This study deals with the comprehensive phytochemical composition and antiviral activity against SARS-CoV-2 of acidic (non-decarboxylated) and neutral (decarboxylated) ethanolic extracts from seven high-cannabidiol (CBD) and two high-Δ9-tetrahydrocannabinol (Δ9-THC) Cannabis sativa L. genotypes. Their secondary metabolite profiles, phytocannabinoid, terpenoid, and phenolic, were determined by LC-UV, GC-MS, and LC-MS/MS analyses, respectively. All three secondary metabolite profiles, cannabinoid, terpenoid, and phenolic, varied significantly among cannabinoid extracts of different genotypes. The dose-response analyses of their antiviral activity against SARS-CoV-2 showed that only the single predominant phytocannabinoids (CBD or THC) of the neutral extracts exhibited antiviral activity (all IC50 < 10.0 μM). The correlation matrix between phytoconstituent levels and antiviral activity revealed that the phenolic acids, salicylic acid and its glucoside, chlorogenic acid, and ferulic acid, and two flavonoids, abietin, and luteolin, in different cannabinoid extracts from high-CBD genotypes are implicated in the genotype-distinct antagonistic effects on the predominant phytocannabinoid. On the other hand, these analyses also suggested that the other phytocannabinoids and the flavonoid orientin can enrich the extract's pharmacological profiles. Thus, further preclinical studies on cannabinoid extract formulations with adjusted non-phytocannabinoid compositions are warranted to develop supplementary antiviral treatments.
Background: The research is aimed at exploring the potential of marigold petal tea (MPT), rich in polyphenol contents, against oxidative stress and obesity in a rat model following a high-fat-sugar diet (HFSD). Methods: The MPT was prepared through the customary method of decoction and was subjected to analysis for its polyphenol composition using reversed-phase high-performance liquid chromatography (RP-HPLC). Two specific doses of MPT, namely, 250 and 500 mg/kg body weight (BW), were chosen for the study-referred to as MPT-250 and MPT-500, respectively. Result: The main phenolic acids and flavonoids identified in MPT, with concentrations exceeding 10 mg/100 mL of tea, included catechin, rutin, salicylic acid, gallic acid, sinapic acid, chlorogenic acid, cinnamic acid, and ellagic acid. The total phenolic (TP) and total flavonoid (TF) contents in MPT were measured to be 5.53 and 7.73 mg/g, respectively. Additionally, MPT demonstrated a 57.2% scavenging capacity with 2,2-diphenyl-1-picrylhydrazyl radical. Notably, the administration of a higher dose (MPT-500) showed a significant reduction in body mass index (BMI) and a 51.24% reduction in the rate of increase in BW compared to the HFSD group. The findings indicated that all the treatment groups, that is, orlistat treatment (OT), MPT-250, and MPT-500 groups, experienced reduced levels of serum total cholesterol (TC), triglyceride (TG), and markers of lipoproteins in contrast to the HFSD group. Moreover, MPT helped restore the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), thereby demonstrating its potential in combating oxidative stress. The MPT-500 group also displayed decreased liver and kidney weights and an improved atherogenic index when compared to the HFSD group. Conclusion: The results clearly indicate that a high dosage of MPT showed antiobesity activity which was comparable to the same effects produced by the conventional drug orlistat.
- MeSH
- Antioxidants * pharmacology MeSH
- Biomarkers * blood MeSH
- Diet, High-Fat * MeSH
- Weight Loss drug effects MeSH
- Liver drug effects metabolism MeSH
- Rats MeSH
- Anti-Obesity Agents * pharmacology MeSH
- Disease Models, Animal * MeSH
- Obesity * drug therapy metabolism MeSH
- Oxidative Stress * drug effects MeSH
- Polyphenols * pharmacology MeSH
- Rats, Sprague-Dawley MeSH
- Plant Extracts pharmacology isolation & purification MeSH
- Diet, Carbohydrate Loading adverse effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The story of aspirin is exciting and complicated. We tried to decipher the role of the main characters, as well as a wide field of pharmacological roles of acetylsalicylic acid, a super-drug, which would not be approved by responsible institutions today but which is still one of the most used medicines on the Earth, as well as in the space (it was used by the astronauts in the Apollo project). Original literature sources were used as much as possible to clean up some misinformation around the topic. The authors are aware that Aspirin is a trademarked name but it has become "popular" in common human speech.
