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The extensive use of azo dyes in textile and pharmaceutical industries pose significant environmental and health risks. This problem requires to be tackled forthwith through a cheap, environmentally friendly and viable approach to mitigate water pollution. In this context, the green synthesis method was used for synthesis of ZnO NPs. These biogenic ZnO NPs were characterized by UV–Vis and Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), high-resolution transmission electron microscopy (HR-TEM) coupled with energy-dispersive X-ray (EDX), dynamic light scattering (DLS) and Zeta potential (ZP) analysis. The characteristic bandgap energy (3.02 eV), crystallite size (18.6 nm), particle size (84 nm), hydrodynamic diameter (101 nm) and ZP (−31.5 mV) all indicated the successful synthesis of the stabilized NPs, which have an absorption edge at 373 nm. Based on the responsive energy band gap to visible light, these NPs demonstrated promising photocatalytic activity for the degradation of toxic dyes with efficiencies of 82.2 and 87.5 % for of methylene blue (MB) and methyl orange (MO), respectively, in only 2 h of sunlight exposure. To evaluate the reaction kinetics and thermodynamic parameters including the activation energy and rate constant, the degradation process was conducted at various temperatures. The effect of temperature showed the highest rate constant values of 0.022 and 0.025 min−1 at 90 °C, and activation energies of 4.1 and 3.8 kJ mol−1 for MO and MB, respectively. A possible degradation mechanism was proposed based on results of the radical scavenging experiments. The photocatalyst showed recyclability for five consecutive cycles with a simple regeneration. CMFE@ZnO NPs have also exhibited great antibacterial potential by inhibiting the growth of Gram-positive (S. aureus (13 mm) and B. subtilis (14 mm)) and Gram-negative (E. coli (17 mm) and P. multosida (15 mm)) bacterial strains. As a result, these CMFE@NPs may have great commercial importance in reducing the concentration of azo dyes and drug-resistant bacteria in textile and pharmaceutical industry effluents.

Traditional healers have used the shrub Calotropis procera (CP) for many years for various therapies. The present study investigated the bioactive constituents of ethanolic extract of CP leaf and dried latex using gas chromatography-mass spectrometry and Fourier transforms infrared spectroscopy. The identification and characterization of the compounds were confirmed by examining the constituents' mass spectrum fragmentations and FT-IR spectra and comparing the results with those in the literature. The tail-flick method was used to investigate the analgesic properties of the extract and its anti-inflammatory activities using a rat model of formalin-induced oedema. Acute oral toxicity in rats was studied per OECD recommendations. Twenty male rats were divided into four groups and received an ethanolic extract of the leaves and dried milky sap of CP (200 mg/Kg) in groups 1, 2, and 3. Group 4 rats were administered aspirin 50 mg/kg as a positive control. The CP dried latex extract has the highest content of lupeol and its acetate derivative compared to its leaf extract. The CP dried latex extract inhibited inflammation more significantly than the ethanolic leaf extract and the drug indomethacin at a higher dosage (200 mg/kg). The ethanolic extracts showed analgesia comparable to aspirin. It suggests that fatty acids and their esters, particularly ethyl linoleate (8.96%), ethyl palmitate (7.99%), ethyl linoleate (6.98%), and palmitic acid (5.18%), may be valuable biomarkers for characterizing leaf and latex samples and describing the medicinal potential of CP.

The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances pro-apoptotic factors while decreasing anti-apoptotic factors. Additionally, it regulates the immune response by up-regulating programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression, and can impact proteasome and/or aggresome degradation, endoplasmic reticulum function, cell cycle arrest, apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this study, we sought to elucidate the precise molecular mechanism by which Vorinostat inhibits HDACs. A deeper understanding of these mechanisms could improve our understanding of cancer cell abnormalities and provide new therapeutic possibilities for cancer treatment.

Abstract Peroxisome proliferator-activated receptor-γ (PPAR-γ) partial agonists or antagonists, also termed as selective PPAR-γ modulators, are more beneficial than full agonists because they can avoid the adverse effects associated with PPAR-γ full agonists, such as weight gain and congestive heart disorders, while retaining the antidiabetic efficiency. In this study, we designed and synthesized new benzylidene-thiazolidine-2,4-diones while keeping the acidic thiazolidinedione (TZD) ring at the center, which is in contrast with the typical pharmacophore of PPAR-γ agonists. Five compounds (5a–e) were designed and synthesized in moderate to good yields and were characterized using spectral techniques. The in vivo antidiabetic efficacy of the synthesized compounds was assessed on streptozotocin-induced diabetic mice using standard protocols, and their effect on weight gain was also studied. Molecular docking and molecular dynamics (MD) simulation studies were performed to investigate the binding interactions of the title compounds with the PPAR-γ receptor and to establish their binding mechanism. Antidiabetic activity results revealed that compounds 5d and 5e possess promising antidiabetic activity comparable with the standard drug rosiglitazone. No compound showed considerable effect on the body weight of animals after 21 days of administration, and the findings showed statistical difference (p

Diabetes is a complex disease that affects a large percentage of the world's population, and it is associated with several risk factors. Self-management poses a significant challenge, but natural sources have shown great potential in providing effective glucose reducing solutions. Flavonoids, a class of bioactive substances found in different natural sources including medicinal plants, have emerged as promising candidates in this regard. Indeed, several flavonoids, including apigenin, arbutin, catechins, and cyanidin, have demonstrated remarkable anti-diabetic properties. The clinical effectiveness of these flavonoids is linked to their potential to decrease blood glucose concentration and increase insulin concentration. Thus, the regulation of certain metabolic pathways such as glycolysis and neoglycogenesis has also been demonstrated. In vitro and in vivo investigations revealed different mechanisms of action related to flavonoid compounds at subcellular, cellular, and molecular levels. The main actions reside in the activation of glycolytic signaling pathways and the inhibition of signaling that promotes glucose synthesis and storage. In this review, we highlight the clinical efficiency of natural flavonoids as well as the molecular mechanisms underlying this effectiveness.

Ferroptosis is a newly discovered non-apoptotic and iron-dependent type of cell death. Ferroptosis mainly takes place owing to the imbalance of anti-oxidation and oxidation in the body. It is regulated via a number of factors and pathways both inside and outside the cell. Ferroptosis is closely linked with brain and various neurological disorders (NDs). In the human body, the brain contains the highest levels of polyunsaturated fatty acids, which are known as lipid peroxide precursors. In addition, there is also a connection of glutathione depletion and lipid peroxidation with NDs. There is growing evidence regarding the possible link between neuroinflammation and multiple NDs, such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and stroke. Recent studies have demonstrated that disruptions of lipid reactive oxygen species (ROS), glutamate excitatory toxicity, iron homeostasis, and various other manifestations linked with ferroptosis can be identified in various neuroinflammation-mediated NDs. It has also been reported that damage-associated molecular pattern molecules including ROS are generated during the events of ferroptosis and can cause glial activation via activating neuroimmune pathways, which subsequently leads to the generation of various inflammatory factors that play a role in various NDs. This review summarizes the regulation pathways of ferroptosis, the link between ferroptosis as well as inflammation in NDs, and the potential of a range of therapeutic agents that can be used to target ferroptosis and inflammation in the treatment of neurological disorders.

