Investigation of in vitro biological activity of young Hordeum vulgare leaf in correlation with its bioactive compounds.

Young shoots of cereals are widely regarded as superfoods with health benefits attributed to their potential antioxidant activity and antioxidant-related effects (e.g. anticancer). The current study aimed to examine the chemical characteristics of Hordeum vulgare methanolic and aqueous extracts and assess their antioxidant activity using the DDPH and ORAC. Furthermore, the inhibitory effect of xanthine oxidase was screened. TLC bioautography was employed to determine the polarity of the compounds present in the extracts that exhibited the most potent free radical scavenging activity. Total flavonoid content of the methanolic and aqueous extracts was 0.14 mg QE/g and 0.012 mg QE/g, respectively. The antioxidant activity of the methanolic extract was found to be more potent, with a value of 0.97 ± 0.13 mmol TE/g than the aqueous extract which had no activity. This study presents novel findings on the xanthine inhibitory activity of H. vulgare. The methanolic extract demonstrated moderate inhibition of xanthine oxidase with a value of 23.24%. The results of our study were compared with the phytochemical and pharmacological analysis of Triticum aestivum, and further comparison was made with the data reported in the literature. Inconsistencies were observed in the chemical and pharmacological properties of H. vulgare, which could be a result of using herbal material harvested in different vegetative phases and various methods used for extraction. The findings of our study indicate that the timing of the harvest and extraction method may play crucial role in attaining the optimal phytochemical composition of H. vulgare, hence enhancing its pharmacological activity.

Rapid Detection of Adulteration in Boswellia Extracts with Citric Acid by UPLC-HRMS and 1H NMR.

Boswellia serrata ole-gum-resin extracts (BSEs) are commonly used as food supplements, especially in osteoarthritis management. The quality standard is established by determining 11-keto-ß-boswellic acid (KBA) and acetyl-11-keto-boswellic acid (AKBA) content using high-performance liquid chromatography (HPLC) or assessing the total boswellic acid (TBA) content by titrimetry. The limited geographical distribution of Boswellia species and increasing industrial demand could increase the risk of adulteration in Boswellia-containing products. In this study, 14 BSEs from commercial sources, used in food supplements, were analyzed in comparison with a USP Reference Standard extract. The KBA and AKBA content was determined by HPLC, whereas the TBA content was determined by titration. Targeted UHPLC-high-resolution mass spectrometry (HRMS) was applied to identify the carboxylic acid content in the samples. The 1H NMR spectra of extracts were also analyzed. Only two products met the criteria for KBA and AKBA content. Although, the TBA content complied with the expected amount, 10 extracts contained citric acid levels of 6-11% even though citric acid is not a cha-racteristic component of BSEs. Our results suggest undeclared addition of citric acid to comply with declared contents of TBA when using titration methods. Incorporation of citric acid to industrial samples - in order to alter the outcomes of the titration analysis - was demonstrated for the first time.

Allelopathic studies with furanocoumarins isolated from Ducrosia anethifolia. In vitro and in silico investigations to protect legumes, rice and grain crops.

Six different furanocoumarins were isolated from the aerial parts of Ducrosia anethifolia and tested in vitro for plant cell elongation in etiolated wheat coleoptile. They were also tested for their ability to control three different weeds: ribwort plantain, annual ryegrass, and common purslane. These compounds exhibited strong inhibition of plant cell elongation. In the case of (+)-heraclenin, the IC50 was lower than 20 µM, indicating a better inhibition than the positive control Logran®. Computational experiments for docking and molecular dynamics revealed for the investigated furanocoumarins bearing an epoxide moiety an improved fitting and stronger interaction with the auxin-like TIR1 ubiquitin ligase. Furthermore, the formed inhibition complex remained also stable during dynamic evaluation. Bidental interaction at the active site, along with an extended hydrogen-bond lifetime, explained the enhanced activity of the epoxides. The in vitro weed bioassay results showed that Plantago lanceolata was the most affected weed for germination, root, and shoot development. In addition, (+)-heraclenin displayed better inhibition values than positive control even at 300 µM concentration.

