Neuroendocrine and cellular mechanisms in stress resilience: From hormonal influence in the CNS to mitochondrial dysfunction and oxidative stress.

Recent advancements in neuroendocrinology challenge the long-held belief that hormonal effects are confined to perivascular tissues and do not extend to the central nervous system (CNS). This paradigm shift, propelled by groundbreaking research, reveals that synthetic hormones, notably in anti-inflammatory medications, significantly influence steroid psychosis, behavioural, and cognitive impairments, as well as neuropeptide functions. A seminal development in this field occurred in 1968 with McEven's proposal that rodent brains are responsive to glucocorticoids, fundamentally altering the understanding of how anxiety impacts CNS functionality and leading to the identification of glucocorticosteroids and mineralocorticoids as distinct corticotropic receptors. This paper focuses on the intricate roles of the neuroendocrine, immunological, and CNS in fostering stress resilience, underscored by recent animal model studies. These studies highlight active, compensatory, and passive strategies for resilience, supporting the concept that anxiety and depression are systemic disorders involving dysregulation across both peripheral and central systems. Resilience is conceptualized as a multifaceted process that enhances psychological adaptability to stress through adaptive mechanisms within the immunological system, brain, hypothalamo-pituitary-adrenal axis, and ANS Axis. Furthermore, the paper explores oxidative stress, particularly its origin from the production of reactive oxygen species (ROS) in mitochondria. The mitochondria's role extends beyond ATP production, encompassing lipid, heme, purine, and steroidogenesis synthesis. ROS-induced damage to biomolecules can lead to significant mitochondrial dysfunction and cell apoptosis, emphasizing the critical nature of mitochondrial health in overall cellular function and stress resilience. This comprehensive synthesis of neuroendocrinological and cellular biological research offers new insights into the systemic complexity of stress-related disorders and the imperative for multidisciplinary approaches in their study and treatment.

Identification of Helicobacter pylori-carcinogenic TNF-alpha-inducing protein inhibitors via daidzein derivatives through computational approaches.

Gastric cancer is considered a class 1 carcinogen that is closely linked to infection with Helicobacter pylori (H. pylori), which affects over 1 million people each year. However, the major challenge to fight against H. pylori and its associated gastric cancer due to drug resistance. This research gap had led our research team to investigate a potential drug candidate targeting the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein. In this study, a total of 45 daidzein derivatives were investigated and the best 10 molecules were comprehensively investigated using in silico approaches for drug development, namely pass prediction, quantum calculations, molecular docking, molecular dynamics simulations, Lipinski rule evaluation, and prediction of pharmacokinetics. The molecular docking study was performed to evaluate the binding affinity between the target protein and the ligands. In addition, the stability of ligand-protein complexes was investigated by molecular dynamics simulations. Various parameters were analysed, including root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), hydrogen bond analysis, principal component analysis (PCA) and dynamic cross-correlation matrix (DCCM). The results has confirmed that the ligand-protein complex CID: 129661094 (07) and 129664277 (08) formed stable interactions with the target protein. It was also found that CID: 129661094 (07) has greater hydrogen bond occupancy and stability, while the ligand-protein complex CID 129664277 (08) has greater conformational flexibility. Principal component analysis revealed that the ligand-protein complex CID: 129661094 (07) is more compact and stable. Hydrogen bond analysis revealed favourable interactions with the reported amino acid residues. Overall, this study suggests that daidzein derivatives in particular show promise as potential inhibitors of H. pylori.

Design, Physical Characterizations, and Biocompatibility of Cationic Solid Lipid Nanoparticles in HCT-116 and 16-HBE Cells: A Preliminary Study.

In this study, pEGFP-LUC was used as a model plasmid and three distinct cationic lipids (dioleyloxy-propyl-trimethylammonium chloride [DOTMA], dioleoyl trimethylammonium propane [DOTAP], and cetylpyridinium chloride [CPC]) were tested along with PEG 5000, as a nonionic surfactant, to prepare glyceryl monostearate (GMS)-based cationic solid lipid nanoparticles (cSLNs). Both the type and quantity of surfactant had an impact on the physicochemical characteristics of the cSLNs. Thermal analysis of the greater part of the endothermic peaks of the cSLNs revealed they were noticeably different from the individual pure compounds based on their zeta potential (ZP ranging from +17 to +56 mV) and particle size (PS ranging from 185 to 244 nm). The addition of cationic surfactants was required to produce nanoparticles (NPs) with a positive surface charge. This suggested that the surfactants and extensive entanglement of the lipid matrix GMS provided support for the behavioral diversity of the cSLNs and their capacity to interface with the plasmid DNA. Additionally, hemolytic assays were used to show that the cSLNs were biocompatible with the human colon cancer HCT-116 and human bronchial epithelial 16-HBE cell lines. The DOTMA 6-based cSLN was selected as the lead cSLN for further ex vivo and in vivo investigations. Taken together, these new findings might provide some guidance in selecting surfactants to prepare extremely efficient and non-toxic cSLN-based therapeutic delivery systems (e.g., gene therapy).

