Agomelatine improves memory and learning impairments in a rat model of LPS-induced neurotoxicity by modulating the ERK/SorLA/BDNF/TrkB pathway.

The mutual interplay between neuroinflammation, synaptic plasticity, and autophagy has piqued researchers' interest, particularly when it comes to linking their impact and relationship to cognitive deficits. Being able to reduce inflammation and apoptosis, melatonin has shown to have positive neuroprotective effects; that is why we thought to check the possible role of agomelatine (AGO) as a promising candidate that could have a positive impact on cognitive deficits. In the current study, AGO (40 mg/kg/day, p.o., 7 days) successfully ameliorated the cognitive and learning disabilities caused by lipopolysaccharide (LPS) in rats (250 µg/kg/day, i.p., 7 days). This positive impact was supported by improved histopathological findings and improved spatial memory as assessed using Morris water maze. AGO showed a strong ability to control BACE1 activity and to rein in the hippocampal amyloid beta (Aß) deposition. Also, it improved neuronal survival, neuroplasticity, and neurogenesis by boosting BDNF levels and promoting its advantageous effects and by reinforcing the pTrkB expression. In addition, it upregulated the pre- and postsynaptic neuroplasticity biomarkers resembled in synapsin I, synaptophysin, and PSD-95. Furthermore, AGO showed a modulatory action on Sortilin-related receptor with A-type repeats (SorLA) pathway and adjusted autophagy. It is noteworthy that all of these actions were abolished by administering PD98059 a MEK/ERK pathway inhibitor (0.3 mg/kg/day, i.p., 7 days). In conclusion, AGO administration significantly improves memory and learning disabilities associated with LPS administration by modulating the ERK/SorLA/BDNF/TrkB signaling pathway parallel to its capacity to adjust the autophagic process.

A new firewall in the fight against breast cancer: in-vitro and in-silico studies correlating chemistry to apoptotic activity of Otostegia fruticosa.

Breast cancer is the most devastating disease for women. There is a great demand for new sources to treat this disease. Medicinal plants are an indispensable source of bioactive compounds with wide range of pharmacological activities. In-vitro cytotoxic activity of Otostegia fruticosa methanolic extract against human breast cancer was studied using MCF-7 cell line. The extract showed mildly potent activity (IC50 = 51 ± 9.836 µg/mL) in comparison to the standard anticancer doxorubicin (IC50 = 7.467 ± 1.05 µg/mL). Potential compounds responsible for activity have been identified using Molecular Operating Environment (MOE) module on the major compounds detected by HPLC-MS/MS technique against estrogen alpha receptor (ERα+: PDB ID 2JF9). 3,5-di-O-dicaffeoylquinic acid, hyperoside and rutin showed similar binding and antagonistic interaction with the estrogen alpha receptor as tamoxifen in several poses. The retrieved results confirm that we can add this plant to a powerful arsenal that combats this insidious disease.

Hepatoprotective Effect of Silver Nanoparticles at Two Different Particle Sizes: Comparative Study with and without Silymarin.

Silver nanoparticles have been used for numerous therapeutic purposes because of their increased biodegradability and bioavailability, yet their toxicity remains questionable as they are known to interact easily with biological systems because of their small size. This study aimed to investigate and compare the effect of silver nanoparticles' particle size in terms of their potential hazard, as well as their potential protective effect in an LPS-induced hepatotoxicity model. Liver slices were obtained from Sprague Dawley adult male rats, and the thickness of the slices was optimized to 150 µm. Under regulated physiological circumstances, freshly cut liver slices were divided into six different groups; GP1: normal, GP2: LPS (control), GP3: LPS + AgNpL (positive control), GP4: LPS + silymarin (standard treatment), GP5: LPS + AgNpS + silymarin (treatment I), GP6: LPS + AgNpL + silymarin (treatment II). After 24 h of incubation, the plates were gently removed, and the supernatant and tissue homogenate were all collected and then subjected to the following biochemical parameters: Cox2, NO, IL-6, and TNF-α. The LPS elicited marked hepatic tissue injury manifested by elevated cytokines and proinflammatory markers. Both small silver nanoparticles and large silver nanoparticles efficiently attenuated LPS hepatotoxicity, mainly via preserving the cytokines' level and diminishing the inflammatory pathways. In conclusion, large silver nanoparticles exhibited effective hepatoprotective capabilities over small silver nanoparticles.

Nanotechnology applications for treatment of hepatic infections via modulating Hepatic histopathological and DNA alterations.