Safety and risks of CBD oils purchased online: unveiling uncertain quality and vague health claims.

Introduction: The unmet need for highly effective, naturally derived products with minimal side effects results in the over-popularity of ever-newer medicinal plants. In the middle of 2010, products containing cannabidiol (CBD), one of the special metabolites of Cannabis sativa, started to gain popularity. For consumers and healthcare providers alike, the legal context surrounding the marketing of CBD products is not entirely clear, and the safety of using some products is in doubt. Companies in the online medicinal product market profit from the confusion around CBD oils. Methods: In our study, we employed a complex method known as risk-based safety mapping of the online pharmaceutical market, which included health claim content analysis of online stores, test purchases, and labeling and quantitative analysis of the CBD content. Results: There were discovered 16 online retailers selling an average of 2-7 goods and CBD oils with a concentration of 3%-5% (30-50 mg/mL) CBD. The majority (n/N = 10/16, 62.5%) displayed potential health-related benefits indirectly on their website, and in the case of one web shop (n/N = 1/16, 6.3%), we detected COVID-19-related use. Altogether, 30 types of purported "indications" were collected. A total of 12 CBD oil products were test-purchased from online retailers in December 2020. Upon evaluating the packaging and product information, we noticed that three products (n/N = 3/12, 25%) lacked instructions on use, hence increasing the risk of inappropriate application and dosing. The cannabidiol content was quantified using UHPLC. The measured CBD concentrations of the products ranged from 19.58 mg/mL to 54.09 mg/mL (mean 35.51 mg/mL, median 30.63 mg/mL, and SD ± 12.57 mg/mL). One (8.33%) product was underlabeled, five (41.67%) were over-labeled, and only every second product (50%) was appropriately labeled based on the quantitative assessment of CBD concentration. Discussion: Further research and quality control are necessary to establish the regulatory context of the usage and classification of CBD and other cannabinoids in nonmedicinal products (e.g., food supplements), as authorities and policymakers worldwide struggle with the uncertainties surrounding CBD products.

Antiproliferative and cytotoxic effects of sesquiterpene lactones isolated from Ambrosia artemisiifolia on human adenocarcinoma and normal cell lines.

CONTEXT: Ambrosia artemisiifolia L. (Asteraceae) contains sesquiterpene lactones as characteristic secondary metabolites. Many of these compounds exert antiproliferative and cytotoxic effects. OBJECTIVE: To isolate the sesquiterpene lactones from the aerial part of A. artemisiifolia and to elucidate their cytotoxic, antiproliferative and antibacterial effects. MATERIALS AND METHODS: The compounds were identified by one-dimensional (1D) and 2D NMR, HR-MS spectroscopy from the methanol extract. Isolated compounds were investigated for their cytotoxic and antiproliferative effects on human colonic adenocarcinoma cell lines and human embryonal lung fibroblast cell line using MTT assay. The selectivity of the sesquiterpenes was calculated towards the normal cell line. To check the effect of drug interactions between compounds and doxorubicin, multidrug-resistant Colo 320 cells were used. RESULTS: A new seco-psilostachyinolide derivative, 1,10-dihydro-1'-noraltamisin, and seven known compounds were isolated from the methanol extract. Acetoxydihydrodamsin had the most potent cytotoxic effect on sensitive (Colo205) cell line (IC50 = 7.64 µM), also the strongest antiproliferative effect on Colo205 (IC50 = 5.14 µM) and Colo320 (IC50 = 3.67 µM) cell lines. 1'-Noraltamisin (IC50 = 8.78 µM) and psilostachyin (IC50 = 5.29 µM) showed significant antiproliferative effects on the multidrug-resistant Colo320 cell line and had moderate selectivity against human embryonal lung fibroblast cell line. Psilostachyin C exhibited cytotoxic effects on Colo205 cells (IC50 = 26.60 µM). None of the isolated compounds inhibited ABCB1 efflux pump (EP; P-glycoprotein) or the bacterial EPs. DISCUSSION AND CONCLUSIONS: Acetoxydihydrodamsin, 1'-noraltamisin, and psilostachyin showed the most remarkable cytotoxic and antiproliferative activity on tumour cell lines and exerted selectivity towards MRC-5 cell line.