Plants belonging to the genus Prosopis L. (family Fabaceae, subfamily Mimosoideae) have gained significant popularity in traditional medicine due to their potential as anticancer, antidiabetic, anti-inflammatory, and antibacterial compounds. The primary objective of this work was to determine the phytochemical composition of the ethanolic extract derived from Prosopis juliflora leaves, as well as to assess its antibacterial and cytotoxic properties. The phytochemical screening using GC-MS revealed the presence of phytosteroids, ketone, esters, diisooctyl phthalate, and triterpenes. Besides, varying amounts of some silicon derivatives, which were reported to have antimicrobial activity, were detected with octasiloxane, which showed the highest amount (18.47%). 6-Ethoxy-6-methyl-2-cyclohexenone (antioxidant, antidiabetic, antiobesity, and antimicrobial) was detected in considerable quantity. Cytotoxic activity was seen in human breast cancer (MCF-7), human ovary adenocarcinoma (A2780), and human colon adenocarcinoma (HT-29) cell lines, as well as in normal human fetal lung fibroblasts (MRC-5), when subjected to the MTT assay. The plant extract exhibited the highest level of activity (5.75 μg/mL) against the A2780 cell line, with the MCF-7 cell line showing a somewhat lower level of activity (18.49 μg/mL). The antibacterial effect of the plant extracts was evaluated against four standard Gram-positive and four standard Gram-negative. The antimicrobial potential was observed only against Staphylococcus aureus which recorded a 14.5 ± 0.05 mm inhibition zone. The present study has demonstrated the identification of bioactive constituents in P. juliflora plant extracts, which exhibit significant cytotoxic activity against breast and colon malignancies. The study also highlighted P. juliflora extract as an antibacterial against S. aureus.

The purpose of immunization is the effective cellular and humoral immune response against antigens. Several studies on novel vaccine delivery approaches such as micro-particles, liposomes & nanoparticles, etc. against infectious diseases have been investigated so far. In contrast to the conventional approaches in vaccine development, a virosomes-based vaccine represents the next generation in the field of immunization because of its balance between efficacy and tolerability by virtue of its mechanism of immune instigation. The versatility of virosomes as a vaccine adjuvant, and delivery vehicle of molecules of different nature, such as peptides, nucleic acids, and proteins, as well as provide an insight into the prospect of drug targeting using virosomes. This article focuses on the basics of virosomes, structure, composition formulation and development, advantages, interplay with the immune system, current clinical status, different patents highlighting the applications of virosomes and their status, recent advances, and research associated with virosomes, the efficacy, safety, and tolerability of virosomes based vaccines and the future prospective.

In continuation of our reserach for synthesizing heterocyclic derivatives with a broad range of biological activities, the current research was performed to synthesize 3β-hydroxypregn-5-ene-20-one derivatives of coumarin, isoxazole, pyrazole, pyridine and pyrimidine and screen for antitumor activity. Synthesis of amino-thiopephen derivatives (1a-1b) was performed through reaction of 3β-hydroxypregn-5-ene-20-one with ethyl cyanoacetate or malononitrile and sulphur. 3β-Hydroxypregn-5-ene-20-one was reacted with ethyl cyanoacetate in the presence of hydrazine, urea or thiourea to obtain aminopyrazole (3), aminopyrimidine (4a-4b) derivatives, respectively. The amino-thiophene derivatives (1a-1b) further reacted with either phenylisothiocyanate or benzoylisothiocyanate to form fused thienopyrimidine derivatives (5a-5d). The products 1a and 1b were also treated with ethyl cyanoacetate to afford cyanoacetamidothiophene derivatives (6a-6b) which were converted to fused thienopyridone derivatives (7a-7b) through cyclization reaction. The compounds 6a and 6b were allowed to react with different carbonyl compounds including salicyaldehyde, cyclopentanone-sulphur mixture, acetylacetone and malonaldehyde to prepare coumarin (8a-8b), cyclopentylthiophene (9a-9b) and 2-pyridinone (10a-10d) derivatives respectively. Furthermore, the reactions of hydroxylamine hydrochloride and benzoylacetonitrile with the compounds 6a-6b separately afforded new aminoisoxazole (12a-12b) and phenylpyridone (14a-14b) derivatives, respectively. The structures of new products were established through IR, 1H NMR, 13C NMR spectroscopic and mass spectrometric analysis. The synthesized compounds (1a-1b to 14a-14b) displayed in-vitro antitumor activity against human cell-lines, including MCF-7 (breast adenocarcinoma), SF-268 (CNS cancer) and NCI-H460 (non-small lung cancer cell). The results suggested that all the screened products exhibited cell growth inhibitory activity in a dose-dependents manner. However, the compound 12a showed highest level of inhibition against all three cell-lines.

Breast cancer (BC) is the second most common malignancy in the world. Numerous studies have demonstrated the association between human leukocyte antigen (HLA) and cancer. The occurrence and development of BC are closely linked to genetic factors. Human leukocyte antigens G and E (HLA-G and HLA-E) are non-classical major histocompatibility complex (MHC) class I molecules. These molecules play an important role in immune surveillance by inhibiting the cytotoxic and natural killer T cells responsible for immune escape. The expression of HLA-G and HLA-E has been associated with several diseases, including tumors. The HLA system plays a key role in the escape of tumor cells from immune surveillance. This review aims to determine the correlation between BC susceptibility and HLA markers specific HLA alleles such as HLA-B07, HLA-DRB111, HLA-DRB113, and HLA-DRB115 are associated with an increased risk of developing BC. Furthermore, HLA-G mutations have been attributed to an elevated likelihood of metastasis in BC patients. Understanding the complex associations between the HLA system and BC development is critical for developing novel cancer prevention, detection, and treatment strategies. This review emphasizes the importance of analyzing HLA polymorphisms in the management of BC patients, as well as the urgent need for further research in this area.

Khat consumers might use a number of drugs for underlying conditions; however the potential drug-herb interaction between khat and other drugs including Irbesartan (IRB) is unknown. The present study was conducted to evaluate the effects of khat chewing on pharmacokinetic profile of IRB, a commonly available antihypertensive agent. The pharmacokinetic profile of orally administered IRB (15.5 mg/kg) with and without pre-administration of khat (12.4 mg/kg) were determined in Sprague-Dawley rats. IRB was estimated in rat plasma samples using a newly developed HPLC method. The chromatographic separation of the drug and internal standard (IS) was performed on a C-18 column (Raptor C-18, 100 mm × 4.6 mm id.; 5 µm) using a mobile phase consisting of 10 mM ammonium acetate buffer (pH 4.0) and acetonitrile in a ratio 60:40 v/v. Acceptable linearity for IRB was recorded at 1 – 12 µg/mL concentration range (R2 > 0.99). Intra-day and inter-day precision (%RSD = 0.44% − 3.27% and 0.39–1.98% respectively) and accuracy (% recovery = 98.3 – 104.3%) in rat plasma was within the acceptable limit according to USFDA guidelines. The AUC0-t was found to be significantly increased in IRB-khat co-administered rats as compared to rats receiving IRB only; whereas, the Tmax (0.5 h) value remained unchanged. Results of this study revealed that the IRB level considerably increased in rat plasma upon co-administration of khat. This might be due to the inhibition of CYP2D9 by khat which is the principal cytochrome P450 isoform responsible for IRB metabolism.

Objective: This study describes the development of a cost-effective and sensitive immunosensor for rapid detection of the dengue virus (DENV) antigen in human plasma. Methods: Screen-printed carbon electrodes (SPCEs) were used to fabricate the immunosensor by immobilizing the DENV antibodies to its surface using 1-ethyl-3-(3-dimethylamino propyl)carbodiimide hydrochloride/N-hydroxysulfosuccinimide (EDC/s-NHS) as linker. The detection of the antigen–antibody interaction was achieved by linear sweep voltammetry (LSV) using potentiostat instrument and a sensor connector. The developed method was validated as per the ICH guidelines for linearity, sensitivity and accuracy. Results: The developed immunosensors showed excellent sensitivities in detecting the DENV antigens in both phosphate buffer saline (PBS) maintained at pH 7.4 as well as diluted human plasma. The limit of detection (LOD) values obtained in PBS was 0.11 nM; whereas in human plasma, it was calculated to be 0.16 nM. Good linearity was obtained for both PBS and human plasma over a wide range of concentrations showing promising applications of the immunosensor in both qualitative and quantitative detection of dengue virus antigen. Also, the developed immunosensor was able to detect the dengue antigen in 5 min showing rapid detection. Conclusion: A sensitive, reliable and cost-effective biosensor was developed which was able to detect the dengue virus antigen selectively and rapidly.