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic.

Since the appearance in the late of December 2019, SARS-CoV-2 is rapidly evolving and mutating continuously, giving rise to various variants with variable degrees of infectivity and lethality. The virus that initially appeared in China later mutated several times, wreaking havoc and claiming many lives worldwide amid the ongoing COVID-19 pandemic. After Alpha, Beta, Gamma, and Delta variants, the most recently emerged variant of concern (VOC) is the Omicron (B.1.1.529) that has evolved due to the accumulation of high numbers of mutations especially in the spike protein, raising concerns for its ability to evade from pre-existing immunity acquired through vaccination or natural infection as well as overpowering antibodies-based therapies. Several theories are on the surface to explain how the Omicron has gathered such a high number of mutations within less time. Few of them are higher mutation rates within a subgroup of population and then its introduction to a larger population, long term persistence and evolution of the virus in immune-compromised patients, and epizootic infection in animals from humans, where under different immune pressures the virus mutated and then got reintroduced to humans. Multifaceted approach including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, efficacy testing of vaccines and immunotherapies against newly emerged variants, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going SARS-CoV-2 pandemic successfully.

Cardioprotective Effect of Rumex vesicarius Linn. Leaf Extract against Catecholamine-Induced Cardiotoxicity.

Rumex vesicarius (L.) is a folklore medicinal herb that has been used for centuries to cure cardiovascular diseases. The present work was carefully designed to ascertain the pharmacological basis for R. vesicarius's therapeutic efficacy in cardiovascular diseases, as well as the underlying mechanism. In the ex vivo investigation, the aqueous-methanolic leaf extract of R. vesicarius was shown to have endothelium-dependent vasorelaxant effects in rabbit aorta tissue preparations, and its hypotensive responses were quantified by pressure and force transducers coupled to the Power Lab Data Acquisition System. Furthermore, when rabbits were subjected to adrenaline-induced myocardial infarction, R. vesicarius demonstrated cardioprotective characteristics. In contrast to the intoxicated group, the myocardial infarction model showed lower ALP, CK-MB, CRP, LDH, ALT, troponin, and AST levels (p > 0.005−0.000), as well as edema, necrosis, apoptosis, inflammatory cell enrolment, and necrosis. R. vesicarius exhibited significant antioxidant activity and delayed noradrenaline-induced platelet aggregation. Its cardioprotective, anticoagulant, and vasorelaxant properties in both investigations (in vivo and ex vivo) are mediated through partial endothelium-dependent, NO and calcium channel blockade mediated vasorelaxation. The minimizing of adrenaline, oxidative stress, and tissue damage demonstrate its therapeutic efficacy in cardiovascular diseases.

Pharmacological Validation for the Folklore Use of Ipomoea nil against Asthma: In Vivo and In Vitro Evaluation.

