Onosma riedliana Binzet & Orcan, a traditionally used plant species, has been explored for its therapeutic potential in this study. The work presented here is the first report on the phenolic profile and biological activity of this species. Three extracts of varying polarity were prepared, with the methanolic extract containing the highest phenolic content (97.62 ± 0.20 mgGAE/g). Key phenolic compounds identified included pinoresinol, hesperidin, 4-hydroxybenzoic acid, and p-coumaric acid. The methanolic extract exhibited exceptional antioxidant properties, rivaling Trolox as a positive control, primarily attributed to hesperidin and luteolin. Moreover, the ethyl acetate extract demonstrated remarkable inhibition of cholinesterase and tyrosinase enzymes, while the methanolic extract displayed potent activity against carbohydrate hydrolytic enzymes, α-amylase and α-glucosidase. Again, phenolic compounds were shown to be responsible for the inhibition of cholinesterases and tyrosinase, but not for α-amylase and α-glucosidase. These findings underscore Onosma riedliana's potential for incorporation into diverse pharmaceutical formulations, given its multifaceted bioactivity.
Based on the mimicry of microbial metabolites, functionalized indoles were demonstrated as the ligands and agonists of the pregnane X receptor (PXR). The lead indole, FKK6, displayed PXR-dependent protective effects in DSS-induced colitis in mice and in vitro cytokine-treated intestinal organoid cultures. Here, we report on the initial in vitro pharmacological profiling of FKK6. FKK6-PXR interactions were characterized by hydrogen-deuterium exchange mass spectrometry. Screening FKK6 against potential cellular off-targets (G protein-coupled receptors, steroid and nuclear receptors, ion channels, and xenobiotic membrane transporters) revealed high PXR selectivity. FKK6 has poor aqueous solubility but was highly soluble in simulated gastric and intestinal fluids. A large fraction of FKK6 was bound to plasma proteins and chemically stable in plasma. The partition coefficient of FKK6 was 2.70, and FKK6 moderately partitioned into red blood cells. In Caco2 cells, FKK6 displayed high permeability (A-B: 22.8 × 10-6 cm.s-1) and no active efflux. These data are indicative of essentially complete in vivo absorption of FKK6. The data from human liver microsomes indicated that FKK6 is rapidly metabolized by cytochromes P450 (t1/2 5 min), notably by CYP3A4. Two oxidized FKK6 derivatives, including DC73 (N6-oxide) and DC97 (C19-phenol), were detected, and these metabolites had 5-7 × lower potency as PXR agonists than FKK6. This implies that despite high intestinal absorption, FKK6 is rapidly eliminated by the liver, and its PXR effects are predicted to be predominantly in the intestines. In conclusion, the PXR ligand and agonist FKK6 has a suitable pharmacological profile supporting its potential preclinical development.
Although medical cannabis was legalized in Czechia in 2013 and its use in topical treatments of skin disorders is now allowed, galenic formulations prepared from medical cannabis have not been widely implemented in the Czech healthcare system. One of the main reasons is the lack of a straightforward standardized protocol for their preparation. Cannabinoids, e.g., cannabidiol (CBD) and tetrahydrocannabinol (THC), have been shown to have therapeutic effects on various skin conditions, such as atopic dermatitis, psoriasis, scleroderma, acne and skin pigmentation. Recognizing the potential of dermatological treatment with medical cannabis, the present study aimed to evaluate the extraction capacity of various pharmaceutical bases for cannabinoids and the stability of prepared galenic formulations for dermatological applications with respect to cannabinoid content. The results showed that the stability of cannabinoids in formulations depended on the bases' physical and chemical properties. The highest THC decomposition was observed in cream bases and Vaseline, with estimated percentage loss of total content of up to 5.4% and 5.6% per week, respectively. In contrast, CBD was more stable than THC. Overall, the tested bases were comparably effective in extracting cannabinoids from plant material. However, olive oil and Synderman bases exhibited the highest cannabinoid extraction efficiencies (approximately 70%) and the best storage stabilities in terms of the content of monitored compounds. The proposed preparation protocol is fast and easily implementable in pharmacies and medical facilities.
