Simultaneous Analysis for Quality Control of Traditional Herbal Medicine, Gungha-Tang, Using Liquid Chromatography-Tandem Mass Spectrometry.

Gungha-tang (GHT), a traditional herbal medicine, consists of nine medicinal herbs (Cnidii Rhizoma, Pinelliae Tuber, Poria Sclerotium, Citri Unshius Pericarpium, Citri Unshius Pericarpium Immaturus, Aurantii Fructus Immaturus, Atracylodis Rhizoma Alba, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens). It has been used for various diseases caused by phlegm. This study aimed to develop and verify the simultaneous liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis method, using nine marker components (liquiritin apioside, neoeriocitrin, narirutin, naringin, hesperidin, neohesperidin, liquiritigenin, glycyrrhizin, and 6-shogaol) for quality control of GHT. LC-MS/MS analysis was conducted using a Waters TQ-XS system. All marker analytes were separated on a Waters Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 µm) using gradient elution with a distilled water solution (containing 5 mM ammonium formate and 0.1% [v/v] formic acid)-acetonitrile mobile phase. LC-MS/MS multiple reaction monitoring (MRM) analysis was carried out in negative and positive ion modes of an electrospray ionization source. The developed LC-MS/MS MRM method was validated by examining the linearity, limits of detection and quantification, recovery, and precision. LOD and LOQ values of nine markers were calculated as 0.02-8.33 ng/mL and 0.05-25.00 ng/mL. The recovery was determined to be 89.00-118.08% and precision was assessed with a coefficient of variation value of 1.74-8.64%. In the established LC-MS/MS MRM method, all markers in GHT samples were detected at 0.003-16.157 mg/g. Information gathered during the development and verification of the LC-MS/MS method will be useful for the quality assessment of GHT and other herbal medicines.

Effect of Crocus sativus (Saffron) Intake on Top of Standard Treatment, on Disease Outcomes and Comorbidities in Patients with Rheumatic Diseases: Synthesis without Meta-Analysis (SWiM) and Level of Adherence to the CONSORT Statement for Randomized Controlled Trials Delivering Herbal Medicine Interventions.

Rheumatic diseases (RDs) are often complicated by chronic symptoms and frequent side-effects associated with their treatment. Saffron, a spice derived from the Crocus sativus L. flower, is a popular complementary and alternative medicine among patients with RDs. The present systematic review aimed to summarize the available evidence regarding the efficacy of supplementation with saffron on disease outcomes and comorbidities in patients with RD diagnoses. PubMed, CENTRAL, clinicaltrials.gov and the grey literature were searched until October 2021, and relevant randomized controlled trials (RCTs) were screened for eligibility using Rayyan. Risk of bias was assessed using the Cochrane's Risk of Bias-2.0 (RoB) tool. A synthesis without meta-analysis (SWiM) was performed by vote counting and an effect direction plot was created. Out of 125 reports, seven fulfilled the eligibility criteria belonging to five RCTs and were included in the SWiM. The RCTs involved patients with rheumatoid arthritis, osteoarthritis and fibromyalgia, and evaluated outcomes related to pain, disease activity, depression, immune response, inflammation, oxidative stress, health, fatigue and functional ability. The majority of trials demonstrated some concerns regarding overall bias. Moreover, the majority of trialists failed to adhere to the formula elaborations suggested by the CONSORT statement for RCTs incorporating herbal medicine interventions. Standardization of herbal medicine confirms its identity, purity and quality; however, the majority of trials failed to adhere to these guidelines. Due to the great heterogeneity and the lack of important information regarding the standardization and content of herbal interventions, it appears that the evidence is not enough to secure a direction of effect for any of the examined outcomes.

Herbal medicine for cervicogenic dizziness: A protocol for a systematic review and meta-analysis.

