Phytochemical analysis and anti-inflammatory effects of Filipendula vulgaris Moench extracts.

Filipendula vulgaris Moench (dropwort) is used in traditional medicine for relieving various inflammation-related diseases. In the present study, the phytochemical profile of F. vulgaris aerial part (FVA) and root (FVR) methanolic extracts was evaluated by LC-DAD-HRMS analysis. Furthermore, their in vitro and in vivo anti-inflammatory effects, as well as their potential cytotoxicity, were assessed. Results showed that the extracts mainly contain phenolics like flavonoids, hydrolyzable tannins, procyanidins, and phenolic acid derivatives, including gaultherin. No in vitro cytotoxicity was found at the highest concentration (50 µg/mL). FVA extract (50 µg/mL) significantly inhibited cyclooxygenase-1 and -2 (COX-1 and COX-2) activities in vitro (>50% inhibition), and FVR extract considerably inhibited COX-2 activity (52.5 ±â€¯2.7%) without affecting COX-2 gene expression in LPS-stimulated THP-1 cells. The extracts demonstrated prominent in vivo anti-inflammatory potential upon oral administration in rats. Especially FVA extract at 100 and 200 mg/kg significantly inhibited carrageenan-induced edema formation. From these results, it can be concluded that F. vulgaris extracts possess interesting anti-inflammatory properties.

Summer savory (Satureja hortensis L.) extract: Phytochemical profile and modulation of cisplatin-induced liver, renal and testicular toxicity.

The aim of our study was to examine the potential ameliorating effect of the methanolic extract of Satureja hortensis L. (summer savory) aerial parts against cisplatin-induced oxidative damage in renal, hepatic, and testicular tissues. S. hortensis methanol extract at the doses of 50, 100 and 200 mg/kg of body weight were orally administered to Wistar rats once daily for 10 days. Toxicity was induced by intraperitoneal injection of a single dose of cisplatin (7.5 mg/kg of body weight) on the 5th day of the experiment. Applied treatment with S. hortensis extract restored tissue morphology, ameliorated levels of serum parameters for liver, renal and testes function, tissue oxidative stress parameters, and increased Bcl-2/Bax ratio as an indicator of apoptosis in experimental animals caused by application of cisplatin. UHPLC/DAD/HESI-MS/MS analysis revealed that S. hortensis extract was rich in phenolic compounds with rosmarinic acid (24.9 mg/g) as the main compound, followed by caffeic acid (1.28 mg/g) and naringenin (1.06 mg/g). Our findings suggest that S. hortensis may be a valuable source of dietary and pharmacologically important phenolic compounds, especially rosmarinic acid, in pharmaceutical and functional food formulations in order to maintain normal health conditions or as a remedy in various diseases caused by oxidative damage.

Combining in vitro, in vivo and in silico approaches to evaluate nutraceutical potentials and chemical fingerprints of Moltkia aurea and Moltkia coerulea.

Methanolic extracts of Moltkia aurea Boiss. (MA) and Moltkia coerulea (Willd.) Lehm. (MC) were investigated for their antioxidant capacity and enzymatic inhibitory potential against acetylcholinesterase, butyrylcholinesterase, α-amylase, α-glucosidase, and tyrosinase in vitro. MA and MC were also explored for their antimicrobial effect, as well as for their possible genotoxic/antigenotoxic potential on Drosophila melanogaster in vivo. The total bioactive components (phenolic (TPC) and flavonoid contents (TFC)) were determined and liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolite profiling of MA and MC appraised. The plausible docking poses of bioactive compounds to key enzymes were further studied using molecular modelling approach. MA proved to be a better antioxidant with higher TPC and TFC compared to MC. Protocatechuic acid, rutin, hesperidin and malic acid were the most abundant in these extracts. Both MA and MC exhibited antigenotoxic potential with a %R in DNA damage of 60.90 and 53.14% respectively. The docking studies revealed that rutin, hesperidin, and rosmarinic acid have the best scores for all the enzymes tested. MA and MC were found to be rich in phytochemicals with potent antioxidant, antimicrobial, and antigenotoxic activities that can be further studied for the management of neurodegenerative complications, diabetes, and hyperpigmentation.

Alterations of the oxidative status in rat hippocampus and prodepressant effect of chronic testosterone enanthate administration.