A comprehensive phytochemical and pharmacological review on sesquiterpenes from the genus Ambrosia.

Sesquiterpenes are bitter secondary metabolites characteristic to the genus Ambrosia (Asteraceae) and constitute one of the most diverse classes of terpenoids. These compounds exhibit broad-spectrum bioactivities, such as antiproliferative, cytotoxic, antimicrobial, anti-inflammatory, molluscicidal, schistomicidal, larvicidal, and antiprotozoal activities. This review compiles and discusses the chemistry and pharmacology of sesquiterpenes of the Ambrosia species covering the period between 1950 and 2021. The review identified 158 sesquiterpenes previously isolated from 23 different Ambrosia species collected from across the American, African, and Asian continents. These compounds have guaiane, pseudoguaiane, seco-pseudoguaiane, daucane, germacrane, eudesmane, oplopane, clavane, and aromadendrane carbon skeletons. Most sesquiterpene compounds predominantly harbor the pseudoguaiane skeleton, whereas the eudesmanes have the most varied substituents. Antiproliferative and antiprotozoal activities are the most promising bioactivities of sesquiterpenes in Ambrosia and could lead to new pathways toward drug discovery.

Stellaria media tea protects against diabetes-induced cardiac dysfunction in rats without affecting glucose tolerance.

Background and aim: Common chickweed (Stellaria media) tea has traditionally been applied for treatment of various metabolic diseases including diabetes in folk medicine; however, experimental evidence to support this practice is lacking. Therefore, we aimed to assess the effect of Stellaria media tea on glucose homeostasis and cardiac performance in a rat model of diabetes. Experimental procedure: Hot water extract of Stellaria media herb were analyzed and used in this study, where diabetes was induced by fructose-enriched diet supplemented with a single injection of streptozotocin. Half of the animals received Stellaria media tea (100 mg/kg) by oral gavage. At the end of the 20-week experimental period, blood samples were collected and isolated working heart perfusions were performed. Results and conclusion: Compared to the animals receiving standard chow, serum fasting glucose level was increased and glucose tolerance was diminished in diabetic rats. Stellaria media tea did not affect significantly fasting hyperglycemia and glucose intolerance; however, it attenuated diabetes-induced deterioration of cardiac output and cardiac work. Analysis of the chemical composition of Stellaria media tea suggested the presence of rutin and various apigenin glycosides which have been reported to alleviate diabetic cardiomyopathy. Moreover, Stellaria media prevented diabetes-induced increase in cardiac STAT3 phosphorylation. We demonstrated for the first time that Stellaria media tea may beneficially affect cardiac dysfunction induced by diabetes without improvement of glucose homeostasis. Rutin and/or apigenin glycosides as well as modulation of STAT3 signaling may be implicated in the protection of Stellaria media tea against diabetic cardiomyopathy.

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials.

Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically evaluate the frequency of adverse events related to dronabinol or nabilone treatment compared to placebo. Scientific databases were searched for placebo-controlled clinical studies of patients receiving either dronabinol or nabilone therapy with placebo control groups. This meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. There were 16 trials included in the meta-analysis. In the nabilone studies, drowsiness was more than 7 times as frequent in patients treated with nabilone than in the placebo group (OR: 7.25; 95% CI: 1.64-31.95), and the risk of dizziness (OR: 21.14; 95% CI: 2.92-152.75) and dry mouth was also higher (OR: 17.23; 95% CI: 4.33-68.55). The frequency of headache was not different in the two groups. In case of dronabinol, the frequency of dry mouth (OR: 5.58; 95% CI: 3.19-9.78), dizziness (OR: 4.60 95% CI: 2.39-8.83) and headache (OR: 2.90; 95% CI: 1.07-7.85) was significantly higher in the dronabinol groups, whereas in case of nausea, drowsiness and fatigue there was no difference. The severity of adverse events was typically mild-to-moderate and transient. In a risk-benefit assessment, these adverse effects are acceptable compared to the achievable benefit. However, considering the diversity of the adverse effects, more studies are needed to provide a more accurate assessment on the side effect profiles of these two compounds.

Cannabis: medicine, food or illicit drug? / Cannabis: gyógyszer, élelmiszer vagy kábítószer?

Összefoglaló. A kender (Cannabis sativa) gyógyhatásainak megítélése napjainkban változóban van, egyúttal igen ellentmondásos. Munkánk célja a kenderrel és készítményeivel kapcsolatos jogszabályi környezet alakulásának a kender gyógyászati alkalmazásának történetével párhuzamos bemutatása. A kenderrel és tartalomanyagaival kapcsolatos, jelenleg hatályos hazai jogszabályok és nemzetközi egyezmények áttekintése mellett bemutatjuk a kender alkalmazásának történetét a szakirodalmi adatok és a gyógyszerkincs átalakulásának tükrében. A kender ipari pályafutása textilipari alapanyagként kezdodött, de már ezt megelozoen is alkalmazták kábítószerként és gyógyászati célokra. A 20. század során a pszichoaktív szerként való felhasználás vált elterjedtebbé, de a növény hatóanyagainak jobb megismerésével a gyógyászati alkalmazás súlya is nott. Jelenleg a kender több vegyülete (kannabidiol, tetrahidrokannabinol) van forgalomban gyógyszerként világszerte, de félszintetikus kannabinoidot (nabilon) tartalmazó készítmények és különbözo kannabisztermékek is forgalomban vannak gyógyszerként. Napjainkban alkalmazására jellemzo, hogy a racionális gyógyászati használat mellett jelentos a túlzó elvárásokon alapuló, szakszerutlen alkalmazás. Ez részben a kenderrel kapcsolatos jogi szabályozás anomáliáival is magyarázható. Ennek következménye, hogy élelmiszerként elérhetok a kender epilepsziaellenes hatóanyagát tartalmazó termékek, amelyeket számos gyógyhatás reményében használnak orvosi kontroll nélkül. Megállapítható, hogy az új tudományos eredmények, a területen érdekelt vállalkozások céljai, a fogyasztói igények, a piaci realitás és a jogi szabályozás nem minden esetben és szempontból van összhangban. A kannabinoidok hosszabb távú jövojét a bizonyítékokon alapuló gyógyászatban nagyban befolyásolják azok a kutatások, amelyek segítségével pontosabb kép alkotható haszon-kockázat profiljukról. Orv Hetil. 2021; 162(45): 1808-1817. Summary. The opinion about the medicinal value of cannabis (Cannabis sativa) is changing but still remains controversial. The aim of our work was to present the evolution of the regulatory environment of Cannabis and its preparations in parallel with its history as medicine. We reviewed the current national legislation and international conventions on Cannabis and its constituents along with the historical and contemporary medicinal application of Cannabis. The utilisation of Cannabis started in the textile industry, but it was applied for recreational and medicinal purposes beforehand. During the 20th century, it was best known for its psychoactivity whereas its medicinal importance increased after elucidating the bioactivities of the active compounds of the plant. Currently different phytocannabinoids (cannabidiol, tetrahydrocannabinol) are marketed as medicines, but semisynthetic cannabinoids and different cannabis-based products are also approved as medicines. Today, there is a trend that goes beyond the rational and medicinal application thus results in improper form of utilisation. This phenomenon could partly be explained by the anomalies of legislative regulations. As a result, products containing the antiepileptic component of cannabis are available as food and used for different medicinal purposes without medical supervision. Evidently, there is no harmony between the new scientific discoveries, the goals of companies involved, the demands of consumers, market realities and current laws in several aspects. Ongoing studies will help to clarify the benefit-risk profiles of cannabinoids and provide major influence on the future of these compounds in the evidence-based medicine. Orv Hetil. 2021; 162(45): 1808-1817.

