Standard Drug Research Articles

A novel gas sensor based on ZnO nanoparticles self-assembly porous networks for morphine drug detection in methanol

Developing efficient drug-detecting technologies is critical to the fight against their related abuse and trafficking crimes. In the present work, a novel morphine detection device based on metal-oxide-semiconductor (MOS) gas sensors with low-cost, highly sensitive, and portable is designed and fabricated. The exclusive sensitive material, ZnO nanoparticles self-assembly porous networks (ZnO-N) with ample oxygen vacancies (OV) defects prepared by PVP-chelated precipitation followed by a chemical blowing calcination method, is decisive to morphine drug identification. OV defects can modulate the intrinsic electronic structure and endow ZnO-N with more suitable band structures for enhancing oxygen species adsorption and morphine molecules oxidation. The optimal ZnO-N-2 sensor exhibits positive linear relationship response values of 1.1–8.8 in the concentrations of 2–200 ppm toward the standard morphine drug sample at the optimal operating temperature of 250°C. More importantly, the homemade portable device equipped with the ZnO-N-2 sensor can accurately identify the morphine drug and perform early warning. This work innovatively demonstrates the feasibility of MOS gas sensors for the detection of stashing morphine drugs in methanol, which is of great significance for effectively combating global drug-related crimes.

Synthesis, Evaluation and Docking Studies of Disubstituted N-Heterocyclic Derivatives as Anticancer Agents.

Cancer is a chronic disease reported with alarming rates of mortalities every year. Herein, we reported the synthesis of nitrogen based novel heterocyclic disubstituted derivatives and evaluated them against L929 and A549 cell lines using MTT assay. Among all, 6a2 and 6c1 were significantly active against L929 with IC50 value of 2.61±9.58 and 2.64±8.97 µg/mL respectively. Compounds 6a2 and 6c1 were also active against A549 with IC50 value of 2.36±9.20 and 2.43±6.28 µg/mL respectively and were found to be more potent than the standard drug Doxorubicin. A molecular docking study of the active compounds was also done against EGFR, conferring good binding affinity and binding interactions. Further biological investigations may provide valuable insights towards exploring the therapeutic potential of the active compounds in future.

Computational Analysis and Anti‐Hiv/Antifungal Studies of 2‐Aryl‐N1‐Arylacetamido Benzimidazole Derivatives

AbstractMedicinal chemistry highly values the benzimidazole scaffold as a pharmacophore owing to its versatile range of biological functions. In the present study, 17 derivatives of 2‐aryl‐N1‐arylacetamido benzimidazoles 3(a–q) were synthesized by nucleophilic substitution reactions between different 2‐chloro‐N‐(aryl)‐acetamides 2(a–q) and 2‐(4‐chlorophenyl)‐1H‐benzo[d]imidazole (1) in N, N‐dimethylformamide, and evaluated for in vitro anti‐HIV and antifungal activities. Of these derivatives, compounds 3 a, 3 b, 3 i, and 3 n showed moderate inhibitory efficacy against HIV‐1 RT, whereas the remaining compounds showed negligible activity compared to the standard drug efavirenz. In contrast, most of the test compounds demonstrated significant efficacy against fungal strains such as Candida albicans and Aspergillus niger. Compounds 3 a, 3 f, 3 m, and 3 n were the most effective antifungal agents. We applied computational approaches to rationalize the potency of the newly synthesized inhibitors.

Synthesis, Spectral Analysis and Molecular Docking Investigation of Thiadiazole Based Sulfonamide Derivatives: An Effective Approach Toward Alzheimer's Disease