Currently, acetylcholinesterase (AChE) inhibiting drugs in clinical use, such as tacrine, donepezil, rivastigmine, and galanthamine, are associated with serious side effects and short half-lives. In recent years, numerous phytochemicals have been identified as inhibitors of cholinesterases with potential applications in the management of Alzheimer’s disease (AD). In this study three natural coumarins, 2′-O-ethylmurrangatin (1), murranganone (2), and paniculatin (3) isolated previously by our group from the leaves of Murraya paniculata, were tested against the two cholinesterases (ChE) enzymes, AChE and butyrylcholinesterase (BChE) using in vitro assay. Molecular docking was performed to highlight the structural properties that contribute to the molecular recognition pattern in the inhibition of ChE and the structural differences resulting in the selectivity of these compounds toward AChE. Classical enzyme inhibition kinetics data suggested that compounds 2 and 3 were potent inhibitors of AChE and BChE, while 1 was found inactive against both enzymes. The findings from molecular docking studies revealed the competitive and non-competitive inhibition mechanisms of compounds 2 and 3 against both enzymes. Molecular docking and simulations have revealed that hydrogen bonding, mediated by ketone and hydroxyl functionalities in various positions, significantly contributes to the binding of the inhibitor to the receptor. According to MD simulation studies, the stability of the ligand-AChE complex for the most active compound (3) is found to be comparable to that of the widely used drug Tacrine. In addition, to evaluate the drug-likeness of compounds, in silico ADME evaluation was performed, and the compounds presented good ADME profiles. Data suggested that the coumarin nucleus having diverse side chains at the C-8 position can serve as a potential inhibitor of cholinesterases and can act as a lead to develop a new semisynthetic drug for the treatment of AD.

In the current study, aqueous extract of O. scolopendrina (OSE) was used to synthesize AgNPs in a simple and environmentally friendly manner. The biosynthesized OSE-AgNPs were also assessed for its catalytic, antibacterial, anti-diabetic, antioxidant and dye degradation properties. The techniques like UV–visible spectroscopic examinations, TEM, SEM, TGA, zeta potential and FT-IR were used in the characterization investigations. The bioproduction of OSE-AgNPs was preliminary confirmed by UV–visible spectroscopic based investigation followed by microscopic visualization. The synthesized OSE-AgNPs exhibited a reddish brown colour and nearly spherical forms with sizes between 5 and 50 nm quantified by TEM and SEM. The attendance of functional groups like –OH and –NH present in OSE caps on the AgNPs surface was confirmed by FTIR analysis. Interestingly, in the presence of OSE-AgNPs, the degradation of dyes (CV, 95% and EY, 96% in 15 min) were noticeably accelerated. Further, OSE-AgNPs demonstrated substantial antibacterial activity; robust antioxidant properties andnotable anti-diabetic activities. This is the first account on the biosynthetic process of AgNPs using the aqueous extract of O. scolopendrina.

Objectives: Preliminary diagnosis of hepatitis B is performed by measuring the levels of serological markers using enzyme-linked immunosorbent assay (ELISA). Errors in diagnosis of the disease using serum markers might occur due to the presence of metallic salts in diagnostic samples. The present study was designed to evaluate the effects of various metal ions on the diagnosis of recombinant hepatitis B surface antigen (HBsAg). Methods: A simple step sandwich ELISA technique was used to evaluate the effects of metal ions on the diagnosis of HBsAg. Further, the zeta potential, electrical conductivity and redox potential of solutions with proteins and metal salts were measured to evaluate the interaction of these metal ions with the protein. Results: The results showed that recombinant HBsAg significantly interacted with the tested metal ions, with lithium ion showing the highest interaction, followed by barium, aluminium, and nickel as the percent decrease in the free HBsAg concentration in presence of these metal ions were found to be 95.5, 94.1, 93.5, and 91.6%, respectively. Zeta potential of the protein in reaction mixture also changed considerably and marked decrease in the concentration of free HBsAg was observed. This decrease in the concentration of free HBsAg resulted into error in the ELISA test which was negative in presence of these metal ions due to strong interaction with the HBsAg protein. Conclusions: The findings of this study clearly demonstrated that the presence of metal ions in pathological samples can result in interaction with the antigen leading to possible diagnostic errors.

Artemisia arborescens is a medicinal and aromatic plant used in traditionally by the people of Saudi Arabia. This research attempts to evaluate the bioactive constituents of the plant using organic solvents, as well as the antibacterial and anticancer properties of plant extracts. The Phytochemical analysis of methanol extract revealed eleven bioactive constituents, identified by comparing their retention periods and GC-MS profiles to account for 52.45 percent of the studied extract. In the meantime, the extract of pet ether had demonstrated the presence of sixteen significant constituents, six of which were distinct sesquiterpene derivatives. In lipophilic plant extract, three higher alkanes made up 12.49% of the total. These higher alkanes were tetratriacontane (6.55%), hentriacontane (4.17%), and octacosane (1.77%). Studies on antimicrobial activity have revealed that both methanolic and petroleum ether extracts had a broad spectrum of activity against specific human pathogens. Both extracts, however, failed to exhibit any anti-Candida albicans activity. Methanolic extract not shown inhibition in the cell growth of MCF-7 cell, but petroleum ether extract had shown significant anti-cancer activity against MCF-7 cell with an IC50 of 13.49 µg/mL. the results obtained show that A. arborescens have a lot of potential for further research into variety of biological functions, against cancer and microbes.

Human serum albumin (HSA) is a multi-domain macromolecule with diverse ligand binding capability because of its ability to allow allosteric modulation despite being a monomeric protein. Physiologically, HSA act as the primary carrier for various exogenous and endogenous compounds and fatty acids, and alter the pharmacokinetic properties of several drugs. It has antioxidant properties and is utilized therapeutically to improve the drug delivery of pharmacological agents for the treatment of several disorders. The flexibility of albumin in holding various types of drugs coupled with a variety of modifications makes this protein a versatile drug carrier with incalculable potential in therapeutics. This review provides a brief outline of the different structural properties of HSA, and its various binding sites, moreover, an overview of the genetic, biomedical, and allosteric modulation of drugs and drug delivery aspects of HSA is also included, which may be helpful in guiding advanced clinical applications and further research on the therapeutic potential of this extraordinary protein.

This study was performed to evaluate phytochemical composition of Khaya senegalensis stem bark and Azadirachta indica leaf hydroethanolic (80%) extracts using GC-MS technique as a tentative identification method and screen for antioxidant and antidiabetic properties in Wistar rats. Diabetes was induced by intraperitoneal injection of alloxan (150 mg/kg·bw). Animals were divided into groups of six and treated by extracts (400 mg/kg·bw) for 28 days. The results compared with positive and negative control groups of animals. After treatment, blood samples were collected to determine the blood glucose level, lipid profile, liver and kidney function markers, and DPPH free radical scavenging activity was evaluated. Phytochemical investigations revealed that extracts were enriched with a wide range of secondary metabolites such as phenols, saponins, triterpenes, alkaloids, flavonoids, sterols, fatty acids, siloxane derivatives, and anthraquinones in diverse concentrations with reported antioxidant and antidiabetic properties. Biological screening results indicated that both extracts exhibited free-radical scavenging property in DPPH screening, and in that, K. senegalensis stem bark extract (91 ± 0.02%) showed greater reduction than A. indica leaf extract (55 ± 0.03%), with an IC50 of 0.023 ± 0.03 g/mL, which was lower than the reference drug propylgallate (0.077 ± 0.03 g/mL). Both the extracts remarkably reduced the blood glucose concentration in diabetic rats (p

Studies based on the interaction of metals with proteins resulted in the development of promising metal-based compounds with encouraging medicinal potential. This study was aimed to utilize FT-IR and UV-Vis spectroscopic techniques to analyze the interactions of biologically significant metal ions, such as Al3+, Ni+2, and Cu+, with bovine serum albumin (BSA). Different concentrations of metal ions were interacted with BSA, and the complexes were analyzed using the two techniques. The change in the BSA secondary structure components such as β-sheet, β-antiparallel, α-helix, β-turn, and random coil were analyzed using second derivative resolution enhancement. The FT-IR spectroscopy suggested a marked decrease in the C=O stretching (corresponding to amide I) and C=N stretching (corresponding to amide II) intensities. Interestingly, upon complexation, a marked reduction (22.58–29.03%) in the α-helical component was observed with a considerable increase in the random coil component. The intensity of the absorption peak of BSA obtained using UV was observed to increase consecutively as the concentration of Cu+, Al3+, and Ni2+ ions increased. The binding constants for the BSA-Cu+, BSA-Ni+2, and BSA-Al+3 complexes were calculated to be 3.46 × 104 M−1, 1.28 × 104 M−1, and 2.08 × 104 M−1, respectively. It was concluded that the binding interaction decreased in the order Cu+ > Al3+ > Ni2+. These findings were similar to our previous findings using affinity capillary electrophoresis (ACE). Therefore, it can be inferred that the FT-IR and UV techniques might be utilised effectively to assess the metal-protein interaction and can have wide application in routine analysis. These techniques have several advantages in being simple, easy-to-perform, rapid, and affordable over other high-end techniques.

