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Baicalin, which is a flavonoid, was previously shown to exert neuroprotective effects against ischemic injury and oxidative insults. In this study, baicalin was found to induce neuronal differentiation on both C17.2 NSC and primary mouse NSC originated from hippocampuses of E14.5 mouse embryos. The baicalin-mediated differentiation of C17.2 NSC was noted in dose- and time-dependent manners. Baicalin-treated NSC displayed long processes of neurites. The gene expression of neuronal markers, NF-L, TUBB3 and MAP2 was also significantly increased after treated with 20 to 50 muM baicalin on C17.2 NSC. Treating C17.2 NSC with baicalin significantly increased the number of TUBB3 positive cells by 300%. A significant increase in the gene expression of TUBB3 was also observed on primary NSC upon baicalin treatment at 5 to 10 muM. The number of TUBB3 positive cells was increased by 100% after treating with 10 muM baicalin. C17.2 NSC treated with baicalin also increased the gene expression of GABAergic and serotonergic neuronal subtype specific enzymes GAD1 and TPH1. / Nature provides a vast pool of natural compounds with neuroprotection and neurotrophism. A few of these compounds can induce the differentiation of neural stem cells (NSC). There are ample opportunities to discover more natural compounds with differentiation inducing effect on NSC. One of the objectives of this project is to look for novel natural compounds showing neurogenic effect on NSC. This project has established a platform for screening medicinal materials and natural compounds with neural differentiation promoting effect on C17.2 mouse neural stem cell line. Screening results identified total Sanqi saponins, total Renshen saponins, Huangqin extracts and baicalin as potent candidates for inducing this differentiation of NSC. / This project also aims at characterizing the mechanisms involved in the neuronal differentiation effect of baicalin on NSC. Annotation from microarray analysis indicated that baicalin treatment on C17.2 NSC is related to development of tissue and nervous system. qPCR study attested the increased gene expression of nerve growth factor-beta, neurotrophin-3, pro-neural transcriptional factors Ngn1, Ngn2 and NeuroD2. Western blotting showed that baicalin activated ERK1/2 MAP kinase but not JNK and p38 MAP kinases. / This project demonstrated the neurogenic potential of natural resources on NSC. A novel neuronal induction effect of baicalin on NSC was also demonstrated with its mechanisms characterized. This project also revealed that baicalin can be used for promoting functional recovery of post-ischemia animals. / This study showed for the first time that baicalin exerts neuronal differentiation inducing effect on NSC. Another objective of this project is to study whether baicalin can promote functional recovery of animals with ischemia brain injury. Mice having undergone transient occlusion of the bilateral common carotid arteries with blood-reperfusion to induce global cerebral ischemia were treated with baicalin and/or EGFP-NSC. Ischemia animals received implantation of EGFP-NSC into the caudate putamen and/or intravenous injection of baicalin on alternate days for two-week on day seven post-ischemia displayed significant improvement of the cognitive function in terms of the incident of error and escape time in the water T-maze task compared to the control arm of ischemia mice. Data of the study suggested that the therapeutic effect of baicalin would be comparable to that of neural stem cell transplant in improving the cognitive function in a mouse ischemic stroke model. / Li, Ming. / Adviser: P. C. Shaw. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 199-232). / 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, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Absorption study showed that gossypetin was methoxylated and conjugated to form glucuronide during the first-pass metabolism after oral administration. Glucuronide conjugate was the major circulating form in the plasma. As determined by HPLC analysis, the total gossypetin concentration in the plasma was higher than the unchanged gossypetin indicating that most of gossypetin underwent first-pass metabolism. Moreover, urinary excretion was not a main elimination route. / Uses of foods and dietary supplements present a safe chemopreventive strategy. The application of phytochemicals for cancer prevention currently receives a great deal of attention. Flavonoids are known to be antiproliferative and may play an important role in the prevention of carcinogenesis. In addition to epidemiologic studies, basic science research to elucidate mechanisms and evaluate chemopreventive potential of phytochemicals is also necessary. In this study, gossypetin was found to have stronger antiproliferative activity when compared with quercetin, a well studied flavonoid, in human hepatocellular carcinoma (HepG2) cells and human breast carcinoma (MCF-7) cells. The results demonstrated that gossypetin induced growth inhibition in MCF-7 cell line by arresting cell cycle at G0/G1 phase. The inhibition of cell cycle progression was associated with the decrement of cyclin D1 expression, cdk6 kinase activity and phosphorylation of retinoblastoma protein (pRb). Although the cdk inhibitor p21 could not be detected, its upstream protein, p53 tumor suppressor protein, was activated by gossypetin in the MCF-7 cell line. Also, the proliferation of MCF-7 cells was suppressed through down-regulating the Erk1/2 pathway. / Ngai Lei-ka. / "August 2005." / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6156. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 222-250). / 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.

