Biosynthesis of Silver Nanoparticles Using Salvia pratensis L. Aerial Part and Root Extracts: Bioactivity, Biocompatibility, and Catalytic Potential.

The aim of this research was the synthesis of silver nanoparticles (SPA- and SPR-AgNPs) using the aqueous extracts of the aerial (SPA) and the root (SPR) parts of the plant Salvia pratensis L., their characterization, reaction condition optimization, and evaluation of their biological and catalytic activity. UV-Vis spectroscopy, X-ray powder diffraction (XRPD), scanning electron microscopy with EDS analysis (SEM/EDS), and dynamic light scattering (DLS) analysis were utilized to characterize the nanoparticles, while Fourier transform infrared (FTIR) spectroscopy was used to detect some functional groups of compounds present in the plant extracts and nanoparticles. The phenolic and flavonoid contents, as well as the antioxidant activity of the extracts, were determined spectrophotometrically. The synthesized nanoparticles showed twice-higher activity in neutralizing 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) compared with the respective extracts. SPR-AgNPs exhibited strong antimicrobial activity against almost all of the tested bacteria (<0.0039 mg/mL) and fungal strains, especially against the genus Penicillium (<0.0391 mg/mL). Moreover, they were fully biocompatible on all the tested eukaryotic cells, while the hemolysis of erythrocytes was not observed at the highest tested concentration of 150 µg/mL. The catalytic activity of nanoparticles toward Congo Red and 4-nitrophenol was also demonstrated. The obtained results confirm the possibility of the safe application of the synthesized nanoparticles in medicine and as a catalyst in various processes.

Green Synthesis of Silver Nanoparticles Using Salvia verticillata and Filipendula ulmaria Extracts: Optimization of Synthesis, Biological Activities, and Catalytic Properties.

The study's objective was to obtain silver nanoparticles (SVAgNP and FUAgNP) using aqueous extracts of Salvia verticillata and Filipendula ulmaria. The optimal conditions for nanoparticle synthesis were determined and obtained; nanoparticles were then characterized using UV-Vis, Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), Dynamic Light Scattering (DLS), Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM/EDS). SVAgNP and FUAgNP possessed a crystalline structure with 48.42% and 60.41% silver weight, respectively. The highest percentage of nanoparticles in the solution had a diameter between 40 and 70 nm. In DPPH˙ and ABTS˙+ methods, FUAgNP (IC50 15.82 and 59.85 µg/mL, respectively) demonstrated a higher antioxidant capacity than SVAgNP (IC50 73.47 and 79.49 µg/mL, respectively). Obtained nanoparticles also showed pronounced antibacterial activity (MIC ˂ 39.1 µg/mL for most of the tested bacteria), as well as high biocompatibility with the human fibroblast cell line MRC-5 and significant cytotoxicity on some cancer cell lines, especially on the human colon cancer HCT-116 cells (IC50 31.50 and 66.51 µg/mL for SVAgNP and FUAgNP, respectively). The nanoparticles demonstrated high catalytic effectiveness in degrading Congo red dye with NaBH4. The results showed a rapid and low-cost methodology for the synthesis of AgNPs using S. verticillata and F. ulmaria with promising biological potential.

An Overview of the Beneficial Role of Antioxidants in the Treatment of Nanoparticle-Induced Toxicities.

Nanoparticles (NPs) are used in many products and materials for humans such as electronics, in medicine for drug delivery, as biosensors, in biotechnology, and in agriculture, as ingredients in cosmetics and food supplements. Besides that, NPs may display potentially hazardous properties on human health and the environment as a consequence of their abundant use in life nowadays. Hence, there is increased interest of researchers to provide possible therapeutic agents or dietary supplements for the amelioration of NP-induced toxicity. This review summarizes the new findings in the research of the use of antioxidants as supplements for the prevention and alleviation of harmful effects caused by exposure of organisms to NPs. Also, mechanisms involved in the formation of NP-induced oxidative stress and protective mechanisms using different antioxidant substances have also been elaborated. This review also highlights the potential of naturally occurring antioxidants for the enhancement of the antioxidant defense systems in the prevention and mitigation of organism damage caused by NP-induced oxidative stress. Based on the presented results of the most recent studies, it may be concluded that the role of antioxidants in the prevention and treatment of nanoparticle-induced toxicity is unimpeachable. This is particularly important in terms of oxidative stress suppression.

