Panax ginseng: a systematic review of adverse effects and drug interactions.

Panax ginseng C. A. Meyer is a perennial herb native to Korea and China and has been used as an herbal remedy in eastern Asia for thousands of years. Modern therapeutic claims refer to vitality, immune function, cancer, cardiovascular diseases, improvement of cognitive and physical performance and sexual function. A recent systematic review of randomised controlled trials found that the efficacy of ginseng root extract could not be established beyond doubt for any of these indications. In order to obtain a balanced assessment of the therapeutic value of P. ginseng it is also necessary to consider the safety profile. In view of the extremely widespread use of P. ginseng it seems important to ask whether this herbal medicine involves health risks for the consumer. This review was conducted as a systematic attempt to document and evaluate all the available safety data on P. ginseng root extracts. Systematic searches were performed in five electronic databases and the reference lists of all papers located were checked for further relevant publications. All articles containing original data on adverse events and drug interactions with P. ginseng were included. Information was also requested from 12 manufacturers of ginseng preparations, the spontaneous reporting schemes of the WHO and national drug safety bodies. No language restrictions were imposed. Data from clinical trials suggest that the incidence of adverse events with ginseng monopreparations is similar to that with placebo. The most commonly experienced adverse events are headache, sleep and gastrointestinal disorders. The possibility of more serious adverse events is indicated in isolated case reports and data from spontaneous reporting schemes; however, causality is often difficult to determine from the evidence provided. Combination products containing ginseng as one of several constituents have been associated with serious adverse events and even fatalities. Interpretation of these cases is difficult as ingredients other than P. ginseng may have caused the problems. Possible drug interactions have been reported between P. ginseng and warfarin, phenelzine and alcohol. Collectively, these data suggest that P. ginseng monopreparations are rarely associated with adverse events or drug interactions. The ones that are documented are usually mild and transient. Combined preparations are more often associated with such events but causal attribution is usually not possible.     

Prenatal developmental toxicity evaluation of Withania somnifera root extract in Wistar rats

Context: Withania somnifera (L) Dunal (Solanaceae) is an important traditional herbal medicine used for thousands of years and is considered as the Indian ginseng. Reports on the effect of Withania somnifera root (WSR) extract on the developing foetus of pregnant rats including mortality, structural abnormalities, changes in growth and effects on dams are not available. Objective: The present study was performed to evaluate the prenatal developmental toxicity potential of WSR extract in rats. Materials and methods: WSR extract was given orally to pregnant rats during the period of major organogenesis and histogenesis (days 5 to 19 of gestation) at the dose levels of 500, 1000 and 2000?mg/kg/day. Clinical observations including mortality, moribundity, behavioural changes, signs of overt toxicity, body weight, gross pathological changes of dams and foetal analyses including external malformations, skeletal and soft tissue malformations were evaluated. Results: No evidence of maternal or foetal toxicity was observed. WSR extract caused no changes (p?Discussion and conclusion: Under the conditions of the study, the no-observed-effect level (NOEL) of WSR extract for maternal and developmental toxicity was concluded to be at least 2000?mg/kg/day.     

Evidence of clinical efficacy of homeopathy

Objective: To establish, using a systematic review and meta-analysis, whether there is any evidence from randomised controlled clinical trials of the efficacy of homeopathic treatment in patients with any disease. Data sources: Published and unpublished reports of controlled clinical trials available up to June 1998, identified by searching bibliographic databases (Medline, Embase, Biosis, PsychInfo, Cinahl, British Library Stock Alert Service, SIGLE, Amed), references lists of selected papers, hand searching homeopathic journals and conference abstracts, and contacting pharmaceutical companies. Trials selection: Trials were selected using an unblinded process by two reviewers. The selection criteria were randomised, controlled trials in which the efficacy of homeopathic treatment was assessed relative to placebo in patients using clinical or surrogate endpoints. Prevention trials or those evaluating only biological effects were excluded. One hundred and eighteen randomised trials were identified and evaluated for inclusion. Sixteen trials, representing 17 comparisons and including a total of 2617 evaluated patients, fulfilled the inclusion criteria. Data extraction: Data were extracted by two reviewers independently, using a summary form. Disagreements were resolved by a third person. Data synthesis: The evidence was synthesised by combining the significance levels (P values) for the primary outcomes from the individual trials. The combined P value for the 17 comparisons was highly significant P=0.000036. However, sensitivity analysis showed that the P value tended towards a non-significant value (P=0.08) as trials were excluded in a stepwise manner based on their level of quality. Conclusions: There is some evidence that homeopathic treatments are more effective than placebo; however, the strength of this evidence is low because of the low methodological quality of the trials. Studies of high methodological quality were more likely to be negative than the lower quality studies. Further high quality studies are needed to confirm these results. Received: 19 August 1999 / Accepted in revised form: 29 December 1999     