The electrophysiological effects of cannabidiol on action potentials and transmembrane potassium currents in rabbit and dog cardiac ventricular preparations.

Cannabis use is associated with known cardiovascular side effects such as cardiac arrhythmias or even sudden cardiac death. The mechanisms behind these adverse effects are unknown. The aim of the present work was to study the cellular cardiac electrophysiological effects of cannabidiol (CBD) on action potentials and several transmembrane potassium currents, such as the rapid (IKr) and slow (IKs) delayed rectifier, the transient outward (Ito) and inward rectifier (IK1) potassium currents in rabbit and dog cardiac preparations. CBD increased action potential duration (APD) significantly in both rabbit (from 211.7 ± 11.2. to 224.6 ± 11.4 ms, n = 8) and dog (from 215.2 ± 9.0 to 231.7 ± 4.7 ms, n = 6) ventricular papillary muscle at 5 µM concentration. CBD decreased IKr, IKs and Ito (only in dog) significantly with corresponding estimated EC50 values of 4.9, 3.1 and 5 µM, respectively, without changing IK1. Although the EC50 value of CBD was found to be higher than literary Cmax values after CBD smoking and oral intake, our results raise the possibility that potassium channel inhibition by lengthening cardiac repolarization might have a role in the possible proarrhythmic side effects of cannabinoids in situations where CBD metabolism and/or the repolarization reserve is impaired.

CBD, a precursor of THC in e-cigarettes.

The use of cannabidiol (CBD) in electronic cigarettes is widespread. Previously, it was reported that CBD is partly transformed to THC in case smoking as a cigarette, however, the pyrolysis of this compound has not been assessed extensively. The aim of our study was to investigate the effect of temperature on the composition of pyrolysis products of CBD. The experiments were performed in the typical operating temperature range of e-cigarettes (250-400 °C) and at 500 °C under both inert and oxidative conditions, and the pyrolysis products were identified and quantified by GC-MS. Depending on the temperature and atmosphere, 25-52% of CBD was transformed into other chemical substances: Δ9-THC, Δ8-THC, cannabinol and cannabichromene were the predominant pyrolysates in both conditions, all formed by cyclization reaction. THC was the main pyrolysis product at all temperatures under both oxidative and inert conditions. Our results point out that CBD in e-cigarettes can be considered as a precursor of THC, thus it bears all the dangers related to this psychoactive compound. Our findings are fundamental contributions to the safety profile of CBD-based e-cigarettes.

The electrophysiological effect of cannabidiol on hERG current and in guinea-pig and rabbit cardiac preparations.

Cannabis use is associated with cardiovascular adverse effects ranging from arrhythmias to sudden cardiac death. The exact mechanism of action behind these activities is unknown. The aim of our work was to study the effect of cannabidiol (CBD), tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol on cellular cardiac electrophysiological properties including ECG parameters, action potentials, hERG and IKr ion channels in HEK cell line and in rabbit and guinea pig cardiac preparations. CBD increased action potential duration in rabbit and guinea pig right ventricular papillary muscle at lower concentrations (1 µM, 2.5 µM and 5 µM) but did not significantly change it at 10 µM. CBD at high concentration (10 µM) decreased inward late sodium and L-type calcium currents as well. CBD inhibited hERG potassium channels with an IC50 value of 2.07 µM at room temperature and delayed rectifier potassium current with 6.5 µM at 37 °C, respectively. The frequency corrected QT interval (QTc) was significantly lengthened in anaesthetized guinea pig without significantly changing other ECG parameters. Although the IC50 value of CBD was higher than literary Cmax values after CBD smoking and oral intake, our results raise the possibility that hERG and potassium channel inhibition might have a role in the possible proarrhythmic adverse effects of cannabinoids in situations where metabolism of CBD impaired and/or the repolarization reserve is weakened.