Recent studies have highlighted the necessity to thoroughly evaluate medicinal plants due to their therapeutic potential. The current study delves into the phytochemical profile, antioxidant capacity, and hepatoprotective effect of Andrographis paniculata. The investigation specifically targets its effectiveness in mitigating liver dysfunction induced by carbon tetrachloride (CCl4) in Wistar albino rats, aiming to uncover its promising role as a natural remedy for liver-related ailments. A. paniculata leaf extract was screened for phytoconstituents and antioxidant and hepatoprotective effects in Wistar albino rats against CCl4-induced liver dysfunction. Phytochemical analysis revealed the presence of flavonoids, alkaloids, and phenolic compounds in all extracts. The phenolic concentration ranged from 10.23 to 19.52 mg gallic acid per gram of the sample, while the highest flavonoid concentration was found in the ethanol fraction (8.27 mg rutin equivalents per gram). The antioxidant activity varied from 10.23 to 62.23. GC-MS analysis identified several phytochemicals including octadecanoic acid, stigmasterol, phenanthrenecarboxylic acid, and others. Effects of the ethanol extract of A. paniculata were evaluated in four groups of animals. Biochemical estimations of serum glutamine oxaloacetate transaminase, serum glutamine pyruvate transaminase, and serum bilirubin were significantly higher (p < 0.05) in the CCl4-treated group. Treatment with 300 mg/kg b.w. of the ethanol extract of A. paniculata significantly (p < 0.05) decreased these serum enzymes. Lipid peroxidation levels in carbon tetrachloride-treated animals showed a substantial (p < 0.05) rise when compared to untreated animals, while the lipid peroxidation levels were considerably (p < 0.05) reduced after treatment with ethanol extract at 300 mg/kg b.w. Liver biochemical catalase activities were significantly reduced in the carbon tetrachloride-treated animals. The results of this study conclusively demonstrate that A. paniculata extracts are a rich source of phytochemicals and possess significant antioxidant, free radical scavenging, and hepatoprotective properties.

Photodegradation is an efficient strategy for the removal of organic pollutants from wastewater. Due to their distinct properties and extensive applications, semiconductor nanoparticles have emerged as promising photocatalysts. In this work, olive (Olea Europeae) fruit extract-based zinc oxide nanoparticles (ZnO@OFE NPs) were successfully biosynthesized using a one-pot sustainable method. The prepared ZnO NPs were systematically characterized using UV-Vis, FTIR, SEM, EDX and XRD and their photocatalytic and antioxidant activity was evaluated. SEM demonstrated the formation of spheroidal nanostructures (57 nm) of ZnO@OFE and the EDX analysis confirmed its composition. FTIR suggested the modification/capping of the NPs with functional groups of phytochemicals from the extract. The sharp XRD reflections revealed the crystalline nature of the pure ZnO NPs with the most stable hexagonal wurtzite phase. The photocatalytic activity of the synthesized catalysts was evaluated by measuring the degradation of methylene blue (MB) and methyl orange (MO) dyes under sunlight irradiation. Improved degradation efficiencies of 75% and 87% were achieved within only 180 min with photodegradation rate constant k of 0.008 and 0.013 min−1 for MB and MO, respectively. The mechanism of degradation was proposed. Additionally, ZnO@OFE NPs exhibited potent antioxidant activity against DPPH, hydroxyl, peroxide and superoxide radicals. Hence, ZnO@OFE NPs may have potential as a cost-effective and green photocatalyst for wastewater treatment.

Abstract Caffeine is a well-known central nervous system stimulant, which can cause anxiety, insomnia and nervousness. Domestic wastes of caffeinated drinks, beverages and chocolates are the major sources for entry of caffeine in the environmental system. Caffeine has been widely detected in natural water resources. The current study describes a method for efficient removal of caffeine from aqueous solution by a laboratory scale dielectric barrier discharge (DBD) in open air. Caffeine concentrations in various sample solutions were monitored by high-performance liquid chromatography, and the degradation products were identified by directly injecting the sample to mass spectrometer. The consequences of varied parameters such as input power, initial concentration and initial pH of the solution on the degradation of caffeine were investigated. Removal efficiency of caffeine from aqueous solution was 72.6% and 96.6% for the initial concentrations of 100 and 1 µg/mL, respectively, at initial pH 7 after 4 min treatment in DBD plasma system with 60 W input powers. Caffeine removal efficiency was less in acidic solutions (initial pH 4), and insignificant degradation was observed in alkaline solutions (initial pH 10). Furthermore, the degradation of caffeine was also enhanced by increasing the input power in DBD system. The DBD system used in this study has been considered to be fast, effective and economical. It was operated at atmospheric condition in open air without using catalyst, expensive gases or organic solvents, and significant degradation of caffeine was achieved in a short (4 min) treatment time.

Alzheimer’s disease (AD) is perceived with various pathophysiological characteristics such oxidative stress, senile plaques, neuroinflammation, altered neurotransmission immunological changes, neurodegenerative pathways, and age-linked alterations. A great deal of studies even now are carried out for comprehensive understanding of pathological processes of AD, though many agents are in clinical trials for the treatment of AD. Retinoids and retinoic acid receptors (RARs) are pertinent to such attributes of the disease. Retinoids support the proper functioning of the immunological pathways, and are very potent immunomodulators. The nervous system relies heavily on retinoic acid signaling. The disruption of retinoid signaling relates to several pathogenic mechanisms in the normal brain. Retinoids play critical functions in the neuronal organization, differentiation, and axonal growth in the normal functioning of the brain. Disturbed retinoic acid signaling causes inflammatory responses, mitochondrial impairment, oxidative stress, and neurodegeneration, leading to Alzheimer’s disease (AD) progression. Retinoids interfere with the production and release of neuroinflammatory chemokines and cytokines which are located to be activated in the pathogenesis of AD. Also, stimulating nuclear retinoid receptors reduces amyloid aggregation, lowers neurodegeneration, and thus restricts Alzheimer’s disease progression in preclinical studies. We outlined the physiology of retinoids in this review, focusing on their possible neuroprotective actions, which will aid in elucidating the critical function of such receptors in AD pathogenesis.

A number of illegal amphetamine tablets were seized from three different cities of Jazan province of southern Saudi Arabia and were analyzed for amphetamine and methamphetamine contents using LC-MS/MS technique. Analyses were performed using a previously reported method taking 0.1 M ammonium formate buffer (85%) and 15% acetonitrile with 0.1% formic acid as mobile phase with a total runtime of 12 min. This method was successfully applied for the routine analysis of amphetamine and methamphetamine in the seized tablets using amphetamine-D5 and methamphetamine-D5 as internal standards. Hierarchical cluster analysis was performed to establish the similarity between samples. The retention times (RT) for internal standard, amphetamine and methamphetamine were observed to be within 6.0–7.1 min. Ten tablet samples from each city were subjected to analysis and the amount of amphetamine in all the samples were found to be in the range of 9.07–14.77 mg, whereas, the amount of methamphetamine ranged from 0.12 to 0.24 mg in each tablet. Hierarchical cluster analysis showed presence of five clusters of samples indicating different characteristics and possible sources of amphetamine tablets. The largest cluster consisted of 15 samples which are expected to be of the same origin. Both amphetamine and methamphetamine are considered to be illegal products and their illegal trade and use is banned in many countries including Saudi Arabia. Therefore, there is an urgent need of strict regulations worldwide to check the illicit trafficking of these psychoactive substances and should be considered on priority.