Transcatheter arterial chemoembolization combined with or without Chinese herbal therapy for hepatocellular carcinoma: meta-analysis

Objective: Chinese herbal therapy is sometimes used in conjunction with transcatheter arterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC) in Asian countries. This study aims to systemically review the efficacy of Chinese herbal therapy in HCC patients receiving TACE. Methods: Meta-analysis was performed for clinical trials comparing Chinese herbal therapy versus no Chinese herbal therapy given to HCC patients receiving TACE. Publications in 10 electronic databases were extensively searched. Results/conclusion: Chinese herbal therapy was associated with a significant rise in the number of patients with survival > 1-year, 2-year and 3-year, as well as a significant rise in the number of patients who reported complete or partial response and non-deterioration performance status. Chinese herbal therapy also showed significant efficacies in the increase of T cells and natural killer cells, whereas a significant lower blood α-fetoprotein concentration was reported. There were a significant increase in white blood cell count, a significant lower risk in patients with nausea and vomiting, and a significant rise in patients with increased body weight when Chinese herbal therapy was given. The evidence from this review supports the use of Chinese herbal therapy to enhance the efficacy of TACE in HCC patients. However, owing to limited data and heterogeneity of the included studies, further trials are required.     

Botanicals used in complementary and alternative medicine treatment of cancer: clinical science and future perspectives

Background: Botanicals and herbal combinations are among the most common complementary and alternative medicine (CAM) approaches used by cancer patients both for cancer treatment and management of cancer symptoms. Despite their widespread use, however, the safety and efficacy of many botanicals has not been established in controlled clinical trials. Objectives: This article reviews the published evidence for the safety and clinical benefit of botanicals used in the treatment of cancer and cancer symptom management and describes the continuing clinical trials of botanicals with applications in oncology. Methods: Literature searches were conducted in PubMed, EMBASE, Cochrane Clinical Trials databases, Pharmaprojects and CRISP (Computer Retrieval of Information on Scientific Projects) clinical trials databases. Conclusion: A number of botanicals have shown promise for cancer symptom management but need further study. A limited number of multi-agent nutritional supplement approaches are being explored in clinical trials. Botanical immunomodulators and botanical products shown to affect pathways of angiogenesis, apoptosis and cell signaling in vitro have stimulated research interest and may broaden the range of available cancer treatments.     

Botanical medicine and cancer: a review of the safety and efficacy

It is currently estimated that > 50% of all patients diagnosed with cancer explore complementary and alternative medicine – especially herbal medicine. We conducted a comprehensive review to assess the safety and efficacy of herbal medicines commonly used by patients in an attempt to: prevent cancer; treat cancer; and treat adverse effects associated with conventional cancer treatments. Current evidence suggests that Asian ginseng, garlic, green tea, tomatoes and soy intake as part of the diet may be useful in preventing various cancers; additional research is needed in order to determine the efficacy of essiac, evening primrose oil, mistletoe, reishi, shiitake and turmeric as cancer treatments; and ginger may be effective in treating chemotherapy-induced nausea and vomiting.     

Separation and identification of components of the multi-component herbal drug prostanorm

Prostanorm is a multi-component Russian herbal drug comprising a mixture of the extracts of St. John’s wort (Hypericum perforatum L.), goldenrod (Solidago canadensis L.), licorice root (Glycyrrhiza glabra L.), and purple coneflower (Echinacea purpurea L. Moench) rhizomes and roots in equal amounts. An HPLC method for qualitative analysis of the components in the mixed phytopreparation and extracts of all individual raw materials has been developed. The optimum chromatographic conditions for HPLC determination of components of the herbal drug have been determined. Components of the mixed extract are satisfactorily separated and resolved by using an octadecylsilane adsorbent and gradient elution with a mixture of acetonitrile, methanol, phosphate buffer, and dimethylformamide. HPLC analysis was optimized according to chromatographic parameters. The basic biologically active components of the herbal mixture and individual extracts of all herbs were identified. The proposed method ensures determination of the identity of the herbal drug Prostanorm in the form of liquid extract for peroral administration.     

