Cornelian Cherry (Cornus mas L.) Fruit Extract Lowers SREBP-1c and C/EBPα in Liver and Alters Various PPAR-α, PPAR-γ, LXR-α Target Genes in Cholesterol-Rich Diet Rabbit Model.

Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impacts on the functions of the cardiovascular system and the liver. This study aims to assess and compare whether and to what extent two different doses of resin-purified cornelian cherry extract (10 mg/kg b.w. or 50 mg/kg b.w.) applied in a cholesterol-rich diet rabbit model affect the levels of sterol regulatory element-binding protein 1c (SREBP-1c) and CCAAT/enhancer binding protein α (C/EBPα), and various liver X receptor-α (LXR-α), peroxisome proliferator-activated receptor-α (PPAR-α), and peroxisome proliferator-activated receptor-γ (PPAR-γ) target genes. Moreover, the aim is to evaluate the resistive index (RI) of common carotid arteries (CCAs) and aortas, and histopathological changes in CCAs. For this purpose, the levels of SREBP-1c, C/EBPα, ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), fatty acid synthase (FAS), endothelial lipase (LIPG), carnitine palmitoyltransferase 1A (CPT1A), and adiponectin receptor 2 (AdipoR2) in liver tissue were measured. Also, the levels of lipoprotein lipase (LPL), visceral adipose tissue-derived serine protease inhibitor (Vaspin), and retinol-binding protein 4 (RBP4) in visceral adipose tissue were measured. The RI of CCAs and aortas, and histopathological changes in CCAs, were indicated. The oral administration of the cornelian cherry extract decreased the SREBP-1c and C/EBPα in both doses. The dose of 10 mg/kg b.w. increased ABCA1 and decreased FAS, CPT1A, and RBP4, and the dose of 50 mg/kg b.w. enhanced ABCG1 and AdipoR2. Mitigations in atheromatous changes in rabbits' CCAs were also observed. The obtained outcomes were compared to the results of our previous works. The beneficial results confirm that cornelian cherry fruit extract may constitute a potentially effective product in the prevention and treatment of obesity-related disorders.

Sanguinarine-Chelerythrine Fraction of Coptis chinensis Exerts Anti-inflammatory Activity in Carrageenan Paw Oedema Test in Rats and Reveals Reduced Gastrotoxicity.

Inflammatory diseases are a common therapeutic problem and nonsteroidal anti-inflammatory drugs are not deprived of side effects, of which ulcerogenic activity is one of the most frequent. The aim of the study was to evaluate the anti-inflammatory activity of the sanguinarine-chelerythrine (SC) fraction of Coptis chinensis and its influence on the integrity of gastric mucosa. The study was conducted on sixty male rats randomly divided into six experimental groups: two control groups (a negative control group CON and a positive control group CAR); three groups receiving an investigational fraction of C. chinensis (1, 5, 10 mg/kg i.g.) named SC1, SC5, and SC10, respectively; and a group receiving indomethacin (IND) (10 mg/kg i.g.) as a reference drug. In all animals, the carrageenan-induced paw oedema was measured; PGE2 release, TNFα production, and MMP-9 concentration in inflamed tissue were determined. Additionally, the macroscopic and microscopic damage of gastric mucosa was evaluated. Administration of SC dose-dependently inhibited the second phase of carrageenan rat paw oedema and PGE2 release, decreased the production of TNFα, and reduced the concentration of MMP-9, and the efficacy of the highest dose was comparable to the effect of IND. Contrary to IND, no gastrotoxic activity of SC was detected. The investigated sanguinarine-chelerythrine fraction of C. chinensis seems to be a promising candidate for further research on new anti-inflammatory and analgesic drugs characterized with a safer gastric profile compared to existing NSAIDs.

Antibiofilm and Antimicrobial-Enhancing Activity of Chelidonium majus and Corydalis cheilanthifolia Extracts against Multidrug-Resistant Helicobacter pylori.

Helicobacter pylori is a Gram-negative bacterium that colonizes the stomach of about 60% of people worldwide. The search for new drugs with activity against H. pylori is now a hotspot in the effective and safe control of this bacterium. Therefore, the aim of this research was to determine the antibacterial activity of extracts from selected plants of the Papaveraceae family against planktonic and biofilm forms of the multidrug-resistant clinical strain of H. pylori using a broad spectrum of analytical in vitro methods. It was revealed that among the tested extracts, those obtained from Corydalis cheilanthifolia and Chelidonium majus were the most active, with minimal inhibitory concentrations (MICs) of 64 µg/mL and 128 µg/mL, respectively. High concentrations of both extracts showed cytotoxicity against cell lines of human hepatic origin. Therefore, we attempted to lower their MICs through the use of a synergistic combination with synthetic antimicrobials as well as by applying cellulose as a drug carrier. Using checkerboard assays, we determined that both extracts presented synergistic interactions with amoxicillin (AMX) and 3-bromopyruvate (3-BP) (FICI = 0.5) and additive relationships with sertraline (SER) (FICI = 0.75). The antibiofilm activity of extracts and their combinations with AMX, 3-BP, or SER, was analyzed by two methods, i.e., the microcapillary overgrowth under flow conditions (the Bioflux system) and assessment of the viability of lawn biofilms after exposure to drugs released from bacterial cellulose (BC) carriers. Using both methods, we observed a several-fold decrease in the level of H. pylori biofilm, indicating the ability of the tested compounds to eradicate the microbial biofilm. The obtained results indicate that application of plant-derived extracts from the Papaveraceae family combined with synthetic antimicrobials, absorbed into organic BC carrier, may be considered a promising way of fighting biofilm-forming H. pylori.

