Novel Homozygous Mutations in the Genes TGM1, SULT2B1, SPINK5 and FLG in Four Families Underlying Congenital Ichthyosis.

BACKGROUND: Ichthyoses are a large group of hereditary cornification disorders, which are both clinically and etiologically heterogeneous and affect mostly all the skin surface of the patients. Ichthyosis has its origin in an ancient Greek word "ichthys" meaning fish, this is because the ichthyosis patients have dry, thickened, and scaly skin. There is an excess accumulation of epidermal cells resulting in the appearance of continuous and widespread scales on the body. There are many varieties of ichthyosis with a broad spectrum of intensity, severity, and associated symptoms, most of them are extremely rare. Ichthyosis vulgaris is the most frequently occurring type of ichthyoses. METHOD: The present study consists of four Pakistani ichthyosis families (A, B, C, and D). Whole exome sequencing (WES) approach was used to identify the pathogenic sequence variants in probands. The segregation of these variants in other participants was confirmed by Sanger sequencing. RESULTS: Total four variants including, two splice site (TGM1: c.2088 + 1G > A) and (SPINK5: c.882 + 1G > T), a missense (SULT2B1: c.419C > T; p. Ala140Val), and a nonsense (FLG: c.6109C > T; p. Arg2037Ter) variant were identified in families A, C, B, and D, respectively, as causative mutations responsible for ichthyosis in these families. CONCLUSION: Our study unravels the molecular etiology of the four Pakistani ichthyosis families and validates the involvement of TGM1, SULT2B1, SPINK5, and FLG, in the etiology of different forms of ichthyosis. In addition, this study also aims to give a detailed clinical report of the studied ichthyosis families.

Phytochemical Analysis, In Vitro Anticholinesterase, Antioxidant Activity and In Vivo Nootropic Effect of Ferula ammoniacum (Dorema ammoniacum) D. Don. in Scopolamine-Induced Memory Impairment in Mice.

BACKGROUND: Ferula ammoniacum (D. Don) is one of the endemic medicinal plants that is traditionally used to treat a number of diseases. Although the plant has been used to enhance memory, the investigational evidence supporting the nootropic effect was unsubstantial. Hence, the rationale for this study was to assess the potential beneficial effect of F. ammoniacum seed extracts on learning and memory in mice. METHODS: The powdered plant samples (aerial parts) were subjected to extraction ad fractionation. Among the extracts, crude and ethyl acetate extracts were screened for major phytochemicals through HPLC analysis. All the extracts were evaluated for the in vitro anticholinesterase (AChE and BChE) and antioxidant potentials. Among the extracts the active fraction was further assessed for improving learning and memory in mice using behavioural tests like Y-maze and novel object recognition test (NORT) using standard protocols. After behavioural tests, all the animals were sacrificed and brains tissues were assessed for the ex vivo anticholinesterase and antioxidant potentials. RESULTS: Phytochemicals like chlorogenic acid, quercetin, mandelic acid, phloroglucinol, hydroxy benzoic acid, malic acid, epigallocatechin gallate, ellagic acid, rutin, and pyrogallol were identified in crude methanolic extract (Fa.Met) and ethyl acetate fraction (Fa.EtAc) through HPLC. Fa.EtAc and Fa.Chf extracts more potently inhibited AChE and BChE with IC50 values of 40 and 43 µg/mL, and 41 and 42 µg/mL, respectively. Similarly highest free radical scavenging potential was exhibited by Fa.EtAc fraction against DPPH (IC50 = 100 µg/mL) and ABTS (IC50 = 120 µg/mL). The extract doses, 100 and 200 mg/kg body weight significantly (p < 0.01) improved the short-term memory by increasing the percent spontaneous alternation in the Y-maze test along with increasing discrimination index in the NORT that clearly indicated the enhancement in the recognition memory of mice. CONCLUSION: The extracts more potently scavenged the tested free radicals, exhibited anticholinesterase activities, improved the learning abilities and reduced the memory impairment induced by scopolamine in mice model thus suggesting that these extracts could be effectively used for the management of oxidative stress, neurodegenerative diseases and memory loss.

Formulation of Aceclofenac Tablets Using Nanosuspension as Granulating Agent: An Attempt to Enhance Dissolution Rate and Oral Bioavailability.