In a last few decades, anabolic-androgenic steroids (AASs) abuse has become serious health concern especially among adolescents. AASs abuse has been reported to be involved in pathogenesis of various mood disorders, including depression. In order to evaluate the effects of chronic (6 weeks) testosterone enanthate (TE) treatment in supraphysiological dose and exercise on depression-like behavior in rats, 32 male rats were divided into four groups: control (C), testosterone enanthate (T, 20 mg/kg/w, s.c.), exercise (E, swimming for 1 h/day), and combined group-testosterone enanthate plus exercise (T + E). TE produced prodepressant effect in tail suspension test (TST) parameters compared to the control and exercise groups, while exercise induced the opposite effect. Simultaneous TE administration along with exercise attenuated the antidepressant effect of exercise reversing the parameters of TST to the control values. Oxidative stress markers in rat hippocampus were significantly altered following applied protocols. TE administration increased index of lipid peroxidation (TBARS) and decreased superoxide dismutase activity (SOD), while exercise induced the opposite effect, with no change in glutathione (GSH) levels. Our results indicate that TE chronic treatment resulted in clear depressive-like behavior, even abolishing beneficial antidepressant effects of exercise in TST that was accompanied with increased oxidative damage in rat hippocampus. The antidepressant effect of exercise correlated with the improvement of redox status in hippocampal tissue. Behavioral parameters obtained in TST significantly correlated with the levels of oxidative stress markers.

Filipendula ulmaria extracts attenuate cisplatin-induced liver and kidney oxidative stress in rats: In vivo investigation and LC-MS analysis.

Filipendula ulmaria, known as meadowsweet, is a perennial herb found in wild and cultivated habitats in Europe and Asia. Usage of F. ulmaria in traditional medicine is based on diuretic, astringent, antirheumatic, and anti-inflammatory properties of this plant. Exposure to cisplatin at a dose of 7.5 mg/kg caused significant increase in serum parameters of liver and kidneys function and tissue oxidative stress markers along with some histopathological changes in liver and kidney tissues of experimental rats, as well as high level of genotoxicity. Administration of F. ulmaria extracts in three different concentrations (100, 200, and 400 mg/kg/day) for 10 days resulted in a reduction of oxidative stress in tissues and decrease of serum parameters. Moreover, tested extracts attenuated the genotoxicity of cisplatin in reverse dose-dependent manner. F. ulmaria extracts had no in vitro cytotoxic activity at all applied concentrations (IC50 > 50 µg/mL). Tested extracts, rich in polyphenolic compounds, attenuate cisplatin-induced liver and kidney oxidative stress, reduce tissue damage, and enhance the antioxidative status of experimental animals during cisplatin application. Therefore, F. ulmaria extracts may be used as supportive agent for the prevention and amelioration of cisplatin side effects.

In vitro and in vivo assessment of meadowsweet (Filipendula ulmaria) as anti-inflammatory agent.

ETHNOPHARMACOLOGICAL RELEVANCE: Meadowsweet (Filipendula ulmaria (L.) Maxim, Rosaceae) has been traditionally used in most European countries for the treatment of inflammatory diseases due to its antipyretic, analgesic, astringent, and anti-rheumatic properties. However, there is little scientific evidence on F. ulmaria anti-inflammatory effects regarding its impact on cyclooxygenases enzymatic activity and in vivo assessment of anti-inflammatory potential. This study aims to reveal the anti-inflammatory activity of methanolic extracts from the aerial parts (FUA) and roots (FUR) of F. ulmaria, both in in vitro and in vivo conditions. MATERIALS AND METHODS: The characteristic phenolic compounds in F. ulmaria extracts were monitored via high performance thin layer chromatography (HPTLC). The in vitro anti-inflammatory activity of F. ulmaria extracts was evaluated using cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme assays, and an assay for determining COX-2 gene expression. The in vivo anti-inflammatory effect of F. ulmaria extracts was determined in two doses (100 and 200 mg/kg b.w.) with hot plate test and carrageenan-induced paw edema test in rats. Inflammation was also evaluated by histopathological and immunohistochemical analysis. RESULTS: FUA extract showed the presence of rutoside, spiraeoside, and isoquercitrin. Both F. ulmaria extracts at a concentration of 50µg/mL were able to inhibit COX-1 and -2 enzyme activities, whereby FUA extract (62.84% and 46.43% inhibition, respectively) was double as effective as the root extract (32.11% and 20.20%, respectively). Extracts hardly inhibited the level of COX-2 gene expression in THP-1 cells at a concentration of 25µg/mL (10.19% inhibition by FUA and 8.54% by FUR). In the hot plate test, both extracts in two doses (100 and 200mg/kg b.w.), exhibited an increase in latency time when compared with the control group (p<0.05). In the carrageenan-induced acute inflammation test, FUA at doses of 100 and 200mg/kg b.w., and FUR at 200mg/kg, were able to significantly reduce the mean maximal swelling of rat paw until 6h of treatment. Indomethacin, FUA, and FUR extracts significantly decreased inflammation score and this effect was more pronounced after 24h, compared to the control group (p<0.05). CONCLUSIONS: The observed results of in vitro and, for the first time, in vivo anti-inflammatory activity of meadowsweet extracts, provide support of the traditional use of this plant in the treatment of different inflammatory conditions. Further investigation of the anti-inflammatory compounds could reveal the mechanism of anti-inflammatory action of these extracts.

