帕罗西汀联合微生态制剂治疗伴有功能性消化不良症状的焦虑障碍患者疗效

目的 观察帕罗西汀联合微生态制剂对伴有功能性消化不良症状的焦虑障碍患者临床疗效。方法 选取伴有功能性消化不良症状的焦虑障碍患者128例,随机分成两组,每组64例：单用组给予帕罗西汀治疗;联用组除帕罗西汀治疗外,加用微生态制剂（双歧杆菌三联活菌肠溶胶囊）早晚各210 mg（本品为复方制剂,每克含长型双歧杆菌≥1.0×106 CFU、嗜酸乳杆菌≥1.0×106 CFU、粪肠球菌≥1.0×106 CFU),最多早晚各840 mg,共10周。治疗前后应用HAMA量表和水负荷试验进行疗效评定,应用需处理的不良反应症状的量表（ treatment emergent symptoms scale,TESS）进行安全性评定。结果 在10周末,两组患者治疗后HAMA评分均低于治疗前,联用组的显效率高于单用组（P＜0.05）;水负荷试验水负荷量高于治疗前,联用组水负荷量高于单用组。在治疗后第10周末单用组常见胃肠道不良反应有便秘、恶心等,联用组不良反应少,联用组TESS评分显著降低（P＜0.05）。结论 联合微生态制剂对伴有功能性消化不良的焦虑症患者有显著疗效,胃肠道不良反应小。     

Regulative effects of essential oil from Atractylodes lancea on delayed gastric emptying in stress-induced rats

Gastric motor dysfunction induced by psychological stress results in many symptoms of functional dyspepsia (FD). There are a number of herbal medicines that are reported to improve gastrointestinal motor. However, the mechanisms of considerable herbal medicines are not explicit. In the present study, the effects of an essential oil (EO) extracted from Atractylodes lancea on delayed gastric emptying, gastrointestinal hormone and hypothalamic corticotropin-releasing factor (CRF) abnormalities induced by restraint stress in rats were investigated and the mechanism of the EO is also explored.Oral administration of EO for 7 days did not affect normal gastric emptying, but accelerated delayed gastric emptying induced by restraint stress in rats. The EO significantly increased the levels of motilin (MTL) and gastrin (GAS) and decreased the levels of somatostatin (SS) and CRF. The EO did not modify gastric emptying in vagotomized rats that underwent restraint stress, but antagonized delayed gastric emptying induced by intracisternal injection of CRF. These results suggest that the regulative effects of the EO on delayed gastric emptying are preformed mainly via inhibition of the release of central CRF and activation of vagal pathway, which are also involved in the release of gastrointestinal hormones such as MTL, GAS and SS.     

Radical scavenging and anti-inflammatory properties of STW 5 (Iberogast®) and its components

A combination of ethanolic extracts from nine medicinal plants is successfully used in STW 5 (Iberogast^®) for treatment of gastrointestinal disorders. To elucidate possible modes of action, the focus of this study is on antioxidant properties of the phytomedicine STW 5. In fact, functional gastrointestinal diseases, such as non-ulcer dyspepsia (NUD) and irritable bowel syndrome, are often initiated by or correlated to inflammatory processes, where oxidants such as reactive oxygen species (ROS) play a crucial role. Prominent in vivo sources of ROS generation are represented by the enzymes xanthine oxidase (XOD) or myeloperoxidase (MPO). Applying these enzymes in models in vitro, we show that STW 5 and its components possess strong antioxidant activities. Depending on the model investigated, even pro-oxidant activites of single components of STW 5 could be observed. Interestingly, these effects were absent in STW 5, indicating cooperation between the components. Moreover, if one of the component extracts of STW 5 is omitted, the antioxidant activity is reduced. Thus we conclude that all the single extracts combined in STW 5 are of importance for the therapeutic effect, working in concert. The component of STW 5 performing best in vitro differed with the model investigated, respectively, with ROS and ROS generators. In the XOD system, the extracts of lemon balm leaf and peppermint leaf showed the best antioxidant result, whereas concerning MPO driven chlorination reactions, bitter candy tuft extract was the most efficient antioxidant. Best protection against peroxynitrite induced oxidation of methionine like sulfur-compounds exhibited the STW 5 components lemon balm leaf, Matricaria flower and peppermint leaf.     

