Jae Seon Kang

Background and Objective: Various solubilizing agents were used to improve the solubility of gemifloxacin, which has limited water solubility. Furthermore, the solubility enhancement and bioavailability of gemifloxacin were then assessed through in vitro solubility screening and in vivo pharmacokinetic studies in rats. Materials and Methods: Different solubilizing agents, including poloxamer 407, poloxamer 188, Soluplus®, Polyox N80, sodium lauryl sulfate, PEG 4000, L-arginine, L-lysine, β-cyclodextrin, and hydroxypropyl-β-cyclodextrin (HPCD), were evaluated for the associated solubilizing effects, and HPCD was selected as the optimal solubilizer. Gemifloxacin in samples collected from the in vitro and in vivo experiments was quantified using high-performance liquid chromatography (HPLC). Results: In vitro solubility screening showed that the solubility of gemifloxacin reached 69.37 ± 0.71 mg/mL with 4.1 g of HPCD, representing a 1.52-fold increase relative to the control group (45.68 ± 0.37 mg/mL). Further optimization revealed that 0.1 g of HPCD achieved a solubility of 66.27 ± 0.42 mg/mL, with minimal additional improvement at higher concentrations. The HPLC method exhibited excellent linearity (R2 = 0.9998) over the range of 0.03–45 μg/mL. The in vivo pharmacokinetic study demonstrated that the area under the curve (AUC0-∞) of the gemifloxacin–HPCD formulation (Group A: 7.527 ± 0.60 μg⋅h/mL) increased approximately 1.53-fold compared with that of the gemifloxacin-alone group (4.928 ± 0.85 μg⋅h/mL), significantly improving the bioavailability of gemifloxacin. Conclusion: The solubilization strategy using HPCD can effectively improve the solubility and bioavailability of gemifloxacin, representing a promising approach for the development of the associated oral formulations.

Platelets are essential blood components that maintain hemostasis, prevent excessive bleeding, and facilitate wound healing. Reduced platelet counts are implicated in various diseases, including leukemia, hepatitis, cancer, and Alzheimer’s disease. Enhancing megakaryocytic differentiation is a promising strategy to increase platelet production. Compound K (CK), a major bioactive metabolite of ginsenosides from Panax ginseng, has demonstrated anti-cancer and neuroprotective properties. In this study, we investigated the effects of CK on megakaryocytic differentiation and apoptosis in chronic myeloid leukemia (CML) cell lines K562 and Meg-01. CK treatment significantly upregulated the mRNA expression of key megakaryocytic differentiation markers, including CD61, CD41, and CD42a, and promoted the formation of large, multinucleated cells in K562 cells. Additionally, flow cytometry analysis revealed that CK at 5 µM induced apoptosis, a critical process in thrombocytopoiesis, in both K562 and Meg-01 cells. RT² Profiler PCR array analysis further identified a marked increase in the expression of genes associated with the activation of the NLRP3 inflammasome in CK-treated K562 and Meg-01 cells. This study is the first to demonstrate that CK promotes megakaryocytic differentiation and apoptosis through the activation of the ERK/EGR1 and NLRP3 inflammasome pathways. These findings suggest that CK may enhance platelet production, indicating its potential as a therapeutic candidate for platelet-related disorders and other associated diseases.

Myelosuppression is a major adverse effect of chemotherapy. With the increasing number of cancer patients worldwide, there is a growing interest in therapeutic approaches that reduce the adverse effects of chemotherapy. Angelica gigas Nakai (AGN) roots have been widely used in oriental medicine to treat blood-related diseases, including cancer. However, the effects of AGN on myelosuppression have not been studied. Here, we investigated the effects of AGN ethanol extract (AGNEX) on cyclophosphamide-induced myelosuppression. AGNEX treatment significantly decreased white blood cell levels while increasing red blood cell and platelet levels in the peripheral blood. It inhibited thymus and spleen atrophy. It also enhanced serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. qRT-PCR results showed that AGNEX decreased the expression of IL-1b and stem cell factor (SCF) in the bone marrow (BM) while increasing the mRNA expression of IL-3 and IL-6 in the spleen. Although AGNEX did not significantly decrease apoptosis and cell cycle arrest in the BM and splenocytes, AGNEX plays a positive role in cyclophosphamide-induced myelosuppression. AGNEX administration increased BM cells in the femur while decreasing apoptotic BM cells. These findings suggest that AGNEX could be used to treat myelosuppression and as a combination therapy in cancer patients.

The present study investigates the effect of ludartin on spinal cord injury in rat model. Ludartin treatment decreased the expression of myeloperoxidase and malondialdehyde in spinal cord tissues. The expression of glutathione and superoxide dismutase was enhanced. It also exhibited inhibitory effect on reduction of NeuN-positive cells. The proportion of TUNEL positive cells was also regulated. In addition, ludartin treatment prevented the onset of apoptosis which was evident by decrease in caspase-3 and Bax level and increase of Bcl‑2 level. Up-regulation of tumor necrosis factor‑α, inter-leukin‑1β and I interleukin‑6 by spinal cord injury was suppressed by ludartin treatment. There was improvement in locomotion of rats by treatment with ludartin. Ludartin treatment of spinal cord injury rats improves locomotion by inhibiting inflammatory cytokine expression and preventing cell apoptosis. Thus, ludartin has therapeutic importance in spinal cord injury treatment. Video Clip of Methodology: Western Blot Analysis: 6 min 17 sec: Click to watch

Objective: To identify the preventive effect of Angelica gigas Nakai (A. gigas Nakai) extract in a benzalkonium chloride-induced dry eye model. Methods: A total of 28 mice were divided into 4 groups: 1) Normal group: mice received only saline; 2) positive control group: mice received an oral solution without A. gigas Nakai extract at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m.; 3) A. gigas Nakai extract (5 mg); 4) A. gigas Nakai extract (10 mg). Both group 3) and group 4) received an oral solution with A. gigas Nakai extract (either 5 mg/kg or 10 mg/kg) at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m. After 14 d of follow-up, tear volume measurement and fluorescein staining were evaluated for the recovery effects on ocular surface. Histologic analysis was conducted by hematoxylin and eosin staining. Apoptosis on ocular epithelium layer was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Expression of TNF- α was also measured using western blot analysis. Results: An increase in both the tear volume and the sustained fluorescein staining scores was observed, demonstrating the preventive effects of A. gigas Nakai extract. Structure changes such as irregularity of the epithelial layer and corneal epithelial cell death were inhibited in the A. gigas Nakai extract groups. Expression of TNF- α moderately declined; however, its expression level was still higher, compared to the normal group. Conclusions: Results from the current study show the significant preventive effect of A. gigas Nakai extract in a mouse model of benzalkonium chloride-induced dry eye syndrome. Thus, A. gigas Nakai extract could be considered as an oral preventive agent for dry eye syndrome in the future.