Screening Papaveraceae as Novel Antibiofilm Natural-Based Agents.

The antimicrobial properties of herbs from Papaveraceae have been used in medicine for centuries. Nevertheless, mutual relationships between the individual bioactive substances contained in these plants remain poorly elucidated. In this work, phytochemical composition of extracts from the aerial and underground parts of five Papaveraceae species (Chelidonium majus L., Corydalis cava (L.) Schweigg. and Körte, C. cheilanthifolia Hemsl., C. pumila (Host) Rchb., and Fumaria vaillantii Loisel.) were examined using LC-ESI-MS/MS with a triple quadrupole analyzer. Large differences in the quality and quantity of all analyzed compounds were observed between species of different genera and also within one genus. Two groups of metabolites predominated in the phytochemical profiles. These were isoquinoline alkaloids and, in smaller amounts, non-phenolic carboxylic acids and phenolic compounds. In aerial and underground parts, 22 and 20 compounds were detected, respectively. These included: seven isoquinoline alkaloids: protopine, allocryptopine, coptisine, berberine, chelidonine, sanguinarine, and chelerythrine; five of their derivatives as well as non-alkaloids: malic acid, trans-aconitic acid, quinic acid, salicylic acid, trans-caffeic acid, p-coumaric acid, chlorogenic acid, quercetin, and kaempferol; and vanillin. The aerial parts were much richer in phenolic compounds regardless of the plant species. Characterized extracts were studied for their antimicrobial potential against planktonic and biofilm-producing cells of S. aureus, P. aeruginosa, and C. albicans. The impact of the extracts on cellular metabolic activity and biofilm biomass production was evaluated. Moreover, the antimicrobial activity of the extracts introduced to the polymeric carrier made of bacterial cellulose was assessed. Extracts of C. cheilanthifolia were found to be the most effective against all tested human pathogens. Multiple regression tests indicated a high antimicrobial impact of quercetin in extracts of aerial parts against planktonic cells of S. aureus, P. aeruginosa, and C. albicans, and no direct correlation between the composition of other bioactive substances and the results of antimicrobial activity were found. Conclusively, further investigations are required to identify the relations between recognized and unrecognized compounds within extracts and their biological properties.

Botanicals in Postmenopausal Osteoporosis.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and the deterioration of bone microarchitecture leading to bone fragility and an increased risk of fractures. Conventional anti-osteoporotic pharmaceutics are effective in the treatment and prophylaxis of osteoporosis, however they are associated with various side effects that push many women into seeking botanicals as an alternative therapy. Traditional folk medicine is a rich source of bioactive compounds waiting for discovery and investigation that might be used in those patients, and therefore botanicals have recently received increasing attention. The aim of this review of literature is to present the comprehensive information about plant-derived compounds that might be used to maintain bone health in perimenopausal and postmenopausal females.

Pharmacodynamic and pharmacokinetic interactions between simvastatin and diazepam in rats.

BACKGROUND: Statins and benzodiazepines are widely used drugs, especially in ischemic heart disease, where exacerbation caused by anxiety can even lead to cardiac death. There have not been any reports of statin drug interaction with anxiolytics so far, but it is possible that these drugs interact with each other. We examined the effect of chronic oral administration of simvastatin on the anxiolytic activity and pharmacokinetics of diazepam in rats. METHODS: Studies were conducted on male Wistar Han rats treated with simvastatin (2.5, 5, 10, 20mg/kg) for 4-6 weeks, and/or diazepam (2.5, 5, 10mg/kg) administered once on the day of the study. Evaluation of potential pharmacodynamic interaction was based on the behavioral tests: elevated plus maze (EPM) test and the Vogel conflict test (VCT). The assessment of the potential pharmacokinetic interaction was based on measurements of concentrations of diazepam and its metabolites in the blood of animals. RESULTS: Diazepam 5 and 10mg/kg given together with simvastatin 10 and 20mg/kg showed no anxiolytic effect in the EPM test. In the VCT diazepam combinations with simvastatin did not produce any anxiolytic effect either, with an exception of the co-administration of diazepam 10mg/kg and simvastatin 10mg/kg. Simvastatin (20mg/kg) significantly reduced the area under curve (AUC) of diazepam by 51.6% and temazepam by 54.6%. CONCLUSIONS: Abolition of diazepam anxiolytic effect during concomitant use of simvastatin is probably caused by diminished bioavailability of diazepam, although pharmacodynamic interaction between these drugs cannot be excluded.

Omeprazole does not change the oral bioavailability or pharmacokinetics of vinpocetine in rats.

Previous studies proved that food strongly enhanced the bioavailability of vinpocetine. Food may change the pharmacokinetics of a drug by affecting various factors, including gastrointestinal pH. However, the influence of proton pump inhibitor-induced pH alterations on vinpocetine pharmacokinetics is not known. The aim was to evaluate the influence of omeprazole on the pharmacokinetics of oral vinpocetine. One group of male Wistar rats received single oral doses of vinpocetine (2 mg/kg - regimen V). In the second group, omeprazole (10 mg/kg) was administered intraperitoneally for 5 days before vinpocetine administration (regimen OV). For analysis of vinpocetine pharmacokinetics, blood samples were obtained before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 12 h after vinpocetine administration. Vinpocetine concentrations were measured by high performance liquid chromatography (HPLC). The mean values of AUC(0-t), AUC(0-inf) and C(max) in regimen V were very similar to respective values in regimen OV. The mean T(max) in both regimens was estimated for 1.5 h. There were no statistically significant differences between both regimens. In conclusion, omeprazole did not affect the pharmacokinetic profile of vinpocetine.