Balancing the gastrointestinal benefits and risks of nonselective NSAIDs

Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used classes of medications to treat pain and inflammation. However, gastrointestinal complications associated with NSAIDs are prevalent, largely due to the frequent use of these agents. Adverse events associated with NSAIDs include minor side effects, such as dyspepsia, as well as serious complications, such as bleeding and perforation. Although the probability that any given individual user of an NSAID will suffer a serious gastrointestinal complication is fairly low, widespread patient exposure can translate into a major national health burden. The increasing use of aspirin in the prevention of cardiovascular events and the availability of select over-the-counter NSAIDs represent additional challenges to clinicians in their efforts to make the most appropriate therapeutic decisions while minimizing the potential gastrointestinal risks associated with the use of these agents. Side effects such as dyspepsia do not provide adequate warning of gastrointestinal complications, because most complications occur without the presence of antecedent symptoms. Therefore, accurate risk assessment and the management of controllable risk factors are crucial to the safe administration of NSAIDs. This review focuses on the gastrointestinal effects of aspirin, acetaminophen, and other nonselective NSAIDs, and discusses those factors that are associated with increased risk for adverse gastrointestinal events in certain individuals.     

Potential agents for cancer and obesity treatment with herbal medicines from the green garden

Many classes of bioactive drug-like molecules derived from traditional herbal plants are becoming attractive as alternative medicines for the treatment of severe chronic diseases such as cancer and obesity. A set of chemically synthesized drugs that is capable of both inhibiting cancer growth and reducing body weight for treatment of obesity have severe side effects including nausea, vomiting, diarrhea as well as producing increased blood pressure and headache, respectively. For decades, drug candidates from herbal plants have been considered as potential therapeutic agents because they are generally safer, less toxic, and have fewer lethal side effects than chemically synthesized or semi-synthetic drugs. Understanding the key factors affecting pharmacological effects and clinical outcomes has been a critical theme of natural product research. However, standardized sample preparation methods, well-controlled scientific studies, and validation studies are needed before herbal therapeutics can be introduced into the global market. This review will address the current advances in using traditional herbal plants, including the pharmacological effects and the challenges faced during the development of new drugs. The safety issues associated with toxicity and the effectiveness of the herbs in specific diseases such as cancer and obesity are also discussed.     

Extraction methods and chemical standardization of botanicals and herbal preparations

Botanicals and herbal preparations are medicinal preparations, containing a single or two or more medicinal plants. The focus of this review paper is on the analytical methodologies, which included the combination of sample preparation tools and chromatographic techniques for the chemical standardization of marker compounds or active ingredients in botanicals and herbal preparations. The common problems and key challenges in the chemical standardization of botanicals and herbal preparations were discussed. As sample preparation is the most important step in the development of analytical methods for the analysis of constituents present in botanicals and herbal preparations, the strength and weakness of different extraction techniques are discussed. For the analysis of compounds present in the plant extracts, the applications of common chromatographic techniques, such as HPLC, CE, HRGC/MS, HPLC/MS and HPLC/MS/MS are discussed. The strength, weakness and applicability of various separation tools are stated. Procedures for the identification of marker or active compounds in plant extracts, using HPLC/MS, were proposed. Finally, the effects of batch-to-batch variation of the medicinal plants are investigated and discussed.     

