Evaluation of antioxidant, anti-inflammatory, anticancer activities and molecular docking of Moringa oleifera seed oil extract against experimental model of Ehrlich ascites carcinoma in Swiss female albino mice.

The current research intended to evaluate the antitumor properties of Moringa oleifera oil extract (MOE). Fifty-six female Swiss albino mice were employed in this study. Animals were assigned into four groups: control (C) group, moringa oil extract (MOE) group administered (500 mg/kg b. wt) MOE daily via gavage, Ehrlich ascites carcinoma (EAC) group and EAC group administered daily with (500 mg/kg b.wt) MOE for two weeks (EAC/MOE). The results showed that MOE significantly ameliorated the EAC increase in body weight and reduced the EAC cell viability. In addition, they upgraded the levels of hepatic and renal functions, inflammatory cytokines, oxidative stress markers and EAC-induced hepatic and renal histopathological changes. Treatment of EAC with MOE induced antitumor, anti-inflammatory and antioxidant effects and normalized most of the tested parameters besides the histopathological alterations in both renal and hepatic tissues. HPLC for the MOE identified Cinnamic acid, Ellagic acid, Quercetin, Gallic acid, Vanillin and Hesperidin as major compounds. The molecular docking study highlighted the virtual binding of the identified compounds inside the GSH and SOD proteins, especially for Quercetin which exhibited promising binding affinity with good interactive binding mode with the key amino acids. These results demonstrate that the antitumor constituents of MOE against EAC induced oxidative stress and inflammation by preventing oxidative damage and controlling EAC increase.

Optimization of cationic nanoparticles stabilized by poloxamer 188: A potential approach for improving the biological activity of Aloeperryi.

Aloe perryi (AP) has gained considerable interest as a medicinal herb in various biological applications due to its rich phytochemical composition. However, the therapeutic benefits of AP could be potentiated by utilizing nanotechnology. Moreover, cationic solid lipid nanoparticles (CSLNs) possess remarkable characteristics that can greatly enrich a variety of biological uses. An optimization approach was used to achieve high-quality CSLNs to maximize the therapeutic efficacy of AP. Therefore, a factorial design was used to investigate the influence of various variables on the attributes of CSLNs quality. In this study, the factors under investigation were compritol 888 ATO (C-888, X1), poloxamer 188 (PL188, X2), and chitosan (CS, X3), which served as independent variables. The parameters measured as dependent variables included particle size (Y1), zeta potential (Y2), and encapsulation efficiency EE (Y3). The relationship among these variables was determined by Analysis of Variance (ANOVA) and response surface plots. The results revealed that PL188 played a significant role in reducing the particle size of CSLNS (ranging from 207 to 261 nm with 1 % PL188 to 167-229 nm with 3 % PL188). Conversely, an increase in the concentration of CS led to a rise in the particle size. The magnitude of positive zeta potential values was dependent on the increased concentration of CS. Moreover, the higher amounts of C-888 and PL188 improved the EE% of the CSLNs from 42 % to 86 %. Furthermore, a concentration-dependent antioxidant effect of the optimized AP-CSLNs was observed. The antioxidant activity of the optimized AP-CSLNs at 100 µg/mL was 75 % compared to 62 % and 60 % for AP-SLNs and AP solution, respectively. A similar pattern of improvement was also observed with antimicrobial, and anticancer activities of the optimized AP-CSLNs. These findings demonstrated the potential of AP-CSLNs as a carrier system, enhancing the biological activities of AP, opening new possibilities in herbal medicines.

Correction: Mahmoud et al. Neurotoxic Effect of Fipronil in Male Wistar Rats: Ameliorative Effect of L-Arginine and L-Carnitine. Biology 2021, 10, 682.

In the original publication [...].

Chitosan-Coated Solid Lipid Nanoparticles as an Efficient Avenue for Boosted Biological Activities of Aloe perryi: Antioxidant, Antibacterial, and Anticancer Potential.