AbstractAlzheimer's disease (AD), a neurodegenerative condition is expected to affect 152 million in 2050. The current study comprises the evaluation of thiazole based thiadiazole bearing sulfonamide derivatives to treat Alzheimer's disease. A series of compounds (1‐15) were synthesized and were studied for their anti‐Alzheimer's potential. Their IC50 values lie in the range between (19.20±0.20 nM–2.50±0.20 nM) for AChE and (19.80±0.20 nM–3.30±0.50 nM) for AChE. Among all of them, analog 2, 7, 9, and 15 were reported to possess significant activity. Among all the members of series, compound 15 having IC50=2.50±0.20 nM and 3.30±0.50 nM for AChE and BuChE, respectively, emerged as the most promising candidate due to the presence of two electronegative fluorine (F) atoms. The small and highly electronegative fluorine atoms have the ability to block the enzyme's activity by forming strong hydrogen bonds with the amino acids of the target enzymes, thereby inhibiting their function. The efficacy of these novel compounds was studied in comparison to the standard drug donepezil having IC50=5.80±0.30 nM for AChE and IC50=6.30±0.81 nM BuChE. For further assessment of inhibition potential and mode of inhibition, molecular docking study of all the potent compounds was carried out. Further, the structural identity of the synthesized compounds was confirmed using various spectroscopic techniques, including 1H‐NMR, 13C‐NMR, and High‐Resolution Electron Impact (HREI) Mass spectrometry, which provided detailed information about their molecular structure. ADME analysis of all the synthesized compounds confirmed their potential as drugs, indicating favorable pharmacokinetic properties and a promising drug profile.

Synthesis of pyrazole and pyrazoline derivatives of β-ionone: Exploring anti-inflammatory potential, cytotoxicity, and molecular docking insights

In the present paper, pyrazole and pyrazoline derivatives of β-ionone were synthesized. The protocol involved intramolecular oxidative C–H amination of hydrazone to yield corresponding pyrazole in moderate to good yields. Another methodology comprising of condensation of hydrazine hydrochloride with β-ionone in methanol leading to pyrazoline and its oxidative dehydrogenation using hypervalent iodine reagent to synthesize pyrazole is also achieved. One pot methodology for synthesis of pyrazole is also developed by refluxing the hydrazine hydrochloride with β-ionone in acetic acid. The structures of the synthesized compounds were elucidated using 1H NMR, 13C NMR, FTIR and mass spectrometry. All the pyrazole and pyrazoline derivatives were subjected to bovine serum albumin assay for in-vitro anti-inflammatory activity and all the compounds exhibited good to excellent activity. Compounds containing bromo and sulfonamide group exhibited inhibition rates of 87.36 % and 85.82 %, respectively, at a concentration of 0.5 mg/mL, surpassing the efficacy of the standard drug celecoxib (81.67 %). Further, cytotoxicity of the compounds was also evaluated against VERO cell line and all the compounds exhibited the cytotoxic values almost similar to the standard. Molecular docking was performed to study binding affinity of the potent compounds i. e bromo bearing pyrazole and sulfonamide bearing pyrazoline into the crystal structure of COX-II enzyme (PDB ID: 3LN1) at celecoxib binding site to determine the binding energy and interactions.

Computational Identification and Functional Analysis of Potentially Pathogenic nsSNPs in the NLRP3 Gene Linked to Alzheimer's Disease.

Single Nucleotide Polymorphisms (SNPs) are key in understanding complex diseases. Nonsynonymous single-nucleotide polymorphisms (nsSNPs) occur in protein-coding regions, potentially altering amino acid sequences, protein structure and function. Computational methods are vital for distinguishing deleterious nsSNPs from neutral ones. We investigated the role of NLRP3 gene in neuroinflammation associated with Alzheimer's disease (AD) pathogenesis. A total of 893 missense (nsSNPs) were obtained from the dbSNP database and subjected to rigorous filtering using bioinformatics tools like SIFT, Align GVGD, PolyPhen-2, and PANTHER to identify potentially damaging variants. Of these, 18 nsSNPs were consistently predicted to have deleterious effects across all tools. Notably, 16 of these variants exhibited reduced protein stability, while only 4 were predicted to be buried within the protein structure. Among the identified nsSNPs, rs180177442 (R262L and R262P), rs201875324 (T659I), and rs139814109 (T897M) were classified as high-risk variants due to their significant deleterious impact, probable damaging effects, and association with decreased protein stability. Molecular docking and simulation analyses were conducted utilizing Memantine, a standard drug utilized in AD treatment, to investigate potential interactions with the altered protein structures. Additional clinical and genetic investigations are necessary to elucidate the underlying mechanisms that link NLRP3 polymorphisms with the initiation of AD.