Oxidative stress is the key factor that strengthens free radical generation which stimulates lung inflammation. The aim was to explore antioxidant, bronchodilatory along with anti-asthmatic potential of folkloric plants and the aqueous methanolic crude extract of Ipomoea nil (In.Cr) seeds which may demonstrate as more potent, economically affordable, having an improved antioxidant profile and providing evidence as exclusive therapeutic agents in respiratory pharmacology. In vitro antioxidant temperament was executed by DPPH, TFC, TPC and HPLC in addition to enzyme inhibition (cholinesterase) analysis; a bronchodilator assay on rabbit's trachea as well as in vivo OVA-induced allergic asthmatic activity was performed on mice. In vitro analysis of 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) expressed as % inhibition 86.28 ± 0.25 with IC50 17.22 ± 0.56 mol/L, TPC 115.5 ± 1.02 mg GAE/g of dry sample, TFC 50.44 ± 1.06 mg QE/g dry weight of sample, inhibition in cholinesterase levels for acetyl and butyryl with IC50 (0.60 ± 0.67 and 1.5 ± 0.04 mol/L) in comparison with standard 0.06 ± 0.002 and 0.30 ± 0.003, respectively, while HPLC characterization of In.Cr confirmed the existence with identification as well as quantification of various polyphenolics and flavonoids i.e., gallic acid, vanillic acid, chlorogenic acid, quercetin, kaempferol and others. However, oral gavage of In.Cr at different doses in rabbits showed a better brochodilation profile as compared to carbachol and K+-induced bronchospasm. More significant (p < 0.01) reduction in OVA-induced allergic hyper-responses i.e., inflammatory cells grade, antibody IgE as well as altered IFN-α in airways were observed at three different doses of In.Cr. It can be concluded that sound mechanistic basis i.e., the existence of antioxidants: various phenolic and flavonoids, calcium antagonist(s) as well as enzymes' inhibition profile, validates folkloric consumptions of this traditionally used plant to treat ailments of respiration.

Antioxidant and Gastroprotective Activity of Suaeda fruticosa Forssk. Ex J.F.Gmel.

Suaeda fruticosa Forssk. Ex J.F.Gmel is traditionally used for inflammatory and digestive disorders, as a carminative, and for diarrhea. This plant is widely distributed in Asia, Africa, and the Mediterranean region. Aqueous methanolic extract of S. fruticosa (Sf.Cr) was prepared and screened for phytoconstituents through qualitative and GC-MS analysis. Quantification of total phenolic and flavonoid contents was performed, while antioxidant capacity was determined by DPPH, CUPRAC, FRAP, and ABTS assays. The gastroprotective activity was assessed in an ethanol-induced ulcer model. Gastric secretory parameters and macroscopic ulcerated lesions were analyzed and scored for ulcer severity. After scoring, histopathology was performed, and gastric mucus contents were determined. Oral pre-treatment of Sf.Cr demonstrated significant gastroprotection. The gastric ulcer severity score and ulcer index were reduced while the %-inhibition of ulcer was increased dose-dependently. The Sf.Cr significantly elevated the pH of gastric juice, while a decrease in total acidity and gastric juice volume was observed. Histopathology demonstrated less oedema and neutrophil infiltration in gastric mucosa of rats pre-treated with the Sf.Cr in comparison to ethanol-intoxicated animals. Furthermore, the gastric mucus contents were increased as determined by alcian blue binding. Sf.Cr showed marked gastroprotective activity, which can be attributed to antioxidant, antisecretory, and cytoprotective effects.

Pharmacological effects (gastrointestinal, respiratory and vascular) of Calligonum polygonoides: Animal model based studies.

The aim of this study was to analyze gastrointestinal, respiratory and vascular pharmacological effects of 70% hydro-alcoholic extract of Calligonum polygonoides (Cp. Cr) in animal models. All the procedures were carried-out as per previous literature with slight modification where necessary. It was found that Cp. Cr affected significant relaxation of spontaneous and K+ (80 mM) induced contractions. The results showed a corresponding shift of calcium concentration response curves. Similarly Cp. Cr showed relaxant effect on trachea in carbachol (Cch) induced tracheal contractions. Moreover, contractions induced by phenylephrine (1µM) in quarantine rabbit aortic preparations causes Cp. Cr induced relaxation of aortal contractions. Verapamil was used as a standard calcium channel blocker. The findings of this study suggested vasodilator, bronchodilator and spasmolytic effects of Cp. Cr.

A novel approach for the quantification of paclitaxel loaded in ethyl cellulose/kollicoat and ethylcellulose/eudragit colloidal particles by UPLC-PDA.

An optimized rapid reversed phase ultra-performance liquid chromatography (UPLC-PDA) method has been developed and validated for precise and accurate quantification of paclitaxel in drug delivery systems. The chromatographic separation was attained on L1 (USP) column (2.1 ×50 mm, 1.7µm) with an isocratic mobile phase comprised of acetonitrile and water (1:1; flow rate 0.6 mL/min) and detection was executed at 227 nm by PDA detector. The proposed UPLC-PDA method is found to be rapid with retention time of 1.37 min, selective with homogenous peaks and sensitive with Limit of Detection (LOD) of 0.08µg/mL and Limit of Quantification (LOQ) of 2.6µg/mL. The method showed excellent linearity (R2>0.998) over the range of 0.1 to 0.4mg/mL and applied for the paclitaxel quantification in different formulations with no inference of excipients. Thus, the proposed approach has potential for rapid estimation of drug purity, assay and release profile from pharmaceutical preparations.

