Advances in Pharmacological and Pharmaceutical Sciences最新文献

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.

Ginseng has a long history of drug application in China, which can treat various diseases and achieve significant efficacy. Ginsenosides have always been deemed important ingredients for pharmacological activities. Based on the structural characteristics of steroidal saponins, ginsenosides are mainly divided into protopanaxadiol-type saponins (PDS, mainly including Rb1, Rb2, Rd, Rc, Rh2, CK, and PPD) and protopanaxatriol-type saponins (PTS, mainly including Re, R1, Rg1, Rh1, Rf, and PPT). The structure differences between PDS and PTS result in the differences of pharmacological activities. This paper provides an overview of PDS and PTS, mainly focusing on their chemical profile, pharmacokinetics, hydrolytic metabolism, and pharmacological activities including antioxidant, antifatigue, antiaging, immunodulation, antitumor, cardiovascular protection, neuroprotection, and antidiabetes. It is intended to contribute to an in-depth study of the relationship between PDS and PTS.

Nutritional supplements are gaining traction for their effects in mitigating the impacts of various health conditions. In particular, many supplements are being proposed to reduce the impacts of type 2 diabetes (T2D), a metabolic condition that has reached global epidemic proportions. Recently, a supplement of oleic acid (OA) and succinic acid (SA; 1 : 1, w/w) was reported to improve glycaemic control in type 2 diabetic (T2D) Sprague-Dawley (S-D) rats through ameliorating insulin release and sensitivity. Here, we investigate the effects of the supplement (OA and SA) on hepatic and pancreatic function in T2D S-D rats. Eighteen (18) S-D rats were rendered diabetic and were divided into three equal groups: diabetic control, diabetic treatment, and diabetic glibenclamide. Another 12 S-D rats were obtained and served as the normal groups. The animals were treated daily with the vehicle, OA and SA (800 mg/kg body weight (bw); 1 : 1), or glibenclamide (10 mg/kg bw) which served as the positive control. The findings indicated that treatment with the supplement resulted in a 35.69 ± 4.22% reduction (p=0.006) in blood glucose levels (BGL). Analysis of hepatic enzymes depicted that the nutritional supplement reduced the activity of the gluconeogenesis enzyme, glucose-6-phosphatase (G6P) while improved the activity of catabolic enzymes such as glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK). Furthermore, the supplement attenuated oxidative stress through restoration of catalase (CAT) and superoxide dismutase (SOD), while reducing malondialdehyde (MDA) levels. Finally, the supplement showed no liver or kidney toxicity and improved the size and number of pancreatic islets of Langerhans, indicating its potential application in treating T2D. The study highlighted that a supplement of the two organic acids may be beneficial in reducing the rate of pathogenesis of type 2 diabetes. Therefore, it may offer therapeutic value as a dietary or nutritional supplement in the approach against diabetes and its complications.

Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely, rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research starts by clarifying the structural effects of certain mutations, such as the insertion of an aspartate residue at position 345 (Asp-345a), in the PBP2. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely, P551S and F504L, have a significant impact on the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasising rutin's exceptional binding affinity and its potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments, namely, in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for the creation of potent inhibitors and medicinal therapies to combat infectious illnesses.

Sonophoresis is the most approachable mode of transdermal drug delivery system, wherein low-frequency sonophoresis penetrates the drug molecules into the skin. It is an alternative method for an oral system of drug delivery and hypodermal injections. The cavitation effect is thought to be the main mechanism used in sonophoresis. The cavitation process involves forming a gaseous bubble and its rupture, induced in the coupled medium. Other mechanisms used are thermal effects, convectional effects, and mechanical effects. It mainly applies to transporting hydrophilic drugs, macromolecules, gene delivery, and vaccine delivery. It is also used in carrier-mediated delivery in the form of micelles, liposomes, and dendrimers. Some synergistic effects of sonophoresis, along with some permeation enhancers, such as chemical enhancers, iontophoresis, electroporation, and microneedles, increased the effectiveness of drug penetration. Sonophoresis-mediated ocular drug delivery, nail drug delivery, gene delivery to the brain, sports medicine, and sonothrombolysis are also widely used. In conclusion, while sonophoresis offers promising applications in diverse fields, further research is essential to comprehensively elucidate the biophysical mechanisms governing ultrasound-tissue interactions. Addressing these gaps in understanding will enable the refinement and optimization of sonophoresis-based therapeutic strategies for enhanced clinical efficacy.