Advances in Pharmacological and Pharmaceutical Sciences最新文献

This study aims to identify the volatile profile of three essential oils obtained from Eucalyptus polybractea cryptonifera (EPEO), Ormenis mixta (OMEO), and Lavandula burnatii briquet (LBEO) and to examine their combined antibacterial activity that affords the optimal inhibitory ability against S. aureus and E. coli using simplex-centroid mixture design and checkerboard assay. Essential oils (EOs) were isolated by hydrodistillation and characterized using gas chromatography-mass spectrometry (GC-MS) and gas chromatography coupled with flame-ionization detector (GC-FID). The antibacterial activity was performed using disc diffusion and microdilution assays. The chemical analysis revealed that 1,8-cineole (23.75%), p-cymene (22.47%), and α-pinene (11.20%) and p-menthane-1,8-diol (18.19%), α-pinene (10.81%), and D-germacrene (9.17%) were the main components detected in E. polybractea and O. mixta EOs, respectively. However, L. burnatii EO was mainly represented by linalool (24.40%) and linalyl acetate (18.68%). The EPEO, LBEO, and OMEO had a strong antibacterial effect on S. aureus with minimal inhibitory concentrations (MICs) values ranging from 0.25 to 0.5% (v/v). Furthermore, the combination of 1/2048 MIC_EPEO + 1/4 MIC_LBEO showed a synergistic antibacterial effect on S. aureus with a FIC index of 0.25, while the formulation of 1/4 MIC_EPEO + 1/4 MIC_OMEO demonstrated an antibacterial synergistic activity on E. coli with a FIC index of 0.5. Moreover, the simplex-centroid mixture design reported that the most effective combinations on E. coli and S. aureus correspond to 32%/28%/40% and 35%/30%/35% of E. polybractea, O. mixta, and L. burnatii, respectively. Presented information highlights the action of antibacterial formulations of these EOs and suggests their potential applications as alternatives to commercialized drugs to contract the development of bacteria causing serious infections and food deterioration.

Purpose: This study assessed the awareness, actions, and predictors of actions on adverse drug reaction reporting among patients attending a referral hospital in southern highland Tanzania.

Methods: A hospital-based cross-sectional study was conducted from January to August 2022 at Mbeya Zonal Referral Hospital (MZRH) in Mbeya, Tanzania. A total of 792 adult patients with chronic conditions attending outpatient clinics at MZRH were recruited consecutively. A semistructured questionnaire was used to collect demographic characteristics, ADR awareness, and actions when encountering ADR. Data were analyzed using the statistical package for social sciences (SPSS) version 23 and results are summarized using frequency and percentages. Binary logistic regression was used to assess the predictors associated with reporting ADR among patients. P value ≤0.05 was considered statistically significant.

Results: Out of 792, 397 (50.1%) were males and 383 (48.6%) had a primary education level. Only 171 (21.6%) participants previously experienced ADR, and 111 (14.1%) were aware that ADR is an unexpected harm that occurs after medication use. The majority 597 (70.3%) of the participants said will report ADR to healthcare providers, 706 (88.9%) prefer reporting ADR to healthcare providers, and 558 (69.1%) said patients are not aware of the importance of reporting ADR. Patients aged below 65 years of age, unemployed ((AOR (95% CI) = 0.4 (0.18-0.87), self-employed ((AOR (95% CI) = 0.5 (0.32-0.83)), and those who ever encountered ADR ((AOR (95% CI) = 0.1 (0.05-0.11)) were more likely to report the ADR to HCPs compared to the rest.

Conclusions: The majority of patients are not aware of what is ADR and the importance of ADR reporting. Most of the patients prefer to report ADR to healthcare providers. We recommend an awareness campaign to raise awareness of the patients on ADR and other methods of ADR reporting.

Pharmacotherapy, in many cases, is practiced at a suboptimal level of performance in low- and middle-income countries (LMICs) although stupendous amounts of data are available regularly. The process of drug development is time-consuming, costly, and is also associated with loads of hurdles related to the safety concerns of the compounds. This review was conducted with the objective to emphasize the role of pharmacometrics in pharmacotherapy and the drug development process in LMICs for rational drug therapy. Pharmacometrics is widely applied for the rational clinical pharmacokinetic (PK) practice through the population pharmacokinetic (popPK) modeling and physiologically based pharmacokinetic (PBPK) modeling approach. The scope of pharmacometrics practice is getting wider day by day with the untiring efforts of pharmacometricians. The basis for pharmacometrics analysis is the computer-based modeling and simulation of pharmacokinetics/pharmacodynamics (PK/PD) data supplemented by characterization of important aspects of drug safety and efficacy. Pharmacometrics can be considered an invaluable tool not only for new drug development with maximum safety and efficacy but also for dose optimization in clinical settings. Due to the convenience of using sparse and routine patient data, a significant advantage exists in this regard for LMICs which would otherwise lag behind in clinical trials.