BACKGROUND: Nanoparticles are recently playing a potential role in improving drug uptake and the treatment of diseases. A variety of nanoparticles, such as selenium nanoparticles (SeNPs) and Silver nanoparticles (AgNPs) have been used as drug carriers in various ways for treatment of cancers and liver diseases. Our aim in this study is to investigate the ability of AgNPs and SeNPs to target and treat the viral and bacterial infection of liver in rats and cell lines. METHODS: For assessment of antioxidant activity of silver nanoparticles, six adult male albino rats were included in this study, liver slices were taken and assigned to 6 groups. Markers of hepatic functions, oxidative stress and inflammation in liver slices are carried out. While for assessment of antiviral activity of SeNPs, HBV-replicating human cell line HepG2 and normal human cell lines were used, hepatic and inflammatory alterations are determined through quantitative polymerase chain reaction (PCR) and comet assay techniques. RESULTS: The effect of Ag-NPs on interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) levels were reduced in different treated groups with Ag-NPs compared with the control and diseased groups. On the other hand, SeNPs revealed significant alterations in the inflammatory markers as well as DNA damage in the treated HBV- human cell line HepG2 compared to the diseased ones. CONCLUSION: Silver nanoparticles have the ability for producing various hepatic alterations and can inhibit the proliferation of hepatic stellate cells (HSCs) in a dose and size dependent manner. On the other hand, SeNPs showed excellent selectivity towards viral cells in the HepG2 cell lines. Both Ag-NPs and SeNPs might be a promising drug design for treating viral and bacterial liver diseases.

A new arsenal of polyphenols to make Parkinson's disease extinct: HPLC-MS/MS profiling, very interesting MAO-B inhibitory activity and antioxidant activity of Otostegia fruticosa.

Fifteen compounds belong to phenolic acids, derivatives of phenolic acids, iridoids, xanthones and flavonoids were characterized in the methanolic extract of Otostegia fruticosa leaves using HPLC-MS/MS. Extract has been also investigated for its MAO-B inhibitory activity, antioxidant activity, total phenolic and total flavonoid content. The extract exhibited interesting MAO-B inhibitory activity (IC50; 2.24 ± 0.08) compared to the reference compound selegiline (0.55 ± 0.02 µg/mL). It also showed a potent antioxidant activity proven in both DPPH and ORAC assay methods. The extract showed an IC50 of 3.64 ± 1.22 µg/mL in the DPPH test which was significantly lower than that of the standard ascorbic acid which attained an IC50 of 18.3 ± 1.41 µg/mL. Moreover, in the oxygen radical absorbance capacity assay (ORAC) the extract showed a decline in the IC50 to 3.48 ± 1.16 µg/mL as compared to the standard Trolox which exhibited an IC50 of 27.0 ± 13.41.

Selenium and silver nanoparticles: A new approach for treatment of bacterial and viral hepatic infections via modulating oxidative stress and DNA fragmentation.

Nanoparticles are recently playing a potential role in improving drug uptake and the treatment of diseases. A variety of nanoparticles, such as selenium nanoparticles (SeNPs) and silver nanoparticles (AgNPs) have been used as drug carriers in various ways for treatment of cancers and liver diseases. Our aim in this study is to investigate the ability of AgNPs and SeNPs to target and treat the viral and bacterial infection of the liver in rats and cell lines. For assessment of antioxidant activity of AgNPs in rats with induced liver bacterial infection, six adult male albino rats were included in this study, liver slices were taken and assigned to 6 groups. Markers of hepatic functions, oxidative stress, and inflammation in liver slices are carried out. Although for assessment of antiviral activity of SeNPs, hepatitis B virus transfected (HBV)-replicating human cell line HepG2 and normal hepatocyte cells were used, hepatic and inflammatory alterations are determined through quantitative polymerase chain reaction and comet assay techniques. The effect of AgNPs on interleukin-6 and tumor necrosis factor levels were reduced in different treated groups with AgNPs compared with the control and diseased groups. On the other hand, SeNPs revealed significant alterations in the inflammatory markers as well as DNA damage in the treated HBV-human cell line HepG2 compared to the diseased ones. AgNPs have the ability for producing various hepatic alterations and can inhibit the proliferation of hepatic stellate cells (HSCs) in a dose and size-dependent manner. On the other hand, SeNPs showed excellent selectivity towards viral cells in the HepG2 cell lines. Both AgNPs and SeNPs might be promising drug designs for treating viral and bacterial liver diseases.

Amelioration of autoimmunity and inflammation by zinc oxide nanoparticles in experimental rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the lining of the synovial joints and approximately affects 0.5 - 1% of the total population imposing a socioeconomic burden. The current study aimed at investigating the novel possible beneficial effects of using zinc oxide nanoparticles (ZnO NPs) on such devastating disease. The complete Freund's adjuvant (CFA) model was used to mimic RA in rats where ZnO NPs were given orally (2 mg/kg/day) daily for 14 days; and diclofenac Na, the standard drug, was given intraperitoneally (1 mg/kg/day) the day after CFA, daily for 14 days. Our results displayed that ZnO NPs attenuated adjuvant-induced increased production of inflammatory mediators interleukin-1ß (IL-1ß), tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), and total leukocyte count. Besides, they ameliorated autoimmunity through suppression of anti-citrullinated protein auto antibodies (anti-CCP) levels in rats. In conclusion our results highlight the benefits which could be obtained of nanoparticles either alone or in combination with the known anti-arthritic and/or anti-inflammatory agents, giving rise to new protocols to maximize the control of RA.

