Thesis (Ph. D.)--University of Wisconsin, 1964. / Typescript. eContent provider-neutral record in process. Description based on print version record. Bibliography: leaves 93-101.

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Oleanolic and ursolic acid (OA and UA) are triterpenic acids with diverse biological activities that are of interest to the pharmaceutical industry. To investigate the scope for producing these compound using cell suspension cultures of Salvia species, calli from S. officinalis, S. virgata and S. fruticosa were induced using several plant growth regulator (PGR) combinations. Eleven lines were selected for suspension induction from a pool of calli. Six suspension cultures were established successfully and cultivated in the Respiration Activity MOnitoring System® (RAMOS®) to obtain online data on their growth kinetics and to establish appropriate sampling schedules for the determination of their OA and UA production. Based on their observed growth behaviour, OA and UA contents, and aggregation properties, one suspension culture from each studied Salvia species was selected for further optimisation. The μmax values for these suspension cultures ranged from 0.20 to 0.37°d-1, their OA and UA contents were greater than 1.3 and 1.2 mg g-1, respectively, and they afforded maximum volumetric yields of 21.0 mg l-1 for OA and 32.8 mg l-1 for UA. These results will be useful in the development of a refined Salvia suspension-based process for OA and UA production.

Wu Wai Ping. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 163-177). / Abstracts in English and Chinese. / Abstract --- p.i / 摘要 --- p.iv / Acknowledgement --- p.vi / Table of Contents --- p.vii / Abbreviations --- p.x / Chapter Chapter 1 --- General introduction --- p.11 / Chapter 1.1 --- Introduction --- p.11 / Chapter 1.1.1 --- "Origin, processing and delivery form of TCM" --- p.11 / Chapter 1.1.2 --- Problems about the uses of TCM --- p.13 / Chapter 1.1.2.1 --- Quality control --- p.13 / Chapter 1.1.2.2 --- Efficacy --- p.14 / Chapter 1.1.2.3 --- Herb-drug interactions --- p.14 / Chapter 1.1.2.4 --- Authentication --- p.15 / Chapter 1.1.3 --- Commonly used Traditional Chinese Medicine --- p.15 / Chapter 1.2 --- Interactions between TCM and warfarin --- p.17 / Chapter 1.2.1 --- Danshen-warfarin interactions --- p.19 / Chapter 1.3 --- Danshen --- p.20 / Chapter 1.3.1 --- Chemical constituents --- p.20 / Chapter 1.3.2 --- Pharmacological effects of danshen --- p.24 / Chapter 1.3.2.1 --- Anti-oxidant effects --- p.24 / Chapter 1.3.2.2 --- Effects on liver fibrosis --- p.25 / Chapter 1.3.2.3 --- Effects on tumours --- p.26 / Chapter 1.3.2.4 --- Effects on cardiovascular system --- p.26 / Chapter 1.3.2.5 --- Effect on platelet aggregation --- p.27 / Chapter 1.4 --- Warfarin --- p.27 / Chapter 1.4.1 --- Pharmacology --- p.28 / Chapter 1.4.2 --- Pharmacokinetics --- p.30 / Chapter 1.4.3 --- Metabolism --- p.30 / Chapter 1.4.4 --- Warfarin-drug interactions --- p.32 / Chapter 1.4.4.1 --- Pharmacokinetic Interactions --- p.32 / Chapter 1.4.4.2 --- Pharmacodynamic interactions --- p.34 / Chapter 1.5 --- Aim of study --- p.35 / Chapter Chapter 2 --- Effects of danshen extract and some of its active ingredients on warfarin metabolism in rat liver microsomes --- p.36 / Chapter 2.1 --- Introduction --- p.36 / Chapter 2.2 --- Materials and methods --- p.39 / Chapter 2.2.1 --- Chemicals and reagents --- p.39 / Chapter 2.2.2 --- Animals --- p.39 / Chapter 2.2.3 --- Preparation of rat hepatic microsomes --- p.40 / Chapter 2.2.4 --- Protein assay --- p.40 / Chapter 2.2.5 --- Preparation of aqueous fraction and ethanolic fractions of danshen from danshen roots --- p.41 / Chapter 2.2.5.1 --- Aqueous extract of danshen --- p.41 / Chapter 2.2.5.2 --- Ethanolic extract of danshen --- p.42 / Chapter 2.2.6 --- Incubation condition for warfarin metabolism --- p.42 / Chapter 2.2.7 --- Effects of danshen extract and some of its active ingredients on warfarin metabolism in vitro --- p.43 / Chapter 2.2.8 --- Effects of danshen extract and some of its sctive ingredients on enzyme kinetics of warfarin metabolism in vitro --- p.44 / Chapter 2.2.9 --- High Pressure Liquid Chromatography (HPLC) analysis --- p.45 / Chapter 2.2.10 --- Calibration curves and validation of the HPLC systems --- p.48 / Chapter 2.2.11 --- Data analysis --- p.52 / Chapter 2.3 --- Results --- p.53 / Chapter 2.3.1 --- Effects of danshen extract on warfarin metabolism --- p.53 / Chapter 2.3.2 --- Effects of aqueous extract of danshen on warfarin metabolism --- p.60 / Chapter 2.3.3 --- Effects of ethanolic extract of danshen on warfarin metabolism --- p.62 / Chapter 2.3.4 --- Effects of tanshinone I on warfarin metabolism --- p.64 / Chapter 2.3.5 --- Effects of tanshinone IIA on warfarin metabolism --- p.70 / Chapter 2.3.6 --- Effects of cryptotanshinone on warfarin metabolism --- p.76 / Chapter 2.3.7 --- IC20 of danshen extract and its components on warfarin metabolism --- p.82 / Chapter 2.4 --- Discussion --- p.84 / Chapter Chapter 3 --- Effects of danshen extract and some of its active ingredients on warfarin metabolism in human pooled liver microsomes and the human CYP2C9 isoform --- p.89 / Chapter 3.1 --- Introduction --- p.89 / Chapter 3.2 --- Materials and methods --- p.92 / Chapter 3.2.1 --- Chemicals and reagents --- p.92 / Chapter 3.2.2 --- Incubation conditions for warfarin metabolism --- p.92 / Chapter 3.2.3 --- Effects of danshen extract and its components on warfarin metabolism in vitro --- p.93 / Chapter 3.2.4 --- High Pressure Liquid Chromatography (HPLC) analysis --- p.94 / Chapter 3.2.5 --- Calibration curves --- p.95 / Chapter 3.2.6 --- Data analysis --- p.95 / Chapter 3.3 --- Results --- p.96 / Chapter 3.3.1 --- Effects of danshen extract and its components on warfarin metabolism by using human pooled liver microsomes --- p.96 / Chapter 3.3.2 --- Effects of danshen extract and its components on S-warfarin metabolism by using human lymphoblast CYP2C9 isoform --- p.103 / Chapter 3.4 --- Discussion --- p.111 / Chapter Chapter 4 --- Effects of acute and subchonic pretreatment of danshen extract on the pharmacokinetics of warfarin in the rats in vivo --- p.115 / Chapter 4.1 --- Introduction --- p.115 / Chapter 4.2 --- Materials and methods --- p.118 / Chapter 4.2.1 --- Chemicals and reagents --- p.118 / Chapter 4.2.2 --- Animals Table of Contents --- p.118 / Chapter 4.2.3 --- Effects of acute danshen extract pretreatment on the pharmacokinetics of warfarin --- p.119 / Chapter 4.2.4 --- Effects of subchronic danshen extract pretreatment on the pharmacokinetics of warfarin --- p.119 / Chapter 4.2.5 --- Steady state warfarin study --- p.120 / Chapter 4.2.6 --- Sample extraction --- p.120 / Chapter 4.2.7 --- High Pressure Liquid Chromatography (HPLC) analysis --- p.121 / Chapter 4.2.8 --- Calibration curve --- p.121 / Chapter 4.4 --- Results --- p.123 / Chapter 4.3.1 --- Effects of acute danshen extract pretreatment on the pharmacokinetics of warfarin --- p.123 / Chapter 4.3.2 --- Effects of subchronic danshen extract pretreatment on the pharmacokinetics of warfarin --- p.128 / Chapter 4.3.3 --- Steady state warfarin study --- p.136 / Chapter 4.5 --- Discussion --- p.138 / Chapter Chapter 5 --- Effects of danshen extract on the absorption of warfarin by using Caco-2 cells model --- p.142 / Chapter 5.1 --- Introduction --- p.142 / Chapter 5.2 --- Materials and methods --- p.144 / Chapter 5.2.1 --- Materials for Caco-2 cells culture experiment --- p.144 / Chapter 5.2.2 --- Preparation of Caco-2 monolayer --- p.144 / Chapter 5.2.3 --- High Pressure Liquid Chromatography (HPLC) analysis for warfarin --- p.145 / Chapter 5.2.4 --- Calibration curve --- p.145 / Chapter 5.2.5 --- Stability test for warfarin and danshen extract --- p.145 / Chapter 5.2.6 --- Toxicity test of danshen extract on Caco-2 cells --- p.146 / Chapter 5.2.7 --- Transport study --- p.146 / Chapter 5.2.8 --- Data Analysis --- p.147 / Chapter 5.3 --- Results --- p.149 / Chapter 5.3.1 --- Stability of warfarin and danshen extract --- p.149 / Chapter 5.3.2 --- Toxicity test of danshen extract on Caco-2 cells --- p.149 / Chapter 5.3.3 --- Integrity of Caco-2 cells monolayer --- p.152 / Chapter 5.3.4 --- Transport study --- p.152 / Chapter 5.4 --- Discussion --- p.154 / Chapter Chapter 6 --- General discussion --- p.156 / References --- p.163