Purpose: The present research was designed to evaluate the toxicity of tellurium and its prevention by selenium on the pituitary gland in male Wistar rats. Methods: 30 rats were used weighing 200–250 gm, and randomly divided them into five groups. Each group contained an equal number of animals. Group-1 was nominated as control group. Group-2 received an intraperitoneal dose of selenium 0.3 mg per kg body wt. Group-3 was administered with tellurium 4.15 mg per kg body wt. Group-4 was given low-dose (L) of both selenium 0.15 and tellurium 2.075, Group-5 was given High-dose (H) of both selenium 0.3 and tellurium 4.15 mg/kg body wt. orally once in a day. After 15 days of dosing, the behavioral activities- motor co-ordination rotarod and grip strength test were measured. On 16th-day animals were sacrificed and activity of LPO, GSH, caspase-3, caspase-9, GPx, GR, SOD, catalase, and AChE were performed on the pituitary gland as per standard method reported. Results: Se when given together with Te, significantly protects the motor coordination up to 32.5%, and also protects the grip strength up to 75% in group 4 and 5 respectively as compared to group- 3. Se + Te treatment protects the activity of TBARS up to 48.68% and GSH is 58%. As compared to control, it protects caspase-3 up to 118% and caspase-9 up to 83%. The level of AChE was also observed to be modulated by the administration of Se in Group- 4 and 5. Se + Te protected AChE up to 28.6%. Similar findings were observed for the biochemical activities of GPx (140% protection), SOD (458%), GR (159%), and catalase (95%) activities that were protected significantly Se + Te in Group- 4 and 5. Conclusion: Selenium dose-dependently protects behavioral activities. It also protects apoptosis, oxidative stress, and AChE activities in the pituitary gland.

This study was aimed to assess the genotoxicity of brown shammah (BS), a local form of smokeless tobacco, popular in Middle East countries including Yemen, Saudi Arabia and Sudan. The genotoxicity was explored using in vivo chromosomal aberration (CA), micronucleus (MN) and sperm abnormality (SA) assays. In addition, oxidative stress was also determined using various hepatic markers. Swiss albino mice were selected for the study, which were divided in to 5 groups of six animals each. They include, negative control (NC, received only vehicle) as well as positive control group (PC, received vehicle for 2 weeks followed by administration of cyclophosphamide, CP). Depending upon their dose, three BS treated animal groups were BS-100, 300 and 900 mg/kg. Doses of BS were obtained by suspending BS in 0.5% CMC (carboxy methyl cellulose) and orally administered once a day for 2 weeks. Significant augmentation of the average percentage of aberrant metaphase (AM), CA per cells and suppressed mitotic activity was observed on post administration of BS. In addition, BS increased the occurrence of MNPCEs (micronucleated polychromatic erythrocytes) formation, induced cytotoxicity and increased percentage of abnormal sperms as compared to NC. Moreover, BS also induced oxidative stress as the activities of hepatic superoxide dismutase (SOD) and glutathione (GSH) were reduced and malondialdehyde (MDA) content were increased by BS. Cyclophosphamide was utilized as clastogen, showed anticipated positive results and confirmed the sensitivity of test system. Therefore, it may be deduced from the study that the BS possesses genotoxic effects on mice bone marrow and germ cells in vivo. Keywords: Smokeless tobacco, Genotoxicity, Brown shammah, Chromosomal aberration, Micronucleus, Sperm abnormality, Oxidative stress

Smokeless tobacco (SLT) has been reported to have deleterious effects on the health of its users. This study aims to analyze the constituents of locally collected SLT sample extracts (S1–S11) from Tabuk region of Saudi Arabia using GC-MS and investigate their cytotoxic effect on human gingival fibroblasts (hGFs), normal human fibroblasts (MRC5), and two cancer cell lines (HT29 and HepG2) using MTT assay. GC-MS results showed that pyridine, 3-(1-methyl-1H-pyrrol-2-yl)-, tetracyclo[4.4.1.1(7,10).0(2,5)]dodec-3-en-11-ol, and cotinine were found in S1, while ethyl iso-allocholate was traced in S2. Compounds 9,12-octadecadienoic acid, ethyl ester, 7-methyl-Z-tetradecen-1-ol acetate, cis-10-heptadecenoic acid and octadecanoic acid, ethyl ester, and nicotine traces were found in S4, while compound 3,7,11,15-tetramethyl-2-hexadecen-1-ol, tetradecamethyl-hexasiloxane, and phytol in S5. Additionally, octadecamethyl cyclononasiloxane, oleic acid, and trimethylsilyl ester were found in S6 and S9, respectively. Interestingly, extracts S4, S10, and S6 were the most cytotoxic to the normal fibroblasts (hGF and MRC5, with low selectivity index:

Monoclonal antibodies (mAbs) are a fast-growing class of biopharmaceuticals. They are widely used in the identification and detection of cell makers, serum analytes, and pathogenic agents, and are remarkably used for the cure of autoimmune diseases, infectious diseases, or malignancies. The successful application of therapeutic mAbs is based on their ability to precisely interact with their appropriate target sites. The precision of mAbs rely on the isolation techniques delivering pure, consistent, stable, and safe lots that can be used for analytical, diagnostic, or therapeutic applications. During the creation of a biologic, the key quality features of a particular mAb, such as structure, post-translational modifications, and activities at the biomolecular and cellular levels, must be characterized and profiled in great detail. This implies the requirement of powerful state of the art analytical techniques for quality control and characterization of mAbs. Until now, various analytical techniques have been developed to characterize and quantify the mAbs according to the regulatory guidelines. The present review summarizes the major techniques used for the analyses of mAbs which include chromatographic, electrophoretic, spectroscopic, and electrochemical methods in addition to the modifications in these methods for improving the quality of mAbs. This compilation of major analytical techniques will help students and researchers to have an overview of the methodologies employed by the biopharmaceutical industry for structural characterization of mAbs for eventual release of therapeutics in the drug market.

It has been seventy years since a water-soluble version of vitamin E called tocophersolan (also known as TPGS) was produced; it was approved by USFDA in 1998 as an inactive ingredient. Drug formulation developers were initially intrigued by its surfactant qualities, and gradually it made its way into the toolkit of pharmaceutical drug delivery. Since then, four drugs with TPGS in their formulation have been approved for sale in the United States and Europe including ibuprofen, tipranavir, amprenavir, and tocophersolan. Improvement and implementation of novel diagnostic and therapeutic techniques for disease are goals of nanomedicine and the succeeding field of nanotheranostics. Specifically, imaging and treating tumors with nanohybrid theranostics shows promising potential. Docetaxel, paclitaxel, and doxorubicin are examples of poorly bioavailable therapeutic agents; hence, much effort is applied for developing TPGS-based nanomedicine, nanotheranostics, and targeted drug delivery systems to increase circulation time and promote the reticular endothelial escape of these drug delivery systems. TPGS has been used in a number of ways for improving drug solubility, bioavailability improvement, and prevention of drug efflux from the targeted cells, which makes it an excellent candidate for therapeutic delivery. Through the downregulation of P-gp expression and modulation of efflux pump activity, TPGS can also mitigate multidrug resistance (MDR). Novel materials such as TPGS-based copolymers are being studied for their potential use in various diseases. In recent clinical trials, TPGS has been utilized in a huge number of Phase I, II, and III studies. Additionally, numerous TPGS-based nanomedicine and nanotheranostic applications are reported in the literature which are in their preclinical stage. However, various randomized or human clinical trials have been underway for TPGS-based drug delivery systems for multiple diseases such as pneumonia, malaria, ocular disease, keratoconus, etc. In this review, we have emphasized in detail the review of the nanotheranostics and targeted drug delivery approaches premised on TPGS. In addition, we have covered various therapeutic systems involving TPGS and its analogs with special references to its patent and clinical trials.