Dropwort (Filipendula hexapetala Gilib.): potential role as antioxidant and antimicrobial agent.

The aim of this study was to investigate the antioxidant activity of the methanolic extracts of Filipendula hexapetala Gilib. aerial parts (FHA) and roots (FHR) and their potential in different model systems, as well as antimicrobial activity. According to this, a number of assays were employed to evaluate the antioxidant and antimicrobial potential of F. hexapetala extracts. In addition, the antioxidant activity assays in different model systems were carried out, as well as pH, thermal and gastrointestinal stability studies. The phenolic compounds contents in FHA and FHR were also determined. The results showed that F. hexapetala extracts had considerable antioxidant activity in vitro and a great stability in different conditions. The extracts exhibited antimicrobial activity against most of the tested bacterial and fungal species. Also, the extracts contain high level of phenolic compounds, especially aerial parts extract.

Newly discovered chroman-2,4-diones neutralize the in vivo DNA damage induced by alkylation through the inhibition of Topoisomerase IIα: A story behind the molecular modeling approach.

Eight chroman-2,4-diones, namely 2a-h, previously investigated as anticoagulants, of which 2a and 2f as the most active, were evaluated as in vivo genotoxic agents in Wistar rat livers and kidneys using the comet assay. Compounds 2a, 2b, and 2f without genotoxic activity were applied prior to ethyl methanesulfonate (EMS) and diminished EMS-induced DNA damage according to the total score and percentage of reduction. EMS produce harmful O(6)-ethylguanine lesion which is incorporated in aberrant genotoxic GT and TG pairing after ATP-dependent DNA strand breaks have been catalyzed by rat Topoisomerase IIα (rTopIIα, EC 5.99.1.3). Therefore, the mechanism of 2a, 2b, and 2f antigenotoxic activity was investigated on the enzyme level using molecular docking and molecular dynamics simulations insamuch as it had been determined that compounds do not intercalate DNA but instead inhibit the ATPase activity. Calculations predicted that compounds inhibit ATP hydrolysis before the DNA-EMS cleavage is being catalyzed by rTopIIα, prevent EMS mutagenic and carcinogenic effects, and beside anticoagulant activity can even be applied in the cancer treatment to control the rate of anticancer alkylation drugs.

