Advances in Pharmacological and Pharmaceutical Sciences最新文献

Breast cancer is a condition where breast tissue cells grow uncontrollably. Various natural and synthesized compounds, such as quinazoline, have been studied for their potential as anticancer agents. Quinazoline derivatives have shown diverse bioactivities, including antimalarial, antifungal, antimicrobial, and anticancer properties. This research aims to synthesize substituted tetrazoloquinazoline and evaluate its potential as an anticancer agent using molecular docking studies with the Molecular Operating Environment (MOE) software. Furthermore, molecular dynamic was also performed to analyze the binding stability of this protein-ligand complex. Additionally, the physicochemical and pharmacokinetic properties of quinazoline compounds were assessed using the website https://www.swissadme.ch. The cytotoxic activity of the compounds was evaluated using the MTT assay. The docking results revealed that substituted tetrazoloquinazoline exhibited a significantly different range of binding free energy compared to the positive control. Moreover, the substituted tetrazoloquinazoline compounds comply with Lipinski's Rule of Five (Ro5), indicating that they are easily absorbable and have good permeability. The cytotoxic activity of the compounds was found to have an IC₅₀ value of >1000 ppm, classifying them as noncytotoxic. It therefore paved the way for the discovery of promising next-generation drugs against breast cancer.

This study investigated the medicinal potential of Lavatera cashmeriana, a plant traditionally known for its therapeutic properties. The aim was to identify the phytocompounds in L. cashmeriana leaf extract and evaluate its antibacterial, antioxidant, and anticancer effects. Gas chromatography-mass spectrometry analysis was employed to characterize the phytochemical composition of the ethanol extract derived from L. cashmeriana leaves. The antimicrobial potential was assessed through the well diffusion technique, targeting Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. The 2,2-diphenyl-1-picrylhydrazyl assay was conducted to assess antioxidant capabilities, while cytotoxicity against the A549 cancer cell line was determined via the MTT assay. GC-MS analysis identified ten different compounds, with phytol, 1-Eicosanol, and 2,6,10-trimethyl,14-ethylene-14-pentadecne being the most prevalent. The extract exhibited notable antimicrobial efficacy against all bacteria with MIC values ranging from 62.5 to 250 µg/mL. However, C. albicans did not respond. The extract exhibited antioxidative properties with an IC₅₀ value of 86 µg/mL and cytotoxicity with an IC₅₀ value of 69.95 µg/mL against the A549 cancer cell line. The results derived from this study supported the historical use of L. cashmeriana as a medicinal plant and suggested that it can potentially treat a wide range of medical ailments. The identified phytocompounds and the demonstrated antibacterial, antioxidant, and anticancer effects provide scientific evidence for its medicinal properties. However, further investigations are needed to fully understand its safety profile, efficacy, and mechanism of action before recommending it for therapeutic purposes.

Acinetobacter baumannii was identified by the WHO as a priority pathogen in which the research and development of new antibiotics is urgently needed. Plant phytochemicals have potential as sources of new antimicrobials. The objective of the study was to determine the antibacterial activity of extracts of selected Zimbabwean medicinal plants against A. baumannii and determine their possible mode of action. Extracts were prepared from the leaves of the eight plants including the bark of Erythrina abyssinica using solvents of different polarities. Antibacterial activity was evaluated using the microbroth dilution method coupled with the in vitro iodonitrotetrazolium colorimetric assay. The effect of the extracts on membrane integrity was determined by quantifying the amount of protein and nucleic acid leaked from the cells after exposure to the extracts. The effects of the extracts on biofilms were investigated. Toxicity studies were carried out using sheep erythrocytes and murine peritoneal cells. Seven out of eight evaluated plant extracts were found to have antibacterial activity. The Combretum apiculatum acetonie (CAA) extract showed the highest inhibitory activity against A. baumannii with a minimal inhibitory concentration of 125 µg/mL. The minimum inhibitory concentration (MIC) of the CAA extract caused a protein leakage of 32 µg/mL from A. baumannii. The Combretum apiculatum acetonie (CAA), C. apiculatum methanolic (CAM), Combretum zeyheri methanolic (CZM), and Erythrina abyssinica methanolic (EAM) extracts inhibited A. baumannii biofilm formation. The EAM extract was shown to disrupt mature biofilms. The potent extracts were nontoxic to sheep erythrocytes and mouse peritoneal cells. The activities shown by the extracts indicate that the plants have potential as sources of effective antibacterial and antibiofilm formation agents against A. baumannii.