NLC containing Gefitinib (NANOGEF) was prepared using stearic acid, sesame oil and surfactants (sodium lauryl sulfate and tween 80). NANOGEFs were evaluated for particle size, polydispersity index (PdI), zeta potential, entrapment efficiency (EE), stability, release studies and cytotoxicity studies (MTT assay). The optimized NANOGEF exhibited particle size of 74.06 ± 9.73 d.nm, PdI of 0.339 ± 0.029 and EE of 99.76 ± 0.015%. The TEM study revealed spherical shape of NANOGEF formulations. The slow and sustained release behavior was exhibited by all NANOGEFs. The effects of surfactants were observed not only on particle size but also on zeta potential, entrapment efficiency, stability and release studies. The MTT assay revealed 4.5 times increase in cytotoxicity for optimized NANOGEF (IC50 = 4.642 µM) when compared with Gefitinib alone (IC50 = 20.88 µM in HCT-116 cells). Thus NANOGEF may be considered as a potential drug delivery system for the cure of colon cancer.

Since ancient times, Chrysopogon zizanioides has been utilized as a traditional medicinal plant for the treatment of numerous ailments, but neither its plant extract form nor its phytoconstituents have been fully explored. With this in mind, the present research was designed to isolate and structurally characterize one of its chemical constituents and evaluate its cytotoxic potential. Therefore, an ethanolic extract of roots was prepared and subjected to column chromatography using solvents of varying polarities. The obtained pure compound was characterized using various chromatographic and spectroscopic techniques such as high-performance liquid chromatography (HPLC), carbon and proton nuclear magnetic resonance (NMR), and liquid chromatography–mass spectroscopy (LC-MS) and identified as longifolene. This compound was evaluated for its cytotoxic potential using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on the prostate (DU-145), oral (SCC-29B) cancer cell line and normal kidney cell line (Vero cells), taking doxorubicin as a standard drug. The obtained outcomes revealed that longifolene possesses cytotoxic potential against both prostate (IC50 = 78.64 µg/mL) as well as oral (IC50 = 88.92 µg/mL) cancer cell lines with the least toxicity in healthy Vero cells (IC50 = 246.3 µg/mL) when compared to doxorubicin. Hence, this primary exploratory study of longifolene exhibited its cytotoxic potency along with wide safety margins in healthy cell lines, giving an idea that the compounds possess some ability to differentiate between cancerous cells and healthy cells.

The main characteristic feature of diabetes mellitus is the disturbance of carbohydrate, lipid, and protein metabolism, which results in insulin insufficiency and can also lead to insulin resistance. Both the acute and chronic diabetic cases are increasing at an exponential rate, which is also flagged by the World Health Organization (WHO) and the International Diabetes Federation (IDF). Treatment of diabetes mellitus with synthetic drugs often fails to provide desired results and limits its use to symptomatic treatment only. This has resulted in the exploration of alternative medicine, of which herbal treatment is gaining popularity these days. Owing to their safety benefits, treatment compliance, and ability to exhibit effects without disturbing internal homeostasis, research in the field of herbal and ayurvedic treatments has gained importance. Medicinal phytoconstituents include micronutrients, amino acids, proteins, mucilage, critical oils, triterpenoids, saponins, carotenoids, alkaloids, flavonoids, phenolic acids, tannins, and coumarins, which play a dynamic function in the prevention and treatment of diabetes mellitus. Alkaloids found in medicinal plants represent an intriguing potential for the inception of novel approaches to diabetes mellitus therapies. Thus, this review article highlights detailed information on alkaloidal phytoconstituents, which includes sources and structures of alkaloids along with the associated mechanism involved in the management of diabetes mellitus. From the available literature and data presented, it can be concluded that these compounds hold tremendous potential for use as monotherapies or in combination with current treatments, which can result in the development of better efficacy and safety profiles.

Plants have been extensively studied since ancient times and numerous important chemical constituents with tremendous therapeutic potential are identified. Attacks of microorganisms including viruses and bacteria can be counteracted with an efficient immune system and therefore, stimulation of body’s defense mechanism against infections has been proven to be an effective approach. Polysaccharides, terpenoids, flavonoids, alkaloids, glycosides, and lactones are the important phytochemicals, reported to be primarily responsible for immunomodulation activity of the plants. These phytochemicals may act as lead molecules for the development of safe and effective immunomodulators as potential remedies for the prevention and cure of viral diseases. Natural products are known to primarily modulate the immune system in nonspecific ways. A number of plant-based principles have been identified and isolated with potential immunomodulation activity which justify their use in traditional folklore medicine and can form the basis of further specified research. The aim of the current review is to describe and highlight the immunomodulation potential of certain plants along with their bioactive chemical constituents. Relevant literatures of recent years were searched from commonly employed scientific databases on the basis of their ethnopharmacological use. Most of the plants displaying considerable immunomodulation activity are summarized along with their possible mechanisms. These discussions shall hopefully elicit the attention of researchers and encourage further studies on these plant-based immunomodulation products as potential therapy for the management of infectious diseases, including viral ones such as COVID-19.

A number of illegal drug tablets with unknown constituents are supplied to countries around the world, most of which are habit forming. Amphetamine constitutes the majority of illegal tablets supplied to Saudi Arabia. In this study, we investigated illicit amphetamine tablets seized from Jazan region located in the southwest of Saudi Arabia to identify the insidious additives present in them and their health-related risks. Tablets were analyzed for the presence of amphetamine and other additives using gas chromatography-mass spectroscopy (GC-MS) technique. Amphetamine was detected in good to high area % values in all analyzed tablets in the range of 16.29–41.23%. Interestingly, a number of other additives were also detected with amphetamine in most of the tested samples including caffeine, lidocaine, diphenhydramine, and 8-chlorotheophylline in considerable area %. Caffeine may have been added to enhance the psychotic effect of amphetamine, whereas lidocaine was added to prevent the cardiovascular side effects of amphetamine. Diphenhydramine was probably added to prevent other undesirable side effects of amphetamine such as insomnia and tremors. Chemometric hierarchical cluster analysis was carried out to make samples clusters which have similar characteristics. It resulted into a dendrogram tree showing eight clusters signifying different sources of tablet samples. Owing to the toxic effects of amphetamine and other psychoactive constituents in the tested tablets, the illegal trafficking of these tablets should be prevented by all means and public awareness should be increased.

The interaction behavior of Fe3+ with transferrin and apotransferrin (iron-free form) was investigated in this study using affinity capillary electrophoresis. Change in the mass and charge of protein upon binding to the metal ion in the capillary tube led to variation in its migration time and was used to measure the noncovalent binding interactions by fast screening method. Acetanilide was used as the electroosmotic flow (EOF) marker to avoid possible errors due to the change in EOF during the experiment. The binding results were calculated from the mobility ratios of protein (Ri) and EOF marker (Rf) using the formula (Ri − Rf)/Rf or ∆R/Rf. For more comprehensive understanding, the kinetics of the interaction was studied and binding constants were calculated. Results showed that the Fe3+ displayed insignificant interaction with both proteins at lower metal ion concentrations (5–25 μmol/mL). However, transferrin exhibited significant interactions with the metal ion at 50 and 100 μmol/mL (ΔR/Rf = 0.0114 and 0.0201, resp.) concentrations and apotransferrin showed strong binding interactions (ΔR/Rf = −0.0254 and 0.0205, resp.) at relatively higher Fe3+ concentrations of 100 and 250 μmol/mL. The binding constants of 18.968 mmol−1 and −13.603 mmol−1 were recorded for Fe3+ interaction with transferrin and apotransferrin, respectively, showing significant interactions. Different binding patterns of Fe3+ with both proteins might be attributed to the fact that the iron-binding sites in transferrin have already been occupied, which was not the case in apotransferrin. The present study may be used as a reference for the investigation of protein-metal ion, drug-protein, drug-metal ion, and enzyme-metal ion interactions and may be helpful to provide preliminary insight into the new metal-based drug development.

Severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2), previously called 2019 novel CoV, emerged from China in late December 2019. This virus causes CoV disease-19 (COVID-19), which has been proven a global pandemic leading to a major outbreak. As of June 19, 2020, the data from the World Health Organization (WHO) showed more than 8.7 million confirmed cases in over 200 countries/regions. The WHO has declared COVID-19 as the sixth public health emergency of international concern on January 30, 2020. CoVs cause illnesses that range in severity from the common cold to severe respiratory illnesses and death. Nevertheless, with technological advances and imperative lessons gained from prior outbreaks, humankind is better outfitted to deal with the latest emerging group of CoVs. Studies on the development of in vitro diagnostic tests, vaccines, and drug re-purposing are being carried out in this field. Currently, no approved treatment is available for SARS-CoV-2 given the lack of evidence. The results from preliminary clinical trials have been mixed as far as improvement in the clinical condition and reduction in the duration of treatment are concerned. A number of new clinical trials are currently in progress to test the efficacy and safety of various approved drugs. This review focuses on recent advancements in the field of development of diagnostic tests, vaccines, and treatment approaches for COVID-19.

This study was aimed to perform the mechanistic investigations of chalcone scaffold as inhibitors of acetylcholinesterase (AChE) enzyme using molecular docking and molecular dynamics simulation tools. Basic chalcones (C1–C5) were synthesized and their in vitro AChE inhibition was tested. Binding interactions were studied using AutoDock and Surflex-Dock programs, whereas the molecular dynamics simulation studies were performed to check the stability of the ligand–protein complex. Good AChE inhibition (IC50 = 22 ± 2.8 to 37.6 ± 0.75 μM) in correlation with the in silico results (binding energies = −8.55 to −8.14 Kcal/mol) were obtained. The mechanistic studies showed that all of the functionalities present in the chalcone scaffold were involved in binding with the amino acid residues at the binding site through hydrogen bonding, π–π, π–cation, π–sigma, and hydrophobic interactions. Molecular dynamics simulation studies showed the formation of stable complex between the AChE enzyme and C4 ligand.

Acetylcholinesterase (AChE) inhibitors and calcium channel blockers are considered effective therapies for Alzheimer’s disease. AChE plays an essential role in the nervous system by catalyzing the hydrolysis of the neurotransmitter acetylcholine. In this study, the inhibition of the enzyme AChE by Sarcorucinine-D, a pregnane type steroidal alkaloid, was investigated with experimental enzyme kinetics and molecular dynamics (MD) simulation techniques. Kinetics studies showed that Sarcorucinine-D inhibits two cholinesterases—AChE and butyrylcholinesterase (BChE)—noncompetitively, with Ki values of 103.3 and 4.66 µM, respectively. In silico ligand-protein docking and MD simulation studies conducted on AChE predicted that Sarcorucinine-D interacted via hydrophobic interactions and hydrogen bonds with the residues of the active-site gorge of AChE. Sarcorucinine-D was able to relax contractility concentration-dependently in the intestinal smooth muscles of jejunum obtained from rabbits. Not only was the spontaneous spasmogenicity inhibited, but it also suppressed K+-mediated spasmogenicity, indicating an effect via the inhibition of voltage-dependent Ca2+ channels. Sarcorucinine-D could be considered a potential lead molecule based on its properties as a noncompetitive AChE inhibitor and a Ca2+ channel blocker.

Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher’s opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.

The popularity of energy beverages among young adult population is high. These drinks are claimed to boost energy and performance and contain high concentration of caffeine as one of the several ingredients. Discrepancies have been encountered by some of the previous studies between the actual quantity of caffeine present in the product and the amount mentioned on the label, making the determination of caffeine content in these drinks very important. Thus, in this study, we analyzed the caffeine concentration in most popular energy drinks available in Saudi Arabia. The energy drink samples (n = 9) were procured from retail outlets. Sample solutions were prepared in methanol and analyzed for caffeine content by GC-MS. Chromatographic parameters were optimized to achieve optimum resolution and various validation parameters were evaluated. The method was successfully applied for the quantification of caffeine in energy drinks by directly injecting the multifold diluted samples in methanol. The method was linear (r2 = 0.999) over a concentration range of 5–25 µg/mL, specific, precise (%RSD of peak area = 0.56–0.78), and accurate (%recovery = 99.3–101.2%). The amounts of caffeine determined were found in the range of 20.82–33.72 mg/100 mL (52.05–84.3 mg/pack). Results revealed that the amount of caffeine actually present in the tested drinks varied within ±10% range from the amount specified on the product labels. The amounts of caffeine detected in tested beverages were within the USFDA safe upper limit of per-day caffeine consumption, which has indicated that the consumption of one serving of energy drink is unlikely to produce any adverse health effect.

The khat plant has been culturally used in many parts of Africa and the Arabian Peninsula for many years to induce psycho-stimulating effect. Because of the global wide-spreading nature, khat chewing is being considered as a universally growing problem. Catha abbottii, Catha edulis, and Catha transvaalensis are the three species of khat commonly chewed in Saudi Arabia and nearby regions. Khat users usually prefer to chew young leaves over mature ones due to the diverse effects produced by both. Though many of the constituents of khat leaves have been identified, the complete phytochemical profile of young and mature leaves was not performed or compared; also, no evidence is available to affirm the cytotoxicity of young or mature leaves. Therefore, this study aimed to investigate the phytochemical basis of the differential response of the young and mature leaves and to assess the cytotoxicity of young and mature khat leaves. Ethanolic extracts of young and mature leaves of three khat cultivars were subjected to GC-MS. Hierarchical cluster analysis revealed the existence of two major clusters. The extracts of young leaves were found to contain the maximum content of cathinone; however, methoxyamphetamine was found in only one extract of young leaves. Cytotoxicity investigations were also conducted on both types of leaves using three cancer cell lines, human breast adenocarcinoma, human ovary adenocarcinoma, and human colon adenocarcinoma and also normal human fetal lung fibroblast cell line was used. All extracts showed comparable cytotoxicity, IC50 ranging from 22–59 μg/mL on the cancer cells; however, we observed more cytotoxicity against normal cells (IC50: 6–41 μg/mL). The predominant cytotoxicity on normal cells may pose many health hazards to khat consumers.

Salvadora persica L. (Salvadoraceae) is an evergreen shrub growing in the Middle East, Africa, and Southern Asia. It is traditionally known as “miswak” and used as toothbrushes and for the treatment of toothache, gum diseases, boils, chest infection, gonorrhea, headache, spleen troubles, stomachache, and ulcers. To the best of our knowledge, this is the first study aimed at conducting phytochemical, cytotoxic, and antimicrobial investigations of the fruits (berries) of S. persica collected from the Jazan region of Saudi Arabia. Analysis of the ethanol extract of S. persica fruits using GC-MS showed the presence of six esters (20.71%), seven alkanes (15.47%), tetracosamethyl-cyclododecasiloxane (9.91%), eicosamethyl-cyclodecasiloxane (7.27%), and 1-monolinoleoylglycerol (5.17%). The predominant constituents were acetyl dasycarpidan-1-methanol (10.47%), tetracosamethyl-cyclododecasiloxane (9.91%), eicosamethyl-cyclodecasiloxane (7.27%), and 1-monolinoleoylglycerol (5.17%). The petroleum ether extract of the fruits contained mainly eicosamethyl-cyclodecasiloxane (23.81%), 1-monolinoleoylglycerol (11.78%), (Z,Z,Z)-9,12,15-octadecatrienoic acid ethyl ester derivative (10.56%), and tetracosamethyl-cyclododecasiloxane (9.91%). The cytotoxic properties of the ethanol extract were investigated by MTT assay against the breast MCF7, ovary A2780, and colon HT29 cells. The fruit extract of S. persica was selective against the ovarian and colon cancer cells compared to normal fibroblast cells (MRC5) as it showed IC50 values 17.50, 8.35, and 5.12, against MCF7, A2780, and HT29 cells, respectively. Interestingly, the fruit extract was also found to possess selective antimicrobial activity for Streptococcus mutans isolates with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 3.12 and 6.25 mg/mL, respectively. Interestingly, it was found to be ineffective against other Gram-positive as well as Gram-negative microorganisms. This study provides insight into the bioactive components present in the fruits of the plant that can be utilized for its cytotoxic and antimicrobial properties.