Atherosclerosis is the chief cause of acute coronary syndromes and may progress for many years before any noticeable clinical syndromes occur. Hyperlipidemia is the common clinical problem for people adopting a western style of living and it can initiate a series of vascular events that result in atherosclerosis. The pathological processes include the accumulation of modified lipid, mainly oxidized low-density lipoprotein (oxLDL), endothelial cell dysfunction and activation, increase in expression of adhesion molecules, activation and recruitment of inflammatory cells and induction of proliferation and migration of vascular smooth muscle cells. / Endothelial-monocyte adhesion is crucial process for the recruitment of monocyte into intima. DG (7:3), Danshen and SAB were found to inhibit TNF-alpha-induced endothelial-monocyte adhesion. They also showed inhibition on TNF-alpha induced production of chemokines, MCP-1 which promotes the transmigration of monocyte. However, it did not inhibit the production of cytokine, IL-6 which stimulates the expression of adhesion molecules such as VCAM-1 and ICAM-1. / For the in vivo study, DG (7:3) exhibited no anti-hyperlipidemic or hypolipidemic effect against diet-induced hyperlipidemia, nor did it lower cholesterol level in hamsters. Also, it did not inhibit HMG-CoA reductase activity or increase the total fecal sterols excretion. However, DG (7:3) exhibited hypocholesterolemic effect on diet-induced hyperlipidemia in the rabbit model, wherein it could lower plasma total cholesterol and liver cholesterol level. Moreover, it could significantly decrease the atheroma formation. / In the present study, the anti-oxidative effects of herbal extract/compound were measured by three in vitro assays, namely the inhibition of 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH)-induced red blood cells hemolysis, AAPH-induced cardiomyocyte (H9c2) cells death and Cu2+-induced low-density lipoprotein oxidation. The results showed that the aqueous extract of the compound formula Danshen (D) and Gegen (G) (7:3), abbreviated as DG (7:3), and an aqueous extract of Danshen as well as salvianolic acid B (SAB) exhibited anti-oxidant effect, but Gegen did not produce such effect. It was found that SAB showed a stronger anti-oxidant effect than that of ascorbic acid. / Proliferation and migration of vascular smooth muscle cells (vSMCs) are important pathological processes involved in the development of atherosclerosis. DG (7:3), Danshen and SAB were found to inhibit PDGF-induced vSMCs proliferation through G1/S cell cycle arrest. Cyclin D, a main component that governs the transition of G1 phase to S phase, was found to be down-regulated by DG (7:3), Danshen and SAB, as assessed by measurements of both protein and mRNA levels. Moreover, DG (7:3), Danshen and SAB showed anti-migratory effect against platelet-derived growth factor-induced vSMCs migration. / To summarize, DG (7:3) was found to have potential to produce anti-atherosclerotic effect by inhibiting the LDL oxidation, proliferation and migration of vascular SMC, thereby preventing the formation of atheroma plaque. / Koon Chi Man. / "March 2006." / Adviser: Kwok Pui Fung. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6324. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 246-264). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Thesis (Ph. D.)--University of California, Riverside, 2009. / Includes abstract. Title from first page of PDF file (viewed Febrary 1, 2010). Available via ProQuest Digital Dissertations. Includes bibliographical references. Issued in print and online. Available via ProQuest Digital Dissertations.

