This thesis explores the histories of mild to moderate depression and the use of over the counter (OTC) St. John’s wort (St. John’s wort) during the 1990s. In doing so it not only investigates the diagnosis and definition of mental illnesses, it also raises questions about the interface between conventional and alternative medicine. Using a variety of printed sources, including popular media articles, scientific and medical journal publications, and St. John’s wort self-help books, a number of historical themes are explored. This thesis takes issue with existing medical historical studies of depression. Firstly it is argued that they have presented progressive depression histories. Secondly, it is suggested that they have retrospectively diagnosed depression on the basis of similar symptoms. It is therefore argued that illness is specific to the time in which it exists and should be understood within its own historical timeframe. During the 1990s standardised St. John’s wort was promoted as a natural and safe remedy. Adverts and media reports also highlighted the fact that it had a long medical history. Although this thesis establishes that the plant has been traditionally used to treat physical illnesses, it seems that a growing distrust of conventional antidepressants, combined with an established interest in alternative medicine, encouraged some lay people to use the remedy to treat mild mood disorders. It is further argued that lay people have a history of self-treating minor mental illnesses using preparatory and OTC remedies such as preparatory nerve tonics. Not only did lay people desire autonomous treatments, it also seems that standardised St. John’s wort provided a functional role as an OTC remedy. By the 1990s the concepts of responsible self-care and self-treatment were being actively encouraged by medical authorities. Therefore this thesis reclassifies the passive mild to moderately depressed patient as an active consumer. Following an analysis of the popular media it is suggested that the 1990s coverage of depression and its treatments was confusing. Indeed, depression and its treatment with conventional medicines and St. John’s wort were sometimes presented as part of a wider life style choice. Finally, it is argued that by the 1990s standardised St. John’s wort received the same scientific and medical scrutiny as conventional medicines. It is therefore suggested that the remedy represents a situation in which the boundaries between conventional and alternative medicines have become increasingly indistinguishable.

Herbal medicines are widely used in our community. A survey of Australian consumers indicated that 60% had used complementary and/or alternative medicines in the past year with the majority not informing their doctor that they were using herbal medicines. Little is known about the potentially serious consequences of interactions between herbal and conventional medicines. Warfarin has an important role in treating people with heart disease, yet it has a narrow therapeutic range, is highly bound to plasma proteins, and is metabolised by cytochrome P450. This creates the potential for life-threatening interactions with other drugs and foods leading to excessive bleeding. Hence, warfarin is one of the most frequently investigated drugs for interaction studies. Early clinical reports suggest that there exists the potential for an interaction between warfarin and four herbal medicines: St John�s wort, ginseng, ginkgo and ginger. However, these herb-drug combinations have never been conclusively studied. The two clinical studies conducted as part of this research had an identical study design. Twenty-four healthy male subjects were recruited into the two separate studies. This was an open label, three-way crossover randomised study in twelve healthy male subjects, who received a single 25 mg dose of warfarin alone or after 14 days pre-treatment with St John�s wort, or 7 days pre-treatment with ginseng. Dosing with St John�s wort or ginseng was continued for 7 days after administration of the warfarin dose in study I or who received a single 25 mg dose of warfarin alone or after 7 days