- MeSH
- Analgesics chemistry MeSH
- Antipyretics chemistry MeSH
- Aspirin * pharmacology therapeutic use MeSH
- Phytotherapy * methods MeSH
- Platelet Aggregation Inhibitors chemistry MeSH
- Pharmaceutical Preparations * chemistry history MeSH
- Humans MeSH
- Salicylates chemistry pharmacology therapeutic use MeSH
- Salix chemistry physiology MeSH
- Check Tag
- Humans MeSH
The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment.
- MeSH
- Acrylamides chemistry pharmacology administration & dosage MeSH
- Anti-Inflammatory Agents pharmacology administration & dosage chemistry MeSH
- Aspirin * administration & dosage pharmacology chemistry MeSH
- Prostaglandin-Endoperoxide Synthases metabolism MeSH
- Cyclooxygenase Inhibitors pharmacology administration & dosage chemistry MeSH
- Delayed-Action Preparations * MeSH
- Inflammation Mediators metabolism MeSH
- Mice MeSH
- Nanoparticles * chemistry MeSH
- Drug Carriers chemistry MeSH
- Polymers * chemistry administration & dosage MeSH
- Drug Liberation MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Introduction: Based on extensive data from oncology research, the use of phytochemicals or plant-based nutraceuticals is considered an innovative tool for cancer management. This research aimed to analyze the oncostatic properties of Salvia officinalis L. [Lamiaceae; Salviae officinalis herba] using animal and in vitro models of breast carcinoma (BC). Methods: The effects of dietary administered S. officinalis in two concentrations (0.1%/SAL 0.1/and 1%/SAL 1/) were assessed in both syngeneic 4T1 mouse and chemically induced rat models of BC. The histopathological and molecular evaluations of rodent carcinoma specimens were performed after the autopsy. Besides, numerous in vitro analyses using two human cancer cell lines were performed. Results and Conclusion: The dominant metabolites found in S. officinalis propylene glycol extract (SPGE) were representatives of phenolics, specifically rosmarinic, protocatechuic, and salicylic acids. Furthermore, the occurrence of triterpenoids ursolic and oleanolic acid was proved in SPGE. In a mouse model, a non-significant tumor volume decrease after S. officinalis treatment was associated with a significant reduction in the mitotic activity index of 4T1 tumors by 37.5% (SAL 0.1) and 31.5% (SAL 1) vs. controls (set as a blank group with not applied salvia in the diet). In addition, salvia at higher doses significantly decreased necrosis/whole tumor area ratio by 46% when compared to control tumor samples. In a rat chemoprevention study, S. officinalis at a higher dose significantly lengthened the latency of tumors by 8.5 days and significantly improved the high/low-grade carcinomas ratio vs. controls in both doses. Analyses of the mechanisms of anticancer activities of S. officinalis included well-validated prognostic, predictive, and diagnostic biomarkers that are applied in both oncology practice and preclinical investigation. Our assessment in vivo revealed numerous significant changes after a comparison of treated vs. untreated cancer cells. In this regard, we found an overexpression in caspase-3, an increased Bax/Bcl-2 ratio, and a decrease in MDA, ALDH1, and EpCam expression. In addition, salvia reduced TGF-β serum levels in rats (decrease in IL-6 and TNF-α levels were with borderline significance). Evaluation of epigenetic modifications in rat cancer specimens in vivo revealed a decline in the lysine methylations of H3K4m3 and an increase in lysine acetylation in H4K16ac levels in treated groups. Salvia decreased the relative levels of oncogenic miR21 and tumor-suppressive miR145 (miR210, miR22, miR34a, and miR155 were not significantly altered). The methylation of ATM and PTEN promoters was decreased after S. officinalis treatment (PITX2, RASSF1, and TIMP3 promoters were not altered). Analyzing plasma metabolomics profile in tumor-bearing rats, we found reduced levels of ketoacids derived from BCAAs after salvia treatment. In vitro analyses revealed significant anti-cancer effects of SPGE extract in MCF-7 and MDA-MB-231 cell lines (cytotoxicity, caspase-3/-7, Bcl-2, Annexin V/PI, cell cycle, BrdU, and mitochondrial membrane potential). Our study demonstrates the significant chemopreventive and treatment effects of salvia haulm using animal or in vitro BC models.