Aloe perryi (ALP) is an herb that has several biological activities such as antioxidant, antibacterial, and antitumor effects and is frequently used to treat a wide range of illnesses. The activity of many compounds is augmented by loading them in nanocarriers. In this study, ALP-loaded nanosystems were developed to improve their biological activity. Among different nanocarriers, solid lipid nanoparticles (ALP-SLNs), chitosan nanoparticles (ALP-CSNPs), and CS-coated SLNs (C-ALP-SLNs) were explored. The particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and release profile were evaluated. Scanning electron microscopy was used to see the nanoparticles' morphology. Moreover, the possible biological properties of ALP were assessed and evaluated. ALP extract contained 187 mg GAE/g extract and 33 mg QE/g extract in terms of total phenolic and flavonoid content, respectively. The ALP-SLNs-F1 and ALP-SLNs-F2 showed particle sizes of 168.7 ± 3.1 and 138.4 ± 9.5 nm and the zeta potential values of -12.4 ± 0.6, and -15.8 ± 2.4 mV, respectively. However, C-ALP-SLNs-F1 and C-ALP-SLNs-F2 had particle sizes of 185.3 ± 5.5 and 173.6 ± 11.3 nm with zeta potential values of 11.3 ± 1.4 and 13.6 ± 1.1 mV, respectively. The particle size and zeta potential of ALP-CSNPs were 214.8 ± 6.6 nm and 27.8 ± 3.4 mV, respectively. All nanoparticles exhibited PDI < 0.3, indicating homogenous dispersions. The obtained formulations had EE% and DL% in the ranges of 65-82% and 2.8-5.2%, respectively. After 48 h, the in vitro ALP release rates from ALP-SLNs-F1, ALP-SLNs-F2, C-ALP-SLNs-F1, C-ALP-SLNs-F2, and ALP-CSNPs were 86%, 91%, 78%, 84%, and 74%, respectively. They were relatively stable with a minor particle size increase after one month of storage. C-ALP-SLNs-F2 exhibited the greatest antioxidant activity against DPPH radicals at 73.27%. C-ALP-SLNs-F2 demonstrated higher antibacterial activity based on MIC values of 25, 50, and 50 µg/mL for P. aeruginosa, S. aureus, and E. coli, respectively. In addition, C-ALP-SLNs-F2 showed potential anticancer activity against A549, LoVo, and MCF-7 cell lines with IC50 values of 11.42 ± 1.16, 16.97 ± 1.93, and 8.25 ± 0.44, respectively. The results indicate that C-ALP-SLNs-F2 may be promising nanocarriers for enhancing ALP-based medicines.

Identification of bio-active food compounds as potential SARS-CoV-2 PLpro inhibitors-modulators via negative image-based screening and computational simulations.

Despite significant studies on the COVID-19 pandemic, scientists around the world are still battling to find a definitive therapy against the ongoing severe global health crisis. In this study, advanced computational approaches have been employed to identify bioactive food constituents as potential SARS-CoV-2 PLpro inhibitors-modulators. As a validated antiviral drug target, PLpro has gained tremendous attention for therapeutics developments. Therefore, targeting the multifunctional SARS-CoV-2 PLpro protein, ∼1039 bioactive dietary compounds have been screened extensively through novel techniques like negative image-based (NIB) screening and molecular docking approaches. In particular, the three different models of NIB screening have been generated and used to re-score the dietary compounds based on the negative image which is created by reversing the shape and electrostatics features of PLpro protein's ligand-binding cavity. Further, 100 ns molecular dynamics simulation has been performed and MM-GBSA based binding free energies have been estimated for the final proposed four dietary compounds (PC000550, PC000361, PC000558, and PC000573) as potential inhibitors/modulators of SARS-CoV-2 PLpro protein. Employed computational study outcome also has been compared with respect to the earlier experimentally investigated compound GRL0617 against SARS-CoV-2 PLpro protein, which suggests much greater interaction potential in terms of binding affinity and other energetic contributions for the proposed dietary compounds. Hence, the present study suggests that proposed dietary compounds can be suitable chemical entities for modulating the activity of PLpro protein or can be further utilized for optimizing or screening of novel chemical surrogates, however also needs experimental evaluation for entry in clinical studies for better assessment.

Methanolic Phoenix dactylifera L. Extract Ameliorates Cisplatin-Induced Hepatic Injury in Male Rats.