A novel approach for the quantification of paclitaxel loaded in ethyl cellulose/kollicoat and ethylcellulose/eudragit colloidal particles by UPLC-PDA.

An optimized rapid reversed phase ultra-performance liquid chromatography (UPLC-PDA) method has been developed and validated for precise and accurate quantification of paclitaxel in drug delivery systems. The chromatographic separation was attained on L1 (USP) column (2.1 ×50 mm, 1.7µm) with an isocratic mobile phase comprised of acetonitrile and water (1:1; flow rate 0.6 mL/min) and detection was executed at 227 nm by PDA detector. The proposed UPLC-PDA method is found to be rapid with retention time of 1.37 min, selective with homogenous peaks and sensitive with Limit of Detection (LOD) of 0.08µg/mL and Limit of Quantification (LOQ) of 2.6µg/mL. The method showed excellent linearity (R2>0.998) over the range of 0.1 to 0.4mg/mL and applied for the paclitaxel quantification in different formulations with no inference of excipients. Thus, the proposed approach has potential for rapid estimation of drug purity, assay and release profile from pharmaceutical preparations.

The physiologic and physiopathologic roles of perivascular adipose tissue and its interactions with blood vessels and the renin-angiotensin system.

The perivascular adipose tissue (PVAT) refers to an ectopic local deposit of connective tissue that anatomically surrounds most of the blood vessels. While it was initially known only as a structural support for vasculature, the landmark findings of Soltis and Cassis (1991), first demonstrating that PVAT reduces the contractions of norepinephrine in the isolated rat aorta, brought the potential vascular role of PVAT into the limelight. This seminal work implied the potential ability of PVAT to influence vascular responsiveness. Several vasoactive/vasocrine substances influencing vascular homeostasis were successively shown to be released from PVAT that include both adipocyte-derived relaxing and contracting factors. The PVAT is currently recognized as a metabolically active endocrine organ and is eventually considered as the 'protagonist' in vascular homeostasis. It plays prominent defending and opposing roles in vascular function, while the actual vascular influences of PVAT vary with an increase in adiposity. Recent studies have presented compelling evidence implicating the pivotal role of PVAT in the local activation of the renin-angiotensin system (RAS), which substantially impacts vascular physiology and physiopathology. Current findings have advanced our understanding of the role of PVAT in favorably or adversely modulating the vascular function through differential RAS activation. Given that adipocytes also produce major RAS components locally to influence vascular function, this review provides a scientific basis to distinctly understand the key role of PVAT in regulating the autocrine and paracrine functions of vascular RAS components and its potential as an emerging therapeutic target for mitigating cardiovascular complications.

Leucine encoding codon TTG shows an inverse relationship with GC content in genes involved in neurodegeneration with iron accumulation.

We determined various forces involved in shaping codon usage of the genes linked to brain iron accumulation and infantile neuroaxonal dystrophy. The analysis paved the way for determining the forces responsible for composition, expression level, physical properties and codon bias of a gene. An interesting observation related to composition was that, on all the three codon positions, any two of the four nucleotides had similar compositions. CpG, TpA, and GpT dinucleotides were underrepresented with the overrepresentation of TpG dinucleotide. CpG and TpA containing codons ATA, CTA, TCG, and GCG were underrepresented, while TpG dinucleotide containing codon CTG was overrepresented, indicative of compositional constraints importance. GC ending codons were favored when the genome is GC rich, except leucine encoding codon TTG, which exhibits an inverse relationship with GC content. Nucleotide disproportions are found associated with the physical properties of proteins. The values of CAI and ENc are suggestive of low codon bias in genes. Considering the results of neutrality analysis, parity analysis, underrepresentation of TpA and CpG codons, and over-representation of TpG codons, the correlation between the compositional constraints and skew relationships with protein properties suggested the role of all the three selectional, mutational and compositional forces in shaping codon usage with the dominance of selectional pressure.

The Spasmolytic, Bronchodilator, and Vasodilator Activities of Parmotrema perlatum Are Explained by Anti-Muscarinic and Calcium Antagonistic Mechanisms.

