中国黑龙江省嘉荫地区乌云组古果实学研究

白垩纪末至第三纪初（K/T界限，距今约65Ma），恐龙大规模灭绝，爬行类的优势地位被哺乳动物所取代;裸子植物和蕨类急剧衰退，被子植物蓬勃发展，并逐渐成为地表植被的主体，研究这一时期的植物群的结构和特征进而揭示植物演化和环境变迁的规律及其相互关系是当今地球科学、生命科学和环境科学的重要研究内容。黑龙江省嘉荫地区的乌云组产有丰富的植物化石，其地质时代虽未定论，但不超出晚白垩世马斯特里赫特期至早第三纪古新世的范围，处于K/T界限，对其植物群的研究意义重大。乌云植物群以往的研究在古果实学研究方面明显不足、在植物群的性质的认识及乌云组时代的确定等方面存在很大争议。本文重点研究了乌云组的果实和种子化石，增添了新的植物类群，丰富了此植物群的研究内容，对乌云组的时代问题的确定提供了新的证据。 本文研究了乌云组的Nordenskioldia borealis（昆兰树科）、Nyssidium jianyinense sp. nov. （连香树科）、Hypericum zhuii sp. nov. （金丝桃科）、Amersinia obtrullate（广义山茱萸科）、Acer wuyunense sp. nov.（槭树科）等5种果实和种子化石。Nordenskioldia borealis的果无柄、为分果、小果瓣环绕中央柱轮状排列。Nyssidium jianyinense的果序为圆锥果序、蓇葖对生、蓇葖腹缝相对、果皮三层。Hypericum zhuii的种子外形呈长椭圆形、端部具乳突、表面网状、种脊明显、种皮两层、外种皮细胞的垂周壁明显加厚。Amersinia obtrullate果序头状、果镘形、3果室。Acer wuyunense果为翅果、小坚果被明显侧翼、翅强烈下延，包围小坚果。经修订和补充，乌云植物群目前共有维管植物48属60种，其中，蕨类植物4属6种、裸子植物7属7种、被子植物37属48种，被子植物占总种数的80%、占总属数的77%，被子植物占绝对优势。当时的群落类型湿生群落和中生群落类型为主，湿生群落主要有：由Sequoia、Metasequoia、Taxodium、Glyptostrobus等组成的针叶林;以Nyssidium、Trochodendroides占优势的阔叶林。 以Metasequoia占优势的针叶林和以Nyssidium、Trochodendroides等占优势的阔叶林。乌云植物群中热带和亚热带成分占种子植物总属数的54%，而温带成分则占36%，亚热带成分占优势，当时的气候-植被类型为亚热带常绿林或常绿夏绿混交林。Nordenskioldia、Nyssidium、Amersinia、Acer化石的地质分布不早于古新世的地层，这—证据不支持乌云组的地质时代划为晚白垩世，而支持划归古新世的观点。

