The Anti-urolithiatic effect of the roots of Saussurea costus (falc) Lipsch agonist ethylene glycol and magnesium oxide induced urolithiasis in rats.

Phytotherapy, which involves the use of plant extracts and natural compounds for medicinal purposes, is indeed a promising alternative for managing urinary lithiasis. Many plants have been studied for their potential to prevent and treat kidney stones, and they may offer a more natural and potentially less harmful approach compared to conventional treatments. Additionally, phytotherapy may be more cost-effective. The aim of the present study was to investigate the antilithic potential of extracts and essential oils of Saussurea costus (Falc) Lipsch in two in vivo models, one on ethylene glycol-induced calcium oxalate crystal formation and the other to assess the effects of these extracts on magnesium oxide-induced struvite crystal formation. The experiment involved the administration of different doses of aqueous and ethanolic extracts of S. costus (200 and 400 mg/kg) and essential oils (25 and 50 mg/kg) to male Wistar rats, followed by the evaluation of various physiological, biochemical and histopathological parameters. The results demonstrated that the administration of S. costus essential oils and extracts had significant effects on the rats, influencing body weight, urine volume, crystal deposition, cytobacteriological examination of urine, and serum biochemical parameters. Histopathological examinations revealed varying impacts on the kidneys and livers of the treated rats. The findings suggest that S. costus extracts and essential oils may hold promise in inhibiting calcium oxalate crystal formation in vivo and influencing various physiological and biochemical parameters in rats. Overall, the 200 mg/kg ethanolic extract of S. costus demonstrated antilithiatic efficacy, did not exhibit signs of toxicity and reduced the number of crystals in the kidneys. Furthermore, the study did not find a significant effect on reducing struvite crystals.

Developing, validating, and comparing an analytical method to simultaneously detect z-drugs in urine samples using the QuEChERS approach with both liquid chromatography and gas chromatography-tandem mass spectrometry.

Detecting z-drugs, a sedative-hypnotic medication, is also misused for criminal activities. Therefore, the analysis of urine samples is crucial for clinical and forensic purposes. We conducted a study where we developed, validated, and compared an analytical method for simultaneously detecting z-drugs in urine samples. Our approach uses the QuEChERS method for sample preparation, combined with liquid chromatography (LC) and gas chromatography (GC) coupled with tandem mass spectrometry (MS/MS). We optimized the QuEChERS method to effectively extract z-drugs from urine samples while minimizing matrix effects and achieving high recovery rates. After extraction, we split the samples into two parts for analysis using LC-MS/MS and GC-MS/MS. We validated our methods, and the results showed good linearity over a broad concentration range (1-200 ng/mL) for each z-drug. The limits of detection and quantification were within clinically relevant ranges, ensuring sensitivity for detecting z-drugs in urine samples. We compared the two chromatographic techniques by analyzing a set of urine samples spiked with known concentrations of z-drugs using both LC-MS/MS and GC-MS/MS methods and then applied to the real samples. The results were statistically analyzed to assess any significant differences in accuracy and precision above 95 %, and both methods offered reliable and consistent results with the samples as well. In conclusion, our analytical method coupled with both LC-MS/MS and GC-MS/MS using the QuEChERS approach provides a comprehensive and robust solution for the simultaneous detection of z-drugs in urine samples. The choice between the two chromatographic techniques can be based on the specific z-drugs of interest and the required analytical performance. This method holds promise for applications in clinical toxicology, forensic analysis, and monitoring z-drug usage.

QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton's tyrosine kinase (BTK) inhibitors.

