Synthetic polyploidization induces enhanced phytochemical profile and biological activities in Thymus vulgaris L. essential oil.

Essential oil from Thymus vulgaris L. has valuable therapeutic potential that is highly desired in pharmaceutical, food, and cosmetic industries. Considering these advantages and the rising market demand, induced polyploids were obtained using oryzalin to enhance essential oil yield. However, their therapeutic values were unexplored. So, this study aims to assess the phytochemical content, and antimicrobial, antioxidant, and anti-inflammatory activities of tetraploid and diploid thyme essential oils. Induced tetraploids had 41.11% higher essential oil yield with enhanced thymol and γ-terpinene content than diploid. Tetraploids exhibited higher antibacterial activity against all tested microorganisms. Similarly, in DPPH radical scavenging assay tetraploid essential oil was more potent with half-maximal inhibitory doses (IC50) of 180.03 µg/mL (40.05 µg TE/mg) than diploid with IC50 > 512 µg/mL (12.68 µg TE/mg). Tetraploids exhibited more effective inhibition of in vitro catalytic activity of pro-inflammatory enzyme cyclooxygenase-2 (COX-2) than diploids at 50 µg/mL concentration. Furthermore, molecular docking revealed higher binding affinity of thymol and γ-terpinene towards tested protein receptors, which explained enhanced bioactivity of tetraploid essential oil. In conclusion, these results suggest that synthetic polyploidization using oryzalin could effectively enhance the quality and quantity of secondary metabolites and can develop more efficient essential oil-based commercial products using this induced genotype.

Garcinia kola: a critical review on chemistry and pharmacology of an important West African medicinal plant.

Garcinia kola Heckel (Clusiaceae) is a tree indigenous to West and Central Africa. All plant parts, but especially the seeds, are of value in local folklore medicine. Garcinia kola is used in treatment of numerous diseases, including gastric disorders, bronchial diseases, fever, malaria and is used to induce a stimulating and aphrodisiac effect. The plant is now attracting considerable interest as a possible source of pharmaceutically important drugs. Several different classes of compounds such as biflavonoids, benzophenones, benzofurans, benzopyran, vitamin E derivatives, xanthones, and phytosterols, have been isolated from G. kola, of which many appears to be found only in this species, such as garcinianin (found in seeds and roots), kolanone (fruit pulp, seeds, roots), gakolanone (stem bark), garcinoic acid, garcinal (both in seeds), garcifuran A and B, and garcipyran (all in roots). They showed a wide range of pharmacological activities (e.g. analgesic, anticancer, antidiabetic, anti-inflammatory, antimalarial, antimicrobial, hepatoprotective and neuroprotective effects), though this has only been confirmed in animal models. Kolaviron is the most studied compound and is perceived by many studies as the active principle of G. kola. However, its research is associated with significant flaws (e.g. too high doses tested, inappropriate positive control). Garcinol has been tested under better conditions and is perhaps showing more promising results and should attract deeper research interest (especially in the area of anticancer, antimicrobial, and neuroprotective activity). Human clinical trials and mechanism-of-action studies must be carried out to verify whether any of the compounds present in G. kola may be used as a lead in the drug development.

Medical cannabis dimethyl ether, ethanol and butane extracts inhibit the in vitro growth of bacteria and dermatophytes causing common skin diseases.

Cannabis preparations are gaining popularity among patients with various skin diseases. Due to the lack of scientific evidence, dermatologists remain cautious about their prescriptions. So far, only a few studies have been published about the effects of high-potency cannabis extracts on microorganisms (especially dermatophytes) causing skin problems that affect more than 25% of the worldwide population. Even though, the high-potency cannabis extracts prepared by cold extraction are mostly composed of non-psychoactive tetrahydrocannabinolic acid (THCA) and only low amount of THC, their use in topical treatment can be stigmatized. The in vitro antimicrobial and antifungal activity of two high potent cannabis strains extracted by three solvents traditionally or currently used by cannabis users (ethanol; EtOH, butane; BUT, dimethyl ether; DME) was investigated by broth dilution method. The chemical profile of cannabis was determined by high-performance liquid chromatography with ultraviolet detection and gas chromatography with mass spectrometer and flame ionization detector. The extraction methods significantly influenced chemical profile of extracts. The yield of EtOH extracts contained less cannabinoids and terpenes compared to BUT and DME ones. Most of the extracts was predominantly (>60%) composed of various cannabinoids, especially THCA. All of them demonstrated activity against 18 of the 19 microorganisms tested. The minimal inhibitory concentrations (MICs) of the extracts ranged from 4 to 256 µg/mL. In general, the bacteria were more susceptible to the extracts than dermatophytes. Due to the lower content of biologically active substances, the EtOH extracts were less effective against microorganisms. Cannabis extracts may be of value to treat dermatophytosis and other skin diseases caused by various microorganisms. Therefore, they could serve as an alternative or supportive treatment to commonly used antibiotics.