Algae as a Source of Bioactive Compounds to Prevent the Development of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus is a complicated metabolic disorder characterized by hyperglycemia and glucose intolerance. It is considered a new pandemic and its control involves numerous challenges. Although many of the measures are based on improving life habits, diet is also of vital importance due to bioactive compounds present in food. In this regard, several raw materials have been investigated whose bioactivities seem to slow the progression of this disease. Within these matrices, there are algae of importance, such as brown algae, showing to have beneficial effects on glycemic control. These pieces of evidence are increasing every day due to the development of cell or animal models, which lead to the conclusion that bioactive compounds may have direct effects on decreasing hyperglycemia, enhancing insulin secretion and preventing the formation of amyloid plaques.

The Beneficial Role of Filipendula ulmaria Extract in Prevention of Prodepressant Effect and Cognitive Impairment Induced by Nanoparticles of Calcium Phosphates in Rats.

Mineral components of dental composites are used in many medical and dental applications, including preventive, restorative, and regenerative dentistry. To evaluate the behavioural alterations induced by nanosized particles of novel dental composites, by means of depressive level and cognitive functions, experimental groups of rats were chronically administered with nanosized hydroxyapatite (HA), tricalcium phosphate (TCP), and amorphous calcium phosphate (ACP) with or without simultaneous application of Filipendula ulmaria L. (FU) methanolic extract. The significant prodepressant action was observed in groups solely treated with HA and ACP. Besides, prolonged treatment with ACP also resulted in a significant decline in cognitive functions estimated in the novel object recognition test. The adverse impact of calcium phosphates on estimated behavioural functions was accompanied by increased oxidative damage and apoptotic markers in the prefrontal cortex, as well as diminished specific neurotrophin (BDNF) and gabaergic expression. The results of our investigation showed that simultaneous antioxidant supplementation with FU extract prevented calcium phosphate-induced behavioural disturbances, as well as prooxidative and apoptotic actions, with the simultaneous restoration of BDNF and GABA-A receptors in the prefrontal cortex. These findings suggest that FU may be useful in the prevention of prodepressant impact and cognitive decline as early as the manifestation of calcium phosphate-induced neurotoxicity.

Application potential of biogenically synthesized silver nanoparticles using Lythrum salicaria L. extracts as pharmaceuticals and catalysts for organic pollutant degradation.

This study was designed to evaluate the optimal conditions for the eco-friendly synthesis of silver nanoparticles (AgNPs) using Lythrum salicaria L. (Lythraceae) aqueous extracts and their potential application and safe use. AgNPs synthesized using L. salicaria aerial parts (LSA-AgNPs) and root extract (LSR-AgNPs) were characterized by UV-Vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM/EDS), and X-ray powder diffraction (XRPD). Dynamic light scattering (DLS) was used for the determination of the size distribution profiles of the obtained nanoparticles. Both L. salicaria extracts showed high phenolic content, while the flavone C-glucosides orientin, vitexin, and isovitexin were detected in extracts using HPLC. The synthesized AgNPs displayed growth inhibition of the tested bacteria and fungi in concentrations between 0.156 and 1.25 mg mL-1. The studied nanoparticles also showed antioxidant potential and gained selectivity at different concentrations on different cancer cell lines. Concentrations of LSA-AgNPs were found to be 20.5 and 12 µg mL-1 towards A431 and SVT2, respectively, while LSR-AgNPs were effective only against A431 cancer cells (62 µg mL-1). The hemolytic activity of LSA-AgNPs in concentrations up to 150 µg mL-1 was not observed, while LSR-AgNPs in the highest applied concentration hemolyzed 2.8% of erythrocytes. The degradation possibility of Congo red and 4-nitrophenol using LSA-AgNPs and LSR-AgNPs as catalysts was also proven. The results indicate that L. salicaria may be used for the eco-friendly synthesis of AgNPs with possible applications as antimicrobial and selective cytotoxic agents towards cancer cell lines, as well as in catalytic degradation of pollutants.