Parmotremaperlatum is traditionally used in different areas of Pakistan to treat gastrointestinal, respiratory, and vascular diseases. This study evaluates the underlying mechanisms for traditional uses of P. perlatum in diarrhea, asthma, and hypertension. In vitro pharmacological studies were conducted using isolated jejunum, trachea, and aortic preparations, while the cytotoxic study was conducted in mice. Crude extract of P. perlatum(Pp.Cr), comprising appreciable quantities of alkaloids and flavonoids, relaxed spontaneously contracting jejunum preparation, K+ (80 mM)-induced, and carbachol (1 µM)-induced jejunum contractions in a concentration-dependent manner similar to dicyclomine and dantrolene. Pp.Cr showed a rightward parallel shift of concentration-response curves (CRCs) of Cch after a non-parallel shift similarto dicyclomine and shifted CRCs of Ca+2 to rightward much likeverapamil and dantrolene, demonstrating the coexistence of antimuscarinic and Ca+2 antagonistic mechanism. Furthermore, Pp.Cr, dicyclomine, and dantrolene relaxed K+ (80 mM)-induced and Cch (1 µM)-induced tracheal contractions and shifted rightward CRCs of Cch similar to dicyclomine, signifying the dual blockade. Additionally, Pp.Cr also relaxed the K+ (80 mM)-induced and phenylephrine (1 µM)-induced aortic contraction, similarly to verapamil and dantrolene, suggesting Ca+2 channel antagonism. Here, we explored for the first time thespasmolytic and bronchodilator effects of Pp.Crand whether they maybe due to the dual blockade of Ca+2 channels and muscarinic receptors, while the vasodilator effect might be owing to Ca+2 antagonism. Our results provide the pharmacological evidence that P. perlatum could be a new potential therapeutic option to treat gastrointestinal, respiratory, and vascular diseases. Hence, there is a need for further research to explore bioactive constituent of P. perlatum as well as further investigation by suitable experimental models are required to further confirm the importance and usefulness of P. perlatum in diarrhea, asthma, and hypertension treatment.

Superfast Synthesis of Stabilized Silver Nanoparticles Using Aqueous Allium sativum (Garlic) Extract and Isoniazid Hydrazide Conjugates: Molecular Docking and In-Vitro Characterizations.

Green synthesis of silver nanoparticles (AgNPs) was synthesized from fresh garlic extract coupled with isoniazid hydrazide (INH), a commonly used antibiotic to treat tuberculosis. A molecular docking study conducted with the selected compounds compared with anthranilate phosphoribosyltransferase (trpD) from Mycobacterium tuberculosis. The aqueous extract of garlic was prepared and mixed with silver nitrate (AgNO3) solution for the superfast synthesis of stable AgNPs. INH was then conjugated with AgNPs at different ratios (v/v) to obtain stable INH-AgNPs conjugates (AgNCs). The resulting AgNCs characterized by FTIR spectra revealed the ultrafast formation of AgNPs (<5 s) and perfectly conjugated with INH. The shifting of λmax to longer wavelength, as found from UV spectral analysis, confirmed the formation of AgNCs, among which ideal formulations (F7, F10, and F13) have been pre-selected. The zeta particle size (PS) and the zeta potential (ZP) of AgNPs were found to be 145.3 ± 2.1 nm and -33.1 mV, respectively. These data were significantly different compared to that of AgNCs (160 ± 2.7 nm and -14.4 mV for F7; 208.9 ± 2.9 nm and -19.8 mV for F10; and 281.3 ± 3.6 nm and -19.5 mV for F13), most probably due to INH conjugation. The results of XRD, SEM and EDX confirmed the formation of AgNCs. From UV spectral analysis, EE of INH as 51.6 ± 5.21, 53.6 ± 6.88, and 70.01 ± 7.11 %, for F7, F10, and F13, respectively. The stability of the three formulations was confirmed in various physiological conditions. Drug was released in a sustainable fashion. Besides, from the preferred 23 compounds, five compounds namely Sativoside R2, Degalactotigonin, Proto-desgalactotigonin, Eruboside B and Sativoside R1 showed a better docking score than trpD, and therefore may help in promoting anti-tubercular activity.

Pharmacological Justification for the Medicinal Use of Plumeria rubra Linn. in Cardiovascular Disorders.