青蒿开花与青蒿素生物合成相关性的研究-金丝桃和百金花二苯甲酮合酶基因的克隆，异源表达及功能分析

第一部分：青蒿开花与青蒿素生物合成相关性的研究 青蒿素是从中药青蒿中分离出的倍半萜内酯化合物，目前是世界上唯一有效的治疗脑型疟疾和抗氯喹恶性疟疾的药物。青蒿植株中青蒿素含量在开花期最高，但是目前尚不清楚开花与青蒿素生物合成的关系。为此，我们用光周期（短日照）诱导青蒿提前开花，不仅同时获得了开花与不开花的青蒿植株，而且还成功地在同一植株上诱导部分分枝开花，另一部分分枝保持营养生长状态。这一实验体系为研究青蒿开花与青蒿素生物合成的相关性奠定了基础。实验结果表明，开花与不开花青蒿植株青蒿素含量有明显差异。开花植株的青蒿素含量在前2周内逐渐提高，第三周（开花期）达到最高，并保持一周左右，在随后的2周内下降。青蒿植株开花后，叶片便开始老化变黄，逐渐死亡。未开花青蒿植株的青蒿素含量动态在前三周内与开花植株类似，但是这种高青蒿素含量状态能保持较长时间，至少在随后的2周内没有下降。未开花植株的叶片依然保持绿色。这一结果表明，开花不是导致青蒿素含量提高的直接原因。 扫描电镜观察结果表明，幼嫩叶片上的毛状腺体( trichrome)结构是完整的，而在老化的叶片上，则观察到了相当比例(40-50%)破损的腺体。这可能是导致青蒿素含量下降的直接原因。 不同生态型青蒿对光周期的反应是不同的。在北京地区，本地青蒿在8月初便开始开花，而来自四川武陵的青蒿则要到9月份才能开花。根据这一特性，采用“南蒿北栽”的方法，能够使青蒿保持较长时间的营养生长状态，延长适于采收的时间。 第二部分：金丝桃和百金花二苯甲酮合酶基因的克隆，异源表达及功能分析 植物次生代谢物山屯酮( Xanthones)仅存在于龙胆科和藤黄科植物中。它们具有抑制单胺氧化酶，细胞毒素及抗肿瘤活性。 含有1 3个碳原子的二苯甲酮是山屯酮生物合成的中间产物，是由二苯甲酮合酶催化合成的，这一反应是山屯酮生物合成的关键步骤。二苯甲酮合酶已经在金丝桃和百金花细胞悬浮培养系统中检测到，并进行了细致的生化水平上的研究。本研究是在上述研究的基础上，进一步克隆该酶的基因，并进行异源表达及功能分析工作，以便更好地了解和调控山屯酮的生物合成。 用PCR和RT-PCR技术，从金丝桃cDNA文库和逆转录产物中分别克隆到一个基因HBPS1和HBPS2，从百金花cDNA文库中克隆到一个基因CBPS1。HBPS1含有1402个碱基，其开放阅读框架编码390个氨基酸，分子量为42.7 kDa，等电点为6.55。HBPS2含有1398个碱基，其开放阅读框架编码395个氨基酸，分子量为42.8 kDa，等电点为5.78。CBPS1含有1383个碱基，其开放阅读框架编码389个氨基酸，分子量为42.7 kDa，等电点为7.88。与GenBank中序列同源性比较结果表明：在氨基酸水平上，HBPS1与茶（Camellia sinensis）查尔酮合酶的同源性高达92%，HBPS2与萝卜（Raphanus sativus）查尔酮合酶的同源性为64%，CBPS1与茶（Camellia sinensis）查尔酮合酶的同源性为71%。HBPS1与HBPS2的同源性仅为62%。 将三个新克隆的基因的ORF整合到载体pGEX-G上的谷胱甘肽还原酶S基因下游，构建成转化质粒，并在大肠杆菌中诱导表达。结果表明，这三个基因的ORF片段均能被表达成约68 kDa的产物，这与期望的结果一致。 活性检测结果表明，HBPS1是查尔酮合成酶，其底物为香豆酰辅酶A和丙二酸单酰辅酶A，对这两种底物的亲和性KM分别为：香豆酰辅酶A 2.8μM，丙二酸单酰辅酶A，11.2μM。最适反应条件是350C，pH7.0，DTT浓度10 μM。 HBPS2是二苯甲酮合酶，其底物是苯甲丙氨酰辅酶A，和丙二酸单酰辅酶A，对这两种底物的亲和性KM分别为：苯甲丙氨酰辅酶A 2.4 μM，丙二酸单酰辅酶A 9.6μM。最适反应条件是350C，pH 6.5，DTT浓度50 μM。而CBPS1则没有检测到任何活性。从同一种植物中同时获得了查尔酮合酶和二苯甲酮合酶，对研究这两种十分相近的酶的差异表达，酶促反应机制等问题将非常有利。