Aims: To evaluate the prevalence and type of adverse drug reactions (ADRs), together with associated risk factors, among Cuban COVID-19 patients treated with chloroquine (CQ), lopinavir/ritonavir (LPV/r), or interferon α2b (IFN α2b), according to the Cuban protocol.

Materials and methods: A prospective descriptive analysis of ADRs was performed on 200 COVID-19 patients who were admitted consecutively to three hospitals in Havana and Pinar del Río from April to July 2020. Information on demographics, ADRs, outcomes, behavioral, and health-related factors was collected using a validated questionnaire and clinical records. Each potential ADR case was assessed for causality based on the WHO-UMC algorithm, concomitant drug influences, and the presence of any drug-drug interactions (DDI).

Results: The total frequency of ADRs was 55%, with predominantly gastrointestinal disorders and general symptoms (23% vs 20%). 95.1% of ADRs occurred within 10 days after treatment and 42 potential DDI in 55.5% of patients (61/110) were observed. The prevalence of ADRs was: 44%, 30.4%, and 26.4% for IFN α2b, LPV/r, and CQ, respectively. Sex (odds ratio (OR): 0.40 (95% confidence interval (CI): 0.211-0.742), age (OR: 2.36 (95% CI: 1.02-5.44)), and underlying diseases (OR: 0.12 (95% CI: 0.06-0.23)) were independently associated factors for ADRs (P < 0.05).

Conclusions: The frequency of ADRs and potential DDI was high compared to their use during nonpandemic times (e.g., for malaria, HIV, or inflammatory diseases). The safety profile of these drugs when used for COVID-19 treatment showed similar characteristics. Comorbidities, age >37 years old, and female sex were associated with ADRs.

Calendula arvensis L. (Asteraceae) is a famous ornamental and medicinal plant widely distributed in Mediterranean countries and the southern region of Europe. This reputed species is widely used in traditional medicine in the treatment of many disorders and has various bioactivities, especially anti-inflammatory, antiviral, antimutagenic, antimicrobial, insecticidal, antioxidant, and immunomodulatory activities. The present review was conducted to provide a critical review of the comprehensive and current knowledge regarding C. arvensis species, in particular, its taxonomy and geographical distribution, botanical description, medicinal uses, phytochemical compounds, pharmacological properties, and toxicity investigations. The data collected on C. arvensis were obtained using different scientific research databases such as PubMed, SciFinder, SpringerLink, Web of Science, Science Direct, Google Scholar, Wiley Online, and Scopus. Phytochemical screening of different C. arvensis extracts and essential oils showed their richness in bioactive compounds, particularly in fatty acids, sterols, phenolics, flavonoids, saponins, tannins, alkaloids, and terpenoid compounds. The findings of this review showed that the pharmacological activities of C. arvensis confirm its importance and diversity as a traditional remedy for many diseases. This plant presents a wide range of bioactivities, namely, anti-inflammatory, antimicrobial, antitrypanosomial, antitumoral, antimutagenic, and immunomodulatory activities, as well as hemolytic properties and wound treatment. Nevertheless, pharmacokinetic validation and toxicological examinations are required to detect any possible toxicity for future clinical trials.

Medicinal plants are traditionally used in Gabon to treat several types of illnesses. The study's purpose was to determine the toxic, antibacterial, and anti-inflammatory effects of Antrocaryon klaineanum Pierre extracts and to characterize their phytochemical compounds. Toxicity was evaluated on frog tadpoles (Phrynobatrachus africanus Hallowell). The microorganism susceptibility test was performed by the diffusion method, while minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated using the microdilution technique. Anti-inflammatory activity was tested through protein denaturation and membrane stabilization methods. Chromatography and molecular network techniques were used to characterize chemical compounds. The lethality test showed that the lethal concentration (LC₅₀) increased from 110.03 ± 1.25 to 15.86 ± 2.21 μg/mL after 24 and 96 hours of exposure. In tadpoles exposed to 7.81 μg/mL extract, the first mortalities (12.5%) were observed on the fifth day of exposure. A relative decrease in mature erythrocytes exposed to plant extracts was observed. The antibacterial activity shows that the Ak F₂, Ak F₃, and Ak F₄ fractions (from the water-ethanol crude extract) gave the greatest antibacterial activities compared to the other extracts. The water, water-acetone, and water-ethanol extracts showed good inhibition of denaturation. The haemolysis test shows that the extracts exhibited good anti-inflammatory activities. Phytochemical characterisation revealed four major compounds, including monogallate epicatechin and hydroxy-ergostadian. The molecular network revealed five main clusters. Our study shows that A. klaineanum Pierre could be a promising natural product for the isolation of molecules with potential biological activities.