In recent years, there has been a focus on developing and discovering novel Bruton's tyrosine kinase (BTK) inhibitors, as they offer an effective treatment strategy for B-cell malignancies. BTK plays a crucial role in B cell receptor (BCR)-mediated activation and proliferation by regulating downstream factors such as the NF-κB and MAP kinase pathways. To address this challenge and propose potential therapeutic options for B-cell lymphomas, researchers conducted 2D-QSAR and ADMET studies on pyrrolopyrimidine derivatives that act as inhibitors of the BCR site in cytochrome b. These studies aim to improve and identify new compounds that could serve as more potent potential BTK inhibitors, which would lead to the identification of new drug candidates in this field. In our study, we used 2D-QSAR (multiple linear regression, multiple nonlinear regression, and artificial neural networks), molecular docking, molecular dynamics, and ADMET properties to investigate the potential of 35 pyrrolopyrimidine derivatives as BTK inhibitors. A molecular docking study and molecular dynamics simulations of molecule 13 over 10 ns revealed that it establishes multiple hydrogen bonds with several residues and exhibits frequent stability throughout the simulation period. Based on the results obtained by molecular modeling, we proposed six new compounds (Pred1, Pred2, Pred3, Pred4, Pred5, and Pred6) with highly significant predicted activity by MLR models. A study based on the in silico evaluation of the predicted ADMET properties of the new candidate molecules is strongly recommended to classify these molecules as promising candidates for new anticancer agents specifically designed to target Bruton's tyrosine kinase (BTK) inhibition.

Enhancement of Curcumin's Anti-Psoriatic Efficacy via Formulation into Tea Tree Oil-Based Emulgel.

Psoriasis is a chronic inflammatory skin disease characterized by the hyperproliferation and aberrant differentiation of epidermal keratinocytes. It is a debilitating condition that can cause significant physical and emotional distress. Natural anti-psoriatic agents have been investigated as alternatives to conventional allopathic medications, as they have notable limitations and drawbacks. Curcumin and tea tree oil are cost-efficient and effective anti-inflammatory medicines with less adverse effects compared to synthetic psoriasis medications. Our research endeavors to harness the therapeutic potential of these natural compounds by developing an herbal anti-psoriatic topical drug delivery system. This novel method uses curcumin and tea tree oil to create a bi-phasic emulgel drug delivery system. Formulations F1 (gel) and F2 (emulgel) have high drug content percentages of 84.2% and 96.7%, respectively. The emulgel showed better spreadability for cutaneous applications, with a viscosity of 92,200 ± 943 cp compared to the gel's 56,200 ± 1725 cp. The emulgel released 94.48% of the drugs, compared to 87.58% for the gel. These formulations conform to the zero-order and Higuchi models, and their stability over a three-month period is crucial. In vivo, the emulgel healed psoriasis symptoms faster than the usual gel. The gathered results confirmed the emulgel's potential as a drug delivery method, emphasizing the complementary benefits of tea tree oil and curcumin as an effective new therapy for psoriasis.

Synthesis of Quercetin-Loaded Silver Nanoparticles and Assessing Their Anti-Bacterial Potential.

The study delves into the multifaceted potential of quercetin (Qu), a phytoconstituent found in various fruits, vegetables, and medicinal plants, in combination with silver nanoparticles (AgNPs). The research explores the synthesis and characterization of AgNPs loaded with Qu and investigates their pharmaceutical applications, particularly focusing on antibacterial properties. The study meticulously evaluates Qu's identity, and physicochemical properties, reaffirming its suitability for pharmaceutical use. The development of Qu-loaded AgNPs demonstrates their high drug entrapment efficiency, ideal particle characteristics, and controlled drug release kinetics, suggesting enhanced therapeutic efficacy and reduced side effects. Furthermore, the research examines the antibacterial activity of Qu in different solvents, revealing distinct outcomes. Qu, both in methanol and water formulations, exhibits antibacterial activity against Escherichia coli, with the methanol formulation displaying a slightly stronger efficacy. In conclusion, this study successfully synthesizes AgNPs loaded with Qu and highlights their potential as a potent antibacterial formulation. The findings underscore the influence of solvent choice on Qu's antibacterial properties and pave the way for further research and development in drug delivery systems and antimicrobial agents. This innovative approach holds promise for addressing microbial resistance and advancing pharmaceutical formulations for improved therapeutic outcomes.

Screening of Phytochemical, Antimicrobial, and Antioxidant Properties of Juncus acutus from Northeastern Morocco.