Novel polyacetylene derivatives and their inhibitory activities on acetylcholinesterase obtained from <Emphasis Type="Italic">Panax ginseng</Emphasis> roots

In our research program to identify cholinesterase and β-secretase inhibitors, we investigated Ginseng (root of Panax ginseng), a crude drug described as a multifunctional drug in the ancient Chinese herbal book Shennong Ben Cao Jing. Results from hexane and methanol extracts showed moderate inhibitory activities. This suggests that ginseng roots may be effective for the prevention of and therapy for dementia. We then focused on hexane extracts of raw ginseng root and dried ginseng root since the determination of hexane extract constituents has not been studied extensively. Activity-guided fractionation and purification led to the isolation of 4 polyacetylene compounds; homopanaxynol, homopanaxydol, (9Z)-heptadeca-1, 9-diene-4,6-diyn-3-one, and (8E)-octadeca-1,8-diene-4,6-diyn-3,10-diol. The chemical structures of these compounds, including stereochemistry, were determined. This is the first study to identify the structure of homopanaxynol and homopanaxydol. Moreover, the modes of action of some compounds were characterized as competitive inhibitors. This study showed, for the first time, that polyacetylene compounds possess acetylcholinesterase inhibitory activities.     

欧盟草药临床安全性和有效性评估指导原则介绍

欧盟（European Union,EU）于2016年7月发布了《在欧盟草药专论编写中评估公认的和传统的草药产品临床安全性和有效性的指导原则（第一次修订版）》。其中最值得注意的是,草药产品申请注册时可用文献资料替代试验资料,并且可根据文献资料科学性不同,获准不同的适应证。介绍该指导原则的主要内容,期望对我国的中药和植物药研究及其监管有所帮助。     

Übersetzung: Galegae Herba

Abstract

Context: Tragopogon graminifolius DC. (Compositae) (TG) has been proposed as an efficacious remedy for gastrointestinal ulcers in Iranian traditional medicine.

Objective: The present study evaluates the efficacy of TG on experimental colitis and the responsible mechanisms.

Materials and methods: After induction of IBD by 2,4,6-trinitrobenzenesulfonic acid (TNBS), rats received standardized ethanol extract of TG aerial part at 20, 30, or 50?mg/kg/d orally. After 12?d, the rats were sacrificed and the colon was removed and assessed for macroscopic and microscopic changes. Also, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), total antioxidant capacity, myeloperoxidase (MPO), and lipid peroxidation (LPO) were measured in the colon homogenate.

Result: TG extract significantly reduced macroscopic and microscopic scores of colitis with ED₅₀ values of 23 and 39?mg/kg, respectively. MPO was significantly reduced in all plant extract groups with an ED₅₀ value of 41?mg/kg. The ED₅₀ values of extract for inhibition of TNF-α and LPO were 44 and 93?mg/kg, respectively. IL-1β significantly decreased by 50?mg/kg of TG extract (ED₅₀?=?57?mg/kg). Total antioxidant power markedly increased by 50?mg/kg group (ED₅₀?=?43?mg/kg).

Discussion: TG exhibited efficacy on TNBS-induced colitis via anti-inflammatory, immunomodulatory, antioxidant, and mucosal healing properties.

Conclusion: TG possesses promising healing function on colitis. Clinical trials are warranted to prove its efficacy and tolerability in IBD.     

Traditional chinese medicine in treatment of metabolic syndrome

In management of metabolic syndrome, the traditional Chinese medicine (TCM) is an excellent representative in alternative and complementary medicines with a complete theory system and substantial herb remedies. In this article, basic principle of TCM is introduced and 25 traditional Chinese herbs are reviewed for their potential activities in the treatment of metabolic syndrome. Three herbs, ginseng, rhizoma coptidis (berberine, the major active compound) and bitter melon, were discussed in detail on their therapeutic potentials. Ginseng extracts made from root, rootlet, berry and leaf of Panax quinquefolium (American ginseng) and Panax ginseng (Asian ginseng), are proved for anti-hyperglycemia, insulin sensitization, islet protection, anti-obesity and anti-oxidation in many model systems. Energy expenditure is enhanced by ginseng through thermogenesis. Ginseng-specific saponins (ginsenosides) are considered as the major bioactive compounds for the metabolic activities of ginseng. Berberine from rhizoma coptidis is an oral hypoglycemic agent. It also has anti-obesity and anti-dyslipidemia activities. The action mechanism is related to inhibition of mitochondrial function, stimulation of glycolysis, activation of AMPK pathway, suppression of adipogenesis and induction of low-density lipoprotein (LDL) receptor expression. Bitter melon or bitter gourd (Momordica charantia) is able to reduce blood glucose and lipids in both normal and diabetic animals. It may also protect beta cells, enhance insulin sensitivity and reduce oxidative stress. Although evidence from animals and humans supports the therapeutic activities of ginseng, berberine and bitter melon, multi-center large-scale clinical trials have not been conducted to evaluate the efficacy and safety of these herbal medicines.     