Discovery of potential 1,2,4-triazole derivatives as aromatase inhibitors for breast cancer: pharmacophore modelling, virtual screening, docking, ADMET and MD simulation

ABSTRACT Hormone receptor (HR)-positive breast cancer represents tumours that express estrogen and/or progesterone enzymes, which play a crucial role in the growth and proliferation of breast cancer cells. Aromatase inhibitors (AIs) are drugs that inhibit the enzyme aromatase, involved in the biosynthesis of estrogen and are used for the treatment of HR-positive breast cancer. The USFDA-approved nonsteroidal AIs contain 1,2,4-triazole heterocycle. So, in the present study, we screened seventy-eight 1,2,4-triazole analogues from different literature resources and generated a pharmacophore model. After several validation protocols, Hypo1 was selected as the best model and was used as a 3D query for screening 1,2,4-triazole analogues (15,583) obtained from the CHEMBL database. A dataset containing 320 ligands with estimated activity (IC50< 0.1 µM) was subjected to molecular docking against the aromatase enzyme (PDB ID: 3S79). Amongst the 320 ligands, 30 compounds exhibited better binding energy compared to the standard drug letrozole. These 30 hits were further considered for the design of two novel molecules which were initially assessed for their ADMET properties followed by pharmacophore mapping, docking and molecular dynamics simulation. The in silico findings suggest that both the designed molecules can be considered drug-like candidates for the treatment of breast cancer through aromatase inhibition.

Green photoluminescence, supercapacitor and cytotoxic properties of nickel doped haematite nanoparticles

Fe2O3: Ni (1–9 mol.%) nanoparticles (NPs) were synthesized using the co-precipitation method and calcined at 500∘C for 12 h. The crystallite size, phase, crystallinity, and structural parameters were analyzed via powder X-ray diffraction. The Bragg reflections confirmed that the synthesized NPs crystallize in a pure hexagonal crystal structure with space group R-3c. Surface morphology analysis revealed agglomerated NPs of irregular sizes and shapes. Energy Dispersive X-ray Analysis confirmed the presence of Fe, O, and Ni elements, as well as the purity of the sample. Both the direct band gap energy and crystallite size decreased with increasing dopant concentration. Detailed studies were conducted on the photoluminescence and anticancer properties. The CIE coordinates indicated a color tuning from blue to green in the visible region. CIE coordinates and CCT values ranging between 2860 to 9547 k demonstrated that the synthesized nanophosphor material meets the requirements of display technology. Additionally, anticancer properties were investigated using HeLa cells and compared with the standard drug cisplatin for biomedical applications. Electrochemical investigations revealed super capacitance values ranging from 93.43 to 149.13 F/g at a scan rate of 10 mV/s with increasing Ni2+ concentration. Therefore, the synthesized Ni2+-doped hematite NPs show great promise in display technology, the biomedical field, and as supercapacitors in energy storage devices.

Assessment of nebivolol efficacy in experimental models of toxoplasmosis: insights into parasite burden reduction and neuronal protection.

This study investigates the efficacy of nebivolol (NBV) in experimental models of toxoplasmosis, focusing on parasite burden reduction and neuronal protection. In the acute model of experimental toxoplasmosis, Swiss mice infected with RH strain tachyzoites received oral NBV chlorhydrate doses of 2mg/kg/day and 4mg/kg/day for 8days. Treatment with NBV significantly reduced parasite burden compared to vehicle and standard drug (PYR) groups. In the chronic model of experimental toxoplasmosis, C57/BL6 mice infected with the ME49 strain received NBV chlorhydrate 41days post-infection and were evaluated after 10days of treatment. NBV chlorhydrate effectively reduced cyst number and area, as well as bradyzoite burden compared to controls. Histological analysis demonstrated that NBV chlorhydrate preserved neuronal count, with the 4mg/kg/day dose yielding counts similar to non-infected mice. Statistical analysis confirmed significant differences compared to control groups. Furthermore, immunohistochemical analysis revealed a significant reduction in iNOS labeling in the brains of mice treated with NBV chlorhydrate, indicating a decrease in nitric oxide production compared to control groups. These findings suggest NBV's potential as a promising candidate for toxoplasmosis treatment, highlighting its ability to reduce parasite burden and protect neuronal integrity. Further research is warranted to elucidate NBV's mechanisms of action and its clinical application in managing toxoplasmosis.