pre-treatment with recommended doses of ginkgo or ginger from single ingredient products of known quality. Dosing with ginkgo or ginger was continued for 7 days after administration of the warfarin dose in study II. Platelet aggregation, international normalised ratio (INR) of prothrombin time, warfarin enantiomer protein binding, warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured in both studies. Statistical comparisons were made using ANOVA and 95% confidence interval (CI) for mean value and 90% CI for geometric mean ratio value are reported. n study I, the mean (95% CI) apparent clearance of S-warfarin after warfarin alone or with St John�s wort or ginseng were, respectively, 198 (174 � 223) ml/h, 269 (241 � 297) ml/h and 220 (201 � 238) ml/h. The respective apparent clearances of R-warfarin were 110 (94 � 126) ml/h, 142 (123 � 161) ml/h and 119 (106 � 131) ml/h. The mean ratio of apparent clearance for S-warfarin was 1.29 (1.16-1.46) and for R-warfarin was 1.23 (1.11-1.37) when St John�s wort was co-administered. The mean ratio of AUC0-168 of INR was 0.79 (0.70 - 0.95) when St John�s wort was co-administered. The urinary excretion ratio of S-7-hydroxywarfarin after administration of warfarin alone was 0.04 (0.03 � 0.06) mg/h and there was no significant difference following treatment with either St John�s wort 0.03 (0.02 � 0.04) mg/h or ginseng 0.03 (0.02 � 0.04) mg/h. The ratio of geometric means for S-7-hydroxywarfarin UER was 0.82 (0.61-1.12) for St John�s wort, and 0.68 (0.50-0.91) for ginseng. St John�s wort and ginseng did not affect the apparent volumes of distribution or protein binding of warfarin enantiomers. In study II, the mean (95% CI) apparent clearance of S-warfarin after warfarin alone, with ginkgo or ginger were 189 (167 � 210) ml/h, 200 (173 � 227) ml/h and 201 (171 � 231) ml/h, respectively. The respective apparent clearances of R-warfarin were 127 (106 � 149) ml/h, 126 (111 � 141) ml/h and 131 (106 � 156) ml/h. The mean ratio of apparent clearance for S-warfarin was 1.05 (0.98 -1.12) and for R-warfarin was 1.00 (0.93 -1.08) when co-administered with ginkgo. The mean ratio of AUC0-168 of INR was 0.93 (0.81 -1.05) when co-administered with ginkgo. The mean ratio of apparent clearance for S-warfarin was 1.05 (0.97 -1.13) and for R-warfarin was 1.02 (0.95 -1.10) when co-administered with ginger. The mean ratio of AUC0-168 of INR was 1.01 (0.93 -1.15) when co-administered with ginger. The urinary excretion ratio (UER) of S-7-hydroxywarfarin after administration of warfarin alone was 0.04 (0.03 � 0.05) mg/h and there was no significant difference following treatment with either ginkgo 0.04 (0.03 � 0.04) mg/h or ginger 0.03 (0.02 � 0.04) mg/h. The ratio of geometric means for S-7-hydroxywarfarin UER was 1.07 (0.69-1.67) for ginkgo, and 1.00 (0.64-1.56) for ginger. Ginkgo and ginger did not affect the apparent volumes of distribution or protein binding of either S-warfarin or R-warfarin. In conclusion, St John�s wort significantly induced the apparent clearance of both S-warfarin and R-warfarin, which in turn resulted in a significant reduction in the pharmacological effect of rac-warfarin. Ginseng, ginkgo and ginger at recommended doses affect neither clotting status, nor the pharmacokinetics or pharmacodynamics of either S-warfarin or R-warfarin in healthy subjects.

Herbal medicines are widely used in our community. A survey of Australian consumers indicated that 60% had used complementary and/or alternative medicines in the past year with the majority not informing their doctor that they were using herbal medicines. Little is known about the potentially serious consequences of interactions between herbal and conventional medicines. Warfarin has an important role in treating people with heart disease, yet it has a narrow therapeutic range, is highly bound to plasma proteins, and is metabolised by cytochrome P450. This creates the potential for life-threatening interactions with other drugs and foods leading to excessive bleeding. Hence, warfarin is one of the most frequently investigated drugs for interaction studies. Early clinical reports suggest that there exists the potential