- Publication type
- Journal Article MeSH
Bolesť je závažný subjektívny vnem, ktorý hoci má ochranný charakter, pacienta nielen fyzicky, ale aj psychicky vyčerpáva. Farmakologická oblasť vývoja a výskumu liečby a odstraňovania bolesti je od izolovania kyseliny salicylovej stále dynamická a zaujímavá. Po objavení molekulárnej podstaty cyklooxygenázy a jej inhibície sa výskum nasmeroval na selektívne inhibítory COX-2, ktoré však boli veľkým sklamaním. Dnes sa opäť objavuje možnosť ako kombináciou liečiv prispieť pacientovi k bezpečnej a účinnej analgeticko-antiflogistickej liečbe.
Pain is a serious subjective experience, which, although it has a protective nature, it physically and mentally exhausts the patient. The pharmacological field of development and research in the treatment and relief of pain has been dynamic and interesting ever since the isolation of salicylic acid. After discovering the molecular nature of cyclooxygenase and its inhibition, research focused on selective COX-2 inhibitors, but they were a big disappointment. Today, the possibility of contributing to safe and effective analgesic-antiphlogistic treatment for the patient with a combination of drugs is emerging again.
- MeSH
- Anti-Inflammatory Agents, Non-Steroidal pharmacology adverse effects therapeutic use MeSH
- Cyclooxygenase 2 Inhibitors * pharmacology adverse effects therapeutic use MeSH
- Cardiotoxicity MeSH
- Humans MeSH
- Pain Management MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
AIMS: Neuroinflammation is a prominent hallmark in several neurodegenerative diseases (NDs). Halting neuroinflammation can slow down the progression of NDs. Improving the efficacy of clinically available non-steroidal anti-inflammatory drugs (NSAIDs) is a promising approach that may lead to fast-track and effective disease-modifying therapies for NDs. Here, we aimed to utilize the L-type amino acid transporter 1 (LAT1) to improve the efficacy of salicylic acid as an example of an NSAID prodrug, for which brain uptake and intracellular localization have been reported earlier. MAIN METHODS: Firstly, we confirmed the improved LAT1 utilization of the salicylic acid prodrug (SA-AA) in freshly isolated primary mouse microglial cells. Secondly, we performed behavioural rotarod, open field, and four-limb hanging tests in mice, and a whole-brain proteome analysis. KEY FINDINGS: The SA-AA prodrug alleviated the lipopolysaccharide (LPS)-induced inflammation in the rotarod and hanging tests. The proteome analysis indicated decreased neuroinflammation at the molecular level. We identified 399 proteins linked to neuroinflammation out of 7416 proteins detected in the mouse brain. Among them, Gps2, Vamp8, Slc6a3, Slc18a2, Slc5a7, Rgs9, Lrrc1, Ppp1r1b, Gnal, and Adcy5/6 were associated with the drug's effects. The SA-AA prodrug attenuated the LPS-induced neuroinflammation through the regulation of critical pathways of neuroinflammation such as the cellular response to stress and transmission across chemical synapses. SIGNIFICANCE: The efficacy of NSAIDs can be improved via the utilization of LAT1 and repurposed for the treatment of neuroinflammation. This improved brain delivery and microglia localisation can be applied to other inflammatory modulators to achieve effective and targeted CNS therapies.