PURPOSE: The aim of the studies was to fabricate aceclofenac (AC) tablets using nanosuspension as granulating fluid to boost its rate of in vitro dissolution and eventually its oral bioavailability. METHODS: The optimized nanosuspension with particle size of 112±2.01 nm was fabricated using HPMC 1% (w/v), PVP-K30 1% (w/v) and SLS 0.12% (w/v) at 400 watts of ultrasonication energy for 15 min duration and 3 sec pause. Then, the optimized aceclofenac nanosuspension was used as granulating fluid for aceclofenac tablets formulation. The characterization was performed using Malvern zetasizer, SEM, TEM, DSC and P-XRD. The granules were evaluated for the bulk and tapped densities, Hausner's ratio, angle of repose and their resulted values were found within limit. The prepared tablets were tested for average weight, hardness, friability, disintegration, dissolution and in vivo bioavailability in rabbits. RESULTS: The in vitro dissolution data showed the boosted rate of nanosuspension-based tablets compared to the microsuspension-based tablets. The in vivo bioavailability (in rabbits model) of aceclofenac nanosuspension-based tablets (ACN-1, ACN-2) proved an improved absorption as in comparison to the marketed formulation. The Cmax and AUC0→24 of ACN-1 and ACN-2 were 1.53-fold, 1.48-fold and 2.23-fold, 2.0-fold greater than that of the marketed drug, and were 1.74-fold, 1.68-fold and 2.3-fold, 2.21-fold greater in comparison to raw drug. CONCLUSION: This boosted in vitro and in vivo bioavailability may be attributed to reduced particle size of aceclofenac nanoformulations used in tablets. Finally, this will result in faster absorption of these fabricated tablets.

Withania frutescens. L Extract: Phytochemical Characterization and Acute and Repeated Dose 28-Day Oral Toxicity Studies in Mice.

BACKGROUND: Withania frutescens. L (W. frutescens) is a perennial woody medicinal plant belonging to family Solanaceae largely used by the indigenous population to Morocco for the treatment of disease. OBJECTIVE: The purpose of this study was to investigate the chemical composition, acute, and subacute toxicity of W. frutescens extract in mice. MATERIALS AND METHODS: The phytochemical composition of W. frutescens extract was determined using a gas chromatograph (GC/MS). Acute toxicity study was carried out in mice through oral administration of single doses 500 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was performed with oral administration of repeated doses 500 and 2000 mg/kg/day for 28 days. Biochemical parameters (alanine aminotransferase, aspartate aminotransferase, urea, and creatinine), as well as histopathological changes potentially occurred in organs, (liver, kidney, and spleen) were evaluated. RESULTS: The results of chromatographic analysis showed the richness of W. frutescens extract in interesting phytochemical compounds majorly constituted of bicyclo[3.1.1]heptane, 6,6-dimethyl-2-methylene-(C10H16). Regarding acute toxicity study, the results showed no clinical symptoms occurred in treated mice compared to the control group and no histological changes detected in analyzed organs of treated mice with dose put to 2000 mg/kg nor adverse effect on biochemical parameters. CONCLUSION: The outcome of this work showed no toxic effect of W. frutescens in mice up to dose 2000 mg/kg bodyweight. Therefore, this study could scientifically validate further traditional use with safety in the range of tested doses.

Phytochemical Identification, Acute, and Sub-Acute Oral Toxicity Studies of the Foliar Extract of Withania frutescens.

Withania frutescens (W. frutescens) is a medicinal plant widely used to treat several diseases. This work aims to study phytochemical composition as well as acute and subacute toxicity of W. frutescens hydroethanolic extract in mice. The phytochemical composition of W. frutescens extract was performed using gas chromatographic analysis. Acute toxicity was studied in vivo with oral administration of single doses 400 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was studied with the administration of repeated doses of 400 mg/kg/day and 2000 mg/kg/day for 28 days. Phytochemical analysis of W. frutescens hydro-ethanolic extract confirmed the presence of interesting chemical compounds. Acute toxicity results showed no toxic symptoms in mice treated with an increasing dose up to a maximum of 2000 mg/kg. Alongside acute toxicity, subacute data showed no clinical symptoms nor biochemical or histological alteration in mice treated with an increasing dose up to a maximum of 2000 mg/kg compared to the control group (p < 0.05). This study shows no toxic effects in animals treated with W. frutescens extract, and, therefore, this plant can be considered safe in animals up to 2000 mg/kg under both acute and subacute toxicity conditions.

Comparative Cholinesterase, α-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives.