Design, synthesis, α-glucosidase inhibition and hypoglycemic activity of 3-aceto(benzo)hydrazide-1,2,4-triazines as potential anti-diabetic agents

Type 2 diabetes is a common condition that causes the level of glucose in the blood to become too high and α-glucosidase inhibitors are therapeutic agents in managing type 2 diabetes. In the present study, we report a new series of 3-aceto(benzo)hydrazide-1,2,4-triazine analogs as potential therapeutic agents against type 2 diabetes. In the in vitro evaluations, most compounds showed much stronger α-glucosidase inhibitory activity than the standard drug acarbose. Especially, compound 2A, (N'-(5,6-diphenyl-1,2,4-triazin-3-yl)-4-methoxybenzohydrazide) as the most active compound showed IC50 = 12.0 μM which is 60 folds more potent than acarbose. In addition, the MTT test using the three cell lines HCT-116, MDA-MB-231, and A549 showed that the target compounds have low cytotoxic effects with IC50 values in the range of 60–280 μM, therefore they can be considered as safe compounds. Molecular docking studies predicted that the strong inhibitory activity of 2A is related to the interactions generated by the three residues Asp282, Trp481, and Asp616 with the triazine core and hydrazide motif in the active site of the enzyme. The significant inhibitory effect of 2A against α-glucosidase was also confirmed in vivo, where the compound showed equivalent activity to the standard drug acarbose on reducing blood glucose in the tested mice. In conclusion, this study introduces compound 2A as a new lead compound with favorable cytotoxicity, strong α-glucosidase inhibitory activity and in vivo hypoglycemic effect, for future investigation in the treatment of diabetes mellitus.

Curbing Key Digestive Enzymes by Three Plant Extracts for Sustainable Management of Postprandial Hyperglycemia

Background: Diabetes mellitus is a chronic metabolic condition marked by persistently elevated blood sugar levels. Key digestive enzymes viz. α-amylase and α-glucosidase, hydrolyze consumed carbohydrates into glucose which raises the postprandial blood glucose level in a diabetic patient. So, the development of α-amylase and α-glucosidase inhibitors procured from medicinal plants to retard starch digestion is an alternative approach for controlling type 2 diabetes mellitus. Objective: The current study aimed to evaluate the inhibitory potentials of the key digestive enzymes viz. α-amylase and α-glucosidase by the extracts of three medicinal plants; red dragon fruit (Hylocereus polyrhizus) pulp and peel, bamboo (Bambusa vulgaris) shoot, turnip (Brassica rapa L.) shoot and leaf by performing α-amylase and α-glucosidase inhibition assays in vitro. Methods: Inhibition of α-amylase activity was conducted using 3,5-dinitrosalicylic acid method, and 4- Nitrophenyl-α-D-glucopyranoside was used as a substrate to perform α-glucosidase inhibition assay in vitro. Results: Among all the selected sample extracts, red dragon fruit pulp expressed the highest percentage of α-amylase inhibition (59.73 ± 4.33%) at the concentration of 1000 μg/mL which is comparable to standard antidiabetic drug Acarbose (70.59 ± 2.64%), whereas the lowest inhibition was observed in turnip shoot extract (42.48 ± 2.10%) at the same concentration. In terms of α-glucosidase inhibition activity, again, red dragon fruit pulp extract demonstrated the maximum inhibition rate (56.42 ± 2.38%) at 1000 μg/mL concentration. This is respectable in comparison to the reference Acarbose (66.45 ± 1.78%). In contrast, turnip shoot extracts displayed the lowest α-glucosidase inhibition activity (38.27 ± 2.21%) at the same concentration. Conclusion: The current study demonstrated that the red dragon fruit pulp extract possesses substantial antihyperglycemic activity (α-amylase inhibition: 59.73 ± 4.33%, α-glucosidase inhibition: 56.42 ± 2.38%) in vitro, which could be a putative nutraceutical to manage postprandial hyperglycemia.

