Advances in Pharmacological and Pharmaceutical Sciences最新文献

Background: Due to its resistance to common anti-TB drugs, multidrug-resistant tuberculosis (MDR-TB) presents substantial treatment problems. Optimizing therapeutic outcomes requires individualized treatment plans that take into account patient comorbidities, medication susceptibility profiles, and past treatment history. The significance of individualized medication in the treatment of MDR-TB is emphasized in this study.

Methods of review: Current research on tailored treatment plans for MDR-TB is summarized in this review. It highlights how pharmacogenomics, medication sensitivity testing, and patient-centered care can be used to customize treatment plans. The utilization of combination therapies, monitoring and adaptation techniques, and novel treatment options-such as adjuvant therapy and newer agents-are also covered in the review.

Findings: Important findings show that thorough medication susceptibility testing is essential for directing wise treatment decisions. Dosage modifications based on individual metabolic responses can be informed by pharmacogenomic data. Treatment regimen adherence is improved when patients participate in decision-making. Combination therapy involving new drugs has demonstrated potential for increasing therapeutic effectiveness while reducing the emergence of resistance. Frequent monitoring makes it possible to promptly modify therapy in response to the patient response.

Conclusions: Treatment for MDR-TB must be individualized and comprehensive due to its complexity. For individuals with MDR-TB, therapy outcomes can be greatly enhanced while lowering the risk of further resistance by combining host-directed therapies, pharmacological breakthroughs, and continuous patient monitoring. Enhancing customized care solutions in this difficult field of infectious illness management requires ongoing research and innovation.

Background: Leishmaniasis is a neglected tropical disease affecting 12 million people and risks the lives of 350 million people globally. However, it has limited therapeutic options. Clematis simensis Fresen roots are used for the treatment of leishmaniasis in Ethiopian traditional medicine.

Objective: The aim of this study was to evaluate C. simensis Fresen roots' antileishmanial activities and cytotoxic effects.

Methods: In vitro antileishmanial activity of crude extract of C. simensis root and its solvent fractions was evaluated against axenic amastigotes and promastigotes of Leishmania aethiopica and Leishmania donovani. Their cytotoxicity against macrophage cells and red blood cells (RBCs) was evaluated. Median cytotoxic concentration (CC₅₀) and median inhibitory concentration (IC₅₀) were calculated using computer software GraphPad Prism 9.5.0. Data were expressed as mean ± standard error of the mean.

Result: The crude extract and its hexane, chloroform, and aqueous fractions exhibited antileishmanial activities, with IC₅₀ values ranging from 4.43 ± 0.69 to 24.94 ± 4.12 μg/mL against promastigotes and 4.52 ± 1.25 to 34.97 ± 1.77 μg/mL against axenic amastigotes of Leishmania parasites. The cytotoxic effects (CC₅₀) of the extracts were 63.62 ± 4.06 ≤ CC50 ≤ 246.05 ± 32.84 μg/mL against macrophages, but > 1200 μg/mL against RBC. A selectivity index value greater than 1 indicates selective toxicity against Leishmania parasites, whereas a value less than 1 suggests selective toxicity against mammalian cells. In this study, the selectivity indices for the plant extracts ranged from 3.26 to 54.44.

Conclusion: The roots of the plant showed a promising antileishmanial activity that may provide a scientific justification for its use in traditional medicine. Further isolation, identification of active compounds, and establishment of the mechanism of action are warranted.

[This retracts the article DOI: 10.1155/2023/7680518.].

Neurodegenerative diseases (NDs) represent an increasingly important burden of disease, particularly in the aging population. The etiology of NDs like Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) is associated with progressive neuronal degeneration and a paucity of effective therapies. Accumulating evidence suggests that common and intersecting genetic and pathological pathways play a critical role in disease onset and progression, revealing new opportunities for target discovery. Here, we review promising therapeutic targets based on the convergence of genetics, molecular pathology, and cellular signaling in neurodegeneration. This narrative will focus on key proteins (amyloid-beta [Aβ], tau, and α-synuclein) and enzymes (acetylcholinesterase and asparagine endopeptidase [AEP]), including their pathological significance and therapeutic implications. N-Methyl-D-aspartate receptors (NMDARs) and cholinergic receptor subtypes are highlighted as important regulators of neurotoxicity, synaptic transmission, and inflammation. Emerging advances in genomics, neuroimaging, and drug delivery are poised to advance precision medicine strategies for early diagnosis and intervention. Important challenges remain, including the complexity of the blood-brain barrier (BBB), pathology heterogeneity, and the need for new biomarkers. We propose that a shift from phenotype-driven diagnoses to mechanistic, genetically informed approaches may improve treatment efficacy. Target identification, validation, and targeted delivery are critical considerations for the success of future therapeutic development. This integrated view will help to inform and improve drug discovery and personalized medicine approaches in the field of neurodegeneration.