Plumeria rubra (L.) is a traditional folkloric medicinal herb used to treat cardiovascular disorders. The present investigation was methodically planned to investigate the pharmacological foundations for the therapeutic effectiveness of P. rubra in cardiovascular illnesses and its underlying mechanisms. Ex vivo vaso-relaxant effects of crude leaf extract of P. rubra were observed in rabbit aorta ring preparations. Hypotensive effects were measured using pressure and force transducers connected to the Power Lab data acquisition system. Furthermore, P. rubra displayed cardioprotective properties in rabbits when they were exposed to adrenaline-induced myocardial infarction. In comparison to the intoxicated group, the myocardial infarction model showed decreased troponin levels, CK-MB, LDH, ALT, ALP, AST, and CRP, as well as necrosis, apoptosis, oedema, and inflammatory cell enrollment. P. rubra has revealed good antioxidant properties and prolonged the noradrenaline intoxicated platelet adhesion. Its anticoagulant, vasorelaxant, and cardioprotective effects in both in vivo and ex vivo investigations are enabled by blocking L-type calcium channels, lowering adrenaline, induced oxidative stress, and tissue tear, justifying its therapeutic utility in cardiovascular disorders.

Role of Phenolic Compounds in Human Disease: Current Knowledge and Future Prospects.

Inflammation is a natural protective mechanism that occurs when the body's tissue homeostatic mechanisms are disrupted by biotic, physical, or chemical agents. The immune response generates pro-inflammatory mediators, but excessive output, such as chronic inflammation, contributes to many persistent diseases. Some phenolic compounds work in tandem with nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit pro-inflammatory mediators' activity or gene expression, including cyclooxygenase (COX). Various phenolic compounds can also act on transcription factors, such as nuclear factor-κB (NF-κB) or nuclear factor-erythroid factor 2-related factor 2 (Nrf-2), to up-or downregulate elements within the antioxidant response pathways. Phenolic compounds can inhibit enzymes associated with the development of human diseases and have been used to treat various common human ailments, including hypertension, metabolic problems, incendiary infections, and neurodegenerative diseases. The inhibition of the angiotensin-converting enzyme (ACE) by phenolic compounds has been used to treat hypertension. The inhibition of carbohydrate hydrolyzing enzyme represents a type 2 diabetes mellitus therapy, and cholinesterase inhibition has been applied to treat Alzheimer's disease (AD). Phenolic compounds have also demonstrated anti-inflammatory properties to treat skin diseases, rheumatoid arthritis, and inflammatory bowel disease. Plant extracts and phenolic compounds exert protective effects against oxidative stress and inflammation caused by airborne particulate matter, in addition to a range of anti-inflammatory, anticancer, anti-aging, antibacterial, and antiviral activities. Dietary polyphenols have been used to prevent and treat allergy-related diseases. The chemical and biological contributions of phenolic compounds to cardiovascular disease have also been described. This review summarizes the recent progress delineating the multifunctional roles of phenolic compounds, including their anti-inflammatory properties and the molecular pathways through which they exert anti-inflammatory effects on metabolic disorders. This study also discusses current issues and potential prospects for the therapeutic application of phenolic compounds to various human diseases.

Utilization of absorbance subtraction and ratio difference green spectrophotometric methods for the quantification of alfuzosin hydrochloride and tadalafil in their binary mixture.

Alfuzosin hydrochloride and tadalafil fixed-dose combination tablets were recently formulated for the treatment of individuals with lower urinary tract symptoms caused by benign prostatic hyperplasia. Herein, the first spectrophotometric methods for quantitative analysis of alfuzosin hydrochloride and tadalafil in their binary mixture were established. The spectral overlapping of alfuzosin hydrochloride and tadalafil made direct simultaneous analysis unfeasible. Therefore, two mathematical methods were used to solve these overlapping spectra: absorbance subtraction and ratio difference. The absorbance subtraction method manipulates the zero absorption spectra of the studied drugs at the isoabsorptive point (272 nm) and uses the absorbance factor of pure ALF to calculate the absorbance of the studied drugs in the mixture at the isoabsorptive point. The ratio spectra method, on the other hand, manipulates the ratio spectra of the studied drugs, which are obtained by dividing each drug's zero absorption spectra by a divisor spectrum from the second drug. The ratio amplitude difference between 251 nm and 211 nm was directly proportional to alfuzosin hydrochloride, whereas between 292 nm and 222 nm it was directly proportional to tadalafil. The methods used were verified in accordance with the recommendations of the ICH and demonstrated adequate linear regression in working ranges of 1-15 µg/mL for alfuzosin hydrochloride and 3-40 µg/mL for tadalafil. The methods were accurate, precise, and selectively employed to quantify alfuzosin hydrochloride and tadalafil in their combined tablets.