BACKGROUND: Herbal medicines are empirically used to treat cervicogenic dizziness. However, till date there have been no systematic review to evaluate the efficacy and safety of these medicines. Therefore, this study protocol describes the methods for evaluating the efficacy and safety of herbal medicine for cervicogenic dizziness. METHODS AND ANALYSIS: The following electronic academic databases will be searched up to December 2019 without language or publication status restrictions: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL), together with Korean, Chinese, and Japanese databases. Any randomized controlled trials related to herbal medicine for cervicogenic dizziness will be included. The functional outcomes and the vertebrobasilar artery hemodynamic states will be evaluated as primary outcomes. The total effective rate, hematological conditions, and adverse events will be assessed as secondary outcomes. Study selection, data extraction, quality assessment of studies, and qualitative evaluation of clinical evidence will be performed by 2 independent reviewers. The methodological quality of the included studies will be evaluated using a revised Cochrane risk-of-bias tool for randomized trials. The strength of evidence from the included data will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Data synthesis will be performed as either a fixed-effects or a random-effects model using Review Manager software version 5.3. The results will be reported as a risk ratio for dichotomous outcomes and as a mean difference or standardized mean difference for continuous outcomes. ETHICS AND DISSEMINATION: No ethical approval is required since the individual clinical information of the patient is not used. The findings of this systematic review will be disseminated through the peer-reviewed publications or conference presentations. REVIEW REGISTRY UNIQUE IDENTIFYING NUMBER: reviewregistry1036.

DNA metabarcoding to unravel plant species composition in selected herbal medicines on the National List of Essential Medicines (NLEM) of Thailand.

Traditional medicines are widely traded across the globe and have received considerable attention in the recent past, with expectations of heightened demand in the future. However, there are increasing global concerns over admixture, which can affect the quality, safety, and efficacy of herbal medicinal products. In this study, we aimed to use DNA metabarcoding to identify 39 Thai herbal products on the Thai National List of Essential Medicines (NLEM) and assess species composition and admixture. Among the products, 24 samples were in-house-prepared formulations, and 15 samples were registered formulations. In our study, DNA metabarcoding analysis using ITS2 and rbcL barcode regions were employed to identify herbal ingredients mentioned in the products. The nuclear region, ITS2, was able to identify herbal ingredients in the products at the genus- and family-levels in 55% and 63% of cases, respectively. The chloroplast gene, rbcL, enabled genus- and family-level identifications in 58% and 73% of cases, respectively. In addition, plant species were detected in larger numbers (Family identified, absolute %) in registered herbal products than in in-house-prepared formulations. The level of fidelity increases concerns about the reliability of the products. This study highlights that DNA metabarcoding is a useful analytical tool when combined with advanced chemical techniques for the identification of plant species in highly processed, multi-ingredient herbal products.

Traditional Chinese herbal bath therapy for insomnia: A protocol for systematic review.

INTRODUCTION: Insomnia is a major public health problem. Due to the side effects of pharmacological therapy, people are seeking to choose complementary and alternative therapies for insomnia disorder. Traditional Chinese herbal bath therapy is an important complementary therapy which combines advantages of Chinese herbs and bathing therapy. This protocol describes the methodology of a systematic review assessing the effectiveness and safety of traditional Chinese herbal bath therapy for insomnia. METHODS AND ANALYSIS: Reporting of this review will be adherent to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We will electronically search the following seven databases from inception to January 23, 2020: PubMed, Cochrane database (CENTRAL), EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Database, and Wanfang Database. Parallel randomized controlled trials evaluating the effectiveness and safety of traditional Chinese herbal bath therapy for insomnia will be included. Study selection, data extraction and assessment of risk of bias will be performed independently by two researchers. The sleep quality will be assessed as the primary outcome. Global symptom improvement, anxiety and depression, and adverse events will be evaluated as secondary outcomes. The Cochrane's risk of bias tool will be utilized for assessing the methodological quality of included studies. Revman software (v.5.3) will be used for data synthesis and statistical analysis. Data will be synthesized by either fixed-effects or random-effects model according to a heterogeneity test. If it is not appropriate for a meta-analysis, a descriptive analysis will be conducted. GRADE system will be used to assess the quality of evidence. PROSPERO REGISTRATION NUMBER: CRD42020168507.

Exploring the efficacy and safety of herbal medicine on Korean obese women with or without metabolic syndrome risk factors: A study protocol for a double-blind, randomized, multi-center, placebo-controlled clinical trial.