INTRODUCTION: The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays. METHODS: In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis-Menten kinetics. RESULTS: In AChE inhibitory assay, compounds 1 and 2 exhibited IC50 of 343.45 and 422.98 µM, respectively, against AChE enzyme. Similarly, both the compounds showed IC50 of 276.86 and 357.91 µM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC50 of 157.71 and 471.79 µM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC50 values of 297.98, 332.94, and 825.92 µM against DPPH, ABTS, and H2O2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2. CONCLUSION: Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.

Isolation of Quercetin from Rubus fruticosus, Their Concentration through NF/RO Membranes, and Recovery through Carbon Nanocomposite. A Pilot Plant Study.

In this study, an attempt has been made to devise a method for a large-scale production of quercetin from a medicinal plant. The natural products are first isolated from plants and then synthesized commercially. During their synthesis, a number of impurities or side products are also formed, most of which are carcinogenic. Plant products have limited side effects. Therefore, they are considered safe to be used for systemic uses. In the Rubus fruticosus fruit, the ethyl acetate extract was loaded to 50 optimized silica gel columns. The effluents of columns were passed through the membrane system for concentration. A 100% recovery was achieved from the drain pipe in case of reverse osmosis membrane when the specified rely of the pilot plant was set on 25% rejection. About 95% recovery was achieved through the NF membrane while the 5% loss in permeate was recovered through magnetic carbon nanocomposite (characterized through a bar magnet, SEM, XRD, and EDX). The equilibrium time of adsorption was 83 min and followed by pseudo-first-order kinetics. The adsorption equilibrium data fitted well to the Langmuir isotherm model. Through the devised method, quercetin was successfully concentrated with high efficiencies; however, further studies are needed to validate the method.

Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations.

Zika virus (ZIKV) is one of the mosquito borne flavivirus with several outbreaks in past few years in tropical and subtropical regions. The non-structural proteins of flaviviruses are suitable active targets for inhibitory drugs due to their role in pathogenicity. In ZIKV, the non-structural protein 5 (NS5) RNA-Dependent RNA polymerase replicates its genome. Here we have performed virtual screening to identify suitable ligands that can potentially halt the ZIKV NS5 RNA dependent RNA polymerase (RdRp). During this process, we searched and screened a library of ligands against ZIKV NS5 RdRp. The selected ligands with significant binding energy and ligand-receptor interactions were further processed. Among the selected docked conformations, top five was further optimized at atomic level using molecular dynamic simulations followed by binding free energy calculations. The interactions of ligands with the target structure of ZIKV RdRp revealed that they form strong bonds within the active sites of the receptor molecule. The efficacy of these drugs against ZIKV can be further analyzed through in-vitro and in-vivo studies.

Pharmacological Evaluation of Aldehydic-Pyrrolidinedione Against HCT-116, MDA-MB231, NIH/3T3, MCF-7 Cancer Cell Lines, Antioxidant and Enzyme Inhibition Studies.

PURPOSE: The current work was designed to synthesize a bioactive derivative of succinimide and evaluate it for anti-Alzheimer, anticancer and anti-diabetic potentials. METHODS: The compound was synthesized by Michael addition of butyraldehyde with N-phenylmaleimide. The synthesized compound was screened for biological potentials including anti-cholinesterase, in-vitro anti-diabetic, antioxidant and anthelmintic potentials. The anti-cholinesterase potential was evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), anti-diabetic potential against α-glucosidase, antioxidant potential against ABTS, DPPH and H2O2 and anthelmintic potential against Perethima posthuma and Ascaridia galli respectively. RESULTS: The compound demonstrated significant AChE and BChE inhibition i.e., 71.34±1.92 and 73.42 ±1.92 at the concentration of 1000 µg/mL respectively. Other dilutions exhibited concentration-dependent inhibitory activity against both enzymes. In the MTT assay, the newly synthesized compound was found active against all of the cell lines viz, HCT-116, MDA-MB231, NIH/3T3 and MCF-7 and the highest cytotoxicity potential was observed against the colon cancer cell line (HCT-116) with an IC50 value of 78 µg/mL exhibiting its highest potential. Moreover, the compound exhibited prominent α-glucosidase inhibitory potentials (79.86±2.54% at 1000 µg/mL) with IC50 value of 156.23 µg/mL. Further, our test compound exhibited considerable scavenging activity against DPPH, ABTS and H2O2 free radicals with percent inhibitions of 75.84±1.58, 72.85±1.17 and 54.82±1.82 and IC50 values of 84.36, 139.74 and 752.21 µg/mL respectively. Our test sample exhibited significant anthelmintic potentials. It demonstrated significant paralysis and death of the test worms in an unbelievably short time in comparison with albendazole. CONCLUSION: Going into the detail of all observations, it may be deduced that the newly synthesized succinimide derivative could be an important drug candidate against neurodegenerative disorders like Alzheimer's disease, cancer, diabetes mellitus and worms. Further detailed studies in animal models are required for in-vivo analysis of the compound.