In vitro and in vivo assessment of the genotoxicity and antigenotoxicity of the Filipendula hexapetala and Filipendula ulmaria methanol extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: The two species of Filipendula genus, Filipendula hexapetala Gilib. and Filipendula ulmaria (L.) Maxim are a traditional herbal medicine widely used to treat haemorrhoids, diarrhoea, fever, rheumatism and arthritic pain, kidney problems, to stop bleeding, and the common cold, as well as food supplements. However, no scientific study has been performed to validate genotoxic and/or antigenotoxic potentials of these two Filipendula species. AIM OF THE STUDY: The aim of the present study was to examine the genotoxic and possible in vitro and in vivo DNA protection potential of methanol extracts of F. hexapetala and F. ulmaria. MATERIALS AND METHODS: The genotoxicity of different concentrations of F. hexapetala and F. ulmaria methanol extracts from roots and aerial parts (20, 40 and 80 mg/ml), mixed with standard food for Drosophila, was evaluated in vivo in the anterior midgut of Drosophila melanogaster using a modified alkaline comet assay. The protective effects of the highest dose of extracts were observed in somatic cells of third-instar larvae against ethyl methanesulphonate (EMS)-induced genotoxicity. Also, DNA protection activity of methanol extracts from F. hexapetala and F. ulmaria (100, 200, and 400 µg/ml) against hydroxyl radical-induced DNA damage was determined under in vitro conditions. RESULTS: The results showed that methanol extracts from the root and aerial part of F. hexapetala at a concentration of 20mg/ml indicated the absence of genotoxicity. Also, there were no statistically significant differences in total scores between any of the groups treated with F. ulmaria root extract and the negative control group, while F. ulmaria aerial part extract possess weak genotoxic effects depending on the concentrations. The percentage reduction in DNA damage was more evident in the group of larvae simultaneously treated with EMS and the highest dose of F. hexapetala root or aerial part extracts and F. ulmaria root extract (91.02, 80.21, and 87.5%, respectively) and less expressive in the group simultaneously treated with F. ulmaria aerial part extract (54.7%). F. hexapetala root and aerial part extracts and F. ulmaria root extract possess strong capabilities to protect DNA from being damaged by hydroxyl radicals. CONCLUSIONS: It can be concluded that F. hexapetala root and aerial part extracts and F. ulmaria root extract demonstrated the absence of genotoxic activity. The extracts appeared to have antigenotoxic effect, reducing the levels of DNA damage induced by EMS by more than 80%. Also, F. hexapetala root and aerial part extracts and F. ulmaria root extracts could effectively protect against hydroxyl radical-induced DNA damage.

Bioactivity, stability and phenolic characterization of Filipendula ulmaria (L.) Maxim.

The purpose of the present study was to evaluate the antioxidant and antimicrobial potential of Filipendula ulmaria (L.) Maxim. methanolic extracts, their stabilities under different pH and thermal conditions and in vitro digestibility. The results showed a considerable content of phenolic compounds in the extracts, especially total phenolic acids (47.47 mg CAE g(-1)) and flavonoids (45.47 mg RUE g(-1)) in aerial parts. HPLC analysis indicated the presence of spiraeoside in the aerial part extract. The extracts revealed an interesting antimicrobial effect against the tested microorganisms, especially bacteria E. coli and E. faecalis (MIC 0.156-0.625 mg mL(-1)), and fungi P. cyclopium and F. oxysporum (MIC 2.5-5 mg mL(-1)). The extracts exerted high antioxidant activities, particularly the root extract, paralleled by their considerable activities against the lipid oxidation process. The results of this study suggest that both extracts potentially could be functional food ingredients considering their good antioxidant and antimicrobial activities, and stability under different conditions.

Serum albumin binding analysis and toxicological screening of novel chroman-2,4-diones as oral anticoagulants.

Two chroman-2,4-dione derivatives, namely 2a and 2f, were tested as in vivo anticoagulants by seven days of continuous per os application to adult male Wistar rats in a concentration of 20 mg/kg of body weight. Derivatives were selected from a group of six previously intraperitoneally applied compounds on the basis of presenting remarkable activity in a concentration of 2 mg/kg of body weight. The derivatives 2a and 2f are VKORC1 inhibitors, and comparison of the absorption spectra, association, and dissociation constants suggested that the compounds will be bound to serum albumin in the same manner as warfarin is, leading to transfer towards the molecular target VKORC1. After oral administration, the compounds proved to be anticoagulants comparable with warfarin, inasmuch as the measured prothrombin times for 2a and 2f were 56.63 and 60.08 s, respectively. The INR values of 2a and 2f ranged from 2.6 to 2.8, recommending them as useful therapeutics in the treatment of patients suffering from thromboembolic events and atrial fibrillation. The high percentage of binding and high binding affinity of 2a and 2f towards serum albumin reduced the risk of induced internal bleeding. Several kinds of toxicity studies were performed to investigate whether or not 2a and 2f can cause pathological changes in the liver, kidneys, and DNA. The catalytic activity of serum enzymes, concentration and catalytic activity of liver and kidney oxidative stress markers and enzymes, respectively, as well as the observed hepatic and renal morphological changes indicated that the compounds in relation to warfarin induced irrelevant hepatic toxicity, no increment of necrosis, and inconsiderable oxidative damage in the liver and kidneys. Estimation of DNA damage using the comet assay confirmed that 2a and 2f caused no clinically significant genotoxicity. The higher activity and lower toxicity of 2f recommended this compound as a better drug candidate than 2a.