Herbal products, especially Hypericum perforatum extracts, have been widely used as first-line treatments for mild to moderate depression. Recently, several randomized, controlled clinical trials have been conducted to evaluate the efficacy of another plant, saffron (Crocus sativus), in mild to moderate depression. We have carried out a literature review of currently available published randomized, controlled clinical trials to give an up-to-date evaluation of the efficacy of saffron in mild to moderate depression, compared to placebo or routinely used antidepressants. The meta-analysis is reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using the PICO (patients, intervention, comparison, outcome) format and was conducted using the statistical programs Comprehensive Meta-analysis and RevMan. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for relevant studies. Only placebo or active controlled, randomized clinical studies involving patients suffering from mild to moderate depression and using pharmacological doses of saffron per os were included. Hedgesʼ g was used to calculate effect sizes. Risk of bias was assessed using the Cochrane Collaboration tool, and heterogeneity was tested by both performing the Cochranʼs Q test and calculating Higginsʼ I² indicator. Eleven randomized trials were included in the qualitative analysis, and nine were pooled for statistical analysis. According to the present meta-analysis, saffron has a significant effect on the severity of depression. Available data from randomized, controlled clinical trials support that saffron is significantly more effective than placebo (g = 0.891; 95% CI: 0.369 – 1.412, p = 0.001), and non-inferior to tested antidepressant drugs (g = − 0.246; 95% CI: − 0.495 – 0.004, p = 0.053).

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.

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.

The members of the Prangos genus (Apiaceae) have been widely applied in the Iranian traditional medicine internally and externally for different purposes. The aim of this review is to summarize the ethnomedicinal and food applications of Prangos species and to gather the phytochemical and pharmacological data on this genus. Among the 129 constituents isolated from Prangos species, coumarin derivatives are the main compounds. Several papers report the compositions of essential oils obtained from different plant parts, mostly containing monoterpene and sesquiterpene hydrocarbons. Various pharmacological activities of essential oils, crude extracts or isolated compounds of the Prangos species have been observed, primarily in in vitro experiments. Antioxidant, antimicrobial, cytotoxic and anti-proliferative activities have been the most extensively studied. The efficacy and safety of Prangos plants have not been assessed in animal experiments or clinical trials. Although their furocoumarin content might be a source of adverse effects, toxic effects of Prangos species have not been reported. It can be concluded, that further preclinical and clinical data are necessary to assess the rationale and safety of the medicinal and food use of Prangos species.

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.