- Publikační typ
- časopisecké články MeSH
Cannabinoids, a class of compounds derived from Cannabis sativa L., have recently become more widely accessible for public consumption in the form of diverse cannabis products, in parallel with weakening the measures that so far restricted their availability. The US Food and Drug Administration has approved several cannabis-derived drugs for management of various diseases as well as chemotherapy-induced nausea and vomiting. Besides the attenuation of adverse effects of chemotherapy, numerous reports about cannabinoid-mediated anticancer effects further motivate cancer patients to support their therapy with such products. Here we present a set of preclinical data with human cell culture models, suggesting that cannabidiol and cannabis extracts may effectively counteract the anticancer effects of the clinically widely used standard-of-care platinum-based drugs. We show that even low concentrations of cannabinoids reduced the toxicity of cisplatin, oxaliplatin, and carboplatin, an effect which was accompanied by decreased platinum adduct formation and a set of commonly used molecular markers. Mechanistically, our results excluded the possibility that the observed enhanced survival of cancer cells was mediated transcriptionally. Instead, trace metal analyses strongly indicate an inhibitory impact of cannabinoids on intracellular platinum accumulation, thereby implicating changes in cellular transport and/or retention of these drugs as the likely cause of the observed biological effects. Our study raises the possibility that the desirable effect of counteracting adverse effects of chemotherapy might, at least for some cannabinoids, reflect impaired cellular availability, and consequently attenuation of the anticancer effects of platinum drugs. DATA AVAILABILITY: All data supporting the conclusions are available in the article and supplementary files. Raw data are available upon request from the corresponding author.
Konopí pro léčebné použití bylo úspěšně inkorporováno do české klinické praxe, zejména v oborech algeziologie a neurologie. Současnou legislativní úpravou je léčebné konopí možné používat rovněž v dermatologii v indikaci povrchová léčba dermatóz a slizničních lézí. Toto využití je nicméně prozatím opomíjeno, zejména také z důvodu neexistence standardizovaného postupu přípravy dermálních lékových forem v lékárnách a rovněž kvůli nemožnosti využití standardizovaných extraktů léčebného konopí, které jsou například dostupné v zahraničí. Ovlivnění endokanabinoidního systému topicky na úrovni pokožky nicméně skýtá zajímavý farmakologický cíl u řady kožních onemocnění. Předkládaný přehled si klade za cíl shrnout dostupné informace a potenciál využití léčebného konopí při topické dermální aplikaci.
Cannabis for medical use has been successfully incorporated into Czech clinical practice, especially in the fields of algesiology and neurology. Under the current legislation, medical cannabis can also be used in dermatology in the indication surface treatment of dermatoses and mucosal lesions. However, this use is so far neglected, mainly due to the lack of a standardized procedure for the preparation of dermal dosage forms in pharmacies and also due to the unavailability of standardized medicinal cannabis extracts, which are available abroad. However, influencing the endocannabinoid system topically at the skin level provides an interesting pharmacological target for a number of skin diseases. The present review aims to summarize the available information and the potential use of medical cannabis in topical dermal application.
- MeSH
- aplikace kožní MeSH
- kožní nemoci terapie MeSH
- lidé MeSH
- marihuana pro léčebné účely * farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Konopí pro léčebné použití bylo úspěšně inkorporováno do české klinické praxe, zejména v oborech algeziologie a neurologie. Současnou legislativní úpravou je léčebné konopí možné používat rovněž v dermatologii v indikaci povrchová léčba dermatóz a slizničních lézí. Toto využití je nicméně prozatím opomíjeno, zejména také z důvodu neexistence standardizovaného postupu přípravy dermálních lékových forem v lékárnách a rovněž kvůli nemožnosti využití standardizovaných extraktů léčebného konopí, které jsou například dostupné v zahraničí. Ovlivnění endokanabinoidního systému topicky na úrovni pokožky nicméně skýtá zajímavý farmakologický cíl u řady kožních onemocnění. Předkládaný přehled si klade za cíl shrnout dostupné informace a potenciál využití léčebného konopí při topické dermální aplikaci.
Cannabis for medical use has been successfully incorporated into Czech clinical practice, especially in the fields of algesiology and neurology. Under the current legislation, medical cannabis can also be used in dermatology in the indication surface treatment of dermatoses and mucosal lesions. However, this use is so far neglected, mainly due to the lack of a standardized procedure for the preparation of dermal dosage forms in pharmacies and also due to the unavailability of standardized medicinal cannabis extracts, which are available abroad. However, influencing the endocannabinoid system topically at the skin level provides an interesting pharmacological target for a number of skin diseases. The present review aims to summarize the available information and the potential use of medical cannabis in topical dermal application.