This study investigated the ameliorative potential of methanolic date flesh extract (MDFE) against cisplatin-induced hepatic injury. Twenty male rats (weighing 180-200 g) were allocated into four groups: control; date flesh (DF) group (oral 600 mg/kg MDFE for 21 days); Cis group (7.5 mg/kg i.p. at day 16); and date flesh/cisplatin (DF/Cis) group (oral 600 mg/kg MDFE for 21 days and 7.5 mg/kg i.p. at day 16). Hepatic biochemical parameters in sera, and inflammatory and oxidant/antioxidant hepatic biomarkers were estimated. Hepatic histological changes and the immunohistochemistry of cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), and alpha smooth muscle actin (α-SMA) were assessed. Pretreatment with MDFE decreased Cis-triggered liver biochemical parameters, oxidative stress, inflammatory biomarkers, and histological damage. Moreover, MDFE treatment reduced Cis-induced hepatic NF-κB, COX-2, and α-SMA protein expression. MDFE exerted a hepatoprotective effect when used concomitantly with Cis. Its effect was mediated via its antioxidant and anti-inflammatory ingredients.

Structure-based identification of galectin-1 selective modulators in dietary food polyphenols: a pharmacoinformatics approach.

In this study, a set of dietary polyphenols was comprehensively studied for the selective identification of the potential inhibitors/modulators for galectin-1. Galectin-1 is a potent prognostic indicator of tumor progression and a highly regarded therapeutic target for various pathological conditions. This indicator is composed of a highly conserved carbohydrate recognition domain (CRD) that accounts for the binding affinity of ß-galactosides. Although some small molecules have been identified as galectin-1 inhibitors/modulators, there are limited studies on the identification of novel compounds against this attractive therapeutic target. The extensive computational techniques include potential drug binding site recognition on galectin-1, binding affinity predictions of ~ 500 polyphenols, molecular docking, and dynamic simulations of galectin-1 with selective dietary polyphenol modulators, followed by the estimation of binding free energy for the identification of dietary polyphenol-based galectin-1 modulators. Initially, a deep neural network-based algorithm was utilized for the prediction of the druggable binding site and binding affinity. Thereafter, the intermolecular interactions of the polyphenol compounds with galectin-1 were critically explored through the extra-precision docking technique. Further, the stability of the interaction was evaluated through the conventional atomistic 100 ns dynamic simulation study. The docking analyses indicated the high interaction affinity of different amino acids at the CRD region of galectin-1 with the proposed five polyphenols. Strong and consistent interaction stability was suggested from the simulation trajectories of the selected dietary polyphenol under the dynamic conditions. Also, the conserved residue (His44, Asn46, Arg48, Val59, Asn61, Trp68, Glu71, and Arg73) associations suggest high affinity and selectivity of polyphenols toward galectin-1 protein.

Identification of potent food constituents as SARS-CoV-2 papain-like protease modulators through advanced pharmacoinformatics approaches.

The current ongoing pandemic of COVID-19 urges immediate treatment measures for controlling the highly contagious SARS-CoV-2 infections. The papain-like protease (PLpro), which is released from nsp3, is presently being evaluated as a significant anti-viral drug target for COVID-19 therapy development. Particularly, PLpro is implicated in the cleavage of viral polyproteins and antagonizes the host innate immune response through its deubiquitinating and deISGylating actions, thus making it a high-profile antiviral therapeutic target. The present study reports a few specific food compounds that can bind tightly with the SARS-CoV-2 PLpro protein identified through extensive computational screening techniques. Precisely, extensive advanced computational approaches combining target-based virtual screening, particularly employing sub-structure based similarity search, molecular docking, molecular dynamics (MD) simulations, and MM-GBSA based binding free energy calculations have been employed for the identification of the most promising food compounds with substantial functional implications as SARS-CoV-2 PLpro protein inhibitors/modulators. Observations from the present research investigation also provide a deeper understanding of the binding modes of the proposed four food compounds with SARS-CoV-2 PLpro protein. In docking analyses, all compounds have established essential inter-molecular interaction profiles at the active site cavity of the SARS-CoV-2 PLpro protein. Similarly, the long-range 100 ns conventional MD simulation studies also provided an in-depth understanding of probable interactions and dynamic behaviour of the SARS-CoV-2 PLpro protein-food compound complexes. Binding free energies of all molecular systems revealed a strong interaction affinity of food compounds towards the SARS-CoV-2 PLpro protein. Moreover, clear-cut comparative analyses against the known standard inhibitor also suggest that proposed food compounds may act as potential active chemical entities for modulating the action of the SARS-CoV-2 PLpro protein.

Neurotoxic Effect of Fipronil in Male Wistar Rats: Ameliorative Effect of L-Arginine and L-Carnitine.

