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.

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.

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.

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols.

A library of pinane-based 2-amino-1,3-diols was synthesised in a stereoselective manner. Isopinocarveol prepared from (-)-α-pinene was converted into condensed oxazolidin-2-one in two steps by carbamate formation followed by a stereoselective aminohydroxylation process. The relative stereochemistry of the pinane-fused oxazolidin-2-one was determined by 2D NMR and X-ray spectroscopic techniques. The regioisomeric spiro-oxazolidin-2-one was prepared in a similar way starting from the commercially available (1R)-(-)-myrtenol (10). The reduction or alkaline hydrolysis of the oxazolidines, followed by reductive alkylation resulted in primary and secondary 2-amino-1,3-diols, which underwent a regioselective ring closure with formaldehyde or benzaldehyde delivering pinane-condensed oxazolidines. During the preparation of 2-phenyliminooxazolidine, an interesting ring-ring tautomerism was observed in CDCl3.

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.