Current Pharmaceutical Design - Volume 29, Issue 27, 2023

With a prevalence rate of 6.6 per 100,000 women, ovarian cancer is the third most lethal gynecological tumor in the world. Several factors like family history, nulliparity, late menopause, genetic mutation, and an unhealthy lifestyle contribute to increasing the risk of ovarian cancer development. Novel research studies suggest that ovarian cancer may be caused by changes in the lipid metabolic profile that trigger inflammatory responses. Moreover, ovarian cancer patients will eventually experience chemoresistance. Statin, a competitive inhibitor of HMG-CoA reductase that is a lipid-lowering drug with pleiotropic effects, seems to be the best choice to deal with this therapeutic issue. The aim of this review is to highlight the pharmacotherapeutic potential of statins, especially the repurposing of statin drugs for antitumor mechanisms. This review will also provide a brief summary of the meta-analysis, and case-control observational studies carried out to examine the impact of statins on risk reduction and survival in ovarian cancer patients. Furthermore, this review will discuss the nanotechnological approach for improving the drug's bioavailability and safe and targeted delivery with controlled release of active ingredients, making statins more effective in preventing and treating ovarian cancer.

Currently, and globally, we are facing the worst epidemic of psychoactive drug abuse resulting in the loss of hundreds of thousands of lives annually. Besides alcohol and opioid use and misuse, there has been an increase in illicit abuse of psychostimulants. Epigenetics is a relatively novel area of research that studies heritable alterations in gene expression. Long-term administration of psychoactive drugs may lead to transcriptional changes in brain regions related to drug-seeking behaviors and rewards that can be passed down transgenerationally. Epigenetic biomarkers such as DNA methylation and histone modifications contribute to disease diagnoses. This review aims to look at the epigenetic modifications brought forth by psychoactive drug abuse.

Due to the high mortality rate of COVID-19 and its high variability and mutability, it is essential to know the body's defense mechanisms against this virus. Saliva has numerous functions, such as digestion, protection, and antimicrobial effects. Salivary diagnostic tests for many oral and systemic diseases will be available soon because saliva is a pool of biological markers. The most important antiviral and antibacterial compounds identified in saliva include lysozyme, lactoferrin (LF), mucins, cathelicidin, salivary secretory immunoglobulin (SIgA), chromogranin A, cathelicidin, salivary agglutinin (SAG) (gp340, DMBT1), α, β defensins, cystatin, histatins, secretory leukocyte protease inhibitor (SLPI), heat shock protein (HSP), adrenomedullin and microRNA (miRNAs). Antimicrobial peptides (AMPs) in saliva could be used in the future as models for designing effective oral microbial antibiotics. The antiviral properties of the peptides in saliva may be one of the future treatments for the COVID-19 virus. In this review, we investigate compounds with antiviral and antibacterial properties in saliva and the importance of these compounds in saliva in exposure to the COVID-19 virus. Due to the transmission route of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) into the oral cavity in the lower and upper respiratory tract, studies of salivary antiviral properties in these patients are very important. Some of the antiviral effects of saliva, especially mucin, α, β-defensins, IgA, IgG, IgM, lysozyme, SAG, SLPI, and histatins, may play a greater role in neutralizing or eliminating COVID-19.

Background: Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of cannabis. Historically, rodent studies examining the effects of THC have used intraperitoneal injection as the route of administration, heavily focusing on male subjects. However, human cannabis use is often through inhalation rather than injection. Objective: We sought to characterize the pharmacokinetic and phenotypic profile of acutely inhaled THC in female rats, compared to intraperitoneal injection, to identify any differences in exposure of THC between routes of administration. Methods: Adult female rats were administered THC via inhalation or intraperitoneal injection. Serum samples from multiple time points were analyzed for THC and metabolites 11-hydroxy-delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol using ultra-performance liquid chromatography-tandem mass spectrometry. Rats were similarly treated for locomotor activity analysis. Results: Rats treated with 2 mg/kg THC intraperitoneally reached a maximum serum THC concentration of 107.7 ± 21.9 ng/mL. Multiple THC inhalation doses were also examined (0.25 mL of 40 or 160 mg/mL THC), achieving maximum concentrations of 43.3 ± 7.2 and 71.6 ± 22.5 ng/mL THC in serum, respectively. Significantly reduced vertical locomotor activity was observed in the lower inhaled dose of THC and the intraperitoneal injected THC dose compared to vehicle treatment. Conclusion: This study established a simple rodent model of inhaled THC, demonstrating the pharmacokinetic and locomotor profile of acute THC inhalation, compared to an i.p. injected THC dose in female subjects. These results will help support future inhalation THC rat research which is especially important when researching behavior and neurochemical effects of inhaled THC as a model of human cannabis use.

Background: In recent years, pulmonary fibrosis (PF) has increased in incidence and prevalence. Qingzaojiufei decoction (QD) is a herbal formula that is used for the treatment of PF. Objective: In this research, network pharmacology and molecular docking methods were used to explore the major chemical components and potential mechanisms of QD in the treatment of PF. Methods: The principal components and corresponding protein targets of QD were used to screen on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) and high-throughput experiment-and reference-guided database (HERB), Cytoscape 3.7.2 was used to construct the drug-component-target network. PF targets were collected by GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The protein-protein interaction (PPI) network was constructed by importing compound-disease intersection targets into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape3.7.2. We further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersecting targets. In the last, we validated the core targets and active compounds by molecular docking. Results: The key compounds of quercetin, (-)-epigallocatechin-3-gallate, and kaempferol of QD were obtained. The key targets of AKT1, TNF, and IL6 of QD were obtained. The molecular docking results show that quercetin, (-)-epigallocatechin-3-gallate and kaempferol work well with AKT1, TNF and IL6. Conclusion: This research shows the multiple active components and molecular mechanism of QD in the treatment of PF and offers resources and suggestions for future studies.

Background: Research proved that coenzyme Q10-loaded NLC effectively removes skin wrinkles, therefore, such a formulation with good characteristics is still the research goal. Objective: This study investigated the effect of solid lipids and surfactant type on the physical characteristics of Q10-NLC. We aimed to achieve the optimum formulation for producing NLC with long-term stability and high Entrapment efficiency (E.E.) %. We compared the experimental results with the output of the Molecular dynamic (M.D.) simulations. Methods: To develop Q10-NLC, various solid lipids, MCT oil, and surfactants were employed. The formulations were prepared by high-shear homogenization and ultrasound methods. Stability studies were carried out 1,3, and 6 months at 4, 25, and 40°C. The optimized NLC formulations were characterized by photon correlation spectroscopy (PCS), Transmission electron microscopy (TEM), Differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR). E.E. % was determined by HPLC analysis. Atomistic M.D. simulations of two model systems were performed to gain insights into the self-assembled process of co-Q10 with other formulation components. Results: Statistical analysis (Two-way ANOVA) revealed that solid lipid and surfactant factors had a significant influence on particle size, PDI, and zeta potential (***p < 0.0001). According to the results, F1 and F6 formulations had desirable surface characterizations, physicochemical stability, and high E.E. %. The atomistic M.D. simulations confirmed that the F1 system (best) was more stable than the F31 system (worst). Conclusion: The solid lipids: tripalmitin and compritol, stabilized with 4% tween 80 and 1% span 80, have produced stable NLC with the best surface characteristics that could be a promising formulation for the delivery of Q10. Atomistic M.D. simulation has confirmed the stability of F1 in comparison to F31.