The ameliorative effect of L-arginine (LA) and L-carnitine (LC) against fipronil (FPN)-induced neurotoxicity was explored. In this case, 36 adult male rats were randomly divided into six groups: group I received distilled water, group II received 500 mg/kg LA, group III received 100 mg/kg LC, group IV received 4.85 mg/kg FPN, group V received 4.85 mg/kg FPN and 500 mg/kg LA and group VI received 4.85 mg/kg FPN and 100 mg/kg LC for 6 weeks. Cognitive performance was assessed using Barnes maze (BM). Serum corticosterone, brain total antioxidant capacity (TAC), malondialdehyde (MDA) and dopamine were measured. Histopathology and immunohistochemistry of ionized calcium-binding adaptor (Iba-1), doublecortin (DCX) and serotonin (S-2A) receptors were performed. Fipronil induced noticeable deterioration in spatial learning and memory performance. In addition, FPN significantly (p < 0.05) diminished brain antioxidant defense system and dopamine coincide with elevated serum corticosterone level. Histopathological examination revealed degenerative and necrotic changes. Furthermore, Iba-1 and DCX were significantly expressed in cortex and hippocampus whereas S-2A receptors were significantly lowered in FPN group. However, administration of LA or LC alleviated FPN-induced deteriorations. In conclusion, LA and LC could be prospective candidates for mitigation of FPN-induced neurotoxicity via their antioxidant, anti-inflammatory and neuropotentiating effects.

Assessment of modulatory activity of Uncaria tomentosa extract against fipronil immunotoxicity in male rats.

This study has investigated the effect of using the Uncaria tomentosa (UT) extract against immunotoxicity that induced by fipronil (FP) in male Wistar rats. Twenty-eight, male Wistar rats were assigned randomly into four groups (7 rats each). Control group received distilled water. FP group received FP 9.7 mg/kg b. wt orally via gastric tube. UT group received 120 mg/kg b. wt. of UT extract orally. FP-UT group received both FP and UT (9.7 and 120 mg/kg b.wt, respectively) for 30 days. Hematological parameters, malondialdehyde (MDA), total antioxidant capacity (TAC), estradiol, histamine and immunoglobulin E (IGE) were assayed. Histopathological and electron microscopical examinations were performed to the lymphoid organs. Hematological parameters, were decreased in the FP group than the control group. There was a rise in MDA of FP group followed by a decrease in TAC content with histological and ultrastructure degenerative changes. UT extract treatment ameliorated the FP-induced perturbations for the former parameters. The results showed that FP treatment exerted an immunotoxic effect through acting as an endocrine disruptor and allergic, pro-inflammatory that was confirmed by histopathological and ultrastructure study of the lymphoid organs. Uncaria tomentosa extract could successfully modulate FP-induced immunotoxicity by diminishing all the studied parameters.

The effect of dietary supplementation with Nigella sativa (black seeds) mediates immunological function in male Wistar rats.

This experiment aimed to investigate the effect of dietary Nigella sativa on the cell-mediated immune response. Eighteen male Wistar rats were divided equally into a control group and treated groups that received black seeds at rates of 30 and 50 g/kg in the diet (Sa30 and Sa50 groups, respectively, for 30 days. The weight gain, feed intake, feed conversion ratio (FCR), and cell-mediated immune response were monitored after the injection of 0.1 mL of 10% phytohemagglutinin (PHA). The intumesce index, serum total antioxidant capacity (TAC), catalase (CAT), interleukin-12 (IL-12), gamma interferon (γ-IF) and tumor necrosis factor alpha (TNF-α) were determined. Histopathological examination and an immunohistochemistry analysis of splenic caspase-3 and CD8 were performed. Nigella sativa significantly improved the weight gain and FCR. Intumesce index of Sa50 group was significantly increased. Nigella sativa significantly increased TAC, CAT, IL-12, γ-IF and TNF-α. A histological examination of PHA-stimulated foot pads showed increased leukocyte infiltration and edema in a dose-dependent pattern. Splenic caspase-3 and CD8 showed significant decreases and increases, respectively, in the Sa30 and Sa50 groups. The results indicate that Nigella sativa seeds exhibit immunostimulatory function through their antioxidant potential, induction of cytokine production, promotion of CD8 expression and reduction of splenic apoptosis.

Identification of bioactive compounds from Glycyrrhiza glabra as possible inhibitor of SARS-CoV-2 spike glycoprotein and non-structural protein-15: a pharmacoinformatics study.