Hepatic diseases represent a public health problem. Among the approaches to their management is the use of traditional treatments based on the use of medicinal plants. In Benin, several recipes based on Cochlospermum tinctorium are used in the treatment of hepatitis without a real scientific basis. This study aimed to evaluate the hepatoprotective effects and acute oral toxicity of 10 of these recipes. The variables studied were the variety of C. tinctorium (wild form vs. cultivated form), the species associated with C. tinctorium (Combretum micranthum vs. Chromolaena odorata), and the proportion of C. tinctorium in the recipe (1; 4/5; 1/2). The hepatoprotective effect of these extracts at doses of 100, 200, and 400 mg/kg/bw was evaluated in Wistar rats subjected to hepatotoxicity induction through the administration of 5 g/kg of paracetamol. Acute oral toxicity was assessed following the OECD 423 protocol. The results revealed an absence of acute oral toxicity for the 10 recipes. The hepatoprotective tests conducted indicated that the hepatoprotective effect of C. tinctorium is dose dependent. The wild variety of C. tinctorium had a better hepatoprotective effect than the cultivated one. The association with C. micranthum enhances the hepatoprotective effect of C. tinctorium, unlike that with C. odorata. This study emphasizes that the combination of C. tinctorium with C. micranthum in the treatment of hepatitis is scientifically justified and it exhibits a dose-dependent hepatoprotective effect.

Background: Helicobacter pylori (H. pylori), a widespread bacterial pathogen, is associated with various gastrointestinal diseases, including gastric cancer. Statins, widely prescribed cholesterol-lowering agents, have demonstrated pleiotropic effects, including potential antimicrobial properties. This in vitro study investigated the direct antibacterial effects of three clinically approved statins, simvastatin, atorvastatin, and rosuvastatin, against H. pylori isolates.

Methods: H. pylori strains were isolated from gastric biopsies of dyspeptic patients and identified by microbiological techniques. The minimum inhibitory concentrations (MICs) of statins were determined using the agar dilution method, and their antimicrobial activity was evaluated by the disc diffusion method using different concentrations of simvastatin, atorvastatin, rosuvastatin, tetracycline, and amoxicillin. Scanning electron microscopy (SEM) was employed to examine the morphology of H. pylori cells.

Results: The minimum inhibitory concentration (MIC) values (μg/mL) of atorvastatin, rosuvastatin, simvastatin, tetracycline, and amoxicillin against H. pylori were 240 ± 20, 450 ± 20, 460 ± 15, 155 ± 30, and 140 ± 20, respectively. In the disc diffusion assay, atorvastatin and rosuvastatin produced significantly larger inhibition zones compared to simvastatin at all concentrations tested (p < 0.05). The inhibition zone diameters (mm) increased with higher statin concentrations, ranging from 9 ± 1.4 to 13 ± 1.4 for atorvastatin, 8 ± 0.9 to 11 ± 0.6 for rosuvastatin, and 5 ± 1.3 to 6 ± 1.4 for simvastatin at the highest tested concentration (1200 μg/ml). SEM analysis revealed the characteristic spiral morphology of H. pylori cells.

Conclusion: Statins demonstrated varying degrees of antibacterial activity against H. pylori isolates, with atorvastatin exhibiting the highest potency. While the observed effects were lower than those of conventional antibiotics, these findings suggest the potential of statins as adjunctive agents or alternative therapeutic options, warranting further investigation through in vivo studies and clinical trials.

Background: Self-medication practice is the use of medicine without consulting health professionals to treat self-recognized illness by the general population including pregnant women. Inappropriate self-medication practice during pregnancy may pose harmful consequences for the fetus as well as the mother. There is not given much attention on the practice of self-medication among pregnant women in our setting. Therefore, this study aimed to assess the prevalence of self-medication practice and associated factors among pregnant women who attended antenatal care at North Shewa Zone public hospitals.

Methods: An institution-based cross-sectional study was conducted from June 01, 2022 to July 30, 2022, among 650 pregnant women who attended antenatal care at North Shewa Zone public hospitals. A multistage sampling technique was employed. The questionnaires were pretested. A structured interviewer-administered questionnaire and reviewed medical records were used for data collection. Epi-data version 4.6.2 and SPSS version 20 were utilized for data entry and analysis, respectively. Bivariate and multivariable logistic regression was done to identify associated factors, and P values less than 0.05 were considered statistically significant.