Antioxidant and Anti-Inflammatory Activity of Five Medicinal Mushrooms of the Genus Pleurotus.

Within the group of higher fungi, edible medicinal mushrooms have a long history of being used as food and in folk medicine. These species contain biologically active substances with many potential beneficial effects on human health. The Pleurotus genus is representative of medicinal mushrooms because Pleurotus ostreatus is one of the most commonly cultivated culinary mushrooms. In our study, we focused on lesser-known species in the genus Pleurotus and measured their antioxidant and anti-inflammatory activity. We prepared extracts of the mushrooms and analyzed them using HPLC-HRMS, GC-MS, and 1H-NMR. Significant differences in biological activities were found among the Pleurotus spp. extracts. A MeOH extract of P. flabellatus was the most active as a radical scavenger with the highest ORAC, while a chloroform extract had significant anti-inflammatory COX-2 activity. The 80% MeOH extract of P. flabellatus contained the highest amounts of ergosterol, ergothioneine, and mannitol. The 80% MeOH extract of P. ostreatus Florida was the most active in the NF-κB inhibition assay and had the highest content of ß-glucans (43.3% by dry weight). Given the antioxidant and anti-inflammatory properties of P. flabellatus, the potential therapeutic usefulness of this species is worth evaluating through in-depth investigations and confirmation by clinical trials.

Synthesis and biological evaluation of cationic TopFluor cholesterol analogues.

Cholesterol is not only a major component of the cell membrane, but also plays an important role in a wide range of biological processes and pathologies. It is therefore crucial to develop appropriate tools for visualizing intracellular cholesterol transport. Here, we describe new cationic analogues of BODIPY-Cholesterol (TopFluor-Cholesterol, TF-Chol), which combine a positive charge on the sterol side chain and a BODIPY group connected via a C-4 linker. In contrast to TF-Chol, the new analogues TF-1 and TF-3 possessing acetyl groups on the A ring (C-3 position on steroid) internalized much faster and displayed slightly different levels of intracellular localization. Their applicability for cholesterol monitoring was indicated by the fact that they strongly label compartments with accumulated cholesterol in cells carrying a mutation of the Niemann-Pick disease-associated cholesterol transporter, NPC1.

The Chemical Composition of Oils and Cakes of Ochna serrulata (Ochnaceae) and Other Underutilized Traditional Oil Trees from Western Zambia.

Currently, the negative effects of unified and intensive agriculture are of growing concern. To mitigate them, the possibilities of using local but nowadays underused crop for food production should be more thoroughly investigated and promoted. The soybean is the major crop cultivated for vegetable oil production in Zambia, while the oil production from local oil-bearing plants is neglected. The chemical composition of oils and cakes of a three traditional oil plant used by descendants of the Lozi people for cooking were investigated. Parinari curatellifolia and Schinziophyton rautanenii oils were chiefly composed of α-eleostearic (28.58-55.96%), linoleic (9.78-40.18%), and oleic acid (15.26-24.07%), whereas Ochna serrulata contained mainly palmitic (35.62-37.31%), oleic (37.31-46.80%), and linoleic acid (10.61-18.66%); the oil yield was high (39-71%). S. rautanenii and O. serrulata oils were rich in γ-tocopherol (3236.18 µg/g, 361.11 µg/g, respectively). The O. serrulata oil also had a very distinctive aroma predominantly composed of p-cymene (52.26%), m-xylene (9.63%), γ-terpinene (9.07%), o-xylene (7.97), and limonene (7.23%). The cakes remaining after oil extraction are a good source of essential minerals, being rich in N, P, S, K, Ca, and Mg. These plants have the potential to be introduced for use in the food, technical, or pharmaceutical industries.