Variable neuroprotective role of Filipendula ulmaria extract in rat hippocampus.

We evaluated the influence of an antioxidant-rich extract of Filipendula ulmaria L. on anxiety levels induced by nano-sized particles of different calcium phosphates. Rats in experimental groups were administered with either nano-sized hydroxyapatite, tricalcium phosphate, or amorphous calcium phosphate in the presence of Filipendula ulmaria extract. Appropriate behavioral tests were performed to assess anxiety levels, while oxidative status and apoptosis parameters were determined in the hippocampus samples. The applied calcium phosphates increased oxidative stress markers in hippocampal tissue, accompanied by an enhanced pro-apoptotic mechanism. Moreover, the hippocampal immunoreactivity for brain-derived neurotrophic factor and GABAergic-A receptors was significantly lower following calcium phosphate nanoparticles intake. The observed functional and morphological alterations in the rat hippocampus occurred simultaneously with the anxiogenic response estimated in behavioral testing. The neuroprotective effect of Filipendula ulmaria was markedly manifested by the attenuation of oxidative damage induced by amorphous calcium phosphate and enhanced anti-apoptotic action in the rat hippocampus. The increased hippocampal immunoreactivity for brain-derived neurotrophic factor, GABAergic-A receptors and significant anxiolytic-like effects of Filipendula ulmaria may suggest a beneficial role of antioxidant supplementation in preventing anxiogenic response to nano-sized calcium phosphates.

Antioxidant Supplementation in the Treatment of Neurotoxicity Induced by Platinum-Based Chemotherapeutics-A Review.

Cancer represents one of the most pernicious public health problems with a high mortality rate among patients worldwide. Chemotherapy is one of the major therapeutic approaches for the treatment of various malignancies. Platinum-based drugs (cisplatin, oxaliplatin, carboplatin, etc.) are highly effective chemotherapeutic drugs used for the treatment of several types of malignancies, but their application and dosage are limited by their toxic effects on various systems, including neurotoxicity. Simultaneously, researchers have tried to improve the survival rate and quality of life of cancer patients and decrease the toxicity of platinum-containing drugs by combining them with non-chemotherapy-based drugs, dietary supplements and/or antioxidants. Additionally, recent studies have shown that the root cause for the many side effects of platinum chemotherapeutics involves the production of reactive oxygen species (ROS) in naive cells. Therefore, suppression of ROS generation and their inactivation with antioxidants represents an appropriate approach for platinum drug-induced toxicities. The aim of this paper is to present an updated review of the protective effects of different antioxidant agents (vitamins, dietary antioxidants and supplements, medicaments, medicinal plants and their bioactive compounds) against the neurotoxicity induced by platinum-based chemotherapeutics. This review highlights the high potential of plant antioxidants as adjuvant strategies in chemotherapy with platinum drugs.

N-Acetylcysteine Protects against the Anxiogenic Response to Cisplatin in Rats.

Since cisplatin therapy is usually accompanied with numerous toxicities, including neurotoxicity, that involve tissue oxidative damage, the aim of this study was to evaluate the possible protective effect of N-acetylcysteine (NAC) on the anxiogenic response to cisplatin (CIS). Thirty-two male Wistar albino rats divided into four groups (control, cisplatin, NAC, and CIS + NAC). All treatments were delivered intraperitoneally. On day one, the control and cisplatin groups received saline while the NAC and CIS + NAC groups were administered with NAC (500 mg/kg). On the fifth day, the control group received saline while the CIS group was treated with cisplatin (7.5 mg/kg), the NAC group again received NAC (500 mg/kg), and the CIS + NAC group was simultaneously treated with cisplatin and NAC (7.5 and 500 mg/kg, respectively). Behavioral testing, performed on the tenth day in the open field (OF) and elevated plus maze (EPM) tests, revealed the anxiogenic effect of cisplatin that was significantly attenuated by NAC. The hippocampal sections evaluation showed increased oxidative stress (increased lipid peroxidation and decline in antioxidant enzymes activity) and proapoptotic action (predominantly by diminished antiapoptotic gene expression) following a single dose of cisplatin. NAC supplementation along with cisplatin administration reversed the prooxidative and proapoptotic effects of cisplatin. In conclusion, the results obtained in this study confirmed that antioxidant supplementation with NAC may attenuate the cisplatin-induced anxiety. The mechanism of anxiolytic effect achieved by NAC may include the decline in oxidative damage that down regulates increased apoptosis and reverses the anxiogenic action of cisplatin.