Ducrosia spp., Rare Plants with Promising Phytochemical and Pharmacological Characteristics: An Updated Review.

The rare genus Ducrosia (Apiaceae family) consists of six species, which are mainly native to Asia, specifically to Iran and Iraq. The aerial parts of D. anethifolia, as the most common species, have been traditionally consumed to relieve headache, backache and colic pain, and have also been used as an anxiolytic, an antidepressant, and for treating insomnia. The antispasmodic and carminative effects of D. assadii, and the analgesic activity of D. flabellifolia, along with the insecticidal activities and use as a remedy of skin infections of D. ismaelis, have been previously documented. Among the 49 non-volatile secondary metabolites identified from D. anethifolia and D. ismaelis, 17 linear furanocoumarins and 8 flavonoids have been characterized. The essential oil compositions of four species, including D. anethifolia, D. assadii, D. flabellifolia and D. ismaelis, have been analyzed, whereby aldehyde hydrocarbons, including decanal (10.1‒74.0%) and dodecanal (7.2‒33.41%), and α-pinene (4.0‒70.3%), were identified as the main aroma constituents. From the species of the genus, the bioactivities of D. anethifolia, as well as D. ismaelis, D. assadii and D. flabellifolia, have been previously investigated. Except one clinical trial, all the pharmacological data are derived from preclinical tests, predominantly focusing on antimicrobial, antioxidant, antiproliferative and cytotoxic activities in vitro, and neuroprotective, antidiabetic and analgesic effects in vivo. Considering the vast ethnobotanical uses of the plants in Iranian folk medicine, the phytochemical and pharmacological analysis of un-investigated species might be promising. Furthermore, due to extensive consumption of the Ducrosia genus, more scientific data are needed to support the safety and efficacy of these plants.

Comprehensive chemotaxonomic analysis of saffron crocus tepal and stamen samples, as raw materials with potential antidepressant activity.

Saffron crocus (Crocus sativus L.) has been widely grown in Iran. Its stigma is considered as the most valuable spice for which several pharmacological activities have been reported in preclinical and clinical studies, the antidepressant effect being the most thoroughly studied and confirmed. This plant part contains several characteristic secondary metabolites, including the carotenoids crocetin and crocin, and the monoterpenoid glucoside picrocrocin, and safranal. Since only the stigma is utilized industrially, huge amount of saffron crocus by-product remains unused. Recently, the number of papers dealing with the chemical and pharmacological analysis of saffron is increasing; however, there are no systematic studies on the chemical variability of the major by-products. In the present study, we harvested saffron crocus flowers from 40 different locations of Iran. The tepals and stamens were separated and subjected to qualitative and quantitative analysis by HPLC-DAD. The presence and amount of seven marker compounds, including crocin, crocetin, picrocrocin, safranal, kaempferol-3-O-sophoroside, kaempferol-3-O-glucoside, and quercetin-3-O-sophoroside were determined. The analytical method was validated for filter compatibility, stability, suitability, accuracy, precision, intermediate precision, and repeatability. Tepal and stamen samples contained three flavonol glycosides. The main constituent of the tepals was kaempferol-3-O-sophoroside (62.19-99.48 mg/g). In the stamen, the amount of flavonoids was lower than in the tepal. The amount of kaempferol-3-O-glucoside, as the most abundant compound, ranged between 1.72-7.44 mg/g. Crocin, crocetin, picrocrocin, and safranal were not detected in any of the analysed samples. Our results point out that saffron crocus by-products, particularly tepals might be considered as rich sources of flavonol glucosides. The data presented here can be useful in setting quality standards for plant parts of C. sativus that are currently considered as by-products of saffron production.