Antitussive and expectorant activities of Potentilla anserina

Context The root of Potentilla anserina L. (Rosaceae) is an herbal medicine that has been used as an antitussive and expectorant drug for thousands of years in Chinese folk medicine.

Objective: This study estimated the antitussive and expectorant effects of P. anserina extract to validate its traditional use.

Materials and methods The antitussive and expectorant activities of the ethanol extract, aqueous extract, and polysaccharides from P. anserina were evaluated using classical animal models.

Results The results showed that in three antitussive tests, the aqueous extract and polysaccharides at high and low doses significantly inhibited the frequency of cough induced by ammonia and sulfur dioxide in mice and by citric acid in guinea pigs, and increased the latent period of cough in guinea pigs. Similarly, the aqueous extract and polysaccharides also showed significant expectorant activity compared with the control in phenol red secretion experiments. Polysaccharides at dose of 600?mg/kg enhanced tracheal phenol red output by 121.1%, the ammonium chloride (positive control) at dose of 1000?mg/kg by 117.4%. However, the ethanol extract at a high dose (600?mg/kg) has antitussive activity only in the sulfur dioxide induced coughing test. Moreover, the polysaccharides at the same dose showed better bioactivity than the aqueous extract in all tests.

Discussion and conclusion The results of the present study provide evidence that P. anserina can be used as an antitussive and expectorant herbal medicine and that polysaccharides may be the main active ingredients of P. anserina responsible for its bioactivities.     

Experimental, extrapolated and truncated areas under the concentration–time curve in bioequivalence trials

Objective: The extrapolated area under the concentration–time curve (AUC_0–∞) for any drug is considered by operating guidelines as the primary parameter related to the extent of absorption in single-dose bioavailability and bioequivalence trials. Not more than 20% should be added to the experimental AUC (AUC_0–t) in the extrapolating procedure. However, in certain specific cases, it is problematic and, in other cases, impossible to respect the above requirement. It was intended to demonstrate that truncated AUC or AUC_0–t would be used in bioequivalence trials when the AUC cannot be extrapolated. Methods: AUC_0–t and truncated AUC were compared at various time intervals with AUC_0–∞ in a series of 19 single-dose bioequivalence trials covering 15 different drugs, each carried out on 12–24 healthy volunteers. Point estimators and 90% confidence intervals in the 0.80–1.25 and 0.70–1.43 ranges were statistically processed using log-transformed parameters. Results: In all the trials considered, overlapping point estimators and 90% confidence intervals were invariably obtained, regardless of the AUC used. Conclusion: The use of AUC_0–t or truncated AUC may be considered an ancillary procedure in bioequivalence trials when AUC cannot be extrapolated. This occurs with most extended-release formulations, endogenous substances, and poorly absorbed drugs. It also occurs in trials with one or more poor metabolisers, with drugs possessing very long elimination half-lives, and with bioassays having problems of sensitivity that preclude sufficiently precise plasma concentration measurement over the required sampling period. Received: 16 June 1999 / Accepted in revised form: 3 August 1999     

