Current Pharmaceutical Design - Volume 31, Issue 29, 2025

Zuo Gui pill (ZGP) is a herbal compound formulation used to treat knee osteoarthritis (KOA), but its underlying mechanisms are still unclear. This study aimed to initially elucidate the molecular mechanisms of ZGP in treating KOA using network pharmacology and molecular docking techniques.

We collected information on the drug compounds and targets from TCMSP, HERB, BATMAN-TCM, and UniProt databases, as well as the KOA-related targets from DisGeNET, GeneCards, OMIM, and GEO databases. Afterward, we obtained the hub targets of ZGP and KOA. The biological processes and major pathways of the hub targets were analyzed by GO and KEGG, and three networks were constructed to illustrate the mechanisms of ZGP for the treatment of KOA. Finally, molecular docking was carried out to verify the binding of the main compounds to the key targets.

Through the network pharmacological analysis, we screened important compounds in ZGP, such as quercetin, kaempferol, wogonin, isorhamnetin, and 138 hub targets, including PTGS2, NOS3, AKT1, MAPK1, which are enriched in PI3K-Akt, MAPK, TNF, IL-17, HIF-1, and other signaling pathways. The molecular docking results showed that the main compounds and key targets have high affinity, which further demonstrated the molecular mechanisms and provided a basis for the clinical application of ZGP.

This study illustrates the specific mechanisms of ZGP in the treatment of KOA using network pharmacology and molecular docking techniques, which lays the foundation for further research on its pharmacological mechanisms.

Synthetic cannabinoids are one of the most identified abused drugs nowadays. Their popularity is due to their psychoactive effects, which resemble delta 9 tetrahydrocannabinol. This study investigates the genotoxic potential of three synthetic cannabinoids of indazole-passed drugs, AB-Fubinaca, AMB- Fubinaca, and EMB-Fubinaca (at a final concentration of 200 nM).

Genotoxicity was examined using Sister Chromatid Exchanges (SCEs) and Chromosomal Aberrations (CAs) assays in cultured human lymphocytes. Blood for lymphocyte cultures was obtained from healthy adult young males.

A significant increase in the frequency of SCEs was detected for all examined drugs (range: 5.4-6.1, p < 0.05) compared to the control group (4.70 ± 0.31). The order of synthetic cannabinoids in terms of their ability to induce SCEs was EMB-Fubinaca (6.04 ± 0.63) > AMB-Fubinaca (5.65 ± 0.6) > AB-Fubinaca (5.33 ± 0.58). None of the examined drugs induced significant changes to the frequency of CAs (p > 0.05). Additionally, there were no effects of the synthetic cannabinoids at the studied concentration on proliferation and mitotic indices.

Synthetic cannabinoids have been found to increase the frequency of SCEs in cultured human lymphocytes. The results should be confirmed in in vivo studies using lymphocytes derived from synthetic cannabinoid users.

Tamoxifen citrate (TMC), an antiestrogenic drug, is employed in the healing of advanced breast cancer. However, its oral and parenteral route-associated side effects and solubility issues restricted its medical utilizations.

The research aimed to prepare a tamoxifen citrate-loaded transethosomal gel (TMC TEsG) to enhance TMC entrapment efficiency, in vitro dissolution, and ex vivo permeation.

TMC TEs were developed employing an HPH method and optimized using 2³ factorial designs. The optimized TMC TEs were converted into TMC TEsG by cold dispersion. TMC TEs and TMC TEsG were estimated for particle size, microscopic, functional group interaction, crystalline, in vitro dissolution, ex vivo permeation, spreadability, TMC content, and texture analysis.

The optimization study revealed the suitability and validity of 2³ designs for developing TMC TEs. TMC TEs with particle size ~163.1 nm and zeta potential of ~-26.8 mV improved the physical stability and skin permeation. TMC TEs showed a high entrapment efficiency of ~84.49%. TEM depicts spherical and sealed structure vesicles of TMC TEs. Physical analysis supported the formation of TMC TEs. Vesicles improved the dissolution (~96%) compared to pure TMC (~68%). The TMC TEsG increased the permeation (~82%) compared to TMC gel (~55%). TMC TEsG with pH (~5.61), viscosity (~4077.5 cps), and spreadability (~49.84 g.cm/s) exhibiting safety and easy applicability to the skin.

Outcomes suggest the transdermal permeation potential of design-generated flexible TMC TEs and, thus, could be employed to treat skin-related diseases.

The Qizhi Kebitong formula (QKF) has been utilized as a traditional Chinese medicine (TCM) remedy for over two decades in treating diabetic peripheral neuropathy (DPN) with notable clinical efficacy. However, its precise mechanism and bioactive constituents remain elusive.

Through ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) analysis was used to identify the primary components of QKF. Nerve conduction function in mice was assessed by measuring sensory thresholds and nerve conduction velocities. Laser speckle contrast imaging (LSCI) was used to examine the effect of QKF on foot pads and perineural blood flow in mice. Additionally, Transmission electron microscopy (TEM) and various pathologic stains were utilized to observe QKF's therapeutic effect on sciatic nerve (SN) damage in DPN mice. The impact of QKF on the pathological mechanism of the DPN model was explored through qRT-PCR, Western blot, and immunohistochemistry.

Our results demonstrated that QKF improved phenotypic features in a mouse model of DPN, increased blood flow around the foot pad and SN, and somewhat repaired the pathological structure and function of SN. Furthermore, the study revealed that QKF slowed down the progression of DPN by inhibiting the endoplasmic reticulum (ER) stress apoptosis signaling pathway mediated by PERK/ATF4/CHOP pathway.

The significant neuroprotective effects of QKF in experimental DPN mice were confirmed by our findings, which offer important scientific evidence supporting its potential utilization in DPN treatment.