Isolation, pharmacological evaluation and molecular docking studies of bioactive compounds from Grewia optiva.

BACKGROUND: Traditionally, Grewia optiva is widely used for the treatment of many diseases like dysentery, fever, typhoid, diarrhea, eczema, smallpox, malaria and cough. METHODS: Shade-dried roots of G. optiva were extracted with methanol. Based on HPLC results, chloroform and ethyl acetate fractions were subjected to silica column isolation and four compounds: glutaric acid (V), 3,5 dihydroxy phenyl acrylic acid (VI), (2,5 dihydroxy phenyl) 3',6',8'-trihydroxyl-4H chromen-4'-one (VII) and hexanedioic acid (VIII) were isolated in pure form. Ellman's assay was used to determine the anticholinesterase potential of isolated compounds while their antioxidant potential was estimated by DPPH and ABTS scavenging assays. RESULTS: Amongst the isolated compounds, VI and VII exhibited excellent percent inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (83.23±1.11, 82.72±2.20 and 82.11±2.11, 82.23±1.21, respectively, at 1000 µg/mL) with IC50 of 76, 90, 78 and 92 µg/mL, respectively. Highest percent radicals scavenging against DPPH and ABTS (87.41±1.20 and 86.13±2.31) with IC50 of 64 and 65 µg/mL, respectively, were observed for compound VII. Molecular docking studies also supported the binding of compound VI and VII with the target enzyme. The para-hydroxyl group of the phenolic moiety is formed hydrogen bonds with the active site water molecule and the side chain carbonyl and hydroxyl residues of enzyme. CONCLUSION: The isolated compounds inhibited the DPPH and ABTS-free radicals, and AChE and BChE enzymes. It was concluded that these compounds could be used in relieving the oxidative stress and pathological symptoms associated with excessive hydrolysis of acetyl and butyryl choline. The results of the study were supported by docking studies for compounds VI and VII.

Enzyme Inhibitory, Antioxidant And Antibacterial Potentials Of Synthetic Symmetrical And Unsymmetrical Thioureas.

BACKGROUND: In this study, 2 symmetrical and 3 unsymmetrical thioureas were synthesized to evaluate their antioxidant, antibacterial, antidiabetic, and anticholinesterase potentials. METHODS: The symmetrical thioureas were synthesized in aqueous media in the presence of sunlight, using amines and CS2 as starting material. The unsymmetrical thioureas were synthesized using amines as a nucleophile to attack the phenyl isothiocyanate (electrophile). The structures of synthesized compounds were confirmed through H1 NMR. The antioxidant potential was determined using DPPH and ABTS assays. The inhibition of glucose-6-phosphatase, alpha amylase, and alpha glucosidase by synthesized compounds was used as an indication of antidiabetic potential. Anticholinesterase potential was determined from the inhibition of acetylcholinesterase and butyrylcholinesterase by the synthesized compounds. RESULTS: The highest inhibition of glucose-6-phosphatase was shown by compound V (03.12 mg of phosphate released). Alpha amylase was most potently inhibited by compound IV with IC50 value of 62 µg/mL while alpha glucosidase by compound III with IC50 value of 75 µg/mL. The enzymes, acetylcholinesterase, and butyrylcholinesterase were potently inhibited by compound III with IC50 of 63 µg/mL and 80 µg/mL respectively. Against DPPH free radical, compound IV was more potent (IC50 = 64 µg/mL) while ABTS was more potently scavenged by compound I with IC50 of 66 µg/mL. The antibacterial spectrum of synthesized compounds was determined against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Agrobacterium tumefaction and Proteus vulgaris). Compound I and compound II showed maximum activity against A. tumefaction with MIC values of 4.02 and 4.04 µg/mL respectively. Against P. vulgaris, compound V was more active (MIC = 8.94 µg/mL) while against S. aureus, compound IV was more potent with MIC of 4.03 µg/mL. CONCLUSION: From the results, it was concluded that these compounds could be used as antibacterial, antioxidant, and antidiabetic agents. However, further in vivo studies are needed to determine the toxicological effect of these compounds in living bodies. The compounds also have potential to treat neurodegenerative diseases.