Safety implications regarding use of phytomedicines

Objective Since the approach of the general population to phytomedicine is that the therapy therapy is natural and therefore safe, the aim of this study was to investigate the relationship between the use of herbal compounds, alone or in combination with traditional drugs, and the appearance of side-effects among a sample of Italian women. Methods Our research was conducted over a 5–month period in the outpatient ambulatories of an urban university general hospital. The sample population consisted of women who were interviewed about phytotherapy use on the basis of a pre-structured questionnaire. Results Among 1,063 women contacted, 1,044 completed the interview and 491 (47%) reported taking at least one herbal compound in the last year; 272 women (55.4%) consumed only phytomedicines, while 219 (44.6%) also took traditional drugs. Seventy-three different herbal products were used, 32 were consumed in association with traditional drugs. Forty-seven of 491 (9.6%) women reported side-effects, 22 after taking only phytomedicines (8.1%), 25 in combination with traditional drugs (11.4%). The observed adverse manifestations included the following: gastrointestinal after dandelion, propolis or fennel; cardiovascular after liquorice, ginseng, and green tea; dermatological after propolis, thyme, arnica, and passionflower; and neurological after guarana and liquorice. Drugs taken in association and potentially involved in adverse reactions were NSAIDs, antibiotics, benzodiazepines, antihypertensives and oral contraceptives. In some cases (n=5), side-effects were so serious to justify an admission to the hospital. In 29/47 of cases (61.7%), the adverse reaction was not communicated to the doctor. Conclusions Our data confirm that herbal products are largely taken on a self-treatment basis, and users have the convinction that these therapies are natural and therefore safe.     

The treatment of eczema with Chinese herbs: a systematic review of randomized clinical trials

AIMS: Chinese herbal treatments are being promoted as a treatment for eczema. The aim of this study was to systematically review the evidence for or against this notion. METHODS: Extensive literature searches were carried out to identify all randomised clinical trials on the subject. Data were extracted from these in a predefined standardized fashion. RESULTS: Only two randomized clinical trials were located. Both imply that a complex mixture of Chinese herbs is more effective than placebo in treating eczema. Yet several caveats exist, most importantly the lack of independent replication. Adverse effects have also been reported. CONCLUSIONS: At present it is unclear whether Chinese herbal treatments of eczema do more good than harm.     

A systematic review of vinpocetine therapy in acute ischaemic stroke

Objectives: To determine whether vinpocetine decreases short- and long-term case fatality and proportion of dependent survivors if administered within 2 weeks of stroke onset. Methods: All published and unpublished trials were attempted to be identified using the standard search strategy of the Cochrane Collaboration Stroke Review Group, using MEDLINE searches performed with all known manufacturer code names and trade names of vinpocetine and by contacting manufacturers of vinpocetine to give information of all randomised controlled trials on vinpocetine in stroke. Researchers who participated in trials on vinpocetine in Hungary were asked for further information. Only truly randomised, unconfounded clinical trials that compared the effect of vinpocetine to either placebo or another reference treatment for acute stroke where treatment started no later than 14 days after stroke onset were eligible for inclusion. Data synthesis and analysis was performed using the Cochrane Review Manager software (RevMan version 3.0). Results: Among the identified studies on vinpocetine in stroke, only one fulfilled the selection criteria for inclusion in the review. No death occurred in the study groups and no statistically significant difference was found in dependency between the treatment and the placebo groups. No adverse effects were reported. Conclusions: Based on only one small randomised controlled unconfounded study, presently there is not enough evidence to decide whether the administration of vinpocetine does or does not decrease case fatality and dependency in acute stroke. Received: 16 December 1998 / Accepted in revised form: 2 March 1999     

Carotid intima-media thickness as a surrogate marker for cardiovascular disease in intervention studies

ABSTRACT

Background: Cardiovascular trials using clinical endpoints to assess efficacy typically require followup of large numbers of participants for 3–5 years. This disadvantage has encouraged the search for well-validated surrogate markers for cardiovascular disease (CVD). These markers may provide earlier indications of efficacy in trials involving fewer participants. One approach gaining interest in recent years is the measurement of atherosclerotic progression, a major underlying cause of CVD.

Scope: This review article aims to further substantiate the evidence supporting the use of measurement of carotid intima-media thickness (CIMT) as a surrogate marker for atherosclerosis and cardiovascular risk.

Findings: CIMT has consistently been related to future CVD events in population studies. CIMT is significantly related with other markers for CVD risk, such as elevated levels of risk factors and presence of atherosclerosis in the coronary arteries. Furthermore, almost all lipid-lowering trials and a large number of blood pressure lowering trials have consistently shown a reduction in progression of CIMT. In addition, the ultrasound technique for measuring CIMT is safe and highly reproducible.

Conclusion: Thus, CIMT may be used as a surrogate endpoint in clinical trials to enable the benefits of new therapies or regimens to be more rapidly translated into clinical practice.