Faculty of Health SCiences School of Therapantic Sciences(pharmacy and Pharmaciology) 9604111j vanessa8@absamail.co.za / The genus Salvia, commonly known as the sages is a member of the mint family (Lamiaceae). In Latin, ‘sage’ means "to save" and the Romans called it "sacred herb". Throughout history it has been used for depression, fever, respiratory infections, women's complaints, sleep inducer, diuretic, gargles and sick room use. The essential oil is reported to have anti-inflammatory, antimicrobial, antioxidant, antiseptic, antispasmodic, astringent, diuretic, antihypertensive and insecticidal properties. Of the 900 species recorded worldwide, 30 are indigenous to South Africa where they are used extensively in traditional healing. The aerial parts of twelve samples were hydrodistilled and the essential oil analysed by GC-MS. The essential oil composition varied quantitatively and qualitatively within the different Salvia species analysed. Linalool was the only compound that was present in all the essential oils. β-caryophyllene and caryophyllene oxide were present in all essential oil with the exception of S. stenophylla. The essential oil as well as methanol and acetone extracts were tested for antimicrobial activity on a number of bacteria and fungi. No species showed activity against Cryptococcus neoformans, Candida albicans nor Alternaria alternata. All test samples studied demonstrated variable degrees of antibacterial activity with the exception of four test samples; S. disermas (methanol and acetone) from the Walter Sisulu Botanical Garden; S. disermas (methanol) from Mossel Bay and S. lanceolata (methanol). Gram-positive organisms were more sensitive to the test samples than the Gram-negative organisms. In general, the extracts were far more active than the essential oils. Thin layer chromatography indicated that all methanol extracts possess antioxidant activity. All methanol extracts contain the antioxidant compound, rosmarinic acid. It is evident that, in addition to rosmarinic acid, other polar and non-polar compounds are present in all Salvia species that also act as antioxidants.

Memoria para optar al título profesional de Ingeniero en Recursos Naturales Renovables / Salvia hispanica L., conocida como Chía, es una especie vegetal anual de verano originaria de Mesoamérica de climas tropicales y subtropicales y por lo tanto es sensible a las heladas. Es una especie económicamente importante, ya que produce a nivel de semillas ácido α linolénico (ALA, Omega-3), con probados efectos beneficiosos para la salud. Se considera como un alimento funcional y la demanda de su semilla y otros subproductos ha aumentado tanto internacional como nacionalmente. Al no existir producción comercial en Chile, se investigaron los lugares donde esta planta se podría cultivar, de manera satisfacer la demanda nacional. Para ello se planteó como objetivo general una zonificación climática de adaptabilidad del cultivo de Chía en el territorio de Chile, de acuerdo a dos objetivos específicos. Estos objetivos fueron cuantificar los principales requerimientos climáticos de la Chía y elaborar una cartografía de adaptabilidad climática de la Chía en Chile. La metodología se basó en el uso de un Modelo de Distribución de Especies, el modelo Maxent. Este es un software diseñado para encontrar la distribución potencial de las especies a partir de información incompleta de presencia u ocurrencia de una especie. Para ello se utilizaron 78 datos georreferenciados de presencia de la Chía a nivel mundial e información climática raster del proyecto Worldclim.