五种毛壳霉属和曲霉属真菌代谢产物及细胞毒活性

毛壳霉属(Chaetomium)和曲霉属(Aspergillus)真菌产生多种具有生物活性的化合物。为系统阐明两属微生物的次生代谢物，对三种毛壳霉、两种曲霉真菌分别进行固态发酵，以色谱和波谱技术研究发酵物中的成分，分离鉴定了51个化合物，其中23个为新化合物，测试了部分化合物对肿瘤细胞的活性。 1、从螺卷毛壳霉（C. cochloides）固态发酵物中分离鉴定了11个化合物，3个新化合物为螺卷毛壳霉素A~C（1~3）。化合物1、3及dethio-tetra (methylthio) chetomin（4）对Bre-04、Lu-04和N-04细胞株生长抑制的GI50值为0.05~7.0 μg/mL。 2、从印度毛壳霉（C. indicum）固态发酵物中鉴定的三个异喹啉生物碱印度毛壳霉素A~C（12~14）代表两类骨架新颖的异喹啉生物碱。 3、从巴西毛壳霉（C. brasiliense）固态发酵物中鉴定了11个化合物，其中Mollicellins I~J（15~16）、2-Hydroxymethyl-6-methylmethyleugenin（19）为新化合物。化合物16和Mollicellin H（18）对Bre-04、Lu-04、N-04细胞株生长抑制的GI50值在2.5~8.6 μg/mL。 4、从土曲霉（A. terreus）固态发酵物中鉴定了18个化合物。5个为新化合物为Terretonin A~D（24~27）和Asterrelenin（28），24~27为二倍半萜化合物，28为吲哚生物碱。 5、从杂色曲霉(A. versicolor）固态发酵物中鉴定了16个化合物。9个新的化合物Brevianamides K~N (40~43)、Averins A~C (44~46)和Glyanphenines A~B (47~48)代表三种类型的生物碱。 6、综述了1997－2007年间新的二倍半萜的研究进展。 The fungi of the genera Chaetomium and Aspergillus produce various secondary metabolites with biological activities. In order to systematically study the secondary metabolites, the solid-state fermented rice culture of three species of Chaetomium and two of Aspergillus were chemically studied. By the means of chromatograhy and spectroscopy, 55 compounds were isolated and identified, among of them 23 were new ones. The biological activities of some compounds were investigated. 1. From the fungus C. cochliodes, three new epipolythiodioxopiperazines, chaetocochins A-C (1-3) were isolated, together with 8 known ones (4-11). Compounds 1, 3 and 4 showed growth inhibitory effects against cancer cell lines Bre-04, Lu-04 and N-04 with GI50 values from 0.05 to 7.0 μg/mL. 2. Three novel isoquinolines Chaetoindicins A-C (12-14) were isolated and identified from the fungus C. indicum. Chaetoindicin A, Chaetoindicins B-C represented two classes of novel carbon skeletons. 3. Three new compounds, Mollicellins I-J (15-16), and 2-hydroxymethyl-6-methylmethyleugenin (19), were isolated from C. brasiliense. Compound 16 and Mollicellin H (18) showed growth inhibitory effects against cancer cell lines Bre-04, Lu-04 and N-04 with GI50 values from 2.5 to 8.6 μg/mL. 4. Eighteen compounds were isolated from the fungus A. terreus. Terretonin A-D（24 - 27）and Asterrelenin（28） are new compounds belonging to sesterterpoids and indole-ralated alkaloid, respectively. 5. From the fungus A. versicolor, sixteen secondary metabolites, including nine new ones, Brevianamides K-N (40-43), Averins A-C (44-46), and Glyanphenines A-B (47-48), were isolated and identified. Brevianamides K-N (40-43), Averins A-C (44-46), and Glyanphenines A-B (47-48) represented three classes of alkaloids. 6. New sesterterpenes and their bioactivities reported from 1997 to 2007 were summarized.

Inibidores de germinacao em frutos e sementes de pequi.