Introduction: Improving treatment standards by auditing care quality using WHO and INRUD drug-use indicators is essential in low- and middle-income countries. This study aims to assess prescription practices at KCRH General Outpatient Clinics and identify risk factors for polypharmacy.

Methods: This retrospective descriptive cross-sectional study analyzed prescriptions dispensed in 2022 at the KCRH outpatient pharmacy. Using a stratified random sampling, prescriptions were reviewed using a WHO/INRUD-based data abstraction form. Core drug-use indicators were determined, and logistic regression analyses were performed using STATA Version 14.

Results: Of the 920 prescriptions, 69.2% were for adults and 57.0% for females. Analgesics (32.3%) and antibiotics (29.0%) were most frequently prescribed. Overall, 84.1% of the prescriptions contained antibiotics, 8.7% injectables, 97.6% generics, and 95.6% were from the KEML. The mean number of drugs per prescription was 2.7. Antibiotic prescribing was associated with lower odds of polypharmacy (aOR: 0.18; 95% CI: 0.10-0.42).

Conclusion: Interventions to promote rational antibiotic use are necessary, including educating healthcare providers and patients about the risks of antibiotic overuse.

Traditional Thai herbal medicine has been used for centuries to treat various diseases, including cancer. One notable formulation, Santakatpuakaln (STK), has been employed to manage cancers, particularly of the gastrointestinal (GI) tract, such as liver and colorectal cancers (CRCs). Despite its historical use, scientific validation of its efficacy and safety remains vastly limited. In this study, we prepared an ethanol extract of STK and evaluated its anticancer properties in vitro. STK demonstrated significant cytotoxic activity against CRC cell lines (HCT15, NCI-H508, HT29, and HCT116) and the liver cancer cell line HepG2 while sparing noncancerous colonic epithelial cells (FHC), suggesting a potential therapeutic window. The cytotoxic activity of STK was accompanied by apoptosis. Additionally, STK inhibited tumor spheroid growth and suppressed HCT116 cell migration in transwell assays, indicating both cytotoxic and antimigratory effects. These findings support the traditional use of STK in cancer management and warrant further investigation into its active compounds, mechanisms of action, and therapeutic potential.

Drug repurposing, the process of identifying new therapeutic uses for existing drugs, has emerged as a cost-effective and time-saving alternative to traditional drug development. This strategy leverages the known pharmacological and safety profiles of approved or investigational drugs to accelerate their clinical application for other diseases. In recent years, repurposed drugs have played a crucial role in addressing treatment gaps in complex and multifactorial diseases such as cancer, neurodegenerative disorders and infectious diseases. This review highlights prominent examples where repurposed drugs have successfully transitioned from laboratory findings to clinical application. We discuss key molecular mechanisms, including polypharmacology and target pathway modulation that enable repositioning. Emphasis is also placed on advances in computational approaches, network pharmacology and data-driven tools that enhance repurposing efforts. Additionally, we outline the challenges related to regulatory hurdles, intellectual property and clinical validation. By analysing these success stories, we aim to provide a strategic framework to guide future drug repurposing initiatives.

Buspirone hydrochloride, an anxiolytic agent, has two interconvertible polymorphic forms that may affect its physicochemical properties and therapeutic efficacy. Despite this relevance, polymorphism is often neglected in pharmaceutical analyses, potentially leading to inconsistent results and compromised drug performance. This study investigates the polymorphism, stability, solubility, and flow properties of commercial samples of buspirone hydrochloride, focusing on how polymorphic transformations affect pharmaceutical performance. Samples from two international suppliers were stored under controlled and stress conditions (humidity and temperature) in open and closed vials. Structural characterization used Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction, while flow and density properties were determined by Carr index and Hausner ratio. Solubility of pure polymorphic Forms 1 and 2 was evaluated in physiologically relevant pH media using high-performance liquid chromatography. The Indian sample contained a mixture of Forms 1 and 2, whereas the Finnish sample consisted exclusively of Form 2. Under stress, Form 2 converted to Form 1, completely in open vials and partially in closed ones, confirming the greater thermodynamic stability of Form 1. Among the analytical methods, differential scanning calorimetry proved to be the most effective in distinguishing polymorphic forms and identifying mixtures. Both forms showed pH-dependent solubility, with peak dissolution at pH 1.2, and very poor flow properties, requiring formulation adjustments. Solubility data supported a preliminary classification of both polymorphs as Biopharmaceutics Classification System Class I or Class III, although permeability differences remain unexplored. These findings advance the understanding of buspirone hydrochloride's polymorphic properties, supporting the development of more effective formulations.