Evaluation of the effect of Lepidium meyenii Walpers in infertile patients: A randomized, double-blind, placebo-controlled trial.

Male infertility refers to the inability to conceive a natural pregnancy in a fertile female, and approximately 15% of reproductive-aged couples worldwide face this problem. Several plants were used to treat fertility disorders and, among them, Lepidium meyenii, a folk medicament of Andean regions, is still used to enhance vitality and treat sterility in humans and domestic animals. The aim of the study was to evaluate the effects of L. meyenii Walpers on infertile patients by a randomized, double-blind, placebo-controlled trial. Fifty patients suffering from various reproductive-related problems were enrolled for 16 weeks to evaluate the effect of yellow maca on semen quality and serum hormone levels. Treatment with maca improved the percentage of sperm concentration by 40%, whereas the placebo improved by 76% after 8 and 16 weeks of treatment, but the results were statistically non-significant. No statistically significant change in hormone levels was reported by using maca, except a decrease in the level of free testosterone. Results are not sufficient to assess the efficacy of maca on male fertility. Further investigation and trials are required to obtain conclusive results.

Medicinal Use of Testosterone and Related Steroids Revisited.

Testosterone derivatives and related compounds (such as anabolic-androgenic steroids-AAS) are frequently misused by athletes (both professional and amateur) wishing to promote muscle development and strength or to cover AAS misuse. Even though these agents are vastly regarded as abusive material, they have important pharmacological activities that cannot be easily replaced by other drugs and have therapeutic potential in a range of conditions (e.g., wasting syndromes, severe burns, muscle and bone injuries, anemia, hereditary angioedema). Testosterone and related steroids have been in some countries treated as controlled substances, which may affect the availability of these agents for patients who need them for therapeutic reasons in a given country. Although these agents are currently regarded as rather older generation drugs and their use may lead to serious side-effects, they still have medicinal value as androgenic, anabolic, and even anti-androgenic agents. This review summarizes and revisits the medicinal use of compounds based on the structure and biological activity of testosterone, with examples of specific compounds. Additionally, some of the newer androgenic-anabolic compounds are discussed such as selective androgen receptor modulators, the efficacy/adverse-effect profiles of which have not been sufficiently established and which may pose a greater risk than conventional androgenic-anabolic agents.

Effect of Artemisia absinthium and Malva sylvestris on Antioxidant Parameters and Abomasal Histopathology in Lambs Experimentally Infected with Haemonchus contortus.

This study evaluated the effect of Artemisia absinthium and Malva sylvestris on antioxidant response and histopathological changes in the abomasa of the Haemonchus contortus infected lambs. Twenty-four lambs were divided into four groups: unsupplemented lambs (UNS), lambs supplemented with A. absinthium (ART), lambs supplemented with M. sylvestris (MAL), and lambs supplemented with both plants (ARTMAL). Lambs were infected orally with approximately 5000 third-stage (L3) larvae of H. contortus. The experiment was conducted for 75 d (days), all animals were then slaughtered; and the abomasal tissues were examined for antioxidant parameters and histopathology. The concentration of malondialdehyde in the abomasal mucosa was lower in ARTMAL (p < 0.05), and the total antioxidant capacity was higher in MAL (p < 0.05), than in UNS. Increased mucus production was observed in the ARTMAL. The number of mast cells in UNS and ART was significantly higher than the number in MAL (p < 0.01 and p < 0.05). Plasma cell numbers were higher in ARTMAL than the number in MAL (p < 0.05). Abomasal tissue regenerated more frequently in ARTMAL. These results represent the first report of the impact of A. absinthium and M. sylvestris on antioxidant parameters and local immune responses of abomasal mucosa of lambs infected with a GIN parasite.

Polyketide Derivatives in the Resistance of Gerbera hybrida to Powdery Mildew.