for an interaction between warfarin and four herbal medicines: St John�s wort, ginseng, ginkgo and ginger. However, these herb-drug combinations have never been conclusively studied. The two clinical studies conducted as part of this research had an identical study design. Twenty-four healthy male subjects were recruited into the two separate studies. This was an open label, three-way crossover randomised study in twelve healthy male subjects, who received a single 25 mg dose of warfarin alone or after 14 days pre-treatment with St John�s wort, or 7 days pre-treatment with ginseng. Dosing with St John�s wort or ginseng was continued for 7 days after administration of the warfarin dose in study I or who received a single 25 mg dose of warfarin alone or after 7 days pre-treatment with recommended doses of ginkgo or ginger from single ingredient products of known quality. Dosing with ginkgo or ginger was continued for 7 days after administration of the warfarin dose in study II. Platelet aggregation, international normalised ratio (INR) of prothrombin time, warfarin enantiomer protein binding, warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured in both studies. Statistical comparisons were made using ANOVA and 95% confidence interval (CI) for mean value and 90% CI for geometric mean ratio value are reported. n study I, the mean (95% CI) apparent clearance of S-warfarin after warfarin alone or with St John�s wort or ginseng were, respectively, 198 (174 � 223) ml/h, 269 (241 � 297) ml/h and 220 (201 � 238) ml/h. The respective apparent clearances of R-warfarin were 110 (94 � 126) ml/h, 142 (123 � 161) ml/h and 119 (106 � 131) ml/h. The mean ratio of apparent clearance for S-warfarin was 1.29 (1.16-1.46) and for R-warfarin was 1.23 (1.11-1.37) when St John�s wort was co-administered. The mean ratio of AUC0-168 of INR was 0.79 (0.70 - 0.95) when St John�s wort was co-administered. The urinary excretion ratio of S-7-hydroxywarfarin after administration of warfarin alone was 0.04 (0.03 � 0.06) mg/h and there was no significant difference following treatment with either St John�s wort 0.03 (0.02 � 0.04) mg/h or ginseng 0.03 (0.02 � 0.04) mg/h. The ratio of geometric means for S-7-hydroxywarfarin UER was 0.82 (0.61-1.12) for St John�s wort, and 0.68 (0.50-0.91) for ginseng. St John�s wort and ginseng did not affect the apparent volumes of distribution or protein binding of warfarin enantiomers. In study II, the mean (95% CI) apparent clearance of S-warfarin after warfarin alone, with ginkgo or ginger were 189 (167 � 210) ml/h, 200 (173 � 227) ml/h and 201 (171 � 231) ml/h, respectively. The respective apparent clearances of R-warfarin were 127 (106 � 149) ml/h, 126 (111 � 141) ml/h and 131 (106 � 156) ml/h. The mean ratio of apparent clearance for S-warfarin was 1.05 (0.98 -1.12) and for R-warfarin was 1.00 (0.93 -1.08) when co-administered with ginkgo. The mean ratio of AUC0-168 of INR was 0.93 (0.81 -1.05) when co-administered with ginkgo. The mean ratio of apparent clearance for S-warfarin was 1.05 (0.97 -1.13) and for R-warfarin was 1.02 (0.95 -1.10) when co-administered with ginger. The mean ratio of AUC0-168 of INR was 1.01 (0.93 -1.15) when co-administered with ginger. The urinary excretion ratio (UER) of S-7-hydroxywarfarin after administration of warfarin alone was 0.04 (0.03 � 0.05) mg/h and there was no significant difference following treatment with either ginkgo 0.04 (0.03 � 0.04) mg/h or ginger 0.03 (0.02 � 0.04) mg/h. The ratio of geometric means for S-7-hydroxywarfarin UER was 1.07 (0.69-1.67) for ginkgo, and 1.00 (0.64-1.56) for ginger. Ginkgo and ginger did not affect the apparent volumes of distribution or protein binding of either S-warfarin or R-warfarin. In conclusion, St John�s wort significantly induced the apparent clearance of both S-warfarin and R-warfarin, which in turn resulted in a significant reduction in the pharmacological effect of rac-warfarin. Ginseng, ginkgo and ginger at recommended doses affect neither clotting status, nor the pharmacokinetics or pharmacodynamics of either S-warfarin or R-warfarin in healthy subjects.

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.