Antioxidant Effects of Satureja hortensis L. Attenuate the Anxiogenic Effect of Cisplatin in Rats.

Numerous adverse effects of cisplatin-based therapy are usually accompanied by enhanced oxidative damage and cell apoptosis in various tissues. Even neurotoxic manifestations of cisplatin administration, such as the anxiogenic effect, appear along with the increased oxidative stress and apoptotic indicators in certain brain regions. Thirty-five Wistar albino male rats were divided into seven groups: control, cisplatin (received a single dose of cisplatin: 7.5 mg/kg), three groups with oral administration of Satureja hortensis L. methanolic extract (SH) (low: 50 mg/kg, middle: 100 mg/kg, and high dose: 200 mg/kg) along with cisplatin application, a group with the extract in high dose alone, and a silymarin group (cisplatin and silymarin: 100 mg/kg), in order to evaluate the antioxidant effects of SH on cisplatin-induced increase in the anxiety level. After completing 10-day pretreatments, behavioral testing was performed in the open field and the elevated plus maze, followed by an investigation of oxidative stress and apoptosis parameters in hippocampal tissue samples. Cisplatin administration resulted in anxiogenic-like behavior, increased lipid peroxidation, and proapoptotic markers accompanied by the decline in antioxidant and antiapoptotic defense. The administration of extract alone did not significantly alter any of the estimated parameters. When applied along with cisplatin, SH in a dose of 100 mg/kg induced the significant anxiolytic effect with concomitant recovery of antioxidant and antiapoptotic activity indicators, while both lower and higher doses of the extract failed to improve the adverse effects of cisplatin administration. The beneficial effects of the middle dose of SH were equivalent to the same dose of silymarin, as a "golden standard." Our results indicate that the antioxidant supplementation with SH in an optimal dose significantly improved the oxidative status and it had antiapoptotic effect in the rat hippocampus disturbed by cisplatin administration, which was accompanied with attenuation of cisplatin-induced anxiogenic effect.

Analysis of Wild Raspberries (Rubus idaeus L.): Optimization of the Ultrasonic-Assisted Extraction of Phenolics and a New Insight in Phenolics Bioaccessibility.

A simple and efficient ultrasonic-assisted extraction (UAE) technique was developed in order to find optimal conditions for the extraction of total phenolic compounds, flavonoids and anthocyanins in wild raspberry (Rubus idaeus L.) fruits. Several extraction variables, including methanol composition (v/v, %), solid-solvent ratio (g/mL), time (min) and extraction temperature (°C) were optimized using response surface methodology (RSM). Under optimal conditions for extraction, the total phenolics were found in the concentration of 383 mg GAE/100 g of fresh fruit weight, while HPLC-PDA analysis of the optimized extract showed the presence of cyanidin-3-glucoside, cyanidin-3-sophoroside, catechin, gallic and ellagic acid. The experimental values of DPPH and ABTS radical scavenging activities were 29.0 and 39.5 µmol Trolox/g of fresh fruit weight, respectively. In vitro simulated gastrointestinal digestion showed great raspberry phenolics stability. Our study assessed the bioaccessible phenolics in wild raspberry fruits and showed optimal conditions for the effective extraction of bioactive compounds for their analysis.

Exercise Attenuates Anabolic Steroids-Induced Anxiety via Hippocampal NPY and MC4 Receptor in Rats.