Fabrication and characterization of glimepiride nanosuspension by ultrasonication-assisted precipitation for improvement of oral bioavailability and in vitro α-glucosidase inhibition.

PURPOSE: We aimed to enhance the solubility, dissolution rate, oral bioavailability, and α-glucosidase inhibition of glimepiride (Glm) by fabricating its nanosuspension using a precipitation-ultrasonication approach. METHODS: Glm nanosuspensions were fabricated using optimized processing conditions. Characterization of Glm was performed using Malvern Zetasizer, scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. Minimum particle size and polydispersity index (PDI) values were found to be 152.4±2.42 nm and 0.23±0.01, respectively, using hydroxypropyl methylcellulose: 6 cPs, 1% w/v, polyvinylpyrrolidone K30 1% w/v, and sodium lauryl sulfate 0.12% w/v, keeping ultrasonication power input at 400 W, with 15 minutes' processing at 3-second pauses. In vivo oral bioavailability was assessed using rabbits as a model. RESULTS: The saturation solubility of the Glm nanosuspensions was substantially enhanced 3.14-fold and 5.77-fold compared to unprocessed drug in stabilizer solution and unprocessed active pharmaceutical ingredient. Also, the dissolution rate of the nanosuspensions ws substantially boosted when compared to the marketed formulation and unprocessed drug candidate. The results showed that >85% of Glm nanosuspensions dissolved in the first 10 minutes compared to 10.17% of unprocessed Glm), 42.19% of microsuspensions, and 19.94% of marketed tablets. In-vivo studies conducted in animals, i.e. rabbits, demonstrated that maximum concentration and AUC0-24 with oral dosing were twofold (5 mg/kg) and 1.74-fold (2.5 mg/kg) and 1.80-fold (5 mg/kg) and 1.63-fold (2.5 mg/kg), respectively, and compared with the unprocessed drug formulation. In-vitro α-glucosidase inhibition results showed that fabricated nanosuspensions had a pronounced effect compared to unprocessed drug. CONCLUSION: The optimized batch fabricated by ultrasonication-assisted precipitation can be useful in boosting oral bioavailability, which may be accredited to enhanced solubility and dissolution rate of Glm, ultimately resulting in its faster rate of absorption due to nanonization.

Computational Study of Natural Compounds for the Clearance of Amyloid-Βeta: A Potential Therapeutic Management Strategy for Alzheimer's Disease.

Alzheimer's disease (AD) is a widespread dynamic neurodegenerative malady. Its etiology is still not clear. One of the foremost pathological features is the extracellular deposits of Amyloid-beta (Aß) peptides in senile plaques. The interaction of Aß and the receptor for advanced glycation end products at the blood-brain barrier is also observed in AD, which not only causes the neurovascular anxiety and articulation of proinflammatory cytokines, but also directs reduction of cerebral bloodstream by upgrading the emission of endothelin-1 to induce vasoconstriction. In this process, RAGE is deemed responsible for the influx of Aß into the brain through BBB. In the current study, we predicted the interaction potential of the natural compounds vincamine, ajmalicine and emetine with the Aß peptide concerned in the treatment of AD against the standard control, curcumin, to validate the Aß peptide-compounds results. Protein-protein interaction studies have also been carried out to see their potential to inhibit the binding process of Aß and RAGE. Moreover, the current study verifies that ligands are more capable inhibitors of a selected target compared to positive control with reference to ΔG values. The inhibition of Aß and its interaction with RAGE may be valuable in proposing the next round of lead compounds for effective Alzheimer's disease treatment.

An ethnobotanical study of medicinal plants used to treat skin diseases in northern Pakistan.