Powdery mildew is a common disease affecting the commercial production of gerbera flowers (Gerbera hybrida, Asteraceae). Some varieties show a certain degree of resistance to it. Our objective was to identify biomarkers of resistance to powdery mildew using an 1H nuclear magnetic resonance spectroscopy and chemometrics approach in a complex, fully factorial experiment to suggest a target for selection and breeding. Resistant varieties were found to differ from those that were susceptible in the metabolites of the polyketide pathway, such as gerberin, parasorboside, and gerberinside. A new compound probably involved in resistance, 5-hydroxyhexanoic acid 3-O-ß-D-glucoside, was described for the first time. A decision tree model was built to distinguish resistant varieties, with an accuracy of 57.7%, sensitivity of 72%, and specificity of 44.44% in an independent test. Our results suggest the mechanism of resistance to powdery mildew in gerbera and provide a potential tool for resistance screening in breeding programs.

Advances in the Determination of Anabolic-Androgenic Steroids: From Standard Practices to Tailor-Designed Multidisciplinary Approaches.

Anabolic-androgenic steroids (AASs), a group of compounds frequently misused by athletes and, unfortunately, also by the general population, have lately attracted global attention; thus, significant demands for more precise, facile, and rapid AAS detection have arisen. The standard methods ordinarily used for AAS determination include liquid and gas chromatography coupled with mass spectrometry. However, good knowledge of steroid metabolism, pretreatment of samples (such as derivatization), and well-trained operators of the instruments are required, making this procedure expensive, complicated, and not routinely applicable. In the drive to meet current AAS detection demands, the scientific focus has shifted to developing novel, tailor-made approaches leading to time- and cost-effective, routine, and field-portable methods for AAS determination in various matrices, such as biological fluids, food supplements, meat, water, or other environmental components. Therefore, herein, we present a comprehensive review article covering recent advances in AAS determination, with a strong emphasis on the increasingly important role of chemically designed artificial sensors, biosensors, and antibody- and fluorescence-based methods.

Vapors of Volatile Plant-Derived Products Significantly Affect the Results of Antimicrobial, Antioxidative and Cytotoxicity Microplate-Based Assays.

Volatile plant-derived products were observed to exhibit broad spectrum of biological effects. However, due to their volatility, results of conventional microplate-based bioassays can be significantly affected by the vapors. With aim to demonstrate this phenomenon, antimicrobial, antioxidant, and cytotoxic activities of three essential oils (Alpinia elegans, Cinnamomum iners, and Xanthostemon verdugonianus), one supercritical CO2 extract (Nigella sativa), and four plant-derived compounds (capsaicin, caryophyllene oxide, 8-hydroxyquinoline, and thymoquinone) were evaluated in series of experiments including both ethylene vinyl acetate (EVA) Capmat sealed and nonsealed microplates. The results clearly illustrate that vapor transition to adjoining wells causes false-positive results of bioassays performed in nonsealed microtiter plates. The microplate layout and a duration of the assay were demonstrated as the key aspects defining level of the results affection by the vapors of volatile agents. Additionally, we reported biological activities and chemical composition of essential oils from A. elegans seeds and X. verdugonianus leaves, which were, according to our best knowledge, analyzed for the first time. Considering our findings, certain modifications of conventional microplate-based assays are necessary (e.g., using EVA Capmat as vapor barrier) to obtain reliable results when biological properties of volatile agents are evaluated.

Flavonoids and Related Members of the Aromatic Polyketide Group in Human Health and Disease: Do They Really Work?

Some aromatic polyketides such as dietary flavonoids have gained reputation as miraculous molecules with preeminent beneficial effects on human health, for example, as antioxidants. However, there is little conclusive evidence that dietary flavonoids provide significant leads for developing more effective drugs, as the majority appears to be of negligible medicinal importance. Some aromatic polyketides of limited distribution have shown more interesting medicinal properties and additional research should be focused on them. Combretastatins, analogues of phenoxodiol, hepatoactive kavalactones, and silymarin are showing a considerable promise in the advanced phases of clinical trials for the treatment of various pathologies. If their limitations such as adverse side effects, poor water solubility, and oral inactivity are successfully eliminated, they might be prime candidates for the development of more effective and in some case safer drugs. This review highlights some of the newer compounds, where they are in the new drug pipeline and how researchers are searching for additional likely candidates.

Natural Products and their (Semi-)Synthetic Forms in the Treatment of Migraine: History and Current Status.