Salvia divinorum is a hallucinogenic herb from the mint family, Lamiaceae. An estimated 1.8 million people over the age of 12 have used S. divinorum in their lifetime as of 2008. The abuse of S. divinorum is attractive to teens and young adults who wish to experiment with psychoactive materials. The plant material and extracts are widely available via the Internet, and it is known that S. divinorum will not show up on common drug screens. The active component in S. divinorum is salvinorin A, which is a non-nitrogenous diterpene that is a highly selective kappa opioid receptor (KOR) agonist, reported to be the most potent naturally occurring hallucinogen. Since salvinorin A is such a selective and potent agonist of the KOR, there is interest in researching analogues in efforts to develop and understand therapeutic drugs for depression, schizophrenia, and other mental illnesses, resulting in the discovery of analogues with increased potency. These semi-synthetic salvinorin analogues have been abused by spraying the drug on innocuous plant material or on cigarette papers as a substrate for smoking. This practice poses a significant health risk, as most new analogues will have little safety and toxicity data associated with common abuse routes. Chemical characterization of the potent analogue, salvinorin B ethoxymethyl ether (SB-EME) was performed in order to develop methods of differentiation from Salvia divinorum and salvinorin A. These characterization techniques include HPLC, UV/Vis, NMR, and a colorimetric assay with Ehrlich's reagent. Adulteration of other plant materials with salvinorin A and analogues was performed and analyzed to determine if fortified materials can be detected by colorimetric assay. The validation studies of the HPLC method for SB-EME were found to be accurate (%RE < 12%), precise (RSD = 12%), and linear (R2 = 0.9993) over the mass range of 0.038 µg - 4.8 µg. The LOD was determined to be 0.038 µg, and the LOQ was determined to be 0.113 µg. Significant matrix effects were observed when using Salvia officinalis as a blank matrix, affecting the accuracy and selectivity of the method. However, the purified solutions of SB-EME had baseline resolution from salvinorin A and salvinorin B, which allows for easy qualitative distinction if adulterated samples are suspected. UV/Vis analysis provided a rapid and facile SB-EME characterization method. The UV/Vis trace for SB-EME was distinguishable from both salvinorin A and salvinorin B. NMR analysis confirmed the structures of salvinorin A, salvinorin B and SB-EME, with resonances specific to each compound. The colorimetric assay with Ehrlich's reagent provided a red-orange result with salvinorin B and SB-EME, similar to salvinorin A. While this does not provide differentiation in the field, it does allow all materials related to Salvia divinorum to be identified and collected for further analysis in the lab, as this colorimetric analysis allows easy distinction from common kitchen herbs such as mint, basil, and sage. Characterization of the colored species in the assay with Ehrlich's reagent was performed with UV/Vis, HPLC, and NMR. The UV/Vis analysis showed a new peak at 500 nm in the aqueous layer, which would correspond to a red-orange color. HPLC analysis revealed a new, highly retained peak from the DCM layer of the assay. 1H NMR analysis indicated that the backbone of the salvinorins was not stable in acid, and the molecule that creates the color was likely a degraded analogue. The analysis of the adulterated plant materials by colorimetric assay was inconclusive, as color intensity decreased as concentration of spiked standard increased. HPLC analysis of the vial remnants after the colorimetric assay confirm recoveries of the spiking compounds up to an average of 22% for salvinorin A, 96% for salvinorin B, and 41% for SB-EME over all matrices, indicating incomplete deposition of standard material onto the plant material. In conclusion, salvinorin B ethoxymethyl ether can be detected in the field through the use of Ehrlich's reagent as a colorimetric assay. Further laboratory tests, including HPLC and UV/Vis, were shown to easily distinguish the ether derivative from salvinorin A and B.