Acute colitis was induced by exposing male SD rats to 4% DSS in drinking water for 8 days. Rats were divided into four groups as follows: DSS group---DSS-induced colitis; DSS + SRE group---SRE, 100 mg/kg/day in addition to DSS; Ctr + SRE group---SRE alone; and Ctr group---sham control group. The colon damage was elucidated by macroscopic, histological, electrophysiological and biochemical assessment. Orally administered SRE significantly reduced the colonic damage in all four aspects. However, baicalein did not show similar effect in the same experiment. / In summary, our finding indicated that both SRE and its major flavonoid, baicalein, could stimulate chloride secretion in human colonic T84 cells and mucosa freshly isolated from human colon. Although SRE was effective in treating acute DSS-induced ulcerative colitis, baicalein is unlikely the active anti-inflammatory component of SRE. Nevertheless, the results demonstrated that this TCM has a scientific basis for its effectiveness. Our data support further evaluation of the therapeutic potential of SRE for the treatment of IBD. / In TCM, Scutellariae radix and Coptidis Rhizoma (CR) derived compounds have been frequently used for gastroenteritis and secretory diarrhea. Our laboratory findings suggested that the major flavonoid component of SR, baicalein, stimulates chloride secretion in rat distal colon, probably via CFTR activation (Ko et al., 2002). In contrast, limited information about the cellular mechanism of chloride secretion induced by SR in human colonic epithelia is available. Therefore, the effect of Scutellariae radix extract (SRE) on electrolyte transport in a human colonic epithelial cell line, T84, was examined using the short-circuit current (ISC) technique. Results demonstrated that SRE stimulated a Cl--dependent secretion across T84 cells, probably via both Ca2+- and cAMP-mediated pathway. / On the other hand, the cellular mechanism of baicalein-induced Cl - secretion in T84 cells was further investigated. It was found that the secretory mechanisms involve protein kinase A (PKA)-, adenylate cyclase (AC)- and luminal cAMP-dependent Cl- channels, most likely cystic fibrosis transmembrane conductance regulator (CFTR) and serosal 293B-sensitive K + channels. However, the action of baicalein cannot be solely explained by its cAMP-elevating effect. In addition, the effect of baicalein could be potentiated by the inhibition of mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI3K). Furthermore, it was found that inhibition of protein kinase C (PKC) delta limited the baicalein-induced chloride secretion. / Our laboratory has found that baicalein (Ko et al., 2002 and Yue et al., 2003) stimulates chloride secretion in rat distal colon and human colonic T84 cells. As it is known that responses in the animal model or the cell line may not completely reflect the in vivo physiology, it is important to study the above responses in human colon. With scarce supply of freshly isolated human colonic mucosa, the results showed that the effect of SRE and baicalein on ion transport in human samples is similar to that obtained in T84 cell line and rat model. / Scutellariae radix (SR) is the dry root of Scutellariae baicalensis Georgi (Huangqin). SR has been employed for centuries as a traditional Chinese medicine (TCM) for various purposes. It contains a large amount of flavonoids such as baicalein, baicalin, and wogonin, which possess a number of beneficial bioactivities including anti-oxidant, anti-bacterial and anti-inflammatory, etc. / Ulcerative colitis (UC), an inflammatory bowel disease (IBD), has been known for more than half a century. Recent studies have shown that two flavonoids derived from SR, baicalein and wogonin, might alleviate the symptoms of IBD. Moreover, SR is the major component of Hange-shasshin-to (HST), one of the Chinese herbal formulas, which has been reported to suppress the pathogenesis of IBD. The above scientific background led us to examine the effect of SRE administration on DSS-induced colitis in rats in a way to evaluate new treatments potentially applicable to UC in humans. / Chung, Ho Lam. / "August 2007." / Adviser: W. H. Ko. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0925. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references. / 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. / Abstract in English and Chinese. / School code: 1307.