Juncus acutus, acknowledged through its indigenous nomenclature "samar", is part of the Juncaceae taxonomic lineage, bearing considerable import as a botanical reservoir harboring conceivable therapeutic attributes. Its historical precedence in traditional curative methodologies for the alleviation of infections and inflammatory conditions is notable. In the purview of Eastern traditional medicine, Juncus species seeds find application for their remedial efficacy in addressing diarrhea, while the botanical fruits are subjected to infusion processes targeting the attenuation of symptoms associated with cold manifestations. The primary objective of this study was to unravel the phytochemical composition of distinct constituents within J. acutus, specifically leaves (JALE) and roots (JARE), originating from the indigenous expanse of the Nador region in northeastern Morocco. The extraction of plant constituents was executed utilizing an ethanol-based extraction protocol. The subsequent elucidation of chemical constituents embedded within the extracts was accomplished employing analytical techniques based on high-performance liquid chromatography (HPLC). For the purpose of in vitro antioxidant evaluation, a dual approach was adopted, encompassing the radical scavenging technique employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the total antioxidant capacity (TAC) assay. The acquired empirical data showcase substantial radical scavenging efficacy and pronounced relative antioxidant activity. Specifically, the DPPH and TAC methods yielded values of 483.45 ± 4.07 µg/mL and 54.59 ± 2.44 µg of ascorbic acid (AA)/mL, respectively, for the leaf extracts. Correspondingly, the root extracts demonstrated values of 297.03 ± 43.3 µg/mL and 65.615 ± 0.54 µg of AA/mL for the DPPH and TAC methods. In the realm of antimicrobial evaluation, the assessment of effects was undertaken through the agar well diffusion technique. The minimum inhibitory concentration, minimum bactericidal concentration, and minimum fungicidal concentration were determined for each extract. The inhibitory influence of the ethanol extracts was observed across bacterial strains including Staphylococcus aureus, Micrococcus luteus, and Pseudomonas aeruginosa, with the notable exception of Escherichia coli. However, fungal strains such as Candida glabrata and Rhodotorula glutinis exhibited comparatively lower resistance, whereas Aspergillus niger and Penicillium digitatum exhibited heightened resistance, evincing negligible antifungal activity. An anticipatory computational assessment of pharmacokinetic parameters was conducted, complemented by the application of the Pro-tox II web tool to delineate the potential toxicity profile of compounds intrinsic to the studied extracts. The culmination of these endeavors underpins the conceivable prospects of the investigated extracts as promising candidates for oral medicinal applications.

Neuroprotective effects of trigonelline in kainic acid-induced epilepsy: Behavioral, biochemical, and functional insights.

Trigonelline, an alkaloid found in the seeds of Trigonella foenum-graecum L. (fenugreek), has been recognized for its potential in treating various diseases. Notably, trigonelline has demonstrated a neuroprotective impact by reducing intrasynaptosomal calcium levels, inhibiting the production of reactive oxygen species (ROS), and regulating cytokines. Kainic acid, an agonist of kainic acid receptors, is utilized for inducing temporal lobe epilepsy and is a common choice for establishing kainic acid-induced status epilepticus, a widely used epileptic model. The neuroprotective effect of trigonelline in the context of kainic acid-induced epilepsy remains unexplored. This study aimed to induce epilepsy by administering kainic acid (10 mg/kg, single subcutaneous dose) and subsequently evaluate the potential anti-epileptic effect of trigonelline (100 mg/kg, intraperitoneal administration for 14 days). Ethosuccimide (ETX) (187.5 mg/kg) served as the standard drug for comparison. The anti-epileptic effect of trigonelline over a 14-day administration period was examined. Behavioral assessments, such as the Novel Object Recognition (NOR) test, Open Field Test (OFT), and Plus Maze tests, were conducted 2 h after kainic acid administration to investigate spatial and non-spatial acquisition abilities in rats. Additionally, biochemical analysis encompassing intrasynaptosomal calcium levels, LDH activity, serotonin levels, oxidative indicators, and inflammatory cytokines associated with inflammation were evaluated. Trigonelline exhibited significant behavioral improvements by reducing anxiety in open field and plus maze tests, along with an amelioration of memory impairment. Notably, trigonelline substantially lowered intrasynaptosomal calcium levels and LDH activity, indicating its neuroprotective effect by mitigating cytotoxicity and neuronal injury within the hippocampus tissue. Moreover, trigonelline demonstrated a remarkable reduction in inflammatory cytokines and oxidative stress indicators. In summary, this study underscores the potential of trigonelline as an anti-epileptic agent in the context of kainic acid-induced epilepsy. The compound exhibited beneficial effects on behavior, neuroprotection, and inflammation, shedding light on its therapeutic promise for epilepsy management.