Background: Mood and Anxiety disorders have a profound personal and socioeconomic impact. Response and remission rates from orthodox pharmacotherapies currently have moderate efficacy: more options are needed. Herbal and complementary medicines offer promise for the treatment of depression and anxiety, however research in this area is still in its infancy. Aims: To research the current evidence for herbal and complementary medicines in the treatment of mood (specifically unipolar depression) and anxiety disorders. To identify areas of interest where there are gaps in the literature, and to subsequently conduct two clinical trials in these areas. The research design aimed to create a thesis ‘by publication’, detailing 13 publications that pertain to the area of herbal and complementary medicine and mood and anxiety disorders. Process: Initial literature reviews on herbal medicine and psychiatric disorders, nutritional medicine and major depression, and exercise and depression were conducted to develop knowledge in the area and ascertain the gaps in the literature. Results revealed that in respect to nutritional medicines, varying levels of supportive evidence exists for using omega-3, folate, Sadenosyl methionine (SAMe), and L-Tryptophan as monotherapies and with synthetic pharmacotherapies to treat unipolar depression. A review of exercise in the treatment of depression revealed robust evidence for the use of physical activity as a mood elevating intervention. In regards to herbal interventions, Hypericum perforatum (St John’s wort: SJW) and Piper methysticum (Kava) were found to have the most evidence in the herbal treatment of depression and anxiety, respectively. A subsequent literature review was conducted on these herbal medicines. SJW was revealed via review of randomised controlled studies and meta-analyses to be equally effective to antidepressants in treating major depressive disorder. This activity is posited to occur via modulation of neurotransmission and neuroendocrine pathways, including non-selective inhibition of re-uptake of serotonin, dopamine, norepinephrine, decreased degradation of neurochemicals and sensitisation and binding to various neuroreceptors, dopaminergic activity (prefrontal cortex) and cortisol/hypothalmic pituitary adrenal -axis modulation. Kava was also revealed to have meta-analytic evidence in support of anxiolytic activity. This is postulated to occur via GABA membrane modulation, weak GABA binding and blockage of voltage-gated channels, and β-adrenergic downregulation. From this review a deficit in the area of treating comorbid depression and anxiety was identified, and no studies were found using SJW and Kava concomitantly. Due to this, the first study was formulated and conducted, hypothesising that a combination of SJW and Kava may be more effective in reducing participants’ co-occurring depression and anxiety than placebo. First clinical trial: A world-first randomised, placebo-controlled, crossover pilot trial was conducted, involving SJW and Kava in the treatment of major depressive disorder and comorbid anxiety. Twenty eight adults with major depressive disorder and co-occurring anxiety were recruited. After a placebo run-in of two weeks, the trial had a crossover design testing SJW and Kava against placebo over two controlled phases, each of four weeks. The primary analyses used intention-to-treat and completer analyses. On both intention-to-treat (p = 0.047) and completer analyses (p = 0.003), SJW and Kava gave a significantly greater reduction in selfreported depression on the Beck Depression Inventory II over placebo in the first controlled phase. However in the crossover phase, a replication of those effects in the delayed medication group did not occur. Nor were there significant effects on anxiety or quality of life. Possible explanations for the absence of anxiolysis may include a potential interaction with SJW, the presence of depression, or an inadequate dose of Kava. Furthermore, the high dropout significantly reduced the statistical power of the study, precluding firm conclusions. Second clinical trial: The next study sought to determine if the presence of depression affected participants’ anxiolysis from Kava by using a sample of people with chronic anxiety and varying levels of depression. The hypothesis was that higher levels of depression may truncate the anxiolytic effect from Kava. A supplementary aim of the study was to use an aqueous extract of Kava, which in light of hepatotoxic effects from acetone and ethanol based preparations (and incorrect plant parts and cultivars) may be