At present, the world is facing a pandemic named as COVID-19, caused by SARS-CoV-2. Traditional Chinese medicine has recommended the use of liquorice (Glycyrrhiza species) in the treatment of infections caused by SARS-CoV-2. Therefore, the present investigation was carried out to identify the active molecule from the liquorice against different protein targets of COVID-19 using an in-silico approach. The molecular docking simulation study of 20 compounds along with two standard antiviral drugs (Lopinavir and Rivabirin) was carried out with the help of Autodock vina software using two protein targets from COVID-19 i.e. spike glycoprotein (PDB ID: 6VSB) and Non-structural Protein-15 (Nsp15) endoribonuclease (PDB ID: 6W01). From the observed binding energy and the binding interactions, glyasperin A showed high affinity towards Nsp15 endoribonuclease with uridine specificity, while glycyrrhizic acid was found to be best suited for the binding pocket of spike glycoprotein and also prohibited the entry of the virus into the host cell. Further, the dynamic behavior of the best-docked molecules inside the spike glycoprotein and Nsp15 endoribonuclease were explored through all-atoms molecular dynamics (MD) simulation study. Several parameters from the MD simulation have substantiated the stability of protein-ligand stability. The binding free energy of both glyasperin A and glycyrrhizic acid was calculated from the entire MD simulation trajectory through the MM-PBSA approach and found to high binding affinity towards the respective protein receptor cavity. Thus, glyasperin A and glycyrrhizic acid could be considered as the best molecule from liquorice, which could find useful against COVID-19. Communicated by Ramaswamy H. Sarma.

Anti-obesity potential of Moringa olifera seed extract and lycopene on high fat diet induced obesity in male Sprauge Dawely rats.

Present research explored the anti-obesity effect of Moringa olifera seed oil extract and lycopene (LYC). Forty eight male Sprauge Dawely rats were divided equally into 6 groups. Group Ι (C) served as control, group ΙΙ (MC) was given Moringa olifera seed oil extract (800 mg/kg b.wt) for 8 weeks, group ΙΙΙ (LC) was given (20 mg/kg b.wt) LYC for 8 weeks, group ΙV (O) received high fat diet (HFD) for 20 weeks, group Ñ´ (MO), was given HFD for 20 weeks and received (800 mg/kg b.wt) Moringa olifera seed oil extract for last 8 weeks and group Ñ´Ι (LO), received HFD for 20 weeks and was given (20 mg/kg b.wt) LYC for last 8 weeks. Hematology, lipid peroxidation and antioxidants, non-esterified fatty acids (NEFA), glucose, lipid profile, serum liver and kidney biomarkers, inflammatory markers, leptin, resistin and heart fatty acid binding protein (HFABP) were determined. Also histopathology for liver, kidney and aorta were performed besides immunohistochemistry (IHC) for aortic inducible nitric oxide synthase (iNOS). Administration of Moringa olifera seed oil extract and LYC significantly ameliorated the HFD induced hematological and metabolic perturbations as well as reduced leptin and resistin. Both treatments exerted these effects through promotion of antioxidant enzymes and reducing lipid peroxidation as well as inflammatory cytokines along with reduced iNOS protein expression. Administration of Moringa olifera seed oil extract and LYC have anti-obesity potential in HFD induced obesity in male Sprauge Dawely rats.

Fast and efficient immunoaffinity column cleanup and liquid chromatography-tandem mass spectrometry method for the quantitative analysis of aflatoxins in baby food and feeds.

An ultra high performance liquid chromatography-tandem mass spectrometric method has been developed for the highly sensitive and selective determination of regulated aflatoxins. The extraction of aflatoxins from baby food matrices were performed using liquid-liquid extraction procedure followed by immunoaffinity column cleanup. The higher sensitivity for the determination of target aflatoxins was fulfilled by applying a preconcentration step with immunoaffinity columns after acetonitrile-water extraction. The enhanced selectivity was attained with the triple quadrupole mass analyzer operated in electrospray positive ionization mode. Method validation was tested in five different baby food matrices by recovery experiments. Satisfactory recoveries, between 92 and 103%, with relative standard deviations lower than 8% were achieved in all the tested matrices. The proposed method was found to be specific as no interference peaks were observed for blank samples. The limit of detection of the method was found to be in the range of 0.003-0.008 ng/mL. The validated method was fruitfully applied to the screening of aflatoxins in baby foods and feeds sample retailed in local markets of Riyadh, Saudi Arabia. The obtained levels of all analyzed aflatoxins were below the regulation limits set by European Agency.