Eco-friendly graphene quantum dots as a novel spectrofluorimetric probe for lamivudine quantification with evaluation of its greenness and blueness profiles.

In this study, graphene quantum dots (GQDs) were employed for quantitatively analyzing lamivudine using a fluorescence quenching technique. This approach allows for sensitive determination of the concentration of lamivudine in different matrices without requiring derivatization. The mechanism behind the fluorescence intensity quenching between GQDs and lamivudine molecules was explored using the Stern Volmer equation, revealing dynamic quenching behavior. Additionally, various factors affecting fluorescence quenching efficiency such as pH, GQDs concentration, and incubation time were carefully tuned. Moreover, our developed method successfully met ICH guidelines for validation parameters including linearity, accuracy, precision, and selectivity demonstrating excellent performance. The results showed good accuracy and precision, with a mean recovery value of 101.91% for method accuracy and a relative standard deviation of 0.682 and 1.489 for intraday and interday precision, respectively. Finally, the greenness and blueness of the developed method were also investigated to assess its environmental friendliness and analytical practicality. Greenness evaluation using the AGREE tool demonstrated that the developed method has a low environmental impact with an AGREE score of 0.75, Besides, the blueness evaluating using the BAGI tool indicated that the developed method is practical, reliable, and well-suited for routine analysis of lamivudine in various samples.

Development of fluorescence chemo sensor for selective histamine determination in spiked human plasma samples.

Histamine is crucial for controlling a variety of physiological processes and its dysregulation is linked to various pathological conditions, including allergic disorders, autoimmune diseases and inflammatory conditions. Herein, a novel fluorescence chemo sensor was produced to measure histamine in the pure form and spiked human plasma matrix. The proposed method is based on chemical transformation of histamine into a fluorescent product, N-(2-(1H-imidazol-4-yl) ethyl)-2-bromoacetamide, exhibiting unique fluorescence properties compared to non-fluorescent histamine molecule. This transformation occurs through a sequence of chemical reactions involving the interaction of histamine with trimethylamine, resulting in the formation of a nucleophilic intermediate that subsequently reacts with electrophilic bromoacetyl bromide. The transformed fluorescent product demonstrates an emission at 340 nm after being excited at 250 nm. Significant concentration-dependent fluorescence enhancement was obtained enabling histamine determination. The procedures were examined for accuracy, precision, selectivity, and robustness in line with the ICH M10 recommendations. The method exhibits a lower limit of quantification at 0.25 ng/mL and dynamic detection throughout a linearity range of 1-200 ng/mL, providing accurate assessment of histamine in the plasma matrix.

Augmented least squares, a powerful chemometric approach for the spectroscopic analysis of the antiretroviral therapy abacavir, lamivudine and dolutegravir in their ternary mixture.

Augmented least squares models such as concentration residual augmented classical least squares (CRACLS) and spectral residual augmented classical least squares (SRACLS) are powerful chemometric approaches that can be applied for spectroscopic analysis of many pharmaceutical compounds. Herein, both CRACLS and SRACL have been employed for UV spectral analysis of three antiretroviral therapy namely abacavir (ACV), lamivudine (LMV) and dolutegravir (DTG) in their ternary mixture. A partial factorial design has been utilized for calibration set construction then both CRACLS and SRACLS models have been optimized regarding the number of iterations and principal components, respectively, using a leave-one-out cross-validation procedure. It was found that a higher number of iterations and principal components were required for modelling the minor component DTG indicating more augmentation procedures to improve the models' accuracy. Validation of the proposed models was performed using external validation set of 13 mixtures and different validation parameters have been evaluated regarding models' predictive abilities. Both models showed excellent performance for analyzing ACV and LMV with relative root mean square error of prediction (RRMSEP) below 2 %. However, higher RRMSEP values around 5 % were observed for the minor component DTG suggesting that these models should be utilized with caution when analyzing minor components in mixtures. Furthermore, the suggested models have been applied for analyzing ACV, LMV and DTG in their pharmaceutical formulation and excellent agreement was observed between the suggested models and the reported chromatographic method posing these models as powerful chemometric approaches for quality control analysis of many pharmaceutical compounds.