BACKGROUND: The prevalence of obesity among women is increasing. Obesity is associated with various metabolic syndromes; conventional treatments are limited and may induce serious adverse events due to polytherapy regimens. Currently, demands for complementary and alternative medicine that has a proven safety profile for the treatment of obesity with or without metabolic risk factors are increasing.Our team of preclinical experts reported a significant anti-obesity effect of the Korean herbal medicine, Galgeun-tang (GGT). Thus, we designed this trial to explore the effects of GGT among obese women to accumulate optimal clinical evidence.Obesity is not only a component of metabolic syndrome and a factor associated with an increased risk of cardiovascular disease but is also related to insulin resistance. Previous research has confirmed that an increasing body mass index is highly related with increased risk of metabolic syndrome among overweight and obese individuals. The effectiveness of the Korean medicine herbal formula, GGT on obesity has been previously reported. The objective of this study is to assess the efficacy and safety of GGT for weight loss among obese Korean women with or without high risk for metabolic syndrome. METHODS/DESIGN: This study is a randomized, double-blinded, placebo-controlled, multi-center clinical trial. A total of 160 participants will be randomly distributed in 2 groups, the GGT group or the placebo group in a 1:1 ratio using a web-based randomization system. Each group will be administered GGT or placebo 3 times a day for 12 weeks. The primary endpoint is to assess the change in weight from baseline. The secondary endpoints are the following: the changes in body composition measurements, anthropomorphic measurements, obesity screening Laboratory tests, patient self-reported questionnaires, and economic evaluation outcomes. Adverse events will also be reported. DISCUSSION: The findings of this study will confirm methodologies regarding the efficacy and safety of GGT for weight loss among obese Korean women with or without metabolic risk factors.

Safety and efficacy of Chinese herbal bath for psoriasis vulgaris: A protocol for systematic review and meta-analysis.

BACKGROUND: Psoriasis is a common, chronic, and recurrent skin inflammatory disease, with psoriasis vulgaris considered as the most prevalent type of psoriasis. Chinese herbal bath, a type of traditional Chinese medicine, is an external therapy widely used to treat psoriasis vulgaris in China, and it has achieved satisfactory clinical effects. However, there are few studies evaluating the safety and efficacy of Chinese herbal bath compared with other external therapies administered under similar conditions. The purpose of this study is to comprehensively evaluate the clinical safety and efficacy of Chinese herbal bath in the treatment of psoriasis vulgaris through a systematic evaluation of the literature, so as to provide a reference basis for future clinical applications. METHODS: PubMed, Embase, CENTRAL, the Web of Science, the China Biology Medicine Database (CBM), the China National Knowledge Database (CNKI), the Wan Fang Database, and the Chong Qing VIP Database will be searched to collect randomized controlled trials of Chinese herbal bath used to treat psoriasis vulgaris. The search time limits will be from the establishment of the database to December 2019. Two researchers will independently screen the studies, extract data, and evaluate the risk of bias of the studies. Meta-analysis will be carried out with the RevMan5.3 software. The mean difference will be used as the effect index for the measurement data, and the odds ratio will be used as the effect index for the enumeration data. The 95% confidence interval will be provided for each effect. Heterogeneity among the results of each study will be evaluated by the Chi-square test. RESULTS: This study will comprehensively evaluate the clinical safety and efficacy of Chinese herbal bath in the treatment of psoriasis vulgaris, so as to provide a reference basis for future clinical applications. CONCLUSION: This study will provide a theoretical basis for the standardized administration of Chinese herbal bath. OSF REGISTRATION NUMBER:: doi: 10.17605/OSF.IO/4HRPJ.

Novel application of neural network modelling for multicomponent herbal medicine optimization.

The conventional method for effective or toxic chemical substance identification of multicomponent herbal medicine is based on single component separation, which is time-consuming, labor intensive, inefficient, and neglects the interaction and integrity among the components; therefore, it is necessary to find an alternative routine to evaluate the components more efficiently and scientifically. In this study, sodium aescinate injection (SAI), obtained from different manufacturers and prepared as "components knockout" samples, was chosen as the case study. The chemical fingerprints of SAI were obtained by high-performance liquid chromatography to provide the chemical information. The effectiveness and irritation of each sample were evaluated using anti-inflammatory and irritation tests, and then "Gray correlation" analysis (GCA) was applied to rank the effectiveness and irritability of each component to provide a preliminary judgment for product optimization. The prediction model of the proportions of the expected components was constructed using the artificial neural network. The results of the GCA showed that the irritation sorting of each SAI component was in the order of B > A > G > J > I > H > D > F > E > C and the effectiveness sorting of SAI components was in the order of D > C > B > A > F > E > H > I > G > J; the predictive proportion of SAI was optimized by the BP neural network as A: B: C: D: E: F = 0.7526: 0.5005: 5.4565: 1.4149: 0.8113: 1.0642. This study provided a scientific, accurate, reliable, and efficient approach for the proportion optimization of multicomponent drugs, which has a good prospect of popularization and application in product upgrading and development of herbal medicine.