BACKGROUND: Migraine may be described as a headache with moderate to extreme pain that is often accompanied by incapacitating neurological symptoms. It is estimated that 12% of the world population suffers from migraine. Although a number of drugs have been used for treatment of migraine, most of these are not effective for every patient and may have undesirable side-effects. Thus, there is an enormous unmet need in current migraine therapy for discovering safer and more effective agents. METHODS: The information summarized in this review was obtained through extensive literature review and search of relevant books and articles with the use of Web of Knowledge and SciVerse Scopus databases. RESULTS: Greater understanding of the molecular mechanisms underlying the etiopathogenesis of migraine is helpful in identifying novel targets for antimigraine drugs such as cannabinoid, histamine, and melatonin receptors. In the past, natural product-derived constituents have served as an invaluable source of numerous medicinally useful antimigraine agents and it may be expected that further promising drug candidates from natural products will be discovered for antimigraine pharmacotherapy with better efficacy and fewer adverse-effects. CONCLUSION: The discovery of novel targets in migraine therapy has opened new horizons for compounds that have not been clinically tested or that previously failed in clinical trials as potential antimigraine drugs. Ginkgolide B, melatonin, histamine, oxytocin, various ribosomal peptide toxins, kavalactones, devil's claw-derived compounds, salvinorin A and petasin are among those agents that show considerable promise as novel drugs in migraine prevention and treatment. It is necessary to conduct more research to better understand their antimigraine action, to confirm their effectiveness and safety, and to introduce them into clinical practice.

Screening of medicinal plants traditionally used in Peruvian Amazon for in vitro antioxidant and anticancer potential.

Plants mentioned in this study have numerous records in traditional Peruvian medicine being used in treatment of cancer and other diseases likely to be associated with oxidative stress. Amongst the eight plant species tested, only Dysphania ambrosioides exhibited combinatory antioxidant and anti-proliferative effect on a broad spectrum of cancer cells (DPPH and ORAC values = 80.6 and 687.3 µg TE/mg extract, respectively; IC50 against Caco-2, HT-29 and Hep-G2 = 129.2, 69.9 and 130.6, respectively). Alkaloids and phenolic compounds might significantly contribute to anticancer/antioxidant activity of this plant. The results justify the traditional medicinal use of this plant. Our findings further suggest that D. ambrosioides might serve as a prospective material for further development of novel plant-based antioxidant and/or anti-proliferative agents. Detailed analysis of chemical composition together with toxicology assessments and in vivo antioxidant/anti-proliferative activity of this plant should be carried out in order to verify its potential practical use.

In Vitro Antistaphylococcal Synergistic Effect of Isoflavone Metabolite Demethyltexasin with Amoxicillin and Oxacillin.

Staphylococcal infections are often hard to treat due to increasing resistance, especially to ß-lactams. Previous studies described the synergy between common antibiotics and isoflavonoids; however, little is yet known about the combinatory effects of antibiotics with products of human isoflavone metabolism. In this study, demethyltexasin (DT), a human body metabolite of soybean isoflavones, was evaluated for its possible antistaphylococcal combinatory effect with amoxicillin and oxacillin. For comparison, common therapeutically used combination of amoxicillin/clavulanic acid was tested. DT showed strong synergistic interactions against most of Staphylococcus aureus strains when combined with amoxicillin (sum of fractional inhibitory concentrations [ΣFIC] 0.257-0.461) and oxacillin (ΣFIC 0.109-0.484). When oxacillin was combined with DT, resistance to this antibiotic was overcome in many cases. Moreover, antibiotic/DT combinations were effective mainly against methicillin-resistant S. aureus (MRSA); however, the commonly used drug amoxicillin/clavulanic acid was effective only against sensitive strains. Our results indicated DT as a compound able to act synergistically with ß-lactams. In addition, some combinations are effective against MRSA and decrease staphylococcal resistance. To the best of our knowledge this is the first report of the antimicrobial synergistic effects of isoflavone human body metabolite with common antibiotics. DT seems to be a possible candidate for further research focused on antistaphylococcal drug development, especially against antibiotic-resistant strains.

Non-steroidal anti-inflammatory drugs in the watercourses of Elbe basin in Czech Republic.