A Tranquilizer-Anticholinergic Preparation in Functional Gastrointestinal Disorders: A Double-Blind Evaluation

Chlordiazepoxide plus clidinium bromide (Librax®) was evaluated and compared with a placebo by means of a random sample, double-blind crossover technique in 42 patients presenting ordinary functional gastrointestinal disorders.Results:• 73.9 percent excellent-to-good response to the active drug in patients receiving it before they received the placebo, compared with 44.5 percent in those who did not receive it until after the placebo period.• 58.9 percent excellent-to-good response to the active drug in patients who received it after the placebo period, as compared with 31.8 percent in those receiving the placebo last.• Overall clinical response 67.5 percent excellent-to-good with the active drug as compared with 37.5 percent with the placebo.• Excellent-to-good results in 12 follow-up patients receiving the known active drug.• Statistically significant symptomatic response in four of eight target symptoms.The tranquilizer-anticholinergic preparation used appeared to improve not only patient outlook and attitudes but to effectively relieve both the physiologic and psychic manifestations of common functional gastrointestinal disorders.     

The effects of herbal oxytocics on the isolated "stripped" myometrium model

Decoctions of Agapanthus africanus and Clivia miniata are used as oxytocic agents in South African traditional herbal medicine. Aqueous extracts of A. africanus and C. miniata leaves have been shown to possess similar uterotonic activities in the isolated whole uterus preparation. The uterus however, comprises a myometrial and an endometrial layer and the activity of both oxytocin and the prostaglandins differs in these layers. The aim of this study was to determine the uterotonic activity of the herbal remedies in an endometrium-free preparation (i.e. "stripped" myometrium) and, if active, whether this effect could be related to prostaglandin synthesis or to interaction with specific receptors. The effects of the herbal extracts were tested on the isolated "stripped" rat myometrium preparation. Both herbal extracts caused a direct contractile response by the isolated tissue. Pretreatment of the myometrium with either plant extract augmented the initial response to acetylcholine. Preincubation with atropine inhibited the response to cumulative dosage of Agapanthus extract but had no effect on the response to Clivia. Indomethacin administration did not affect the response of the myometrium to cumulative dosage of acetylcholine, oxytocin or Clivia extract but inhibited the response to Agapanthus extract. These results clearly indicate that the Agapanthus and Clivia herbal extracts exhibited uterotonic activity in this model. The study illustrates that the "stripped" myometrium model has successfully differentiated between the mechanisms of action of two herbal oxytocics compared to the whole uterus preparation where their uterotonic activity was thought to be similar.     

Functional dyspepsia – A multicausal disease and its therapy

Functional dyspepsia is a common chronic disorder with non-specific upper abdominal symptoms which can not be explained by organic or biochemical abnormalities. The dyspeptic symptoms are very compromising and bothersome and result in a substantial reduction of quality of life. The substantial direct and indirect medical and economical costs induce a high socioeconomic interest in the pathogenesis and the treatment options of this disease. Over the past 30 years several theories about the etiology of the symptoms in functional dyspepsia patients have been put forward. These include disorders of gastrointestinal motility, acid secretion, visceral hypersensitivity, adaptation and accommodation, Hp-infection, mucosal inflammation and finally genetic predisposition. There is increasing evidence that functional dyspepsia is a multi-causal disorder, which leads to altered processing of afferent information from the gastrointestinal tract to the CNS. Autonomic hypersensitivity and altered central processing could be a common phenomenon whereas motility changes, inflammation or altered secretion could increase neural afferent inputs. Treatment of this complex disorder could and should involve these different levels of symptom generation. Thus different approaches with anti-secretory, spasmolytic, prokinetic and anti-inflammatory effects and most preferably reduction of visceral hypersensitivity seem logical. This could explain the variety of drugs which show a positive symptomatic response. This could also offer the conclusion, whether a combination of these drugs could be clinically superior which remains to be proven. And this could offer a logical approach for the use of substances with a multi-target action, e.g. STW 5.     