Utilizando frutos de pequi, coletados na regiao de Sete Lagoas-MG, em 1986, foi avaliada a presenca de inibidores de germinacao nas sementes e nas partes do fruto que envolvem (polpa, espinhos e endocarpo). A extracao foi a 5ºC por 24 horas, utilizando dois solventes: agua e metanol a 80%. Para testar a presenca de inibidores, foram utilizadas sementes de alface (Lactuca sativa L.), cultivar repolhuda, com 88,5% de germinacao. Os extratos aquoso e metanolico do endocarpo e dos espinhos e o extrato metanolico da polpa diminuiram, significativamente, tanto a velocidade como a porcentagem de germinacao. O extrato aquoso da polpa não afetou o numero de sementes germinadas, porem diminuiu a velocidade de germinacao. Os extratos aquosos e metanolicos da semente não apresentaram qualquer efeito de inibicao da germinacao.

Antracnose: nova doença do pequizeiro no cerrado.

Acesso em: 17 nov. 2003.

Contributions to the bryological flora of the tropical and subtropical forests from the Argentina (Bryophyta, Musci).

The authors present here a list of 32 mosses belonging to 15 families: Brachytheciaceae, Cryphaeaceae, Entodontaceae, Hedwigiaceae, Hypnaceae, Leptodontaceae, Meteoriaceae, Neckeraceae, Pilotrichaceae, Polytrichaceae, Pterobryaceae, Racopilaceae, Rigodiaceae, Stereophyllaceae, and Trachypodaceae, all collected in the mountainous forests of the Yungas of the NW of the Argentina (Jujuy, Salta, Catamarca and Tucumán provinces), and also in the rainforests from the NE of the country (Misiones province). Eight species: Atrichum polycarpum, Chrysohypnum elegantulum, Pilosium chlorophyllum, Pilotrichella flexilis, Porotrichodendron lindigii, Pseudotrachypus martinicensis, Steerecleus scariosus, and Thamnobryum fasciculatum are new records for the bryologic flora from Argentina. Braunia imberbis and Squamidium brasiliense are two new records for the bryophytic flora of the Catamarca province; Porotrichodendron superbum is new for the Salta province, while Forsstroemia coronata is the first record for the Catamarca and Jujuy provinces. Aerolindigia capillacea, Braunia reflexifolia, Chryso-hypnum diminutivum, Meteorium deppei and Meteoridium remotifolium are five new citations for the Jujuy province, and Schoenobryum concavifolium is new for the bryophytic flora of the Misiones province. Many studied species occur more frequently in the Yungas than in the NE rainforests; others show separated distribution but live in both areas, the Yungas and Paranaense area, and others are more or less restricted to the Paranaense rainforest of the NE of Argentina. The taxonomy of species is updated, and comments are included on bibliographical precedents, ecology and chorology of each taxon.

Reading of audiovisual productions of contemporary art in art education

This article focuses on the reading of audiovisual productions of contemporary art as a creative process, seeking to analyse which effects of meaning the articulations between the visual and sound systems produce, and the meaning that children give to then. It describes a video art, identifying the languages that compose it and the relationships that link them. Such reading exercise had as corpus of analysis the Chair video art, by Masaru Ozaki, and counted with the theoretical and methodological support of the discourse semiotics, especially with studies on assembly procedures that articulate visual and auditory languages. Also, it presents a focal study with the meanings that a group of children gave to the video art. The findings indicate the importance of including the reading of audiovisual productions of contemporary art at school through the problematization of effects of meaning produced by the interrelation between different languages. And they suggest some subsidies that allow teachers from different areas of knowledge to reflect about the visuality in their pedagogical practice; the choice of the audiovisual materials taken to the classroom and other ways of seeing these texts edited.