- MeSH
- Anti-Inflammatory Agents, Non-Steroidal * pharmacology MeSH
- Intracellular Signaling Peptides and Proteins metabolism MeSH
- Salicylic Acid pharmacology MeSH
- Lipopolysaccharides MeSH
- Microglia metabolism MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Neurodegenerative Diseases * metabolism MeSH
- Neuroinflammatory Diseases * drug therapy MeSH
- Prodrugs * pharmacology MeSH
- Proteome metabolism MeSH
- Inflammation drug therapy metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: In this review, we present a contemporary look at the management of travellers' diarrhoea (TD), and we discuss the potential role of a microbiome as well as the administration of live microorganisms in order to prevent TD. METHODS: We performed a comprehensive search using the PubMed and Web of Science databases for the period 2014-2021, looking for original and review articles on travellers' diarrhoea. RESULTS: TD belongs among the most frequent illnesses experienced by travellers. For the most part, it is manifested as an acute yet self limiting condition, and only in a few cases proceeds to a prolonged form. Epidemiological analyses have shown that the majority of TD cases are caused by bacterial infections. In practice, pharmacological therapy is often used in the prevention and treatment of TD, since patients naturally seek preventive measures against the development of its severe course and its impact on planned activities. Bismuth salicylate is a strongly recommended TD prophylaxis but is not available on all European Union markets. Although the antibiotic prophylaxis is not generally recommended in guidelines, some antibiotic or chemotherapeutic agents are accessible over-the-counter in certain countries, and travellers are routinely encouraged to use them preventively. This routine can alter the microbiome of the traveller and promote the spread of drug resistant bacteria in their place of residence. Probiotic administration is considered safe, although the quality of evidence in favour of its prophylactic use in TD is currently low. CONCLUSIONS: The challenge for public health authorities is to educate personnel that can directly influence the behaviour of travellers through safe and effective pharmacological alternatives to antibiotics. Manipulation of the gut microbiome using specific probiotic strains can represent a safe and promising intervention.
- MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Travel MeSH
- Humans MeSH
- Microbiota * MeSH
- Diarrhea * prevention & control MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes' coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84-1.27 and OR: 1.08, 95% CI: 0.86-1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use.
- MeSH
- Aspirin therapeutic use MeSH
- Genome-Wide Association Study MeSH
- Diet MeSH
- Genotyping Techniques MeSH
- Polymorphism, Single Nucleotide MeSH
- Colorectal Neoplasms blood epidemiology genetics prevention & control MeSH
- Salicylic Acid administration & dosage blood MeSH
- Humans MeSH
- Mendelian Randomization Analysis MeSH
- Risk Factors MeSH
- Case-Control Studies MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
... TOXICITY 610 -- DESOMORPHINE (KROKODIL) 612 -- CONTENTS ¦ xi -- ACETAMINOPHEN POISONING 613 -- SALICYLATE ... ... HYPERKALEMIA 856 -- HYPOKALEMIA 858 -- PULMONARY EMBOLISM 859 -- PERICARDIAL EFFUSION 860 -- DIGOXIN EFFECT ... ... , TOXICITY 861 -- TRICYCLIC ANTIDEPRESSANT EFFECT 862 -- LIMB LEAD REVERSAL 863 -- LOW VOLTAGE 864 -- ...
Fifth edition xl, 1016 stran : ilustrace ; 28 cm
- MeSH
- Emergencies MeSH
- Critical Care MeSH
- Wounds and Injuries MeSH
- Emergency Treatment MeSH
- Publication type
- Atlas MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- urgentní lékařství
- NML Publication type
- kolektivní monografie
