinal. / Hypericum polyanthemum is a native plant of South Brazil that contains compounds such as flavonoids, tannins, phloroglucinol derivatives (uliginosin B) and benzopyrans: HP1 (6-isobutyryl-5,7-dimethoxy-2,2-dimethylbenzopyran), HP2 (7-hydroxy-6-isobutyryl-5- methoxy-2,2-dimethylbenzopyran), and HP3 (5-hydroxy-6-isobutyryl-7-methoxy-2,2- dimethylbenzopyran). These metabolites are responsible for biological activities such as monoamine oxidase inhibitor, antiproliferative and antitumoral. In this work changes in biomass and bioactive metabolites after elicitation with the fungi Nomuraea riley added as freeze dried culture (DC) or as freeze dried autoclaved cell powder (DACP) for short and long periods of time have been investigated in Hypericum polyanthemum plants grown under controlled conditions and after 18 weeks of field acclimatization. Plants treated with DACP showed increased concentrations of the benzopyrans while the DC affected negatively or did not alter the synthesis of these compounds. Nevertheless, low levels of uliginosin B were detected in all treatments. Long time treatment of field grown acclimatized plants with DACP triggered plant growth doubling the biomass and chemical analyses demonstrated increased total phenolic compounds yields in the vegetative parts of plants submitted to the treatments. Furthermore, the analysis showed different pattern of metabolites accumulation, with higher yields of benzopyrans and uliginosin B accumulated in the reproductive parts of the plants treated with DACP during all experiment. The elevation of bioactive metabolites levels in response to the elicitor suggests that these compounds are inducible in plant defense response of H. polyanthemum. The results obtained are relevant since the plant did not suffer injury. Then, the system described represents a new approach in plant research aimed to optimize the conditions for biomass and accumulation of secondary metabolites.
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Avaliação do efeito crônico dos inibidores da PKC, tamoxifeno, Hypericum perforatum e lítio em ratos wistar machos e fêmeasBorges, Cenita Pereira January 2017 (has links)
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.
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