- MeSH
- aplikace kožní MeSH
- kožní nemoci terapie MeSH
- lidé MeSH
- marihuana pro léčebné účely * farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
This study presents the very first report on the in vitro antiviral activity of selected essential oils of Lamiaceae plant species and their monoterpenes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nineteen essential oils were obtained by hydrodistillation of dried plant material, and their monoterpene profiles were determined. In addition, the exact concentrations of each monoterpene that were found at a significant level were defined. Both essential oils and their monoterpene components were tested for cytotoxic and antiviral activity against SARS-CoV-2 in infected Vero 76 cells. The results showed that the essential oils of four Mentha species, i.e., M. aquatica L. cv. Veronica, M. pulegium L., M. microphylla K.Koch, and M. x villosa Huds., but also Micromeria thymifolia (Scop.) Fritsch and Ziziphora clinopodioides Lam., and five different monoterpenes, i.e., carvacrol, carvone, 1,8-cineol, menthofuran, and pulegone, inhibited the SARS-CoV-2 replication in the infected cells. However, the antiviral activity varied both among essential oils and monoterpenes. Carvone and carvacrol exhibited moderate antiviral activity with IC50 concentrations of 80.23 ± 6.07 μM and 86.55 ± 12.73 μM, respectively, while the other monoterpenes were less active (IC50 > 100.00 μM). Structure-activity relations of related monoterpenes showed that the presence of keto and hydroxyl groups is associated with the activity of carvone and carvacrol, respectively. Furthermore, the carvone-rich essential oil of M. x villosa had the greatest activity among all active essential oils (IC50 127.00 ± 4.63 ppm) while the other active oils exhibited mild (140 ppm < IC50 < 200 ppm) to weak antiviral activity (IC50 > 200 ppm). Both essential oils and monoterpenes showed limited or no cytotoxicity against Vero 76 cells. Hierarchical cluster analysis showed that the differences in the antiviral activity of essential oils were directly attributed to the antiviral efficacies of their particular single monoterpenes. The findings presented here on the novel antiviral property of plant essential oils and monoterpenes might be used in the development of different measures against SARS-CoV-2.
- Publikační typ
- časopisecké články MeSH
Tasteful morels (Morchella sp.) are one of the most popular mushrooms, both economically and scientifically. Due to their beneficial constituents, they are classified as functional foods. This study focuses on the chemical composition and biological activities of a wild edible mushroom, Morchella steppicola Zerova. The metal composition of this species reveals high levels of biogenic elements. However, according to the levels of iron and cobalt, and calculated health risk indices, this mushroom can be recommended for occasional consumption. Also, M. steppicola is found to be rich in gallic acid, protocatechuic acid, 4-hydroxybenzoic acid, and vanillic acid. Statistical analysis showed that mainly 4-hydroxybenzoic and vanillic acids are responsible for both antioxidant and inhibition of enzymes α-amylase and tyrosinase. Presented work acknowledges the fact that this mushroom has significant potential to be used for the treatment of several human disorders, similarly to other members of this genus.
- MeSH
- Agaricales * chemie MeSH
- antioxidancia chemie MeSH
- Ascomycota * MeSH
- fenoly analýza MeSH
- lidé MeSH
- minerály MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cannabis is a plant containing a mixture of chemical substances of unique composition, and therefore it has vast array of applications. Hemp fiber and shives are used in the paper, construction and textile industries. Hemp seeds and products have high nutritional value for humans. They contain significant amounts of essential amino acids and represent a source of ω-3 and ω-6 essential fatty acids. In addition, cannabis flowers contain a broad spectrum of secondary metabolites (phytocannabinoids, terpenoids, and phenylpropanoids), which possess beneficial properties against various disorders. This review summarizes the current knowledge of cannabis chemistry, as well as its utilization for various purposes. Special attention is focused on the biosynthesis of phytocannabinoids.
- Klíčová slova
- fytokanabinoidy,
- MeSH
- Cannabis * chemie klasifikace metabolismus MeSH
- marihuana pro léčebné účely MeSH
- Publikační typ
- práce podpořená grantem MeSH
Directional transport of the phytohormone auxin is a versatile, plant-specific mechanism regulating many aspects of plant development. The recently identified plant hormones, strigolactones (SLs), are implicated in many plant traits; among others, they modify the phenotypic output of PIN-FORMED (PIN) auxin transporters for fine-tuning of growth and developmental responses. Here, we show in pea and Arabidopsis that SLs target processes dependent on the canalization of auxin flow, which involves auxin feedback on PIN subcellular distribution. D14 receptor- and MAX2 F-box-mediated SL signaling inhibits the formation of auxin-conducting channels after wounding or from artificial auxin sources, during vasculature de novo formation and regeneration. At the cellular level, SLs interfere with auxin effects on PIN polar targeting, constitutive PIN trafficking as well as clathrin-mediated endocytosis. Our results identify a non-transcriptional mechanism of SL action, uncoupling auxin feedback on PIN polarity and trafficking, thereby regulating vascular tissue formation and regeneration.
- MeSH
- Arabidopsis genetika metabolismus MeSH
- heterocyklické sloučeniny tricyklické metabolismus MeSH
- hrách setý genetika metabolismus MeSH
- kyseliny indoloctové metabolismus MeSH
- laktony metabolismus MeSH
- proteiny huseníčku genetika metabolismus MeSH
- regulace genové exprese u rostlin genetika fyziologie MeSH
- regulátory růstu rostlin metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