Development and Characterization of Terbinafine-Loaded Nanoemulgel for Effective Management of Dermatophytosis.

Dermatophytosis, the most prevalent fungal infection, is witnessing a rising incidence annually. To address this challenge, we developed a terbinafine-loaded oil-in-water nanoemulsion (TH-NE) through the aqueous microtitration method. The formulation comprised olive oil (oil phase), Span 80 (surfactant), and propylene glycol (co-surfactant). Pseudo-phase ternary diagrams and thermodynamic studies underscored the stability of TH-NE. Employing the Box-Behnken design (BBD), we optimized TH-NE, which resulted in a remarkable particle size of 28.07 nm ± 0.5, a low polydispersity index (PDI) of 0.1922 ± 0.1, and a substantial negative zeta potential of -41.87 mV ± 1. Subsequently, TH-NE was integrated into a 1.5% carbopol matrix, yielding a nanoemulgel (TH-NEG). Texture analysis of TH-NEG demonstrated a firmness of 168.00 g, a consistency of 229.81 g/s, negative cohesiveness (-83.36 g), and a work of cohesion at -107.02 g/s. In vitro drug release studies revealed an initial burst effect followed by sustained release, with TH-NEG achieving an impressive 88% release over 48 h, outperforming TH-NE (74%) and the marketed formulation (66%). Ex vivo release studies mirrored these results, with TH-NEG (86%) and TH-NE (71%) showcasing sustained drug release in comparison to the marketed formulation (67%). Confocal microscopy illustrated that TH-NEG and TH-NE penetrated to depths of 30 µm and 25 µm, respectively, into the epidermal layer. Furthermore, dermatokinetic studies highlighted the enhanced drug penetration of TH-NEG compared to TH-NE through mouse skin. In summary, our study establishes TH-NEG as a promising carrier for terbinafine in treating dermatophytosis, offering improved drug delivery and sustained release potential.

Obtaining New Candidate Peptides for Biological Anticancer Drugs from Enzymatic Hydrolysis of Human and Bovine Hemoglobin.

Enzymatic hydrolysis of bovine and human hemoglobin generates a diversity of bioactive peptides, mainly recognized for their antimicrobial properties. However, antimicrobial peptides stand out for their ability to specifically target cancer cells while preserving rapidly proliferating healthy cells. This study focuses on the production of bioactive peptides from hemoglobin and evaluates their anticancer potential using two distinct approaches. The first approach is based on the use of a rapid screening method aimed at blocking host cell protein synthesis to evaluate candidate anticancer peptides, using Lepidium sativum seed germination as an indicator. The results show that: (1) The degree of hydrolysis (DH) significantly influences the production of bioactive peptides. DH levels of 3 to 10% produce a considerably stronger inhibition of radicle growth than DH 0 (the native form of hemoglobin), with an intensity three to four times greater. (2) Certain peptide fractions of bovine hemoglobin have a higher activity than those of human hemoglobin. (3) The structural characteristics of peptides (random coil or alpha helix) play a crucial role in the biological effects observed. (4) The α137-141 peptide, the target of the study, was the most active of the fractions obtained from bovine hemoglobin (IC50 = 29 ± 1 µg/mL) and human hemoglobin (IC50 = 48 ± 2 µg/mL), proving to be 10 to 15 times more potent than the other hemoglobin fractions, attributed to its strong antimicrobial potential. The second approach to assessing anticancer activity is based on the preliminary in vitro analysis of hydrolysates and their peptide fractions, with a focus on the eL42 protein. This protein is of major interest due to its overexpression in all cancer cells, making it an attractive potential target for the development of anticancer molecules. With this in mind, astudy was undertaken using a method for labeling formylase (formyl-methionyl-tRNA transformylase (FMTS)) with oxidized tRNA. This approach was chosen because of the similarities in the interaction between formylase and the eL42 protein with oxidized tRNA. The results obtained not only confirmed the previous conclusions but also reinforced the hypothesis that the inhibition of protein synthesis plays a key role in the anticancer mechanism of these peptides. Indeed, the data suggest that samples containing α137-141 peptide (NKT) and total hydrolysates may have modulatory effects on the interaction between FMTS and oxidized tRNA. This observation highlights the possibility that the latter could influence molecular binding mechanisms, potentially resulting in a competitive situation where the ability of substrate tRNA to bind efficiently to ribosomal protein is compromised in their presence. Ultimately, these results suggest the feasibility of obtaining candidate peptides for biological anticancer drugs from both human and bovine hemoglobin sources. These scientific advances show new hope in the fight against cancer, which affects a large number of people around the world.