益生菌促进胃肠道健康的机制及应用

人体胃肠道内生活着大量微生物,它们影响着宿主的健康.益生菌是一种活的微生物,对维持肠黏膜屏障功能、调节免疫功能和促进营养物质的代谢吸收等具有重要作用;对肠道菌群紊乱、功能性消化不良、肠胃炎、腹泻、便秘、肠绞痛、肠易激综合征、炎症性肠病以及幽门螺杆菌感染等胃肠道疾病具有良好的应用.本文对益生菌与胃肠道健康的影响作简要概述...     

The active components and the pharmacological multi-target principle of STW 5 (Iberogast®)

The therapeutic equivalence of the multi-herbal drug combination STW 5 (Iberogast ^®) with two synthetic standard drugs can be explained by an additive or overadditive pharmacological synergism. A review of the different chemical constituents contained in this fixed combination of nine herbal drug extracts and their dominant mechanisms of action shows that they correlate very well with the clinically relevant overall pharmacological profile of the multi-herbal drug combination. This comprises modulatory effects on gastro-intestinal motility, anti-inflammatory action, inhibitory effects on gastric acid production and anti-oxidative and radical-inhibiting properties. As a multi-drug preparation with a multitude of therapeutic targets relevant in functional gastrointestinal diseases, its pharmacological profile of action in accordance with the multi-target principle.     

Helicobacter pylori and Non-malignant Diseases

It is well known that Helicobacter pylori infection is associated with many nonmalignant disorders such as gastritis, peptic ulcer, gastroesophageal reflux disease (GERD), gastric polyp, nonsteroidal anti-inflammatory drug (NSAID)/aspirin-induced gastric injury, and functional dyspepsia. In 2008, interesting articles on the association of H. pylori infection with these disorders were presented, some of which intended to reveal the mechanisms of inter-individual differences in response to H. pylori infection, and have demonstrated that genetic differences in host and bacterial factors as well as environmental factors account for these differences. A decline in the occurrence of peptic ulcer related to H. pylori was confirmed. An inverse relationship between H. pylori infection and GERD was also confirmed but the impact of gastric atrophy on the prevention of GERD remained debatable. For NSAID-induced gastric injury, eradication of H. pylori infection has been recommended. During this year, eradication of H. pylori infection was recommended for patients treated with antiplatelet therapy as well as aspirin and NSAID. It was also reported that for patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit.     

Helicobacter pylori and dyspepsia

It is clear that non-ulcer (or functional) dyspepsia is a heterogeneous syndrome that includes a subset of patients with unrecognized gastroesophageal reflux. Patient heterogeneity combined with inadequate study methodology has led to enormous confusion in interpreting the relationship between Helicobacter pylori and non-ulcer dyspepsia. The possibility that H. pylori is associated with gastroesophageal reflux disease may explain, in part, the difficulty in establishing a link between non-ulcer dyspepsia and H. pylori infection. It is unclear whether the prevalence of H. pylori is increased in non-ulcer dyspepsia over and above the background population. H. pylori does not appear to be linked to heartburn or other specific upper gastrointestinal tract symptoms. The results of eradication trials in H. pylori-infected patients with non-ulcer dyspepsia have been equivocal and generally flawed. There is no doubt that H. pylori is not a sufficient cause of non-ulcer dyspepsia, because it is well documented in the literature that dyspepsia can occur in the absence of infection and infection can occur in the absence of symptoms. At this stage, there is insufficient evidence to support the hypothesis that H. pylori is etiologically linked to non-ulcer dyspepsia, but data from well designed large randomized controlled trials of eradication therapy, are awaited with great interest.     