Results: The prevalence of self-medication practice among pregnant women was 65.38%. Housewives (AOR = 0.097 95% CI 0.030, 0.310), farmers (AOR = 0.117, 95% CI 0.028, 0.493), people with health insurance (AOR = 0.507, 95% CI 0.300, 0.858), and people in preconception care (AOR = 0.038, 95% CI 0.011-0.135) were less likely to practice self-medication, while people with primary education (AOR = 3.00, 95% CI 1.217, 7.435), income less than 3,000 birr (AOR = 5.46, 95% CI 1.41, 21.1), participants in the first (AOR = 4.183, 95% CI 2.12, 8.24) and second trimesters (AOR = 2.05, 95% CI 1.18, 3.56), pregnant women who lived in rural areas (AOR = 1.579, 95% CI 1.103-2.260), and people who previously practiced self-medication (AOR = 8.2, 95% CI 5.04, 13.3) were more likely to practice self-medication.

Conclusion: From the present finding, it can be concluded that self-medication among pregnant women is high. Previous self-medication practice, gestation period, educational status, monthly income, no preconception care, no health insurance, being a housewife, farmer, and place of residence were significantly associated with self-medication practice. Therefore, preventive measures such as proper counseling during dispensing, awareness creation programs on preconception care, and enrolling in health insurance programs to minimize the practice of self-medication are necessary.

This work aims to merge ethnopharmacological knowledge with biochemical analysis to enrich our understanding of the significance of the argan tree (Argania spinosa (L.) Skeels) and to valorize its crucial role in the province of Essaouira (Morocco). First, a survey was conducted using semistructured interviews with 325 informants from Essaouira province between February and April 2023. The interviews covered sociodemographic data and information on argan tree uses, whether for therapeutic, cosmetic, or food purposes (i.e., applications, parts used, preparation, and administration). Second, phenolic extracts were prepared from various parts of the argan tree (i.e., leaves, kernels, nut shells, press cake, and oil) and then assessed for their antioxidant potential to scientifically validate their traditional uses. The evaluation of antioxidant activity focused on their free radical scavenging and reducing capacities, using DPPH and FRAP assays. Findings confirmed the cultural significance of the argan tree for the local population, as well as their strong dependence on its products. Indeed, it was noted that argan-based products are widely favored in traditional cuisine, with a prevalence of 83.4%; Amlou is the most commonly consumed food. Therapeutic and cosmetic applications accounted for 48.6% and 28.0%, respectively, predominantly for treating skin and subcutaneous issues (69.5%) and diabetes (19.7%). Argan oil was the most cited argan product used, often consumed raw (97.5%), followed by almonds (22.8%). Cataplasm (26.1%) and maceration (24.6%) were preferred for argan derivative preparation. External application (50.1%) was the primary administration method, followed by oral consumption (38.1%) and massage (27.7%). For in vitro assays, the argan tree could prove to be a promising source of phenolic compounds, especially in the leaves (>4 times richer than other parts, 231.046 ± 5.090 mg GAE/g DW). DPPH and FRAP tests demonstrated notable antiradical potential and reducing power, concentration-dependent. Leaf-derived phenolic extracts exhibited the highest free radical scavenging potential (IC50 = 0.589 ± 0.005 mg/ml) and the best reducing capacity (IC50 = 0.420 ± 0.005 mg/ml), although these potencies remained below the standard used. This study represents valuable documentation that can serve to preserve information on the use of argan products while exploring their phytochemical and pharmacological properties.