Herbal medicine: the science of the art

In the last 50 years science has provided new perspectives on the ancient art of herbal medicine. The present article discusses ways in which the evidence base for the professional use of 'Western' herbal medicine, as therapy to treat disease, known as phytotherapy, can be strengthened and developed. The evidence base for phytotherapy is small and lags behind that for the nutritional sciences, mainly because phytochemicals are ingested as complex mixtures that are incompletely characterised and have only relatively recently been subject to scientific scrutiny. While some methodologies developed for the nutritional sciences can inform phytotherapy research, opportunities for observational studies are more limited, although greater use could be made of patient case notes. Randomised clinical trials of single-herb interventions are relatively easy to undertake and increasing numbers of such studies are being published. Indeed, enough data are available on three herbs (ginkgo (Ginkgo biloba), St John's wort (Hypericum perforatum) and saw palmetto (Serenoa repens)) for meta-analyses to have been undertaken. However, phytotherapy is holistic therapy, using lifestyle advice, nutrition and individually-prescribed mixtures of herbs aimed at reinstating homeostasis. While clinical experience shows that this approach is applicable to a wide range of conditions, including chronic disease, evidence of its efficacy is scarce. Strategies for investigating the full holistic approach of phytotherapy and its main elements are discussed and illustrated through the author's studies at the University of Reading.

Relative effect of litter quality, forest type and their interaction on leaf decomposition in south-east Brazilian forests

Decomposition was studied in a reciprocal litter transplant experiment to examine the effects of forest type, litter quality and their interaction on leaf decomposition in four tropical forests in south-east Brazil. Litterbags were used to measure decomposition of leaves of one tree species from each forest type: Calophyllum brasiliense from restinga forest; Guapira opposita from Atlantic forest; Esenbeckia leiocarpa from semi-deciduous forest; and Copaifera langsdorffii from cerradao. Decomposition rates in rain forests (Atlantic and restinga) were twice as fast as those in seasonal forests (semi-deciduous and cerradao), suggesting that intensity and distribution of precipitation are important predictors of decomposition rates at regional scales. Decomposition rates varied by species, in the following order: E. leiocarpa > C. langsdorffii > G. opposita > C. brasiliense. However, there was no correlation between decomposition rates and chemical litter quality parameters: C:N, C:P, lignin concentration and lignin:N. The interaction between forest type and litter quality was positive mainly because C. langsdorffii decomposed faster than expected in its native forest. This is a potential indication of a decomposer`s adaptation to specific substrates in a tropical forest. These findings suggest that besides climate, interactions between decomposers and plants might play an essential role in decomposition processes and it must be better understood.

Effect of antidepressants on melatonin metabolite in depressed patients

Antidepressants increase melatonin levels, but it is still unclear whether this effect is related to the improvement of depressive symptoms or to unrelated pharmacological action of antidepressants. To answer this question, the effect of antidepressants on 6-sulphatoxymelatonin (aMT6s), the main melatonin urinary metabolite, was examined in drug-free depressed patients - most of them antidepressant-naive. aMT6s was evaluated in 34 depressed patients, before and after 8 weeks of placebo (n = 12) or antidepressant (n = 22; fluoxetine, duloxetine or Hypericum perforatum). Both groups showed an improvement of depressive symptoms after treatment compared to baseline (Hamilton Depression scores): 17.0 +/- 1.4 vs. 9.0 +/- 2.8, P = 0.007 for placebo, and 18.6 +/- 1.1 vs. 11.8 +/- 1.6, P < 0.001 for antidepressants). After treatment, aMT6s levels increased after antidepressants (P < 0.01), but not after placebo (P > 0.05). As depressive symptoms improved both in patients taking antidepressant and in those taking placebo, but an effect of antidepressants could only be seen in those taking antidepressants, we suggest that melatonin changes after antidepressants are more likely due to a pharmacological action of these drugs on melatonin secretion.