Made available in DSpace on 2014-06-11T19:32:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-09-01Bitstream added on 2014-06-13T21:03:35Z : No. of bitstreams: 1 povh_ja_dr_botib.pdf: 514154 bytes, checksum: 54ccc04cdb9b8c8830d238e77200844a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Este estudo objetivou avaliar o efeito de reguladores vegetais e bioestimulantes no desenvolvimento, teor e composição de óleo essencial, teores de flavonóides e fenóis totais, atividade antioxidante e atividade das enzimas peroxidase e polifenoloxidade de plantas de Salvia officinalis L. Para tanto, instalou-se experimento em casa de vegetação, do Departamento de Botânica, Instituto de Biociências, da Universidade Estadual Paulisa - UNESP, Botucatu, SP. O delineamento experimental foi inteiramente casualizado com 6 tratamentos contendo três repetições. As plantas foram tratadas com as seguintes substâncias: 1- controle (água); 2- IBA a 100 mg L-1; 3- GA3 a 70 mg L-1; 4-benzilaminopurina (BAP) a 70 mg L-1; 5- GA3+cinetina+IBA - Stimulate® a 1% e 5- GA4+7+N-(fenilmetil)-1-purina-6- amino - Promalin® a 100 mg L-1. As avaliações fisiológicas foram realizadas em 7 coletas, pelas seguintes características: altura da planta, área foliar, massa seca de caule, folhas e da parte aérea da planta. Para as avaliações fitoquímicas, foram avaliadas a produção de massa seca da parte aérea e rendimento do óleo essencial, aos 90 e 120 D.A.E. As análises bioquímicas foram determinadas nas sete coletas, determinando-se: os teores de flavonóides e fenóis totais, atividade das enzimas peroxidase e polifenoloxidase e atividade antioxidante (CE50). Analisando-se os resultados obtidos foi possível verificar que plantas tratadas com IBA e GA3 promoveram maiores incrementos na produtividade vegetal, principalmente, na formação da parte aérea. A produção de óleo essencial foi incrementada pela aplicação de IBA nas plantas, mas também tratamentos com GA3 e o bioestimulante Stimulate® também influenciaram positivamente no acúmulo de óleo essencial. O maior rendimento de óleo essencial foi obtido na coleta aos 120 D.A.E. Os... / This study aimed at evaluating the effect of plant growth regulators and biostimulants on development, essential oil content and composition, total flavonoid and phenol levels, besides peroxidase, polyphenol oxidase and antioxidant activities in Salvia officinalis L plants. The experiment was carried out in a greenhouse from Department of Botany, Institute of Biosciences, São Paulo State University - UNESP, Botucatu, São Paulo State, Brazil. Experimental design was completely randomized with six treatments and three replicates. Plants were subjected to the following substances: 1- control (water); 2- IBA 100 mg L-1; 3- GA3 70 mg L-1; 4- benzylaminopurine (BAP) 70 mg L-1; 5- GA3+kinetin+IBA - Stimulate® 1%, and 5- GA4+7+ N-(phenylmethyl)-1H-purine-6-amine - Promalin® 100 mg L- 1. Physiological evaluations were performed in seven harvestings and consisted of plant height, leaf area, and dry matter of stem, leaves and shoot. As regards phytochemical evaluations, shoot dry matter and essential oil yield were assessed at 90 and 120 D.A.E. Also, the following biochemical evaluations were performed: total flavonoid and phenol levels, besides peroxidase, polyphenol oxidase and antioxidant (CE50) activities. IBA- and GA3- treated plants had higher plant productivity, mainly concerning shoot formation. IBA application led to an increase in essential oil yield, which was also positively influenced by GA3 and Stimulate®, a biostimulant. The highest essential oil yield was detected at 120 D.A.E. Plant growth regulators, biostimulants and harvesting times did not lead to alterations in the essential oil chemical composition. IBA-treated plants presented the highest total phenol and flavonoid levels. Plants subjected to IBA, GA3 and Promalin® had higher antioxidant activity. Considering enzymatic activities, there was an increase in peroxidases when plants were treated with GA3... (Complete abstract click electronic access below)