Flavonoids were identified and quantified in samples of dry leaves of plant Stevia rebaudiana Bertoni. Content of flavonols (kaempherol, quercetin, myricetin, rutin) and flavons (apigenin, luteolin) were compared in three samples (standard leaves of Stevia rebaudiana Bertoni, Stevia rebaudiana Bertoni origin from Ukraine and from Czech republic), that were extracted by three extraction methods (PSE, ultrasonic extraction, Soxhlet extraction) with two polar solvents, methanol and ethanol, in combination with non-polar hexane. Extracts were analyzed by HPLC with detection UV-VIS. Antioxidant activity and total content of flavonoids in extracts were measured by spectrometry. Stable free radical DPPH. was used for determination of scavenging effect in extracts. PSE was the most effective extraction method with this conditions – 120 °C, dynamic mode and with methanol like solvent.

Call number: LD2668 .T4 1985 R422 / Master of Science

Thesis (MSc (Biochemistry))--University of Stellenbosch, 2009. / This study: 1. Describes the preparation of unfermented and fermented rooibos methanol and aqueous extracts. 2. Investigates the influence of unfermented and fermented rooibos methanol and aqueous extracts on the binding of natural steroid substrates to ovine adrenal microsomal cytochrome P450 enzymes, demonstrating that the binding of natural steroids is inhibited in the presence of rooibos extracts. 3. Describes an assay demonstrating the inhibitory effect of rooibos extracts on the catalytic activity of cytochrome 17α-hydroxylase (CYP17) and cytochrome 21-hydroxylase (CYP21) in ovine adrenal microsomes. 4. Investigates the influence of unfermented and fermented rooibos methanol extracts on the catalytic activity of individual cytochrome P450 enzymes – CYP17 and baboon CYP21, that are expressed in COS1 cells. 5. Demonstrates that fractions of the unfermented rooibos methanol extract inhibits the binding of natural steroid substrate to microsomal cytochrome P450 enzymes as well as the catalytic activity of baboon CYP21 expressed in COS1 cells. 6. Investigates the inhibitory influence of individual rooibos flavonoids on the catalytic activity of baboon CYP21 expressed in COS1 cells.

Thesis (MScAgric)--Stellenbosch University, 1963. / ENGLISH ABSTRACT: no abstract available / AFRIKAANSE OPSOMMING: geen opsomming