The aim of our study was to evaluate the effects of chronic administration of nandrolone-decanoate (ND) or testosterone-enanthate (TE) in supraphysiological doses and a prolonged swimming protocol, alone and in combination with ND or TE, on anxiety-like behavior in rats. We investigated the immunohistochemical alterations of the hippocampal neuropeptide Y (NPY) and melanocortin 4 receptor (MC4R) neurons, as a possible underlying mechanism in a modulation of anxiety-like behavior in rats. Both applied anabolic androgenic steroids (AASs) induced anxiogenic effect accompanied with decreased serum and hippocampal NPY. The exercise-induced anxiolytic effect was associated with increased hippocampal NPY expression. ND and TE increased the number of MC4R, while the swimming protocol was followed by the reduction of MC4R in the CA1 region of the hippocampus. However, NPY/MC4R ratio in hippocampus was lowered by AASs and elevated by exercise in all hippocampal regions. An augmentation of this ratio strongly and positively correlated to increased time in open arms of elevated plus maze, in the context that indicates anxiolytic effect. Our findings support the conclusion that alterations in both hippocampal NPY and MC4R expression are involved in anxiety level changes in rats, while their quantitative relationship (NPY/MC4R ratio) is even more valuable in the estimation of anxiety regulation than individual alterations for both NPY and MC4R expression in the hippocampus.

The Impact of Hippocampal Sex Hormones Receptors in Modulation of Depressive-Like Behavior Following Chronic Anabolic Androgenic Steroids and Exercise Protocols in Rats.

The aim of this study was to evaluate alterations in depressive-like behaviors in rats following chronic administration of a supraphysiological dose of anabolic androgenic steroids (AASs) as well as exposure to a prolonged exercise protocol. The role of hippocampal sex hormones receptors in the modulation of depressive-like behavior was also assessed. A total of 48 male Wistar albino rats were divided into six groups: control, exercise (1 h/day, five consecutive days), nandrolone-decanoate (ND, 20 mg/kg/week, in a single dose), exercise plus ND, testosterone-enanthate (TE, 20 mg/kg/week, in a single dose), and exercise plus TE. After the 6-week protocols were complete, the rats underwent behavioral testing in the tail suspension test (TST). Rats were sacrificed for the collection of blood samples, to determine sex hormones levels, and isolation of the hippocampus, to determine [androgen receptors (AR) and estrogen receptors α (ERα)] expression. ND and TE treatment induced significant depressive-like behavior, opposing the antidepressant effect of exercise. Chronic TE administration elevated testosterone (T) and dihydrotestosterone (DHT) serum levels, and this was augmented by exercise. In contrast, ND and exercise alone did not alter T or DHT levels. There were no changes in serum estradiol levels in any of the groups. Immunohistochemical analysis showed that exercise reduced AR immunoreactivity in all hippocampal regions and increased the ERα expression in the CA1, dentate gyrus (DG), and total hippocampal sections, but not in the CA2/3 region. AASs administration increased AR expression in all hippocampal regions, although not the total hippocampal section in the TE group and did not significantly decrease ERα. The hippocampal AR/ERα expression index was lowered while parvalbumin (PV)-immunoreactivity was enhanced by exercise. AASs administration increased the AR/ERα index and reduced PV-immunoreactivity in the hippocampus. The number of PV-immunoreactive neurons negatively correlated with the antidepressant effects and the AR/ERα ratio. Our results suggest a potential role of the numerical relationship between two sex hormones receptors (stronger correlation than for each individual receptor) in the regulation of depressive-like behavior via the hippocampal GABAergic system in rats, which allow better understanding of the hippocampal sex hormones receptors role in modulation of depressive-like behavior.

The anxiolytic effects of atorvastatin and simvastatin on dietary-induced increase in homocysteine levels in rats.