Effect of Stellaria media Tea on Lipid Profile in Rats.

BACKGROUND: In folk medicine, common chickweed (Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of Materials and Methods. Adult male Wistar rats were divided into 3 groups. The (i) control group received standard laboratory chow, the (ii) hypercholesterolemic group received cholesterol-enriched diet, and the (iii) chickweed-treated hypercholesterolemic group received cholesterol-enriched diet and 100 mg/kg body weight Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of. RESULTS: Cholesterol-enriched diet significantly increased serum total cholesterol, LDL- and HDL-cholesterol levels, but did not affect triacylglycerol concentrations. The addition of chickweed to the diet did not cause any significant change in serum lipid profile or body weight increase. Liver and kidney functions were unaltered and cardiac morphology and function were not changed due to Stellaria media) has traditionally been applied for the treatment of hypercholesterolemia; however, there is no firm experimental proof to support the rationale of this practice. Therefore, we aimed to assess the efficacy and safety of. CONCLUSION: Although chickweed does not seem to be toxic, our results do not support the rationale of its use in the treatment of hypercholesterolemia.

The Effects of a Fixed Combination of Berberis aristata and Silybum marianum on Dyslipidaemia - A Meta-analysis and Systematic Review.

A fixed combination of Berberis aristata and Silybum marianum (Berberol) has been used by patients with dyslipidaemia. The aim of the present meta-analysis was to systematically evaluate the efficacy and safety of a fixed combination of B. aristata and S. marianum (Berberol) on serum lipid levels compared to placebo in a meta-analysis based on randomised, controlled trials. The meta-analysis was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using the PICO (patients, intervention, comparison, outcome) format, and it was registered in the International Prospective Register of Systematic Reviews. The Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web of Science databases were searched for relevant studies. Placebo-controlled clinical studies involving adult patients with a condition of dyslipidaemia and receiving a fixed combination of B. aristata and S. marianum were included. Four randomised trials, including a total of 491 patients, were pooled in statistical analysis. According to the present meta-analysis, Berberol significantly lowered the low-density lipoprotein level, total cholesterol, fasting plasma glucose levels, and the Homeostatic Model Assessment index compared to placebo; however, its effects on the high-density lipoprotein level, triglyceride level, and body mass index were not statistically significant by the end of a 3-month treatment period. Berberol appeared to be safe, and it did not increase the levels of alanine transaminase, aspartate transaminase, and creatine kinase enzymes. Berberol is an effective and presumably safe complementary therapy for the treatment of dyslipidaemia; however, the evidence supporting its use is very limited. The optimum dose and duration of treatment are unclear. A comprehensive evaluation of efficacy and safety is required in further high-quality clinical studies involving larger patient populations.

Effect of green tea on the gastrointestinal absorption of amoxicillin in rats.

BACKGROUND: The investigation of food-drug and plant-drug interactions has become increasingly important. In case of antibiotics, it is essential to achieve and maintain a plasma concentration sufficient for the antimicrobial action. Although, on theoretical basis, the interaction of polyphenols and antibiotics may be hypothesized, experimental data are lacking to assess its clinical relevance. The aim of our study was to assess the interaction between one of the most widely used antibiotics, amoxicillin, and green tea, the most frequently consumed drink with high polyphenol content. METHODS: The effects of green tea on the plasma level of amoxicillin was studied in an in vivo experiment in rats. The plasma level of amoxicillin was monitored by LC-MS/MS for 240 min after oral administration. The polyphenol content of green tea was determined by the Folin-Ciocalteu method. RESULTS: The peak plasma concentration of amoxicillin significantly decreased upon its co-administration with green tea, although the AUC0-240 of the antibiotic did not decrease significantly in the group treated with amoxicillin suspended in green tea. CONCLUSIONS: Our results suggest a potentially relevant interaction between green tea and amoxicillin, worth being further studied in humans.