Hypertrophy Determination of H9c2 Cardiomyoblast Cell Line Using Wright-Giemsa Staining: An Experience in Developing an Acceptable and Easy-to-handle In-vitro Protocol

Introduction Cell-size area (CSA) becomes the standard parameter routinely tested in vitro for cardiac hypertrophy studies. Thus, staining is an essential tool for this purpose. As reported in a previous study, immunofluorescence staining is an established method for CSA. However, because it is expensive and requires a specialized microscope, e.g., immunofluorescence or confocal microscope, it is not applicable in a laboratory with limited equipment. Wright-Giemsa staining is a standard procedure in hematology laboratories and is inexpensive and convenient. Here, we shared our experience developing a CSA determination protocol using Wright-Giemsa in H9c2 cardiomyoblast. Methods The viability tests were performed on H9c2 to determine the effective dosage of angiotensin II and Irbesartan (standard drug). The H9c2 were divided into three groups: the control group (without either angiotensin II or irbesartan), the negative control (with angiotensin II), and the positive control (with angiotensin II and Irbesartan), triplicate for each group. The cells then are acclimatized overnight, serum-starved for one day, and incubated with angiotensin and irbesartan for 48 hours. Lastly, Wright-Giemsa was observed using a light microscope in three fields. The CSA was determined by three independent observers blindly, statistically different if the p&lt;0.05 using ANOVA ways or Kruskal-Wallis. Results After the H9c2 induced by angiotensin-II 1 μM and Irbesartan 1μM, we found the CSA significantly differed among each group (p&lt;0,0001). The negative control has a higher median and interquartile range (IQR) CSA (10.78 (6.79) um2) compared to the control group (median (IQR) 7.27 (4.91) um2) and positive control (median (IQR) 7.849(5.31) um2). Conclusion It can be concluded that the Wright-Giemsa might help determine the CSA for in-vitro hypertrophic studies.

Phytochemical Screening and Pharmacological Activities of Gentiana ornata from Lauribinayak, Rasuwa, Nepal

Gentiana ornata (Wall. ex G. Don) Griseb, also called decorated gentian or showy gentian, has been used as a decoction plant in temperate regions of Nepal. This work aims to evaluate the phytochemical properties, antioxidant values, and pharmacological properties of this plant collected from Lauribinayak, Gosainkunda Rural Municipality, Rasuwa, Nepal. The extract of whole plant was prepared by cold extraction process at 100% ethanol. Then, the qualitative preliminary phytochemical test of plant extract was performed to know its chemical constituents. The total phenolic content using Folin-Ciocalteu method, total flavonoid content using aluminium chloride colorimetric assay and antioxidant potential of the plant extract were also determined by using diphenylpicrylhydrazyl (DPPH) reagent. The pharmacological activities like oral acute toxicity test, antidiarrheal test and anti-ulcer test were also carried out in laboratory animals. The qualitative phytochemical screening showed the presence of flavonoids, steroids, glycosides, anthocyanin, alkaloids, terpenoids, and phenolic constituents. The total phenolic content, total flavonoid content and antioxidant assay value of this plant extract were 242.64±0.280 mg GAE/g, 39.23±0.005 mg QE/g and 42±0.072 µg/mL respectively. The extract showed no morbidity, mortality, toxicity signs, or symptoms in the oral acute toxicity test. Though it could not show considerable antidiarrheal effect by reducing gastrointestinal motility when compared to the standard drug, loperamide, it showed significant anti-ulcer effects by reducing gastric lesions when compared to the standard drug, sucralfate, which may be due to its mucosal protecting nature. Therefore, isolation and purification of phytochemicals responsible for the pharmacological activity of this plant have been recommended.

Synthesis, Structural Characterization, and Computational Studies of Novel Co(II) and Zn(II) Fluoroquinoline Complexes for Antibacterial and Antioxidant Activities.

