Advances in Pharmacological and Pharmaceutical Sciences最新文献

Drug resistance remains a significant problem that threatens antimalarial drug treatment. Hence, the challenge is to find new effective antimalarial drugs. Based on our previous study, aqueous extracts of trisamo (TSM) and jatu-phala-tiga (JPT) had good in vitro antimalarial activities, and these recipes contain multiple beneficial pharmacological effects that could be useful for malaria therapy. Therefore, this study aimed to investigate the antimalarial activity and toxicity of the aqueous extracts of TSM and JPT in mouse models. The aqueous extractions were carried out using the decoction method. Compound identification was conducted using LC-QTOF-MS analysis. The antimalarial activities of TSM and JPT at doses 200, 400, and 600 mg/kg were evaluated against Plasmodium berghei ANKA infection using a four-day suppressive test. The toxic effects of oral administration of the extracts at 2 g/kg dose were determined using an acute toxicity test. The chemical constituents of TSM contained 83 compounds, whereas JPT contained 84 compounds. All doses of the extracts exhibited a significant suppression (p < 0.05) of the parasite compared to the negative control in a four-day test. The maximum activities were observed at 600 mg/kg dose with 67.02% suppression for TSM and 79.34% for JPT, followed by 400 mg/kg dose (57.63% for TSM and 64.79% for JPT) and then 200 mg/kg dose (52.35% for TSM and 54.46% for JPT). In addition, there were no significant differences (p < 0.05) in the RBC, MCV, and MCH levels of mice receiving JPT extract compared to the uninfected control. The WBC level of mice receiving 400 and 600 mg/kg of TSM, and 200 and 400 mg/kg of JPT, was significantly (p < 0.05) lower than the infected control, and the extracts did not significantly prevent the loss of platelets. For the acute toxicity test, there were no signs of toxicity or deaths in mice, and there were no differences in the histology, weight, or enzyme biochemistry of the liver and kidney between the extract and vehicle groups. However, the platelet count in the extract-treated mice was significantly higher than that in the control group. In conclusion, this study suggests that aqueous extracts of TSM and JPT have potent antimalarial activities and could be promising as new candidates for antimalarial drug development.

Cancer is one of the leading causes of death worldwide. First-line treatments usually include surgery, radiotherapy, and/or systemic therapy. These methods can be associated with serious adverse events and can be toxic to healthy cells. Despite the new advances in cancer therapies, there is still a continuous need for safe and effective therapeutic agents. Cysteamine is an aminothiol endogenously synthetized by human cells during the degradation of coenzyme-A. It has been safely used in humans for the treatment of several pathologies including cystinosis and neurodegenerative diseases. Cysteamine has been shown to be a potent antimutagenic, anticarcinogenic, and antimelanoma in various in vitro and in vivo studies, but a review on these aspects of cysteamine's use in medicine is lacking in the current literature. The efficacy of cysteamine has been shown in vitro and in vivo for the treatment of different types of cancer, such as gastrointestinal cancer, pancreatic cancer, sarcomas, hepatocellular carcinoma, and melanoma, leading to the significant reduction of lesions and/or the increase of survival time. Although the mechanisms of action are not fully understood, possible explanations are (i) free radical scavenging, (ii) alteration of the tumor cell proliferation by affecting nucleic acid and protein synthesis or inhibition of DNA synthesis, and (iii) hormone regulation. In conclusion, regarding the high safety profile of cysteamine and the current literature data presented in this article, cysteamine might be considered as an interesting molecule for the prevention and the treatment of cancer. Further clinical studies should be performed to support these data in humans.

Increasing evidence highlights that excessive iron accumulation in the brain plays a vital role in neuronal senescence and is implicated in the pathogenesis of age-related neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Therefore, the chemical compounds that eliminate an iron overload may provide better protection against oxidative stress conditions that cause the accumulation of senescent cells during brain aging. Ebselen has been identified as a strongly useful compound in the research on redox biology mechanisms. We hypothesized that ebselen could alleviate an iron overload-induced oxidative stress and consequently reverses the senescence-like phenotypes in the neuronal cells. In the present study, SH-SY5Y cells were treated with ferric ammonium citrate (FAC) before ebselen, and the evaluation of the cellular iron homeostasis, the indicators of oxidative stress, and the onset of senescence phenotypes and mechanisms were carried out accordingly. Our findings showed that ebselen ameliorated the FAC-mediated iron overload by decreasing the expression of divalent metal transporter 1 (DMT1) and ferritin light chain (FT-L) proteins. In contrast, it increased the expression of ferroportin 1 (FPN1) protein and its correlation led to a decrease in the expression of the cytosolic labile iron pool (LIP). Furthermore, ebselen significantly reduced reactive oxygen species (ROS) and rescued the mitochondrial membrane potential (ΔΨm). Notably, ebselen restored the biomarkers of cellular senescence by reducing the number of senescence-associated β-galactosidase (SA-β-gal) positive cells and senescence-associated secretory phenotypes (SASP). This also suppressed the expression of p53 protein targeting DNA damage response (DDR)/p21 cyclin-dependent kinase (CDK) inhibitor through a mTORC1 signaling pathway. Potentially, ebselen could be a therapeutic agent for treating brain aging and AD by mitigating iron accumulation and restoring senescence in SH-SY5Y cells.

For centuries, communities have used medicinal plants to treat various diseases, such as Sansevieria trifasciata (Asparagaceae), for wound healing. However, a study on the wound-healing activity of this plant has not been conducted. Therefore, this study aimed to evaluate the hydrogel formulations of S. trifasciata extract (HESt) and its activity in wound healing. The HESt formulations were subjected to physical examination, pH measurement, spreading coefficient, rheological study, stability test, and wound-healing activity. Furthermore, the HPMC and carbopol 940 gel-forming agents were used to obtain this formulation. In the incision wound model, the experiment was divided into 5 groups, each consisting of 4 mice. Groups 1 and 2 served as a negative and positive control (octenidine gel), while 3, 4, and 5 were given HESt formulations of 15%, 20%, and 25% (w/w), respectively, for 15 days. Based on the wound healing activity test, HESt 20% and 25% (w/w) groups showed significant (p < 0.05) wound closure area on day 4 and from day 2 to 16. However, the HESt 15% (w/w) group showed no significant difference in wound-healing activity but had a higher closure than the negative control. Based on the evaluation of the hydrogel, all HESt formulations were reported to have fulfilled the standard requirements. The HESt formulations were also reported to be stable at various temperatures in the stability test. Therefore, S. trifasciata leaves extract has the potential to be developed as a wound-healing drug derived from herbal plants formulated into hydrogel preparations.

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.