Biochemical composition of two red seaweed species grown on the Brazilian coast

BACKGROUND: Algae species have been used as an important source of food because they are highly nutritive considering their vitamin, protein, mineral, fiber, essential fatty acid and carbohydrate contents. However, a large number of seaweeds have been poorly studied, especially Brazilian species. Two red macroalgae species from the Brazilian coast (Plocamium brasiliense and Ochtodes secundiramea) were assessed with respect to their total lipid, fatty acid, total nitrogen, protein, amino acid and total carbohydrate contents. RESULTS: The total lipid contents (dry weight) were 36.3 and 35.4 g kg(-1); fatty acid contents were 9.3 and 12.1 g kg(-1); total nitrogen contents were 37.4 and 24.9 g kg(-1); protein contents were 157.2 and 101.0 g kg(-1); amino acid contents were 127.5 and 91.4 g kg(-1); and total carbohydrate contents were 520.3 and 450.7 g kg(-1) for P. brasiliense and O. secundiramea, respectively. CONCLUSION: Considering these compositions, both algae species were determined to have sources of protein, essential amino acids and carbohydrates similar to the edible seaweeds Laminaria japonica and Palmaria palmata. (C) 2011 Society of Chemical Industry

St. Johns wort attenuates irinotecan-induced diarhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis

Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot study in cancer patients found that treatment of SJW alleviated irinotecan-induced diarrhea. In the present study, we investigated whether SJW modulated various pro-inflammatory cytokines including interleukins (IL-1β, IL-2, IL-6), interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) and intestinal epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg for 4 days in combination with oral SJW or SJW-free control vehicle at 400 mg/kg for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines including IL-1β, IL-2, IL-6, IFN-γ and TNF-α and intestinal epithelial apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production of pro-inflammatory cytokines such as IL-1β, IFN-γ and TNF-α was significantly up-regulated in intestine. In the mean time, combined SJW significantly suppressed the intestinal epithelial apoptosis induced by CPT-11 over days 5–11. In particular, combination of SJW significantly inhibited the expression of TNF-α mRNA in the intestine over days 5–11. In conclusion, inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis partly explained the protective effect of SJW against the intestinal toxicities induced by irinotecan. Further studies are warranted to explore the potential for STW as an agent in combination with chemotherapeutic drugs to lower their dose-limiting toxicities.

St Johns wort modulates the toxicities and parmacokinetics of CPT-11 (Irontecan) in rats

CPT-11 is a DNA topoisomerase I inhibitor for the therapy of colorectal cancer, whereas St. Johnrsquos Wort (Hypericum perforatum, SJW) is a widely used herbal anti-depressant. This study aimed to investigate the effects of co-administered SJW on the toxicities and pharmacokinetics of CPT-11 and the underlying mechanisms. The body weight loss, gastrointestinal and hematological toxicities induced by CPT-11, and the pharmacokinetic parameters of CPT-11 were evaluated in rats pretreated with SJW or vehicle. Rats treated with CPT-11 alone experienced rapid decrease in body weight, whereas co-administration of SJW with CPT-11 resulted in lesser body weight loss. The gastrointestinal and hematological toxicities following CPT-11 injection were both alleviated in the presence of SJW. The rat pharmacokinetics of both CPT-11 and its metabolite SN-38 were significantly altered in presence of SJW. In conclusion, co-administered SJW significantly ameliorated the toxicities induced by CPT-11. The protective effect of SJW may be partially due to pharmacokinetic interaction between CPT-11 and SJW.