Research into heterocyclic ligands has increased in popularity due to their versatile applications in the biomedical field. Quinoline derivatives with their transition metal complexes are popular scaffolding molecules in the ongoing pursuit of newer and more effective bioactive molecules. Subsequently, this work reports on the synthesis and possible biological application of new Zn(II) and Co(II) complexes with a bidentate quinoline derivative ligand (H2 L), [(H2 L):(E)-2-(((6-fluoro-2-((2-hydroxyethyl)amino)quinolin-3-yl)methylene)amino)ethanol]. The ligand and its metal complexes were structurally characterized by spectroscopic methods (1H NMR, 13C NMR, Fourier transform infrared (FTIR), UV-vis, fluorescence, and mass spectroscopy), as well as by thermogravimetric and elemental analysis methods. The spectroscopic findings were further supported by density functional theory (DFT) and time-dependent (TD)-DFT calculations. The biological application was examined by investigating the inhibitory action of the complexes against bacterial strains using diffusion and agar dilution methods, and their profiles against two Gram-positive and Gram-negative bacterial strains were supported by molecular docking analysis. To rationalize the in vitro activity and establish the possible mechanism of action, the interactions and binding affinity of the ligand and complexes were investigated against three different bacterial enzymes (Escherichia coli DNA gyrase (PDB ID 6f86), E. coli dihydrofolate reductase B (PDB ID: 7r6g), and Staphylococcus aureus tyrosyl-tRNA synthetase (PDB ID: 1JIJ)) using AutoDock with the standard protocol. The MIC value of 0.20 μg/mL for zinc complex against E. coli and associated binding affinities -7.2 and -9.9 kcal/mol with DNA gyrase (PDB ID 6f86) and dihydrofolate reductase B (PDB ID: 7r6g), as well as the MIC value of 2.4 μg/mL for cobalt(II) complex against Staphylococcus aureus and the associated binding affinity of -10.5 kcal/mol with tyrosyl-tRNA synthetase (PDB ID: 1JIJ), revealed that the complexes' inhibitory actions were strong and comparable with those of the standard drug in the experiments. In addition, the ability of the new quinoline-based complexes to scavenge 1,1-diphenyl-picrylhydrazyl radicals was investigated; the findings suggested that the complexes exhibit potent antioxidant activities, which may be of therapeutic significance.

Review Mechanisms for Advanced Medical Therapies in Japan and Thailand: A Proposal for the Use of Expert Clinical Benefit Assessments at Designated Institutions

AbstractAdvanced new therapies, such as stem cell and gene therapies and xenotransplantation, represent challenges for regulatory and ethical review. Major drug agencies, such as in the U.S., India, and Europe, have asserted regulatory authority and require ethics review by local ethics review committees, using the same strict requirements as those for standard drug approvals. In spite of this, unapproved and undocumented stem cell clinics flourish in all of these places, suggesting that current approaches do not offer patients sufficient protection. Japan has attempted another approach, requiring approvals at local levels for all regenerative medical procedures, and a faster approval of promising new interventions. The Japanese approach has, however, also been criticized as not striking a proper balance between early access and a proper assessment of safety and effectiveness. For smaller and less-resourced countries, such as Thailand, one major challenge is limited expertise to conduct the evaluation of these advanced new therapies. This article provides an overview of the issues facing regulators and proposes that countries should restrict the early adoption of advanced new therapies to specialized clinics with appropriate scientific and ethical expertise for review. Review in these institutions should focus on expert clinical benefit assessments for individual patients being offered such interventions, independently of whether they are offered as research or therapy.

Switching carbamazepine to lacosamide improves gamma-glutamyl transpeptidase levels.