Identification of Traditional Medicinal Plant Extracts with Novel Anti-Influenza Activity

The emergence of drug resistant variants of the influenza virus has led to a need to identify novel and effective antiviral agents. As an alternative to synthetic drugs, the consolidation of empirical knowledge with ethnopharmacological evidence of medicinal plants offers a novel platform for the development of antiviral drugs. The aim of this study was to identify plant extracts with proven activity against the influenza virus. Extracts of fifty medicinal plants, originating from the tropical rainforests of Borneo used as herbal medicines by traditional healers to treat flu-like symptoms, were tested against the H1N1 and H3N1 subtypes of the virus. In the initial phase, in vitro micro-inhibition assays along with cytotoxicity screening were performed on MDCK cells. Most plant extracts were found to be minimally cytotoxic, indicating that the compounds linked to an ethnomedical framework were relatively innocuous, and eleven crude extracts exhibited viral inhibition against both the strains. All extracts inhibited the enzymatic activity of viral neuraminidase and four extracts were also shown to act through the hemagglutination inhibition (HI) pathway. Moreover, the samples that acted through both HI and neuraminidase inhibition (NI) evidenced more than 90% reduction in virus adsorption and penetration, thereby indicating potent action in the early stages of viral replication. Concurrent studies involving Receptor Destroying Enzyme treatments of HI extracts indicated the presence of sialic acid-like component(s) that could be responsible for hemagglutination inhibition. The manifestation of both modes of viral inhibition in a single extract suggests that there may be a synergistic effect implicating more than one active component. Overall, our results provide substantive support for the use of Borneo traditional plants as promising sources of novel anti-influenza drug candidates. Furthermore, the pathways involving inhibition of hemagglutination could be a solution to the global occurrence of viral strains resistant to neuraminidase drugs.     

The microbiome and childhood diseases: Focus on brain‐gut axis

Many childhood diseases such as autism spectrum disorders, allergic disease, and obesity are on the increase. Although environmental factors are thought to play a role in this increase. The mechanisms at play are unclear but increasing evidence points to an interaction with the gastrointestinal microbiota as being potentially important. Recently this community of bacteria and perturbation of its colonization in early life has been linked to a number of diseases. Many factors are capable of influencing this colonization and ultimately leading to an altered gut microbiota which is known to affect key systems within the body. The impact of the microbial composition of our gastrointestinal tract on systems outside the gut is also becoming apparent. Here we highlight the factors that are capable of impacting on microbiota colonization in early‐life and the developing systems that are affected and finally how this may be involved in the manifestation of childhood diseases. Birth Defects Research (Part C) 105:296–313, 2015. © 2015 Wiley Periodicals, Inc.     

Prokinetic effect of a Kampo medicine, Hange-koboku-to (Banxia-houpo-tang), on patients with functional dyspepsia

Limited evidence is available as to whether Kampo medicine modifies gastrointestinal function in humans. We investigated the effect of a Kampo medicine, Hange-koboku-to (Banxia-houpo-tang, HKT), on patients with functional dyspepsia (FD) and on healthy volunteers with regard to gastric motility. The gastric emptying rate (GER) in FD patients was significantly lower than in the healthy subjects. GER in FD patients and in healthy volunteers showed a significant increase after 2 weeks of medication with HKT. Furthermore, gastrointestinal symptoms improved significantly in the FD patients after the administration of HKT. These results suggest that HKT improves delayed gastric emptying and acts as a prokinetic agent.     

黄芪三七复方两种不同制备方法活性组分与功效对比研究

摘要 目的：对比分析黄芪三七复方经本草提取机器快速制备的汤液（HSQ）与传统煎煮汤液（HS）的活性组分、免疫功能及抗氧化活性，探索传统中药复方汤药制备新技术。方法：采用粒度分析仪对黄芪和三七复方本草提取液HSQ和传统汤液HS提取物进行了粒度分析，并用可见分光光度法对其总多糖和总皂苷活性成分的含量进行了分析。腹腔注射抗肿瘤药物阿霉素和灌胃地塞米松分别在NIH小鼠上诱导两种免疫功能紊乱的动物模型。同时，灌胃给予HSQ和HS 连续4周，并通过计算其胸腺和脾脏指数来评估其对免疫功能障碍的调节作用。采用可见光分光光度法测定HSQ和HS与NIH小鼠脑组织匀浆液体外孵育后MDA（丙二醛）含量的变化。结果：与传统汤液HS相比，黄芪三七复方本草提取液HSQ的颗粒平均粒径约为HS的32.7%，尺寸更小、更均一，而且HSQ中总多糖与总皂苷含量显著增加，分别提升27%和50%。在抑制抗肿瘤药物阿霉素引起的小鼠胸腺萎缩，以及激素地塞米松引起的脾脏萎缩等免疫系统紊乱方面也具有更好的活性。另外，黄芪三七复方本草提取液HSQ在体外对MDA生成的抑制率比传统汤液HS高47%，其抗氧化活性更优。结论：相对传统汤液HS，黄芪三七复方本草提取液HSQ拥有更好的微纳形态，具有更高水平的总皂苷与总多糖等活性成分，并且表现出更好的免疫调控与抗氧化活性，该研究对传统汤液制备技术的创新具有较好的示范研究与探索意义。     