The aim of this study was to evaluate the effects of atorvastatin and simvastatin on behavioral manifestations that followed hyperhomocysteinemia induced by special dietary protocols enriched in methionine and deficient in B vitamins (B6, B9, B12) by means of alterations in anxiety levels in rats. Simultaneously, we investigated the alterations of oxidative stress markers in rat hippocampus induced by applied dietary protocols. Furthermore, considering the well-known antioxidant properties of statins, we attempted to assess their impact on major markers of oxidative stress and their possible beneficial role on anxiety-like behavior effect in rats. The 4-week-old male Wistar albino rats were divided (eight per group) according to basic dietary protocols: standard chow, methionine-enriched, and methionine-enriched vitamins B (B6, B9, B12) deficient. Each dietary protocol (30 days) included groups with atorvastatin (3 mg/kg/day i.p.) and simvastatin (5 mg/kg/day i.p.). The behavioral testing was performed in the open field and elevated plus maze tests. Parameters of oxidative stress (index of lipid peroxidation, superoxide dismutase, catalase activity, glutathione) were determined in hippocampal tissue samples following decapitation after anesthesia. Methionine-load dietary protocols induced increased oxidative stress in rat hippocampus, which was accompanied by anxiogenic behavioral manifestations. The methionine-enriched diet with restricted vitamins B intake induced more pronounced anxiogenic effect, as well as increased oxidative stress compared to the methionine-load diet with normal vitamins B content. Simultaneous administration of statins showed beneficial effects by means of both decreased parameters of oxidative stress and attenuation of anxiety. The results obtained with simvastatin were more convincible compared to atorvastatin.

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.

Protective and therapeutic possibility of medical herbs for liver cirrhosis.

Liver damage is a serious medical problem worldwide and is caused by primary or secondary metabolic, microbiological, toxicological, immunological and circulatory etiological factors. The objective of this paper is to analyze the hepatoprotective effect of various plants, their biologically active compounds and extracts and the possibility of these compounds to attenuate complex pathophysiology processes during chronic inflammation and the development of liver cirrhosis. This review summarizes several plants whose hepatoprotective effects have been demonstrated and partially describes the mechanisms of inflammation inhibition. It is known that fibrosis includes an oxidative damage, inflammatory and immune response and star-shaped cells and their activation in hepatocytes. Effects of particular phytocompounds and their anti-inflammatory mechanisms have been studied in several cell lines in vitro, in vivo in different animal models, as well as in some clinical studies. Results suggest that mechanisms include reduction of oxidative stress, suppression of the inflammatory and immune response, as well as the inhibition of the activation of hepatic stellate cells (HSCs), decreasing extracellular matrix (ECM) deposition and induction of apoptosis, protection of hepatocytes from apoptosis and creating apoptotic bodies, which are phagocytic and activate HSCs. Medical herbs are abundant, economical and versatile and thus are potential alternative agents with anti-inflammatory mechanism. They can be a source of bioactive compounds, and with the aim of preventing the formation and progression of fibrosis, they can find wide applications in medical practice. The obtained results should promote further research in order to identify safe and effective protective and therapeutic resources.

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.

Impact of the toxicity of Cylindrospermopsis raciborskii (Woloszynska) Seenayya & Subba Raju on laboratory rats in vivo.

In vivo laboratory studies of toxicity were performed on Wistar rats using a methanol extract produced by the natural population of Cylindrospermopsis raciborskii (abundance of 2.13 × 105 trichomes mL-1) collected at Aleksandrovac Lake (Serbia). HPLC analysis showed that the extract contains 6.65 µg cylindrospermopsin (CYN) mg-1. The rats were killed 24 or 72 h after a single intraperitoneal injection of C. raciborskii extract in concentrations of 1500, 3000, 6000 and 12,000 µg kg-1 body weight (bw) and an equivalent amount of CYN as present in the highest dose of the extract (79.80 µg CYN kg-1 bw). The genotoxic effect on the livers treated with C. raciborskii was evaluated using comet assay and potential induction of oxidative stress as the toxicity mechanism associated with the presence of CYN in extract. The results from the analyses of DNA damage in the comet tail length, tail moment and percentage of DNA in the tail in the liver indicated that administration of extract and CYN present statistically significant difference when compared with the negative control group. Although an increase in the frequency of selected parameters induced by the CYN was observed in the liver, this damage was less than the damage resulting from the administration of the highest dose of extract. The changes in the biochemical parameters of the hepatic damage showed that the application of single doses of the extract and CYN did not cause serious liver damage in rats. The extract and CYN significantly increased oxidative stress in rats' liver after a single exposure.