Cephalosporin is one of the antibiotics that are widely used because of its broad spectrum and high effectiveness. The aim of the present research was to formulate and evaluate the antimicrobial effect of meclizine (ME) alone and in combination with cefixime (CFM) and cefuroxime (CXM). Evaluation of antibacterial activities was determined by using Klebsiella (sensitive and ESBL), Escherichia coli, Staphylococcus aureus (sensitive and MRSA), and Pseudomonas aeruginosa. The molecular docking was conducted for ME and CFM with the crystal structure of beta-ketoacyl-acp synthase III + malonyl/CoA. The results show that ME has the highest minimum inhibitory concentrations (MICs) activity against sensitive Klebsiella spp., followed by sensitive S. aureus. The combination of ME and CXM demonstrated a synergistic activity against both sensitive and resistant S. aureus and sensitive Klebsiella with an interpretation of minimum bactericidal concentration (MBC) of < 0.06, 0.1875, and 0.33, respectively. Meanwhile, partial synergism activity is observed against E. coli, and indifference activity against P. aeruginosa and Klebsiella ESBL with an interpretation FBC of 0.75, 1.2, and 1.25, respectively. The ME and CFM combination showed partial synergism activity against sensitive Klebsiella, E. coli, and P. aeruginosa with an interpretation FBC of 0.625, 0.75, and 0.75, respectively. While indifference activity was recorded against both sensitive and MRSA S. aureus and Klebsiella ESBL with interpretation FBC of 4, 1.25, and 1.5, respectively. The ME and CXM combination showed the highest activity against Gram-positive bacteria and sensitive Klebsiella, while the ME and CFM combination showed the highest activity against Gram-negative bacteria. This combination may consider be a promising formula as an antimicrobial drug.

Pollution from plastic waste has become an urgent issue, requiring solutions to prevent and mitigate diseases caused by plastic waste, particularly those involving nanoplastics (NP). This study specifically focused on investigating the exogenous antioxidant activity of three plant extracts: Mangifera foetida bark (MFB), Mangifera foetida leaves (MFL), and Cinnamomum burmanii leaves (CBL), to enhance the body's defense system and reduce the risk of Type II diabetes. Twenty-five rats (Rattus norvegicus) were randomly assigned to five groups: normal control, negative control, and three treatments that received different plant extracts (200 mg/kg of MFB, MFL, and CBL, respectively) after being exposed to 10 μL/kg NP for 30 days. According to confocal microscopy analysis, NPs were observed entering cells and localizing in the nucleolus more than in the cytoplasmic hepatocyte. This study found that the administration of the plant extract could reduce the level of the proapoptotic enzyme not through the intrinsic pathway but via the extrinsic pathway. Administration of MFB, MFL, and CBL could reduce Caspase-3 significantly (1.07 ± 0.05, 1.03 ± 0.08, 1.05 ± 0.10 ng/L, respectively). This effect is mediated by the upregulation of genes related to glycolipid metabolism, including AKT2, GLUT2, PI3K, FAS, PEPCK, and PK. Administration of MFL significantly upregulated the expression levels of AK2, GLUT2, PI3K, and PK genes compared to the negative control. Administration of CBL extract enhanced the percentage of normal hepatocytes and the diameter of the central vein and decreased the percentage of necrosis, swelling, and the number of Kupffer cells. All treatment groups showed a slight decrease in the level of SGOT and SGPT. Thus, plant extracts could be effective materials exhibiting exogenous antioxidant activity against NP, directly inhibiting proapoptotic signals and regulating glycolipid metabolism. These extracts could be further developed as a preventive or therapeutic strategy to address NP exposure in environmental and clinical settings.