Corrigendum to "Tanshinone-I for the treatment of uterine fibroids: Molecular docking, simulation, and density functional theory investigations" [Saudi Pharm. J. 31(6) (2023) 1061-1067].

[This corrects the article DOI: 10.1016/j.jsps.2023.05.002.].

Enhancing Osteoporosis Treatment through Targeted Nanoparticle Delivery of Risedronate: In Vivo Evaluation and Bioavailability Enhancement.

Risedronate-loaded mPEG-coated hydroxyapatite, thiolated chitosan-based (coated) and non-coated nanoparticles were tested for their potential effects in the treatment of osteoporosis. The prepared nanoparticles were evaluated for their bone-targeting potential by inducing osteoporosis in female Wistar rats via oral administration of Dexona (dexamethasone sodium phosphate). In vivo pharmacokinetic and pharmacodynamic studies were performed on osteoporotic rat models treated with different formulations. The osteoporotic model treated with the prepared nanoparticles indicated a significant effect on bone. The relative bioavailability was enhanced for RIS-HA-TCS-mPEG nanoparticles given orally compared to RIS-HA-TCS, marketed, and API suspension. Biochemical investigations also showed a significant change in biomarker levels, ultimately leading to bone formation/resorption. Micro-CT analysis of bone samples also demonstrated that the RIS-HA-TCS-mPEG-treated group showed the best results compared to other treatment groups. Moreover, the histology of bone treated with RIS-HA-TCS-mPEG showed a marked restoration of the architecture of trabecular bone along with a well-connected bone matrix and narrow inter-trabecular spaces compared to the toxic group. A stability analysis was also carried out according to ICH guidelines (Q1AR2), and it was found that RIS-HA-TCS-mPEG was more stable than RIS-HA-TCS at 25 °C. Thus, the results of present study indicated that mPEG-RIS-HA-TCS has excellent potential for sustained delivery of RIS for the treatment and prevention of osteoporosis, and for minimizing the adverse effects of RIS typically induced via oral administration.

Quality control, phytochemical profile, and biological activities of Crataegus monogyna Jacq. and Crataegus laciniata Ucria fruits aqueous extracts.

The current study aimed to evaluate the phytochemical composition, quality control, and antioxidant, antibacterial, antifungal, antihyperglycemic activities, and toxicity assessment of Crataegus monogyna Jacq (C. monogyna) and Crataegus laciniata Ucria (C. laciniata) fruits aqueous extracts. The quality control of the plant material revealed that it is free of heavy metals and the acidity and ash parameters comply with international standards. HPLC-DAD analysis revealed the presence of eight phenolic compounds in the C. monogyna extract and nine compounds in the C. laciniata extract, with coumaric acid present only in the C. laciniata extract. According to the findings, both extracts are high in total polyphenols, total flavonoids, and condensed tannins. The results of the antioxidant activity revealed that our extracts have significant effects against 2, 2-diphényl 1-picrylhydrazyle (DPPH), and Ferric Reducing Antioxidant Power (FRAP). The antibacterial test revealed that the two extracts tested were effective against four bacterial strains, including Staphylococcus aureus, Escherichia coli, Enterobacter cloacae, and Shigella dysenteria, but were ineffective against Salmonella typhi, and Acinetobacter baumanii. In addition, extracts from both plants showed remarkable antihyperglycemic activity with no acute toxicity. In conclusion, the extracts studied could be a good source of bioactive molecules with antioxidant, antimicrobial, and anti-diabetic activity for pharmaceutical applications.

Graphene Scaffolds: A Striking Approach to Combat Dermatophytosis.