High-Throughput Immunological Analysis of Dictamni Cortex: Implication in the Quality Control of Herbal Medicine.

Quality inconsistency of herbal medicine is an obstacle that limits the extensive use and study of traditional Chinese medicine. Differences in environmental conditions and processing methods of herbal medicine often result in varying clinical outcomes in patients. Standard chemical markers used for the quality control (QC) of herbal medicine are usually the most abundant and characteristic components, which may not be therapeutically relevant or cannot comprehensively reflect the biological quality of the herbs. In view of this, a novel QC method for better assessment of herbal medicine has been developed via bioactivities analysis. Immunological activities of Dictamni Cortex, a typical herbal medicine for the treatment of various inflammatory diseases, from different geographical locations in China, were evaluated. Upon in vitro treatment of their water and ethanol extracts, distinct patterns of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-6, IL-12p70, IL-1ß, and chemokine CXCL8 were released from the lipopolysaccharides- and/or phytohaemagglutinin-stimulated human peripheral blood mononuclear cells (PBMC). Thus, in addition to the commonly used morphological, chemical, or DNA markers, the novel high-throughput profiling of inflammatory cytokines and chemokines of PBMC upon treatment with herbal extracts could be an important reference to help for the quality control of herbal medicine in the future.

Review: Quality of herbal medicinal products: State of the art of purity assessment.

BACKGROUND: The European Pharmacopoeia as well as further legal provisions contain rules for the assessment of potential residues and contaminants in herbal substances and preparations used for the production of herbal medicinal products, e.g. for the assessment of pesticide residues, heavy metals and other elemental impurities, mycotoxins and microorganisms. As a potential contamination caused by weeds, the occurrence of pyrrolizidine alkaloids is being discussed for several years which lead to measures of health authorities limiting the PA content in herbal medicinal products and to measures of industry consisting of reducing the probability of PA occurrence in medicinal plants and the respective products. CONCLUSION: In this context and with regard to all kinds of potential residues or contaminants, collection and evaluation of data from daily analytical practice of manufacturers and suppliers is useful for the assessment of the situation and the definition of testing strategies.

Improving rating scales: Applying Rasch analysis to student pharmacists' attitudes towards herbal medications.

BACKGROUND: This study analyzed the psychometric properties of a cross-sectional survey of student pharmacists' attitudes regarding herbal medications using a polytomous Rasch model. Seven items assessed students' attitudes towards herbal medications using a 6-point agreement scale (0 to 5). Student responses were reviewed to identify outliers and aberrant response patterns, assess scale fit, and perform item analysis. Scale performance was assessed to determine if response categories were independent and equally represented. Items were reviewed for model fit and construct validity with significant item gaps identified using a z-test. IMPACT: A total of 324 students completed the survey. The initial 6-point scale was analyzed. Student responses with outfit mean-square (MNSQ) values >5 were removed, yet the scale did not have appropriate functionality. The categories were merged to form a 4-point scale with no improvement. Therefore, two different 3-point scale options were analyzed: response categories of 0, 1 to 3, and 4 to 5; and response categories of 0, 1 to 4, and 5. With ten students removed, both 3-point scales met the requirements for functionality and all items exhibited good fit with MNSQ values between 0.6 and 1.4, person-separation value of 1.29, and person-reliability value of 0.62. RECOMMENDATIONS: Both 3-point scales met the requirements for Rasch analysis. The most optimal scale was the 0, 1 to 4, and 5 option. DISCUSSION: This study provides findings from the survey validity assessment alongside the survey results, which is useful for readers to have confidence in the quality of the study findings.

A multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of Huangqi Guizhi Wuwutang granule in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by swelling, pain, and synovial damage. Effective methods lack in the treatment of RA. A traditional prescription in use for thousands of years in China, Huangqi Guizhi Wuwutang granule (HGWG) is still chosen to relieve pain and prevent joint malformation in RA patients. However, no evidence-based medical research has been organized to assess the effectiveness and safety of HGWG for RA. METHODS/DESIGN: We will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial to determine whether HGWG can relieve pain and protect joints. We will randomly divide 120 patients with active RA into 2 groups, treated for 12 weeks. Main measurement is the rate of ACR50 score (American College of Rheumatology) from the baseline to 12 weeks. Secondary measurements include rate of ACR20/70, change of Disease Activity Score (DAS) 28, Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient Assessment of Arthritis Pain, Patient Global Assessment of Arthritis, and AIS score. The time points are set as baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, and 48 weeks. In addition, the rate of ACR50 from the baseline to 2 weeks, 4 weeks, 8 weeks, 24 weeks, and 48 weeks' follow-up are also the secondary outcome measures. DISCUSSION: The findings of this research will elucidate the efficacy and safety of HGWG and provide an alternative treatment for RA. In addition, our data will benefit the clinical decision-making on active RA and possibly be incorporated into future guidelines. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03593837.