Breast cancer is the most widespread malignancy in women worldwide. Nanostructured lipid carriers (NLCs) have proven effective in the treatment of cancer. NLCs loaded with imatinib (IMA) (NANIMA) were prepared and evaluated for their in vitro efficacy in MCF-7 breast cancer cells. The hot homogenization method was used for the preparation of NANIMAs. An aqueous solution of surfactants (hot) was mixed with a molten mixture of stearic acid and sesame oil (hot) under homogenization. The prepared NANIMAs were characterized and evaluated for size, polydispersity index, zeta potential, encapsulation efficiency, release studies, stability studies, and MTT assay (cytotoxicity studies). The optimized NANIMAs revealed a particle size of 104.63 ± 9.55 d.nm, PdI of 0.227 ± 0.06, and EE of 99.79 ± 0.03. All of the NANIMAs revealed slow and sustained release behavior. The surfactants used in the preparation of the NANIMAs exhibited their effects on particle size, zeta potential, encapsulation efficiency, stability studies, and release studies. The cytotoxicity studies unveiled an 8.75 times increase in cytotoxicity for the optimized NANIMAs (IC50 = 6 µM) when compared to IMA alone (IC50 = 52.5 µM) on MCF-7 breast cancer cells. In the future, NLCs containing IMA will possibly be employed to cure breast cancer. A small amount of IMA loaded into the NLCs will be better than IMA alone for the treatment of breast cancer. Moreover, patients will likely exhibit less adverse effects than in the case of IMA alone. Consequently, NANIMAs could prove to be useful for effective breast cancer treatment.

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.

Background and Objectives: Khat chewing is considered as a daily habit that is practiced by more than five million people globally. The effect of khat chewing on the surface roughness and the color stability of natural teeth and the material used in the fabrication of dental prosthesis remains unknown. This study was conducted to explore and compare the effect of khat homogenate (KH) on the surface roughness (Ra) and the average color changes (ΔE*) amongst natural teeth and selected shades from different porcelain types, namely, feldspathic metal ceramic (MC) VM13, computer-aided design/computer assisted manufacture (CAD/CAM) feldspathic (Vitablocs Mark II), and multilayer zirconia (Ceramill Zolid PS) porcelains. Materials and Methods: Seventy samples were prepared from natural teeth, feldspathic MC, CAD/CAM Vitablocs Mark II, and zirconia porcelain. The Ra values were measured using a profilometer and expressed in micrometers, whereas the ΔE* values were measured using VITA Easyshade® V spectrophotometer for all samples before and after frequent immersion and thermocycling in KH for 30 days. The surface topography was used to assess the materials surfaces (glazed or polished) after KH immersion by using a white light interferometry machine. Results: Results revealed that the Ra and the ΔE* values of the different types of tested porcelain were influenced by KH. The order of surface roughness values was glazed or polished MC > polished Zircon > polished Vitablocs Mark II > natural teeth. The lowest ΔE* values were recorded for glazed Vitablocs Mark II and MC, and the values could be arranged as polished zircon > natural teeth > glazed zircon > polished MC > polished Vitablocs Mark II. P values were significantly varied (0.05) for both Ra and ΔE*. Conclusions: KH significantly affected both surface parameter and color of glazed or polished porcelain materials and natural teeth.

Shammah is a locally manufactured form of smokeless tobacco (ST) which is traditionally used in Middle Eastern countries including Saudi Arabia, Sudan, and Yemen. Presence of a high concentration of nicotine, in addition to various other toxic and carcinogenic constituents, makes it a serious human health threat. It is an admixture containing powdered tobacco, along with several additives, such as lime, ash, black pepper, volatile oils, and flavoring agents. This study was conducted to investigate the constituents of eight different samples of widely used shammah varieties in the Jazan region of Saudi Arabia using GC-MS and to evaluate their cytotoxic effect against three cancer cell lines representing most of the top malignancies in the region including MCF-7, A2780, and HT29 cancer cells, in addition to MRC5 cells (normal human fetal lung fibroblast) using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. GC-MS analysis showed the presence of nicotine or 3-(1-methyl-2-pyrrolidinyl)pyridine (2.1–91.9% of total constituents detected) in all ST samples, whereas its derivative (1s,2s)-nicotine-N-oxide (0.23–1.62%) was detected in four samples. In addition, several known carcinogenic constituents were also identified, and their carcinogenicity was confirmed by MTT results, in which, all the eight samples promoted the growth of MCF7, A2780, and HT29 cancer cells. The cytotoxic effects of samples against the normal cells MRC5 was proportional to the number of components detected by GC-MS. The ingestion of these constituents through saliva of shammah consumers could be the reason for many cancers including breast, ovary, and colon cancers. These results support the urgent local and international call to educate the users regarding the deleterious effects of shammah to avoid its use.

Proteins play crucial roles in the transportation and distribution of therapeutic substances, including metal ions in living systems. Some metal ions can strongly associate, while others show low affinity towards proteins. Consequently, in the present work, the binding behaviors of Ca2+, Ba2+, Ag+, Ru3+, Cu2+ and Co2+ with bovine serum albumin (BSA) were screened. BSA and the metal ions were allowed to interact at physiological pH and their binding interactions were screened by using FT-IR spectroscopy. Spectra were collected by using hydrated films over a range of 4000⁻400 cm−1. The interaction was demonstrated by a significant reduction in the spectral intensities of the amide I (C=O stretching) and amide II bands (C⁻N stretching coupled to NH bending) of the protein after complexation with metal ions. The binding interaction was further revealed by spectral shifting of the amide I band from 1651 cm−1 (free BSA) to 1653, 1654, 1649, 1655, 1655, and 1654 cm−1 for BSA⁻Ca2+, BSA⁻Ba2+, BSA⁻Ag+, BSA⁻Ru3+, BSA⁻Cu2+ and BSA⁻Co2+ complexes, respectively. The shifting of the amide I band was due to the interactions of metal ions with the O and N atoms of the ligand protein. Estimation of the secondary protein structure showed alteration in the protein conformation, characterized by a marked decrease (12.9⁻40.3%) in the α-helix accompanied by increased β-sheet and β-turn after interaction with the metal ions. The interaction results of this study were comparable with those reported in our previous investigation of metal ion⁻BSA interactions using affinity capillary electrophoresis (ACE), which has proven the accuracy of the FT-IR technique in the measurement of interactions between proteins and metal ions.

The aim of this study was to develop and validate a fast and simple reversed-phase HPLC method for simultaneous determination of four cardiovascular agents—atorvastatin, simvastatin, telmisartan and irbesartan in bulk drugs and tablet oral dosage forms. The chromatographic separation was accomplished by using Symmetry C18 column (75 mm × 4.6 mm; 3.5 μ) with a mobile phase consisting of ammonium acetate buffer (10 mM; pH 4.0) and acetonitrile in a ratio 40:60 v/v. Flow rate was maintained at 1 mL/min up to 3.5 min, and then suddenly changed to 2 mL/min till the end of the run (7.5 min). The data was acquired using ultraviolet detector monitored at 220 nm. The method was validated for linearity, precision, accuracy and specificity. The developed method has shown excellent linearity (R2 > 0.999) over the concentration range of 1–16 µg/mL. The limits of detection (LODs) and limits of quantification (LOQs) were in the range of 0.189–0.190 and 0.603–0.630 µg/mL, respectively. Inter-day and intra-day accuracy and precision data were recorded in the acceptable limits. The new method has successfully been applied for quantification of all four drugs in their tablet dosage forms with percent recovery within 100 ± 2%.