Exclusive physicochemical and biological properties of carbon allotrope graphene have attracted the peer attention of researchers for the synthesis and development of newer topical remedies including films, scaffolds, microspheres, and hydrogels. Here, graphene nanoplatelets (GN) were embedded into a different ratio of polymeric ERL100/ERS100 solution and fabricated in the form of a scaffold through the electrospinning process. FTIR spectra displayed characteristic similar peaks present both in GN and GN-loaded scaffold owing to the compatibility of GN and polymeric mixture. XRD curve revealed a distinct GN peak at nearly 26° whereas from DSC/TGA thermal stability was observed between polymers and graphene nanoplatelets. FESEM images showed ultrathin architecture of GN-loaded scaffold in a range of 280 ± 90 nm. The fabricated scaffold exhibited hydrophilicity (contact angle 48.8 ± 2.8°) and desirable swelling index (646% in skin pH media) which were desired criteria for the scaffold for topical application. In vitro, antifungal activity was conducted through the broth microdilution method against different virulent dermatophytes i.e., Microsporum gypseum, M. canis, M. fulvum, and Trychophyton rubrum. For in vivo evaluation, T. rubrum inoculum was applied on the dorsal surface of each group of Swiss albino mice, and the degree and intensity of mycelial growth or erythema on skin surfaces was visually investigated. The study depicted complete signs of cure after 14 days of application of G3-loaded scaffold on the infected dorsal site. Hence graphene-loaded scaffold represented a possible alternative for the treatment of topical fungal infections caused by dermatophytes.

Mannose-Functionalized Isoniazid-Loaded Nanostructured Lipid Carriers for Pulmonary Delivery: In Vitro Prospects and In Vivo Therapeutic Efficacy Assessment.

Resistance to isoniazid (INH) is common and increases the possibility of acquiring multidrug-resistant tuberculosis. For this study, isoniazid-loaded nanostructured lipid carriers (INH-NLCs) were developed and effectively functionalized with mannose (Man) to enhance the residence time of the drug within the lungs via specific delivery and increase the therapeutic efficacy of the formulation. The mannose-functionalized isoniazid-loaded nanostructured lipid carrier (Man-INH-NLC) formulation was evaluated with respect to various formulation parameters, namely, encapsulation efficiency (EE), drug loading (DL), average particle size (PS), zeta potential (ZP), polydispersity index (PDI), in vitro drug release (DR), and release kinetics. The in vitro inhalation behavior of the developed formulation after nebulization was investigated using an Andersen cascade impactor via the estimation of the mass median aerosolized diameter (MMAD) and geometric aerodynamic diameter (GAD) and subsequently found to be suitable for effective lung delivery. An in vivo pharmacokinetic study was carried out in a guinea pig animal model, and it was demonstrated that Man-INH-NLC has a longer residence time in the lungs with improved pharmacokinetics when compared with unfunctionalized INH-NLC, indicating the enhanced therapeutic efficacy of the Man-INH-NLC formulation. Histopathological analysis led us to determine that the extent of tissue damage was more severe in the case of the pure drug solution of isoniazid compared to the Man-INH-NLC formulation after nebulization. Thus, the nebulization of Man-INH-NLC was found to be safe, forming a sound basis for enhancing the therapeutic efficacy of the drug for improved management in the treatment of pulmonary tuberculosis.

Evaluation of Antioxidant Activity, Cytotoxicity, and Genotoxicity of Ptychotis verticillata Essential Oil: Towards Novel Breast Cancer Therapeutics.

Breast cancer is a disease characterized by the uncontrolled proliferation of malignant cells in breast tissue, and oxidative stress activated by an accumulation of reactive oxygen species (ROS) is associated with its development and progression. Essential oils from medicinal plants, known for their antioxidant and therapeutic properties, are being explored as alternatives. Ptychotis verticillata, also known as Nûnkha, is a medicinal plant native to Morocco, belonging to the Apiaceae family, and used for generations in traditional medicine. This study focuses on the phytochemical characterization of P. verticillata essential oil (PVEO) from the province of Oujda, Morocco, for its therapeutic properties. The essential oil was obtained by hydro-distillation, and its volatile components were analyzed by gas chromatography-mass spectrometry (GC-MS). The results revealed the presence of various aromatic and terpene compounds, with carvacrol being the most abundant compound. PVEO showed antioxidant properties in several tests, including ß-carotene bleaching, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and total antioxidant capacity (TAC). It also demonstrated cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cell lines, with higher selectivity for MDA-MB-231. The results reveal that Ptychotis verticillata essential oil (PVEO) could be a promising natural alternative for the treatment of breast cancer.