A Review of Regulations Applied to Spices, Herbs, and Flavorings-What Has Changed?

A review of the world-wide regulations pertaining to spices, extracts, and flavorings. The areas covered include (1) guidance documents from trade organizations as well as international and regional regulatory bodies, (2) decontamination of spices and herbs, (3) extraction solvents used to make spice and herb oleoresins, and (4) general flavoring regulations. Specific links and references to guidance documents and regulations have been provided where they have been published on government, organization, and trade association websites.

Microscopic investigations and pharmacognostic techniques used for the standardization of herbal drug Nigella sativa L.

A comprehensive account on standardization of herbal drug Nigella sativa L. (Tukhm-e-Kalonji) by using microscopic as well as pharmacognostic parameters. In the field of herbal medicines, the main issues are quality, purity, and effectiveness, as in many cases herbal drugs are knowingly or unknowingly substituted or adulterated with similar species or varieties. In herbal market the seeds of N. sativa are commonly adultered with seeds of Allium cepa L. intentionally or accidentally due to their similar morphology. In the present study, the microscopic characterization of herbal drug was done by morphological, palynological, and anatomical features. A great diversity was found in anatomical features of two species, as irregular epidermal cells, actinocytic stomata, and nonglandular trichomes were found in N. sativa while in A. cepa epidermal cells were rectangular in shape, stomata type was paracytic, and trichomes were absent. Pharmacognostic characterization was made by fluorescence analysis and physiochemical parameters. Physicochemical parameters like moisture content, total ash, acid insoluble ash, water soluble ash, and water insoluble ash were also evaluated. The above parameters, being reported to the first time for the studied plant species, and are significant towards establishing the microscopic and pharmacognostic standards for future identification and authentication of genuine herbal drug. RESEARCH HIGHLIGHTS: Microscopic Investigations for the standardization of herbal drug Nigella sativa L. (Tukhm-e-Kalonji). Pharmacognostic techniques are potentially significant for the standardization of herbal drug Nigella sativa in comparison with its adulterant. Useful for preparation of standards for herbal pharmacopeia.

Authentication of the Herbal Medicine Angelicae Dahuricae Radix Using an ITS Sequence-Based Multiplex SCAR Assay.

The accurate identification of plant species is of great concern for the quality control of herbal medicines. The Korean Pharmacopoeia and the Pharmacopoeia of the People's Republic of China define Angelicae Dahuricae Radix (Baek-Ji in Korean and Bai-zhi in Chinese) as the dried roots of Angelica dahurica or A. dahurica var. formosana belonging to the family Apiaceae. Discrimination among Angelica species on the basis of morphological characteristics is difficult due to their extremely polymorphic traits and controversial taxonomic history. Furthermore, dried roots processed for medicinal applications are indistinguishable using conventional methods. DNA barcoding is a useful and reliable method for the identification of species. In this study, we sequenced the internal transcribed spacer (ITS) region of nuclear ribosomal RNA genes in A. dahurica, A. dahurica var. formosana, and the related species A. anomala and A. japonica. Using these sequences, we designed species-specific primers, and developed and optimized a multiplex sequence-characterized amplified region (SCAR) assay that can simply and rapidly identify respective species, and verify the contamination of adulterant depending on the polymerase chain reaction (PCR) amplification without sequencing analysis in a single PCR reaction. This assay successfully identified commercial samples of Angelicae Dahuricae Radix collected from Korean and Chinese herbal markets, and distinguished them from adulterants. This multiplex SCAR assay shows a great potential in reducing the time and cost involved in the identification of genuine Angelicae Dahuricae Radix and adulterant contamination.

The potential of three different PCR-related approaches for the authentication of mixtures of herbal substances and finished herbal medicinal products.