The objective of the study was to evaluate the pharmacological properties of the methanolic extract of Flacourtia jangomas (Lour.) Raeusch fruits (PFJM) and seeds (SFJM), along with their soluble fractions in ethyl acetate (fruit: PFJE; seed: SFJE) and chloroform (fruit: PFJC; seed: SFJC). Our phytochemical analysis of the examined extracts confirmed the presence of various therapeutically active phytoconstituents, including flavonoids, tannins, glycosides, and alkaloids. Employing the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical quenching method, SFJC exhibited the highest antioxidative potential, with an IC₅₀ of 48.84, compared to ascorbic acid (IC₅₀ 21.77). The thrombolytic activity was assessed through rapid clot analysis of human blood samples, revealing that SFJC demonstrated the highest thrombolytic activity (60.99 ± 2.28%) compared to streptokinase (72.89 ± 2.19%). In the protein denaturation antiarthritic test, the PFJE and SFJC extracts exhibited significant potency, achieving results of 74.28 ± 1.16% and 79.25 ± 0.83%, respectively, at a dose of 500 μg/mL. All samples displayed notable anthelmintic activity by reducing Pheretima posthuma paralysis and death time in a dose-dependent manner compared to albendazole. In both in vivo analgesic tests, SFJC demonstrated substantial (p < 0.01) pain inhibition percentages (tail immersion: 49.46%; acetic acid writhing: 66.43%) at a dose of 600 mg/kg. During neuropharmacological screening, all extracts significantly (p < 0.01;  p < 0.05) and dose-dependently decreased the mice's locomotion activity and motor balance. In the thiopental-induced sedation assay, SFJC significantly decreased the sleep latency time (4.18 ± 0.24 min) and increased the duration of sleep time (85.20 ± 2.39 min) at a higher dose. All samples notably reduced blood glucose levels in the oral glucose tolerance test in a dose-responsive manner, and SFJC exhibited a considerable hypoglycemic impact (7.38 ± 0.44 mmoles/L at 600 mg/kg). The frequency of diarrheal episodes in mice during the antidiarrhea assessment was significantly decreased by the tested plant samples. These findings can serve as a reference for future endeavors to isolate pure bioactive compounds from this plant for the development of novel phytomedicines.

Allergic diseases (ADs) are a major concern when it comes to public well-being. Moringa oleifera Lam is a tropical plant that is used in traditional medicine due to the presence of isothiocyanate. The present study investigated the antiallergic properties of 4-(α-L-rhamnopyranosyloxy)-benzyl isothiocyanate or moringin isolated from Moringa oleifera seeds in the form of alpha-cyclodextrin-moringin (α-CD/MG) complex on rat basophilic leukaemia (RBL-2H3) cell line at both the early and late stages of an allergic reaction. The α-CD/MG complex was initially elucidated using nuclear magnetic resonance (NMR) followed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt proliferation assay to evaluate the cytotoxicity and cell viability with respect to ketotifen fumarate (KF) and α-CD/MG. The release of beta-hexosaminidase (β-hexosaminidase) and histamine was used to determine the level of inhibition in the early stage while the suppression of the release of prostaglandin (PGD2), tumour necrosis factor-alpha (TNF-α), and interleukin (IL-4) was considered in the late stage. Higher concentrations of α-CD/MG (5 μM, p < 0.001) in mast cell degranulation significantly inhibited the expression of β-hexosaminidase, histamine, TNF-α, PGD2, and IL-4 in both the early and late stages. Thus, α-CD/MG can potentially be developed as an antiallergic drug as it has the ability to inhibit allergic responses in the late and early stages.

Cyclophosphamide (Cy) is a prodrug that is mainly bioactivated by cytochrome P450 (CYP) 2B6 enzyme. Several other enzymes are also involved in its bioactivation and affect its kinetics. Previous studies have shown the effect of the enzymes' genetic polymorphisms on Cy kinetics and its clinical outcome. These results were controversial primarily because of the involvement of several interacting enzymes in the Cy metabolic pathway, which can also be affected by several clinical factors as well as other drug interactions. In this review article, we present the effect of CYP2B6 polymorphisms on Cy kinetics since it is the main bioactivating enzyme, as well as discussing all previously reported enzymes and clinical factors that can alter Cy efficacy. Additionally, we present explanations for key Cy side effects related to the nature and site of its bioactivation. Finally, we discuss the role of busulphan in conditioning regimens in the Cy metabolic pathway as a clinical example of drug-drug interactions involving several enzymes. By the end of this article, our aim is to have provided a comprehensive summary of Cy pharmacogenomics and the effect on its kinetics. The utility of these findings in the development of new strategies for Cy personalized patient dose adjustment will aid in the future optimization of patient specific Cy dosages and ultimately in improving clinical outcomes. In conclusion, CYP2B6 and several other enzyme polymorphisms can alter Cy kinetics and consequently the clinical outcomes. However, the precise quantification of Cy kinetics in any individual patient is complex as it is clearly under multifactorial genetic control. Additionally, other clinical factors such as the patient's age, diagnosis, concomitant medications, and clinical status should also be considered.