Tanshinone-I for the treatment of uterine fibroids: Molecular docking, simulation, and density functional theory investigations.

Uterine fibroids (UF), most prevalent gynecological disorder, require surgery when symptomatic. It is estimated that between 25 and 35 percent of women wait until the symptoms have worsened like extended heavy menstrual bleeding and severe pelvic pain. These UF may be reduced in size through various methods such as medical or surgical intervention. Progesterone (prog) is a crucial hormone that restores the endometrium and controls uterine function. In the current study, 28 plant-based molecules are identified from previous literature and docked onto the prog receptors with 1E3K and 2OVH. Tanshinone-I has shown the best docking score against both proteins. The synthetic prog inhibitor Norethindrone Acetate is used as a standard to evaluate the docking outcomes. The best compound, tanshinone-I, was analyzed using molecular modeling and DFT. The RMSD for the 1E3K protein-ligand complex ranged from 0.10 to 0.42 Å, with an average of 0.21 Å and a standard deviation (SD) of 0.06, while the RMSD for the 2OVH protein-ligand complex ranged from 0.08 to 0.42 Å, with an average of 0.20 Å and a SD of 0.06 showing stable interaction. In principal component analysis, the observed eigen values of HPR-Tanshinone-I fluctuate between -1.11 to 1.48 and -1.07 to 1.25 for PC1 and PC2, respectively (1E3K), and the prog-tanshinone-I complex shows eigen values of -38.88 to -31.32 and -31.32 to 35.87 for PC1 and PC2, respectively (2OVH), which shows Tanshinone-I forms a stable protein-ligand complex with 1E3K in comparison to 2OVH. The Free Energy Landscape (FEL) analysis shows the Gibbs free energy in the range of 0 to 8 kJ/mol for Tanshinone-I with 1E3K and 0 to 14 kJ/mol for Tanshinone-I with the 2OVH complex. The DFT calculation reveals ΔE value of 2.8070 eV shows tanshinone-I as a stable compound. 1E3K modulates the prog pathway, it may have either an agonistic or antagonistic effect on hPRs. Tanshinone-I can cause ROS, apoptosis, autophagy (p62 accumulation), up-regulation of inositol requiring protein-1, enhancer-binding protein homologous protein, p-c-Jun N-terminal kinase (p-JNK), and suppression of MMPs. Bcl-2 expression can change LC3I to LC3II and cause apoptosis through Beclin-1 expression.

Revisiting the Flora of Saudi Arabia: Phytochemical and Biological Investigation of the Endangered Plant Species Euphorbia saudiarabica.

Euphorbia plants have a significant place in traditional medicine due to their numerous therapeutic properties, including their anti-tumor effects, which have been observed in several species. In the current study, a phytochemical investigation of Euphorbia saudiarabica methanolic extract led to the isolation and characterization of four secondary metabolites from the chloroform (CHCl3) and ethyl acetate (EtOAc) fractions, which are reported for the first time in this species. One of the constituents, saudiarabicain F (2), is a rare C-19 oxidized ingol-type diterpenoid that has not been previously reported. The structures of these compounds were determined by extensive spectroscopic (HR-ESI-MS, 1D and 2D NMR) analyses. The anticancer properties of the E. saudiarabica crude extract, its fractions and its isolated compounds were examined against several cancer cells. The active fractions were evaluated for their effects on cell-cycle progression and apoptosis induction using flow cytometry. Furthermore, RT-PCR was employed to estimate the gene-expression levels of the apoptosis-related genes. It was demonstrated that the E. saudiarabica CHCl3 and EtOAc fractions suppressed the proliferation of the cancer cells. The MCF-7 cells were the most sensitive to both fractions, with IC50 values of 22.6 and 23.2 µg/mL, respectively. Notably, both fractions caused cell-cycle arrest in the G2/M phase of the treated MCF-7 cells. The inhibition of the MCF-7 cells' proliferation was also linked with apoptosis induction by flow-cytometry analysis. Additionally, the activation of apoptosis by both fractions was demonstrated by an increase in the ratio of Bax to Bcl-2, with an increase in the expression of caspase-7. Among the isolated compounds, glutinol (1) showed potent activity against the MCF-7 cell line, with an IC50 value of 9.83 µg/mL. Our findings suggest that E. saudiarabica has apoptosis-inducing effects and shows promise as a potential source of new chemotherapeutic drugs.

QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing properties.

A structural class of forty glycine transporter type 1 (GlyT1) inhibitors, was examined using molecular modeling techniques. The quantitative structure-activity relationships (QSAR) technology confirmed that human GlyT1 activity is strongly and significantly affected by constitutional, geometrical, physicochemical and topological descriptors. ADME-Tox in-silico pharmacokinetics revealed that L28 and L30 ligands were predicted as non-toxic inhibitors with a good ADME profile and the highest probability to penetrate the central nervous system (CNS). Molecular docking results indicated that the predicted inhibitors block GlyT1, reacting specifically with Phe319, Phe325, Tyr123, Tyr 124, Arg52, Asp475, Ala117, Ala479, Ile116 and Ile483 amino acids of the dopamine transporter (DAT) membrane protein. These results were qualified and strengthened using molecular dynamics (MD) study, which affirmed that the established intermolecular interactions for (L28, L30-DAT protein) complexes remain perfectly stable along 50 ns of MD simulation time. Therefore, they could be strongly recommended as therapeutics in medicine to improve memory performance.

Cytotoxic and genotoxic properties of silver nanoparticles synthesized by ethanolic extract of Salacia chinensis.

In this study, in vitro and in vivo methods were used to evaluate the cytotoxicity and genotoxicity properties of silver nanoparticles (Ag-NPs) made from a crude ethanolic extract of Salacia chinensis. The test Ag-NPs had no cytotoxicity on the fibroblast cell line at a concentration of 100 µg/mL, according to the MTT assay results. The Chinese hamster ovary (CHO) cell line treated with varied concentrations of test Ag-NPs, with a maximum concentration of 200 µg/mL, did not exhibit any appreciable genotoxic activity, either by comparing the results with positive controls of genotoxicity caused by Methyl methane sulfonate and Benzo (a) pyrene at the concentration of 20 µg/mL, the lack of genotoxicity was established. An in vivo study in Swiss albino mice using various concentrations (250, 500, and 1000 mg/kg) of test Ag-NPs, which were compared with positive controls, further confirmed this in vitro result pattern. Contrary to the genotoxicity caused by the positive control, mouse bone marrow micronucleus testing findings revealed the absence of genotoxicity. These findings imply that at the measured doses, the Ag-NPs produced from the crude ethanolic extract of Salacia chinensis do not exhibit any cytotoxicity or genotoxicity.

Phytochemical Compounds, Acute Toxicity, Anti-Inflammatory and Antioxidant Activities of Thymus leptobotrys Murb Essential Oil.

The present study was conducted to evaluate the acute toxicity and anti-inflammatory effect in vivo, as well as the antioxidant activity, of the essential oil of Thymus leptobotrys Murb. The results indicate that the tested essential oil is non-toxic, with an estimated LD50 of 2500 mg kg-1 of mice body weight. The anti-inflammatory test revealed that, at a dose of 200 mg kg-1, the essential oil reduced rat paw edemas by 89.59% within 3 h of oral administration, this reduction in edema size was greater than that obtained with indomethacin (75.78%). The antioxidant activity (IC50) of Thymus leptobotrys Murb essential oil was 346.896 µg mL-1 and 861.136 mg Trolox equivalent/g essential oil in the 2.2-diphenyl1-picryl-hydrazyl radical scavenging capacity (DPPH) and Trolox equivalent antioxidant capacity (TEAC) assays, respectively. The toxicity test reveals an LD50 greater than 2500 mg kg-1 of body weight of mice which classifies it within category 5 of non-toxic substances that can be administered orally. These results suggest that the essential oil of Thymus leptobotrys Murb is not toxic, and it represents a valuable source of anti-inflammatory and antioxidant metabolites.