BACKGROUND: Herbal substances and preparations thereof play an important role in healthcare systems worldwide. Due to the variety of these products regarding origin, composition and processing procedures, appropriate methodologies for quality assessment need to be considered. A majority of herbal substances is administered as multicomponent mixtures, especially in the field of Traditional Chinese Medicine and ayurvedic medicine, but also in finished medicinal products. Quality assessment of complex mixtures of herbal substances with conventional methods is challenging. Thus, emphasis of the present work was directed on the development of complementary methods to elucidate the composition of mixtures of herbal substances and finished herbal medicinal products. HYPOTHESIS/PURPOSE: An indispensable prerequisite for the safe and effective use of herbal medicines is the unequivocal authentication of the medicinal plants used therein. In this context, we investigated the potential of three different PCR-related methods in the characterization and authentication of herbal substances. METHODS: A multiplex PCR assay and a quantitative PCR (qPCR) assay were established to analyze defined mixtures of the herbal substances Quercus cortex, Juglandis folium, Aristolochiae herba, Matricariae flos and Salviae miltiorrhizae radix et rhizoma and a finished herbal medicinal product. Furthermore, a standard cloning approach using universal primers targeting the ITS region was established in order to allow the investigation of herbal mixtures with unknown content. RESULTS: The cloning approach had some limitations regarding the detection/recovery of the components in defined mixtures of herbal substances, but the complementary use of two sets of universal primer pairs increased the detection of components out of the mixture. While the multiplex PCR did not retrace all components in the defined mixtures of herbal substances, the established qPCR resulted in simultaneous and specific detection of the five target sequences in all defined mixtures. CONCLUSION: These data indicate that for authentication purposes, complementary PCR-related methods are highly recommendable for the analysis of herbal mixtures in parallel.

Quality transitivity and traceability system of herbal medicine products based on quality markers.

BACKGROUND: Due to a variety of factors to affect the herb quality, the existing quality management model is unable to evaluate the process control. The development of the concept of "quality marker" (Q-marker) lays basis for establishing an independent process quality control system for herbal products. HYPOTHESIS/PURPOSE: To ensure the highest degree of safety, effectiveness and quality process control of herbal products, it is aimed to establish a quality transitivity and traceability system of quality and process control from raw materials to finished herbal products. STUDY DESIGN: Based on the key issues and challenges of quality assessment, the current status of quality and process controls from raw materials to herbal medicinal products listed in Pharmacopoeia were analyzed and the research models including discovery and identification of Q-markers, analysis and quality management of risk evaluation were designed. METHODS: Authors introduced a few new technologies and methodologies, such as DNA barcoding, chromatographic technologies, fingerprint analysis, chemical markers, bio-responses, risk management and solution for quality process control. RESULTS: The quality and process control models for herbal medicinal products were proposed and the transitivity and traceability system from raw materials to the finished products was constructed to improve the herbal quality from the entire supply and production chain. CONCLUSION: The transitivity and traceability system has been established based on quality markers, especially on how to control the production process under Good Engineering Practices, as well as to implement the risk management for quality and process control in herbal medicine production.

Getting More Than You Paid For: Unauthorized "Natural" Substances in Herbal Food Supplements on EU Market.

As the population in the industrialized world develops preference for what is perceived as a natural and holistic way of disease treatment, the popularity and the number of food supplements on the market, including herbal ones, is experiencing an unprecedented rise. However, unlike herbal medicinal products, intended for treating or preventing disease, current legislation classifies food supplements as products intended for achieving nutritional or physiological effect and to supplement the normal diet. Accordingly, most food supplements are not to be associated with specific health claims. However, either due to the subtle suggestions by the producers or the wishful thinking of the consumers, certain pharmacological effects from food supplements are often expected. Medicinal plants included in food supplements usually do not produce dramatic and instant pharmacological effects. Therefore, in order to meet the expectation of their customers, some producers have turned to the illicit and dangerous practice of adulterating their products with synthetic adulterants, including naturally occurring molecules, having the desired activity. Such practice is prevalent in, although not limited to, food supplements intended for use as weight-loss aids, as well as for sport performance and libido enhancement. The review is focusing on naturally occurring alkaloids, phenylethanolamines, and their semi-synthetic derivatives in food supplements in the European Union as reported by the Rapid Alert System for Food and Feed. Their desired and undesired pharmacological effects, as well as the methods for their detection and quantification in food supplements, will be reviewed.