potentially safer. No previous clinical trials had used a traditional aqueous extract. The Kava Anxiety Depression Spectrum Study (KADSS) was a 3-week placebo-controlled, doubleblind, crossover trial in participants with elevated generalised anxiety. Piper methysticum (Kava) has been withdrawn in European, British, and Canadian markets due to concerns over hepatotoxic reactions. The WHO recently recommended research into ‘aqueous’ extracts of Kava, which may be a safer formulation of the herb (as opposed to non-traditional acetone or ethanol extracts). Sixty adult participants currently experiencing one month or more of generalised anxiety were prescribed 5 tablets per day of Kava containing 50mg of kavalactones (250mg/day). Results revealed the pooled effect of Kava vs. placebo across phases was highly significant (p < 0.0001), with a substantial effect size (d = 2.24, ηp2 = .428). Pooled analyses also revealed highly significant relative reductions on the Beck Anxiety Inventory. A previously undiscovered antidepressant effect was revealed with highly significant reductions of depression scores occurring on the Montgomery-Asberg Depression Rating Scale (p = 0.003, d = 0.75 ηp 2 = .223). The aqueous extract was found to be safe, with no serious adverse effects, and no clinical hepatotoxicity. The aqueous Kava extract appears equally effective in cases where anxiety is accompanied by depression. This should encourage further study and consideration of globally reintroducing aqueous rootstock extracts of Kava for the management of anxiety. Conclusions: A review of the literature revealed that in the area of herbal and nutritional treatments of depression and anxiety, strong evidence exists for SJW in the treatment of depression, and for Kava in the treatment of generalised anxiety. Other herbal medicine monotherapies in the treatment of depression or anxiety or other psychiatric disorders currently have insufficient evidence to firmly recommend use. In respect to nutritional interventions, SAMe, L-Tryptophan, omega-3 and folate have limited evidence as monotherapies, while as adjuvants to antidepressants they have evidentiary support. Aside from exercise and relaxation interventions, other complementary medicine interventions currently possess limited evidence in the treatment of mood and anxiety disorders. The conclusions from the first study indicate that use of SJW and Kava concomitantly appears to not be an effective treatment of anxiety with or without co-occurring depression. The second study supports that an aqueous extract of Kava is an effective acute anxiolytic and tentatively demonstrates antidepressant properties. Possible future steps involve further exploration and clinical studies of promising medicinal plants in the treatment of depression or anxiety as monotherapies (or as augmenting agents with pharmacotherapies), while a larger and longer phase III Kava clinical trial is required to confirm the results of KADSS.

Hyperforin is the component of the medicinal herb St. John's Wort (Hypericum perforatum) responsible for its antidepressant activity. It works by blocking the reuptake of a variety of neurotransmitters through a unique mechanism of action and may be a critical lead for the treatment of depression and possibly other human diseases. However, the therapeutic potential of hyperforin is severely handicapped by its poor water solubility, facile oxidative degradation, and potent activation of pregnane X receptor, leading to increased expression of many genes involved in xenobiotic metabolism. Access to a wide variety of hyperforin analogs is critical for mitigating these shortcomings while maintaining therapeutic activity. While limited semisynthetic manipulation of isolated hyperforin is feasible, total synthesis is the only possible means of obtaining diverse hyperforin analogs. / Chemistry and Chemical Biology

Tyrimo tikslas. Sumodeliuoti puskiečius burnos gleivinės preparatus su skystuoju jonažolių ekstraktu ir pagrįsti jų tinkamumą biofarmaciniais tyrimais. Uždaviniai. 