Non-steroidal anti-inflammatory drugs (NSAIDs) belong to most used pharmaceuticals in the human and veterinary medicine. The widespread consumption of NSAIDs has led to their ubiquitous occurrence in water environment including large river systems. In the present study, concentrations of the five most frequently used NSAIDs (ibuprofen, diclofenac, naproxen, ketoprofen and indomethacin) were determined in the watercourses of the river Elbe basin in Czech Republic. The presence of the pharmaceuticals was measured at 29 sampling sites including urban and rural areas, small creeks and main tributaries of the Elbe monthly from April to December of 2011. For the NSAIDs quantitation, the comprehensive analytical method combing pentafluorobenzyl bromide (PFBBr) derivatization with highly sensitive two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC-TOFMS) was developed. Although the content of all NSAIDs varied at the particular sampling points significantly, total amount of particular compounds was relatively stable during all monitored periods with only non-significant increase in the spring and autumnal months. Ibuprofen was found to be the most abundant drug with maximum concentration of 3210 ng/L, followed by naproxen, diclofenac and ketoprofen (1423.8 ng/L, 1080 ng/L and 929.8 ng/L, respectively). Indomethacin was found only at several sampling sites (maximum concentration of 69.3 ng/L). Concentrations of all compounds except ibuprofen were significantly higher at sampling sites with low flow rates (creeks), followed by the biggest watercourses.

Phenolic composition, antioxidant and anti-proliferative activities of edible and medicinal plants from the Peruvian Amazon

ABSTRACT Among 23 extracts of medicinal and edible plants tested, Mauritia flexuosa L.f., Arecaceae, showed significant antioxidant ability (DPPH and ORAC = 1062.9 and 645.9 ± 51.4 µg TE/mg extract, respectively), while Annona montana Macfad., Annonaceae, demonstrated the most promising anti-proliferative effect (IC50 for Hep-G2 and HT-29 = 2.7 and 9.0 µg/ml, respectively). However, combinatory antioxidant/anti-proliferative effect was only detected in Oenocarpus bataua Mart., Arecaceae (DPPH = 903.8 and ORAC = 1024 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 102.6 and 38.8 µg/ml, respectively) and Inga edulis Mart., Fabaceae (DPPH = 337.0 and ORAC = 795.7 µg TE/mg extract; IC50 for Hep-G2 and HT-29 at 36.3 and 57.9 µg/ml, respectively). Phenolic content was positively correlated with antioxidant potential, however not with anti-proliferative effect. None of these extracts possessed toxicity towards normal foetal lung cells, suggesting their possible use in development of novel plant-based agents with preventive and/or therapeutic action against oxidative stress-related diseases.

In vitro immunomodulatory activity, cytotoxicity and chemistry of some central European polypores.

Context Some mushrooms of the order Polyporales are known for their immunomodulatory actions. Objective The objective of this study is to evaluate the in vitro phagocytic and cytotoxic effects of extracts from polyporales native to Central Europe. Materials and methods The effects of ethanol extracts from 27 polypore species on opsonized zymosan-induced phagocytosis of isolated human neutrophils were tested by a chemiluminescence method. Colon epithelial cell lines, Caco-2 and HT-29, were used for cytotoxicity assays, and extracts were chemically characterized in terms of total phenolic and ß-glucan content. Results We observed phagocytosis or respiratory burst enhancing activity in 17 extracts, of which five species, namely Aurantiporus fissilis (Berk. & M.A. Curtis) H. Jahn ex Ryvarden, Trametes gibbosa (Pers.) Fr., Piptoporus betulinus (Bull.) P. Karst, Neolentinus lepideus (Fr.) Redhead & Ginns, Polyporus squamosus (Huds.) Fr., significantly increased phagocytosis in granulocytes by 205, 181, 158, 155 and 141%, respectively. The ß-glucan content of the three most potent extracts was 58, 42 and 74 mg/g, respectively, and the polyphenol content was 155.6, 133.5 and 155.2 µmol of gallic acid equivalent/g, respectively. Some extracts showed cytotoxic activity, with higher cytotoxicity in Caco-2 than in HT-29 cells. Pycnoporus cinnabarinus (Jacq.) P. Karst. extract was cytotoxic to both cell lines, with IC50 values of 81 and 31 µg/mL, respectively. Discussion and conclusion The most promising extracts were from N. lepideus and Polyporus squamosus, which are edible species and may be considered safe. Our findings support their use as culinary preparations or food supplements for various immunological gut disorders.