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: A comprehensive food frequency questionnaire (FFQ) was developed to assess the daily total flavonoid intake over the past fortnight within a 14-week intervention that consisted of four periods to determine the effect of rooibos consumption on oxidative stress in adults (n=40) at intermediate to high coronary heart disease (CHD) risk. Within the intervention the comprehensive FFQ validity (against six estimated dietary records and biomarkers), reproducibility (on administrations in the washout and control periods six weeks apart as these periods had similar flavonoid intake restrictions) and responsiveness (across the four intervention periods of changed dietary conditions) was evaluated. The baseline period dietary record and FFQ dietary sources found to contribute most to the participants’ daily total flavonoid intake, considering the percentage contribution, and the between-person variation in intake, considering the stepwise multiple regression analysis, formed the food list of the resultant abbreviated FFQ. The validity, reproducibility and responsiveness of the latter were also evaluated within the intervention and its validity (against dietary records) and reproducibility (on re-administration two weeks apart) in an additional group (n=90) being at low and intermediate CHD risk to evaluate its external strength. The validity and reproducibility evaluations of the comprehensive and abbreviated FFQs in the intervention and abbreviated FFQ within the additional group comprised paired difference tests (to establish the ability to estimate group intakes), correlation coefficients (to establish the ability to rank individual participants), category agreement and gross misclassification next to the weighted kappa statistic (to establish the ability to classify the participants into tertiles and quintiles of intake) and Bland-Altman plots (as representation of the limits of agreement between the two dietary assessment methods). Correlation coefficients were also used for biomarker validity evaluations in the baseline period. The repeated measures analysis of variance (ANOVA) (Bonferroni correction) was used for the responsiveness evaluations of the comprehensive and abbreviated FFQs across the intervention periods alongside that of the biomarkers as evidence for the changed dietary conditions. The study demonstrated that the comprehensive FFQ could be modified to a format with a brief food list as few items contributed appreciably to the total flavonoid intake and of which most also contributed to the between-person intake variability. The comprehensive and moreover the abbreviated FFQ in the validity evaluations provided sufficiently accurate daily total flavonoid intake estimates. They could determine the intake at group level in correspondence with that of the dietary records. The participant intakes could additionally be categorized and in particular ranked greatly alike to the dietary record intakes. The Bland-Altman plots revealed proportional bias regarding overestimation at the higher intake level. The reproducibility also appeared to be greatly satisfactory although seasonal fruit exclusions from the abbreviated FFQ food list may hamper its repeated administration. Both FFQs also confirmed the changed total flavonoid intakes across the intervention periods in relation to changes in the expected direction concerning the plasma total polyphenol, conjugated diene and thiobarbituric acid reactive substance concentrations. / AFRIKAANSE OPSOMMING: ‘n Omvattende voedsel frekwensie vraelys (VFV) is ontwikkel om die daaglikse totale flavonoïed inname oor twee agtereenvolgende weke te beraam te midde van ‘n 14-week intervensie. Die intervensie het uit vier periodes bestaan wat die effek van rooibosinname op oksidatiewe stres in volwassenes (n=40), met ‘n intermediêre tot hoë koronêre hartsiekte (KHS) risiko, bepaal het. Binne die intervensie is die geldigheid (teen ses geskatte dieetrekords en biochemiese merkers), herhaalbaarheid (op aanwending ses weke uitmekaar in die uitwas en kontrole intervensie periodes met dieselfde flavonoïed inname bepalings) en waarneembaarheid (oor vier intervensie periodes van veranderde dieet bepalings) van die omvattende VFV geëvalueer. Die dieetbronne in die basislyn periode dieetrekords en vraelyste wat die meeste tot die deelnemers se daaglikse totale flavonoïed inname (baseer op die persentasie bydrae) en die tussen-persoon variasie in inname (baseer op die stapsgewyse meervuldige regressie analise) bygedra het, het die voedsellys van die voortvloeiende verkorte VFV gevorm. Die geldigheid, herhaalbaarheid en waarneembaarheid van dié VFV is binne die intervensie geëvalueer en die geldigheid (teen dieetrekords) en herhaalbaarheid (heradministrasie twee weke later) daarvan in ‘n verdere groep (n=90) met lae en intermediêre KHS risiko as evaluasie van die eksterne vermoë van die VFV. Die geldigheid en herhaalbaarheid evaluasies van die omvattende en verkorte VFV in die intervensie en die verkorte VFV in die verdere groep het bestaan uit gepaarde verskil toetse (bepaling van die groepinname skattingsvermoë), korrelasie koëffisiënte (bepaling van individuele deelnemer rangorde skattingsvermoë), kategorie ooreenstemming en erge wanklassifikasie naas die aangepaste kappa statistiek (bepaling van die vermoë om die deelnemer innames in derdes en vyfdes te klassifiseer) en die Bland-Altman karterings (verteenwoordiging van ooreenstemmingslimiete tussen die twee dieetinname metodes). Korrelasie koëffisiënte is ook gebruik vir biochemiese merker geldigheid evaluasies in die basislyn periode. Die herhaalde metings analise van variansie (ANOVA) (Bonferroni regstelling) is gebruik om die waarneembaarheid evaluasies van die omvattende en verkorte VFV oor die intervensie periodes naas dit van die biochemiese merkers te evalueer as bewys van die veranderde dieet bepalings. Die studie het aangedui dat die omvattende VFV gewysig kon word tot ‘n formaat met ‘n verkorte voedsellys omdat slegs ‘n aantal items merkbaar tot die totale flavonoïed inname bygedra het en die meeste hiervan ook tot die tussen-persoon variasie in inname. Die omvattende en die verkorte VFV het in die geldigheid evaluasies daarvan voldoende akkurate daaglikse totale flavonoïed inname skattings opgelewer omdat groep innames bepaal kon word in ooreenstemming met dit verkry van die dieetrekords en die deelnemer innames bykomend kategoriseer en in besonder grootliks eenders rangeer kon word as met hul dieetrekord innames. ‘n Proporsionele oorskatting by die hoër inname vlakke is wel vir al twee getoon in die Bland-Altman karterings. Die herhaalbaarheid was ook grootliks aanvaarbaar, alhoewel seisoenale vrugte uitsluitings in die verkorte VFV voedsellys die heruitvoering kan bemoeilik. Al twee vraelyste kon ook die veranderinge in die daaglikse totale flavonoïed inname oor die intervensie periodes bevestig in ooreenstemming met veranderinge in die verwagte rigting van die plasma totale polifenool, konjugaat diëne en tiobarbituursuur reaktiewe stof konsentrasies.

published_or_final_version / Biological Sciences / Master / Master of Philosophy