Vol 30, No 4 (2024)

Concomitant use of cannabinoids with other drugs may result in pharmacokinetic drug-drug interactions, mainly due to the mechanism involving Phase I and Phase II enzymes and/or efflux transporters. Cannabinoids are not only substrates but also inhibitors or inducers of some of these enzymes and/or transporters. This narrative review aims to provide the available information reported in the literature regarding human data on the pharmacokinetic interactions of cannabinoids with other medications. A search on Pubmed/Medline, Google Scholar, and Cochrane Library was performed. Some studies were identified with Google search. Additional articles of interest were obtained through cross-referencing of published literature. All original research papers discussing interactions between cannabinoids, used for medical or recreational/adult-use purposes, and other medications in humans were included. Thirty-two studies with medicinal or recreational/adult-use cannabis were identified (seventeen case reports/series, thirteen clinical trials, and two retrospective analyses). In three of these studies, a bidirectional pharmacokinetic drug-drug interaction was reported. In the rest of the studies, cannabinoids were the perpetrators, as in most of them, concentrations of cannabinoids were not measured. In light of the widespread use of prescribed and non-prescribed cannabinoids with other medications, pharmacokinetic interactions are likely to occur. Physicians should be aware of these potential interactions and closely monitor drug levels and/or responses. The existing literature regarding pharmacokinetic interactions is limited, and for some drugs, studies have relatively small cohorts or are only case reports. Therefore, there is a need for high-quality pharmacological studies on cannabinoid-drug interactions.

Background:Chaiqin Qingning capsule (CQQNC) has been used to relieve pain in practice. However, the active components, pain targets, and molecular mechanisms for pain control are unclear.

Objective:To explore the active components and potential mechanisms of the analgesic effect of CQQNC through network pharmacology and in vitro experiments.

Methods:The main active components and the corresponding targets of CQQNC were screened from the TCMSP and the SwissTargetPrediction databases. Pain-related targets were selected in the OMIM, Gene- Cards, and DrugBank databases. These targets were intersected to obtain potential analgesic targets. The analgesic targets were imported into the STRING and DAVID databases for protein-protein interaction (PPI), gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Cytoscape software (V3.7.1) was used to construct an active component-intersection network. Finally, the key components were docked with the core targets. The analgesic mechanism of CQQNC was verified by RAW264.7 cell experiment.

Results:30 active CQQNC components, 617 corresponding targets, and 3,214 pain-related target genes were found. The main active components were quercetin, kaempferol, and chenodeoxycholic acid etc. The key targets were ALB, AKT1, TNF, IL6, TP53, IL1B, and SRC. CQQNC can exert an analgesic effect through PI3K-Akt, MAPK signaling pathways, etc. Molecular docking showed that these active components had good binding activities with key targets. The results of in vitro experiments showed that CQQNC could exert antiinflammatory and analgesic effects through MAPK/AKT/NF-kB signaling pathways.

Conclusion:CQQNC exerts pain control through inhibiting MAPK/AKT/NF-kB signaling pathways.

Background::Oral squamous cell carcinoma (OSCC) and oral lichen planus (OLP) are two separate conditions affecting the mouth and result in varying clinical outcomes and levels of malignancy. Achieving early diagnosis and effective therapy planning requires the identification of reliable diagnostic biomarkers for these disorders. MicroRNAs (miRNAs) have recently received attention as powerful biomarkers for various illnesses, including cancer. In particular, miR-483-5p is a promising diagnostic and prognostic biomarker in various cancers. Therefore, this study aimed to investigate the role of serum miR-483-5p in the diagnosis and prognosis of OLP and OSCC patients by in silico analysis of differential gene expression.

Methods::GSE23558 and GSE52130 data sets were selected, and differential gene expression analysis was performed using microarray data from GSE52130 and GSE23558. The analysis focused on comparing OLP and OSCC samples with normal samples. The genes intersected through the differential gene expression analysis were then extracted to determine the overlapping genes among the upregulated or downregulated DEGs. The downregulated genes among the DEGs were subsequently imported into the miRWalk database to search for potential target genes of miRNA 483-5p that lacked validation. To gain insight into the biological pathways associated with the DEGs, we conducted pathway analysis utilizing tools, such as Enrichr. Additionally, the cellular components associated with these DEGs were investigated by analyzing the String database. On the other hand, blood serum samples were collected from 35 OSCC patients, 34 OLP patients, and 34 healthy volunteers. The expression level of miR-483-5p was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The Kruskal-Wallis test was utilized to investigate the considerable correlation. Moreover, this study explored the prognostic value of miR-483-5p through its association with clinicopathological parameters in OSCC patients.

Results::The results showed that serum expression of miR-483-5p was considerably higher in OSCC patients compared to OLP patients and healthy controls (p 0.0001) and that this difference was statistically significant. Furthermore, elevated miR-483-5p expression was associated with tumor size, lymph node metastasis, and stage of tumor nodal metastasis in OSCC patients (p 0.001, p 0.038, and p 0.0001, respectively). In silico analysis found 71 upregulated genes at the intersection of upregulated DEGs and 44 downregulated genes at the intersection of downregulated DEGs, offering insight into the potential underlying mechanisms of miR-483-5p’s engagement in OSCC and OLP. The majority of these DEGs were found to be involved in autophagy pathways, but DEGs involved in the histidine metabolism pathway showed significant results. Most of these DEGs were located in the extracellular region. After screening for downregulated genes that were invalidated, miRNA 483-5p had 7 target genes.

Conclusion::This study demonstrates the potential of serum miR-483-5p as a promising diagnostic and prognostic biomarker in OSCC and OLP patients. Its upregulation in OSCC patients and its association with advanced tumor stage and potential metastasis suggest the involvement of miR-483-5p in critical signaling pathways involved in cell proliferation, apoptosis, and cell cycle regulation, making it a reliable indicator of disease progression. Nevertheless, additional experimental studies are essential to validate these findings and establish a foundation for the advancement of targeted therapies and personalized treatment approaches.