Herb-drug interactions: a literature review

Herbs are often administered in combination with therapeutic drugs, raising the potential of herb-drug interactions. An extensive review of the literature identified reported herb-drug interactions with clinical significance, many of which are from case reports and limited clinical observations.
Cases have been published reporting enhanced anticoagulation and bleeding when patients on long-term warfarin therapy also took Salvia miltiorrhiza (danshen). Allium sativum (garlic) decreased the area under the plasma concentration-time curve (AUC) and maximum plasma concentration of saquinavir, but not ritonavir and paracetamol (acetaminophen), in volunteers. A. sativum increased the clotting time and international normalised ratio of warfarin and caused hypoglycaemia when taken with chlorpropamide. Ginkgo biloba (ginkgo) caused bleeding when combined with warfarin or aspirin (acetylsalicylic acid), raised blood pressure when combined with a thiazide diuretic and even caused coma when combined with trazodone in patients. Panax ginseng (ginseng) reduced the blood concentrations of alcohol (ethanol) and warfarin, and induced mania when used concomitantly with phenelzine, but ginseng increased the efficacy of influenza vaccination. Scutellaria baicalensis (huangqin) ameliorated irinotecan-induced gastrointestinal toxicity in cancer patients.
Piper methysticum (kava) increased the 'off' periods in patients with parkinsonism taking levodopa and induced a semicomatose state when given concomitantly with alprazolam. Kava enhanced the hypnotic effect of alcohol in mice, but this was not observed in humans. Silybum marianum (milk thistle) decreased the trough concentrations of indinavir in humans. Piperine from black (Piper nigrum Linn) and long (P. longum Linn) peppers increased the AUC of phenytoin, propranolol and theophylline in healthy volunteers and plasma concentrations of rifamipicin (rifampin) in patients with pulmonary tuberculosis. Eleutheroccus senticosus (Siberian ginseng) increased the serum concentration of digoxin, but did not alter the pharmacokinetics of dextromethorphan and alprazolam in humans. Hypericum perforatum (hypericum; St John's wort) decreased the blood concentrations of ciclosporin (cyclosporin), midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline, but did not alter the pharmacokinetics of carbamazepine, pravastatin, mycophenolate mofetil and dextromethorphan. Cases have been reported where decreased ciclosporin concentrations led to organ rejection. Hypericum also caused breakthrough bleeding and unplanned pregnancies when used concomitantly with oral contraceptives. It also caused serotonin syndrome when used in combination with selective serotonin reuptake inhibitors (e.g. sertraline and paroxetine).
In conclusion, interactions between herbal medicines and prescribed drugs can occur and may lead to serious clinical consequences. There are other theoretical interactions indicated by preclinical data. Both pharmacokinetic and/or pharmacodynamic mechanisms have been considered to play a role in these interactions, although the underlying mechanisms for the altered drug effects and/or concentrations by concomitant herbal medicines are yet to be determined. The clinical importance of herb-drug interactions depends on many factors associated with the particular herb, drug and patient. Herbs should be appropriately labeled to alert consumers to potential interactions when concomitantly used with drugs, and to recommend a consultation with their general practitioners and other medical carers.

Herb-drug interactions and mechanistic and clinical considerations

Herbal medicines are often used in combination with conventional drugs, and this may give rise to the potential of harmful herb-drug interactions. This paper updates our knowledge on clinical herb-drug interactions with an emphasis of the mechanistic and clinical consideration. In silico, in vitro, animal and human studies are often used to predict and/or identify drug interactions with herbal remedies. To date, a number of clinically important herb-drug interactions have been reported, but many of them are from case reports and limited clinical observations. Common herbal medicines that interact with drugs include St John's wort (Hypericum perforatum), ginkgo (Ginkgo biloba), ginger (Zingiber officinale), ginseng (Panax ginseng), and garlic (Allium sativum). For example, St John's wort significantly reduced the area under the plasma concentration-time curve (AUC) and blood concentrations of cyclosporine, midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline. The common drugs that interact with herbal medicines include warfarin, midazolam, digoxin, amitriptyline, indinavir, cyclosporine, tacrolimus and irinotecan. Herbal medicines may interact with drugs at the intestine, liver, kidneys, and targets of action. Importantly, many of these drugs have very narrow therapeutic indices. Most of them are substrates for cytochrome P450s (CYPs) and/or P-glycoprotein (P-gp). The underlying mechanisms for most reported herb-drug interactions are not fully understood, and pharmacokinetic and/or pharmacodynamic mechanisms are implicated in many of these interactions. In particular, enzyme induction and inhibition may play an important role in the occurrence of some herbdrug interactions. Because herb-drug interactions can significantly affect circulating levels of drug and, hence, alter the clinical outcome, the identification of herb-drug interactions has important implications.