Carbamazepine (CBZ) use has been limited by multiple adverse reactions. Lacosamide (LCM) is a functional amino acid anti-seizure medication (ASM), approved for focal seizure patients more than 4 years old. It is non-inferior in terms of efficacy to controlled release CBZ and was proven to have better tolerability. This study examines the effect of abruptly changing CBZ to LCM in epilepsy patients with elevated gamma-glutamyl transpeptidase (GGT). Consenting adult patients aged 18 years old and above, with controlled focal seizure disorder for more than 2 years, who were consistently taking CBZ and who had elevated GGT were included in this study. Out of 1526 patients screened, only 12 satisfied the inclusion criteria. After abruptly changing CBZ to LCM, the GGT level significantly dropped from a median of 141.5 to 63.5 IU/L (z = 3.06, p = 0.0005). Moreover, there was significantly lower proportion of patients with abnormal GGT levels after the switch in medications was done (100% vs. 66.7%, McNemar χ2 = 8, p = 0.008). Moderate to high levels of GGT in patients with focal epilepsy can be decreased by changing CBZ to LCM. Moreover, abruptly changing CBZ to LCM without cross-titration may be safe and effective in preventing seizure incidence within a 1-month period. PLAIN LANGUAGE SUMMARY: Although carbamazepine (CBZ) is the standard drug for focal seizures, its numerous side effects, especially in the liver, limits its use in a lot of patients with epilepsy. Gamma-glutamyl transferase (GGT), which is elevated in liver disease of whatever cause including intake of CBZ, is associated with increased mortality. In this study, we found that abruptly changing CBZ to Lacosamide (LCM) can significantly decrease the GGT level in 1 month without apparent increase in seizure recurrence and side effects. Therefore, we conclude that high levels of GGT may be decreased by abruptly changing CBZ to LCM.

In vivo and in silico studies of membrane-stabilizing and clot lysis activities of Trachyspermum ammi

Trachyspermum ammi contains many important phytochemicals, including thymol, which is used to treat many diseases. This study aimed to check the membrane-stabilizing and clot-lysis capacity of the ethanol extract of T. ammi (ETA) and its main chemical component, thymol (THY). For this, we used hypotonic solution-induced erythrocyte lysing and egg-albumin protein denaturation for membrane-stabilizing capacity and human blood clot lysis for anti-atherombosis capacity. Further, we observed in silico study of THY and ntric oxide synthase (NOSs) isoform. The stabilizing effects of ETA and THY on the membrane changed depending on the concentration. At the highest concentration (160 μg/mL), they stopped the most bleeding, while the standard drug, acetylsalicylic acid, stopped less bleeding at the same concentration. In the erythrocyte lysing test, ETA showed 102.60 ± 0.01 and 75.83 ± 1.44% membrane protection. In the egg-albumin denaturation test, they showed 27.62 ± 0.02% and 56.71 ± 0.02% membrane protection, respectively. In our clot lysis experiment, ETA and THY also showed significant and concentration-dependent clot lysis capacity. The IC50 and EC50 values of THY were lower than ETA when it came to keeping the membrane stable and breaking up clots, respectively. In our in silico investigation, THY and NOSs showed significant binding interaction. Taken together, ETA and its major component, THY, exhibited potent membrane stabilizing activity and clot lysis activity in in vitro studies. Further studies are required to elucidate its other active principles and their biological effects, along with possible mechanisms.

Synergisitic anti-colorectal cancer effects of WNT974 combined with artesunate via cooperative regulation of p21, p27, and AKT

ObjectiveTo evaluate the synergistic effects and underlying mechanisms of WNT974 and artesunate (ART) combination therapy in the treatment of colorectal cancer (CRC). MethodsWe conducted an initial assessment of the synergistic impact of WNT974 and ART on cell viability using the MTT assay across eight CRC cell lines with diverse mutation statuses.Subsequently, a 3D in vitro model was utilized to confirm the synergistic effect of the combination. Flow cytometry was employed to analyze cell cycle distribution. The molecular mechanisms were further investigated by examining the expression levels of cell cycle-related proteins (p21, p27, and CDK2) and AKT activity through PCR and Western blot analyses. The in vivo efficacy of the combination therapy was evaluated using a xenograft mouse model of CRC. ResultsThe combination of WNT974 and ART significantly reduced cell viability in all eight CRC cell lines, demonstrating a synergistic effect. Additionally, the combination exhibited synergy in inhibiting 3D spheroid growth. Cell cycle analysis revealed that the combination therapy induced a marked G1/G0 arrest through CDK2 inhibition, surpassing the efficacy of individual treatments. Molecular analysis indicated that the combination therapy upregulated p21 and p27 expression and reduced AKT activity. In vivo, the combination therapy significantly inhibited tumor growth in the xenograft mouse model, notably outperforming 5FU, the standard first-line drug for CRC. ConclusionThe study highlights the synergistic anti-CRC effects of combining WNT974 and ART. This combination induces G1/G0 phase cell cycle arrest by cooperatively regulating p21, p27, and AKT, presenting a promising alternative to current CRC treatments. These findings elucidate the molecular basis of this interaction and provide a scientific foundation for advancing ART combined with WNT94 as a novel therapy for CRC, offering a potential new avenue.