1. Parinkti veikliosios medžiagos (jonažolių ištraukų) sudėtį ir įvertinti jų kokybę 2. Parinkti tinkamas pagalbines medžiagas hidrofilinių puskiečių preparatų formulavimui 3. Sumodeliuoti hidrofilinius puskiečius preparatus su skystuoju jonažolių ekstraktu 4. Pagrįsti hidrofilinių puskiečių preparatų su skystuoju jonažolių ekstraktu kokybę, atliekant veikliųjų junginių atpalaidavimo tyrimą in vitro. Metodai. Suminis flavonoidų kiekis (pagal rutiną) nustatytas spektrofotometriniu metodu. pH reikšmė nustatyta potenciometriniu metodu. Atlikta dinaminės klampos matavimo metodas, biofarmacinis veikliųjų junginių atpalaidavimo iš gelių tyrimas in vitro. Veikliosios medžiagos antimikrobinis aktyvumas nustatytas pagal Ph Eur. 01/2002, 2.6.12 metodą. Tyrimo objektas. Hidrofiliniai puskiečiai preparatai su skystuoju jonažolių ekstraktu (1:1). Tyrimo rezultatai. Pagaminti skystieji jonažolių ekstraktai (1:1) tamsiai rudos spalvos, kuriuose nustatytas suminis flavonoidų kiekis 6,03013 – 6,48663 mg/ml. Jonažolių geliai rudos spalvos, kurių klampa ≥ 0,80 Pa•s, pH reikšmė 4,78-6,63, suminis flavonoidų kiekis ≥ 0,08 mg/ml. Veikliųjų junginių atpalaidavimo tyrimas in vitro parodė, kad po 6 val iš jonažolių karbomero ir poloksamero gelių atpalaiduota apie 16 proc. flavonoidų. Išvados. 1. Remiantis nustatytu suminiu flavonoidų... [toliau žr. visą tekstą] / Purpose of work. To make models of the semi liquid mouth products, containing St. John's Wort extract and validate their suitability for biopharmaceutical research. Tasks. 1. Select the active material substance (St. John's Wort extracts) and assess their quality. 2. Select suitable excipients for the formulation of hydrophilic semi-hard products. 3. To make models of hydrophilic group of semi products with St. John's Wort extract. 4. Substantiate the quality of hydrophilic, semi-hard products with St. John's Wort extract, performing release study in vitro of the active compounds. Methods. The total flavinoid content (by routine) was determined by spectrophotometry. The value of pH is set by potentiometric method. Dynamic viscosity measurement and the study in vitro of the biopharmaceutical active compound release from gels were carried out. The antimicrobial activity of the active substance was determined in accordance with Ph. Eur set. 01/2002 2.6.12 method. The object of study. The effect of hydrophilic semi-hard products containing St. John's Wort extracts (1:1). Results. St. John's Wort extracts liquid (1:1) has been produced in dark brown color with a prescribed amount of total flavinoids from 6.03013 to 6.48663 mg/ml. The gels of St. John's Wort are also in brown colour with a viscosity of ≥ 0.80 Pa•s, a pH value of 4.78 to 6.63, total flavinoid content of ≥ 0.03 mg/ml. The active compounds release study in vitro showed that about 16 pct. flavonoids from St. John's... [to full text]

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]

An immediate demand exists for new tuberculosis (TB) antibiotics due to the ever-increasing spread of drug-resistant strains. The drug-development process goes through four phases, the first (Phase 0) of which is to demonstrate and investigate drug effectiveness and toxicity. This research investigated the effectiveness of the Hypericum perforatum herb (commonly St. John's wort (SJW)) in its growth inhibition of mycobacteria and its viability effect on human lung cells. Organic-solvent SJW extracts were effective at inhibiting every nonpathogenic genetically sequenced Mycobacterium isolate currently available (six isolates) in preliminary studies. Quantitative studies of five Mycobacterium isolates showed an order of concentration sensitivity to the SJW methanol (MeOH) extract as (high to low) M. JLS, M. KMS, M. phlei (not sequenced), M. MCS, B. subtilis, M. smegmatis, and E. coli, with minimal bactericidal concentrations (MBCs) ranging from 0.33-2.66 mg extract/ml. The SJW compounds hyperforin (Hfn), hypericin (Hpn), and pseudohypericin (Phn) were quantified using a novel HPLC method that utilized common HPLC equipment. A crude MeOH extract solution of 133 mg extract/ml contained 2.26 mg Hfn/ml, 0.77 mg Hpn/ml, and 2.67 mg Phn/ml. Purified Hfn had a MBC of between 6-13 μg/ml for M. JLS in the absence of Tween 80. Tween 80 repressed Hfn (46 μg/ml) inhibition of M. JLS at ≥ 0.025% (v/v). Purified Hpn and Phn showed no inhibition of M. JLS at all assayed concentrations, which were ≤ 27 μg/ml and ≤ 25 μg/ml, respectively. Inhibitory results from the five quantitatively assayed Mycobacterium samples could be extrapolated to M. tuberculosis, as these isolates have as high as 72% genetic homology to the pathogen. The crude MeOH extract and Hfn were lethal to the human carcinomic alveolar epithelial lung cell line A549 at 1.3 mg extract/ml (crude extract) and ≥ 11 μg/ml (Hfn), with a Hfn LD50 of 3-6 μg/ml (5.6-11.2 μmol/L). Because Hfn is antiproliferative to a list of other carcinomic cell lines in the same concentration range, the A549 cell line may be added to that list. The addition of M. JLS cells (5x106 cells/cm2) to penicillin-streptomycin-containing A549 culture (which killed the bacteria) did not affect A549 viability.