Background: Recently, there is a lack of studies comparing the renoprotective effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. This study therefore aimed to investigate the renoprotective effects of SGLT-2 inhibitors and DPP-4 inhibitors on Thai patients with type 2 diabetes mellitus.

Methods: Patient medication records of all patients who used those two antidiabetic classes at Fort Wachirawut Hospital were reviewed. Renal function tests, blood glucose levels, and other baseline characteristics were collected. Continuous variables were compared within the group using the Wilcoxon signed-rank test and between groups using the Mann-Whitney U test.

Results: There were 388 and 691 patients with SGLT-2 inhibitors and DPP-4 inhibitors, respectively. The mean estimated glomerular filtration rate (eGFR) of the SGLT-2 inhibitor group was significantly lower from baseline at 18 months of treatment, as well as the DPP-4 inhibitor group. However, the trend of eGFR reduction in patients with baseline eGFR <60 mL/min/1.73 m² was smaller than those with baseline eGFR ≥60 mL/min/1.73 m². In addition, the fasting blood sugar and haemoglobin A1c levels significantly decreased from baseline in both the groups.

Conclusions: Both SGLT-2 inhibitors and DPP-4 inhibitors showed the same trends of eGFR reductions from baseline in Thai patients with type 2 diabetes mellitus. However, SGLT-2 inhibitors should be considered in patients with impaired renal function rather than in all T2DM patients.

Metformin (MET) and rapamycin (RAPA) have been reported to protect against neurodegeneration in cellular and animal models of Parkinson's disease (PD). MET, which is a first-line drug for type 2 diabetes, and RAPA are known as mTORC1 inhibitors. MET also acts as an AMPK activator, which leads to the inhibition of mTORC1 activity. mTORC1 is a downstream target of Akt signaling. Inactivation of Akt/mTORC1 and its downstream S6K1 can promote autophagy, a process involved in PD pathogenesis. Based on their mechanisms and potential benefits, we evaluated the potential protective effect of pretreatment with combinations of MET and RAPA in a 1-methyl-4-phenylpyridinium ion (MPP⁺)-treated SH-SY5Y neuronal cell model of PD. The results showed that MET and RAPA combinations lowered cell viability after exposure to MPP⁺. Increased LC3-II levels by MPP⁺ were not altered by MET and RAPA pretreatment. In normal neuronal cells, MET and RAPA pretreatment inhibited the phosphorylation of both Akt and S6K1, and the phosphorylation remained suppressed after MPP⁺ exposure. These findings suggest that when cells were exposed to MPP⁺, suppressed phosphorylation of both Akt and S6K1 by the MET and RAPA combination may lead to an inappropriate autophagic response, resulting in increased cell death.

This paper investigates the interaction within a liposome-based drug delivery system in silico. Results confirmed that phospholipids, cholesterol, beta-carotene, and vitamin C in the liposome structures interact noncovalently. The formation of noncovalent interactions indicates that the liposomal structures from phospholipid molecules will not result in chemical changes to the drug or any molecules encapsulated within. Noncovalent interactions formed include (i) moderate-strength hydrogen bonds with interaction energies ranging from -73.6434 kJ·mol^-1 to -45.6734 kJ·mol^-1 and bond lengths ranging from 1.731 Å to 1.827 Å and (ii) van der Waals interactions (induced dipole-induced dipole and induced dipole-dipole interactions) with interaction energies ranging from -4.4735 kJ·mol^-1 to -1.5840 kJ·mol^-1 and bond lengths ranging from 3.192 Å to 3.742 Å. The studies for several phospholipids with short hydrocarbon chains show that changes in chain length have almost no effect on interaction energy, bond length, and partial atomic charge.