Exploring Vernonia amygdalina’s leaf extracts for phytochemical screening and its anti-bacterial activities

ABSTRACT The aim of this study was to screen the phytochemicals and assess the antibacterial properties of crude extracts from Vernonia amygdalina leaves against specific pathogenic bacteria. Qualitative and qauntitave analysis was performed on both ethanol and ethyl acetate crude extracts using standardized techniques. The analysis revealed the presence of alkaloids, phenol, flavonoids, terpenoids, saponins, tannins, and cardiac glycosides in the ethanol extract, while saponins and glycosides were absent in the ethyl acetate extract. The quantities of phenols, flavonoids, and alkaloids were determined using Gallic acid, quercetin, and atropine assays, respectively. The ethanol extract contained 154.7 ± 3.6 (mg GAE/g) of total phenols, 33.3 ± 1.8 (mg QE/g) of flavonoids, and 2.4 ± 0.08 (mg AE) of alkaloids, whereas the ethyl acetate extract contained 93.7 ± 3.9 (mg GAE/g) of total phenols, 30.7 ± 8.3 (mg QE/g) of flavonoids, and 1.57 ± 0.3 (mg GAE/g) of alkaloids. This study identified 44 components in the ethanol crude extract and 10 components in the ethyl acetate crude extract. The presence of alkanes, alkenes, amines, carboxylic acids, and alcohols was confirmed by FT-IR analysis. Each crude extract was tested at concentrations of 500 mg/mL, 250 mg/mL, 125 mg/mL, and 62.5 mg/mL using the same method. A concentration of 0.001 mg/mL of Penicillin capsule standard drugs and dimethyl sulfoxide were used as positive and negative controls, respectively. Overall, the results of the study indicated that both crude extracts exhibited antibacterial activity at higher concentrations.

Correction of the cytokine status of patients with true eczema using supravenous laser blood irradiation and imunofan

Objective. To increase the effectiveness of treatment of patients with true eczema by including supravenous laser blood irradiation (NLBI) and imunofan into complex therapy. Material and methods: The study included 132 patients aged 18 to 70 years. The effectiveness of standard drug therapy, additional administration of immunofan, NLBI and complex therapy in improving the clinical symptoms of eczema and correcting circulating and intracellular pro- and anti-inflammatory cytokines was compared. Results: It was found that standard drug therapy poorly corrects clinical and laboratory parameters. A comprehensive treatment program for patients with true eczema, which additionally includes NLBI and Imunofan, helps reduce the percentage of CD3+, CD4+, CD8+ lymphocytes with the induction of pro-inflammatory interleukins (IL) — 2 and IFN-γ, respectively, by 37.9 % — 36.4 % —44.9 % and 42.1 % — 45.6 % — 47.8 %, an increase in the percentage of CD3+, CD4+, CD8+ lymphocytes with the induction of anti-inflammatory IL-4, respectively, by 65.8 % — 68.2 % — 58 %, reduces the levels of circulating pro-inflammatory blood cytokines IL-8, — 18, — 31 respectively by 55.5 % — 54.6 % — 55.4 % against the background of an increase in the level of antiinflammatory IL-4 in the blood — by 61.6 %, which exceeds the therapeutic effects each of the methods included in the treatment complex. The clinical effectiveness of combination therapy is characterized by a decrease in EASI by 76.5 %, which exceeds the results obtained when using individual methods that make up the treatment complex.Key words: true eczema, interleukins, CD+-lymphocytes, laser irradiation of blood, immunofan.