A Unique Acylated Flavonol Glycoside from Prunus persica (L.) var. Florida Prince: A New Solid Lipid Nanoparticle Cosmeceutical Formulation for Skincare.

Polyphenols are known dietary antioxidants. They have recently attracted considerable interest in uses to prevent skin aging and hyperpigmentation resulting from solar UV-irradiation. Prunus persica (L.) leaves are considered by-products and were reported to have a remarkable antioxidant activity due to their high content of polyphenols. This study aimed at the development of a cosmeceutical anti-aging and skin whitening cream preparation using ethanol leaves extract of Prunus persica (L.) (PPEE) loaded in solid lipid nanoparticles (SLNs) to enhance the skin delivery. Chemical investigation of PPEE showed significantly high total phenolic and flavonoids content with notable antioxidant activities (DPPH, ABTS, and ß-carotene assays). A unique acylated kaempferol glycoside with a rare structure, kaempferol 3-O-ß-4C1-(6″-O-3,4-dihydroxyphenylacetyl glucopyranoside) (KDPAG) was isolated for the first time and its structure fully elucidated. It represents the first example of acylation with 3,4-dihydroxyphenyl acetic acid in flavonoid chemistry. The in-vitro cytotoxicity studies against a human keratinocytes cell line revealed the non-toxicity of PPEE and PPEE-SLNs. Moreover, PPEE, PPEE-SLNs, and KDPAG showed good anti-elastase activity, comparable to that of N-(Methoxysuccinyl)-Ala-Ala-Pro-Val-chloromethyl ketone. Besides, PPEE-SLNs and KDPAG showed significantly (p < 0.001) higher anti-collagenase and anti-tyrosinase activities in comparison to EDTA and kojic acid, respectively. Different PPEE-SLNs cream formulae (2% and 5%) were evaluated for possible anti-wrinkle activity against UV-induced photoaging in a mouse model using a wrinkle scoring method and were shown to offer a highly significant protective effect against UV, as evidenced by tissue biomarkers (SOD) and histopathological studies. Thus, the current study demonstrates that Prunus persica leaf by-products provide an interesting, valuable resource for natural cosmetic ingredients. This provides related data for further studying the potential safe use of PPEE-SLNs in topical anti-aging cosmetic formulations with enhanced skin permeation properties.

In-vivo wound healing activity of a novel composite sponge loaded with mucilage and lipoidal matter of Hibiscus species.

Many researches have been undergone to hasten the natural wound healing process. In this study, several Hibiscus species (leaves) were extracted with petroleum ether, methanol, and their mucilage was separated. All the tested species extracts were assessed for their viability percentage using the water-soluble tetrazolium. H.syriacus was the plant of choice to be incorporated in a new drug delivery system and evaluated for its wound healing activity. H.syriacus petroleum ether extract (PEE) showed a high percentage of palmitic and oleic acids while its mucilage demonstrated high glucosamine and galacturonic acid. It was selected to be formulated and pharmaceutically evaluated into three different composite sponges using chitosan in various ratios. Fourier-transformed infrared spectroscopy investigated the chemical interaction between the utilized sponges' ingredients. Morphological characteristics were evaluated using scanning electron microscopy. H.syriacus composite sponge of mucilage: chitosan (1:5) was loaded with three different concentrations of PEE. Medicated formulations were assessed in rat model of excision wound model. The wound healing ability was clearly proved by the clinical acceleration, histopathological examination, and modulation of correlated inflammatory parameters as tumor necrosis factor in addition to vascular endothelial growth factor suggesting a promising valuable candidate that supports the management of excision wounds using single-dose preparation.

Design and optimization of topical terbinafine hydrochloride nanosponges: Application of full factorial design, in vitro and in vivo evaluation.

Terbinafine hydrochloride (THCl) has a broad-spectrum antifungal activity. THCl has oral bioavailability 40%, which increases dosing frequency of the drug, thus leads to some systemic side effects. Sustained release THCl nanosponges hydrogel was fabricated to deliver the drug topically. Pure THCl (drug), polyvinyl alcohol (emulsifier), and ethyl cellulose (EC, polymer to produce nanosponges) were used. THCl nanosponges were produced successfully by the emulsion solvent evaporation method. Based on a 32 full factorial design, different THCl: EC ratios and stirring rates were used as independent variables. The optimized formula selected based on the particle size and entrapment efficiency % (EE) was formulated as topical hydrogel. All formulations were found in the nanosize range except F7and F9. EE was ranged from 33.05% to 90.10%. THCl nanosponges hydrogel released more than 90% of drug after 8 h and showed the highest in vivo skin deposition and antifungal activity. The increase in drug: EC ratio was observed to increase EE and the particle size while higher stirring rate resulted in finer emulsion globules and significant reduction in EE. The drug release profile was slow from dosage form when it was incorporated in entrapped form as nanosponges rather than unentrapped one. The nanosponges hydrogel succeeded to sustain THCl release over 8 h. It showed the highest antifungal activity and skin deposition. THCl nanosponges hydrogel represents an enhanced therapeutic approach for the topical treatment of fungal infection.