Furocoumarin Content of Fennel-Below the Safety Threshold.

Furocoumarins are known for their phototoxic and potential carcinogenic effects. These types of compounds have previously been reported from fennel (Foeniculum vulgare Mill.), a widely used medicinal plant and spice; however, no reliable quantitative data are available on the occurrence of these compounds in fennel fruits. For the first time, we report a comprehensive analysis of fennel fruit samples of different origins, representing a wide range of accessions for their furocoumarin content. Psoralene, 5-methoxypsoralene (bergapten), and imperatorin contents of 33 fennel samples were analyzed using a sensitive liquid chromatography-mass spectrometry (LC-MS) method. When applied at the highest therapeutic dose described in the monograph issued by the European Medicines Agency, the furocoumarin content of the fruits ranged up to 1.22 µg/d, which is below the most restrictive recommendations. Based on our findings, fennel consumption can be considered as safe, at least based on its low furocoumarin content.

The combination of hawthorn extract and camphor significantly increases blood pressure: A meta-analysis and systematic review.

BACKGROUND: A fixed combination of hawthorn and camphor (Korodin Herz-Kreislauf-Tropfen®) has been used in the therapy of hypotension for decades. Although its efficacy was evaluated in clinical trials, these studies have not been critically assessed in meta-analyses. PURPOSE: To systematically evaluate the efficacy of a fix combination of camphor and hawthorn extract (Korodin®) on blood pressure and cognition compared to placebo, in a meta-analysis based on randomized controlled trials (RCTs). STUDY DESIGN: The meta-analysis was carried out following the PRISMA guidelines, using the PICO format, and it was registered in the PROSPERO register. METHODS: The Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web of Science databases were searched for relevant studies. Placebo-controlled clinical studies involving adult patients receiving a fix combination of hawthorn extract and camphor were included. No language or publication year restrictions were applied. RESULTS: Four randomized trials including a total of 221 patients were pooled for statistical analysis. According to the present meta-analysis, the fixed combination of hawthorn and camphor significantly increases systolic and diastolic blood pressure compared to placebo (p-values: 0.017 and 0.049, respectively) and had a beneficial, but not statistically significant effect on the cognitive performance in the connect-the-numbers test (p-value: 0.071). CONCLUSION: Korodin® is an effective and presumably safe complementary therapy for the treatment of hypotension. Its blood pressure increasing effect is confirmed; however, the evidence supporting its use is very limited. The optimum dose and duration of treatment is still unclear. The comprehensive evaluation of efficacy and safety is required in further, high-quality clinical studies, involving larger patient populations and comparable endpoints.

Quality control of Hypericum perforatum L. analytical challenges and recent progress.

OBJECTIVES: The most widely applied qualitative and quantitative analytical methods in the quality control of Hypericum perforatum extracts will be reviewed, including routine analytical tools and most modern approaches. KEY FINDINGS: Biologically active components of H. perforatum are chemically diverse; therefore, different chromatographic and detection methods are required for the comprehensive analysis of St. John's wort extracts. Naphthodianthrones, phloroglucinols and flavonoids are the most widely analysed metabolites of this plant. For routine quality control, detection of major compounds belonging to these groups seems to be sufficient; however, closer characterization requires the detection of minor compounds as well. CONCLUSIONS: TLC and HPTLC are basic methods in the routine analysis, whereas HPLC-DAD is the most widely applied method for quantitative analysis due to its versatility. LC-MS is gaining importance in pharmacokinetic studies due to its sensitivity. Modern approaches, such as DNA barcoding, NIRS and NMR metabolomics, may offer new possibilities for the more detailed characterization of secondary metabolite profile of H. perforatum extracts.