BACKGROUND: Skin diseases are a major health concern especially in association with human immune deficiency syndrome and acquired an immune deficiency. The aim of this study was to document the ethnomedicinal information of plants used to treat skin diseases in Northern Pakistan. This is the first quantitative ethnobotanical study of therapeutic herbs utilized by the indigenous people of Northern Pakistan for skin diseases. METHODS: Interviews were taken to obtain information from 180 participants. Quantitative methods including fidelity level (FL), Frequency of citation (FC), Use-value (UV), Jaccard indices (JI), Family importance value (FIV), Relative frequency of citation (RFC) and Chi-square test were applied. Medicinal plants uses are also compared with 50 national and international publications. RESULTS: In this study, we recorded 106 plant species belonged to 56 floral families for treatment of skin ailments. The dominant life form reported was herb while the preferred method of utilization was powder, along with leaf as the most used plant part. RFC ranges from 0.07 to 0.25% whereas the highest FIV was recorded for family Pteridaceae. FL values range from 36.8 to 100%. The study reported 88% of new plant reports for the treatment of skin diseases. CONCLUSION: The present study revealed the importance of several plants used to treat skin diseases by the local communities of Northern Pakistan. The available literature supported the evidence of plant dermatological properties. Plants having high UV and RFC can be considered for further scientific analysis. There is dire need to create awareness among local, government and scientific communities for the preservation of medicinal species and ethnomedicinal knowledge in Northern Pakistan.

Phytochemical Analysis and Toxicity Study of Aristolochia paucinervis Rhizomes Decoction Used in Moroccan Alternative Medicine: Histopathological and Biochemical Profiles.

ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochia paucinervis (A. paucinervis) (Aristolochiaceae) is a plant frequently used in Moroccan alternative medicine. The aim of the current study is to investigate the phytochemical composition of rhizomes decoction of A. paucinervis (RDA) and to evaluate its acute and subacute toxicity following the OECD guidelines. MATERIALS AND METHODS: The qualitative phytochemical analysis of A. paucinervis was performed using standard qualitative phytochemical procedures. The acute toxicity of rhizomes decoction of the studied plant was evaluated in mice at single doses of 1, 2, and 4 g/kg of body weight for 14 days. In subacute toxicity study, the decoction was orally administered to mice at three different doses (0.5, 1, and 1.5 g/kg/day) for 28 days. Histopathological and biochemical parameters were investigated. RESULTS: The preliminary phytochemical screening showed the presence of flavonoids, saponins, alkaloids, and polyphenols and the absence of anthraquinones, sterols, and terpenes. There was no mortality and no significant changes occurred in animals treated with 1 and 2 g/kg in the acute toxicity model. The signs of toxicity and morbidity were remarkable with the highest tested dose (4g/kg). LD50 (dose required to kill 50% of the test population) was determined as 4 g/kg. Repeated oral administration of 1 and 1.5 g/kg/day of RDA for 28 days induced significant disturbance of serum parameters (AST, ALT, LDH, urea, creatinine). Kidney and liver extracted from mice fed with 1 and 1.5 g/kg/day showed significant histopathological injuries as tubular necrosis, inflammatory infiltrate, tubular degeneration, necrosis, and hepatic cholestasis. Meanwhile, neither histopathological nor biochemical alterations were observed in mice treated with 0.5 g/kg/day of body weight in comparison to the control group. CONCLUSION: RDA showed toxicity in mice at a dose of 1 g/kg/day under subacute toxicity conditions. RDA is safe at a single dose inferior to 4 g/kg of body weight. The plant extract prepared by decoction showed more poisonous effect than the extract prepared by maceration at room temperature.

Separation of Levofloxacin from Industry Effluents Using Novel Magnetic Nanocomposite and Membranes Hybrid Processes.

Magnetic carbon nanocomposite (MCN) was synthesized from waste biomass precursor, pineapple. The prepared adsorbent was characterized using different instrumental techniques and was used to remove levofloxacin (LEV) from effluents. The maximum sorption of LEV was observed at pH 7. Pseudo-2nd-order (PSO) kinetic was found to be the best model that fits well the adsorption kinetics data. For Langmuir adsorption isotherm, the R2 value was higher as compared with other isotherms. The Van't Hoff equation was used for thermodynamic parameters determinations. ΔS° (standard entropy) was positive and ΔG° (standard Gibb's free energy) was negative: -0.37, -1.81, and -3.73 kJmol-1 corresponding to 25, 40, and 60°C. The negative values of ΔG° at different temperatures stipulate that the adsorption of LEV was spontaneous in nature and adsorbent has a considerable affinity for LEV molecules. The MCN was then utilized in hybrid way by connecting with ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) membranes in series and as a result enhanced permeate fluxes were observed. The percent retention of LEV molecules was lower with UF membrane and with NF it was 96%, while it was 100% with RO. For MCN/UF and MCN/NF systems, improvement in % retention was recorded.