Pharmaceutical prerequisites for a multi-target therapy

The quality of a phytomedicine is defined by the quality of the herbal drug, the manufacturing of the drug preparations and the properties of the finished product, taking into account the special requirements of the individual herbal species in accordance with Good Manufacturing Practice (GMP) standards [2003. Medicinal Products for Human and Veterinary Use. Eudralex, vol. 4 (2003/94/EC)]. The quality control of the complete process is based on pharmacognostic methods, characteristic fingerprint chromatograms, defined amounts of marker substances, physicochemical characteristics and microbiological monitoring. For a herbal multi-component preparation used in multi-target therapy, these pharmaceutical prerequisites have to be ensured for all components and for their combination, as is exemplified by Iberogast^® (STW 5) a fixed combination of hydroethanolic extracts of bitter candytuft (Iberis amara), angelica root (Angelicae radix), milk thistle fruit (Silybi mariani fructus), celandine herb (Chelidonii herba), caraway fruit (Carvi fructus), liquorice root (Liquiritiae radix), peppermint herb (Menthae piperitae folium), balm leaf (Melissae folium) and chamomile flower (Matricariae flos) using in the therapy of gastrointestinal compliants (Rösch et al., 2006).The prerequisites for the quality of each of its components according to actual standards are at first the cultivation of the plant material according to the Guidelines for Good Agricultural Practice (GAP) conditions of Medicinal and Aromatic Plants [1998. Z. Arzn. Gew. Pfl. 3, 166–178] to yield a defined raw material of high quality. Characteristic compounds of the extracts had to be identified and different analytical methods such as HPLC, with low coefficients of variation had to be developed to analyze each of the standardized ethanolic extracts and the finished product.At the example of the extract of I. amara these necessary investigations are described. The variability of the plant material in its natural habitats, the identification of characteristic compounds and exemplary chromatograms for fingerprint evaluation and quantification are shown. These data are required for characterization of the profile of the active substances in the finished product.     

Yeast-based screening of natural product extracts results in the identification of prion inhibitors from a marine sponge

ABSTRACT

One of the major medical challenges of the twenty-first century is the treatment of incurable and fatal neurodegenerative disorders caused by misfolded prion proteins. Since the discovery of these diseases a number of studies have been conducted to identify small molecules for their treatment, however to date no curative treatment is available. These studies can be highly expensive and time consuming, but more recent experimental approaches indicate a significant application for yeast prions in these studies. We therefore used yeast prions to optimize previous high-throughput methods for the cheaper, easier and more rapid screening of natural extracts. Through this approach we aimed to identify natural yeast-prion inhibitors that could be useful in the development of novel treatment strategies for neurodegenerative disorders. We screened 500 marine invertebrate extracts from temperate waters in Australia allowing the identification of yeast-prion inhibiting extracts. Through the bioassay-driven chemical investigation of an active Suberites sponge extract, a group of bromotyrosine derivatives were identified as potent yeast-prion inhibitors. This study outlines the importance of natural products and yeast prions as a first-stage screen for the identification of new chemically diverse and bioactive compounds.