Jaesung Pyo

Background: Heat-treated red ginseng contains pharmacologically active ginsenosides such as Rg5 and Rk1 and is increasingly used as a functional food. Because herbal products are frequently co-administered with conventional medications, evaluation of potential cytochrome P450 (CYP)-mediated drug–drug interactions is essential. This study examines their effects on nine cytochrome P450 isoforms to evaluate potential drug–drug interactions. Methods: The CYP enzyme inhibition method was assessed by determining IC50 values using human liver microsomes and specific substrates. Various concentrations of ginsenosides Rg5 and Rk1 were tested, and the reactions were analyzed via UPLC-MS/MS. Positive control inhibitors were included for comparison. Results: Ginsenoside Rg5 and Rk1 exhibited potent inhibitory effects on CYP2A6, with IC50 values of 1.04 and 0.98 μM, respectively, with moderate inhibitory effects observed for several other CYP activities and little or no inhibition observed for the remaining CYP activities. Conclusions: The results indicate potential adverse drug reactions with CYP2A6-metabolized drugs, highlighting the need for further in vivo safety evaluations. These findings provide important information regarding CYP-mediated herb–drug interaction potential associated with heat-processed ginsenosides.

Curcumin exhibits potent anti-inflammatory, antioxidant, and neuroprotective effects. However, its therapeutic potential is severely limited by poor oral bioavailability due to low solubility, rapid metabolism, and poor intestinal permeability. This study evaluated the single-dose pharmacokinetics and relative bioavailability of BNT–C060, a novel double-layered chitosan/alginate-coated nano-liposomal curcumin, versus conventional free curcumin in healthy male volunteers. In this randomized, double-blind, parallel-group trial, 18 healthy males ( n = 9/group) received single oral doses of BNT–C060 (400 mg curcumin-equivalent) or free curcumin (2,000 mg) under fasting conditions. Plasma and urine samples were collected over 24 h for total curcumin analysis (LC–MS/MS after β-glucuronidase treatment). BNT–C060 demonstrated superior dose-normalized pharmacokinetics: 23.2-fold higher plasma AUC _0–t (5.00 vs. 0.22 ng·h/mL/mg), 53-fold higher C _max (1.06 vs. 0.02 ng/mL/mg), and 35.3-fold higher urinary exposure. T _max was earlier (0.86 vs. 3.3 h). A single oral dose of BNT–C060 was generally well tolerated in healthy male volunteers within the evaluated dose range, with no clinically significant safety signals observed under the study conditions. BNT–C060 achieved substantially higher plasma concentrations (C _max 423 ng/mL vs. 34 ng/mL free curcumin) compared with free curcumin, suggesting improved systemic exposure with the nano-liposomal formulation. These proof-of-concept findings provide a rationale for further clinical investigation of this advanced nano-liposomal delivery system.

Objectives: A hangover is a set of unpleasant mental and physical symptoms following heavy alcohol consumption, influenced by factors such as alcohol type, individual tolerance, hydration, and alcohol metabolites. Although these factors are known, the exact pathological mechanisms remain unclear. Previous research has shown a negative correlation between blood alcohol elimination rates and hangover severity. This study aimed to evaluate the acute toxicity and the effects of WON-21, a herbal medicine combination with reported anti-inflammatory, antioxidant properties and the ability to enhance alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzyme activity, on ethanol and acetaldehyde metabolism in an animal model of alcohol-induced hangover.Methods: In the acute toxicity study, WON-21 was evaluated in male rats following the OECD Guideline No. 423. An acute alcohol-induced hangover model was established in rats. Different doses of WON-21 were administered, and blood samples were collected at various time points to measure ethanol and acetaldehyde concentrations. A control group without WON-21 treatment was used for comparison.Results: In the acute toxicity study, no lethal effects or toxic signs were observed during the duration of the study. WON-21 administration resulted in a dose-dependent decrease in blood ethanol and acetaldehyde concentrations compared to the control group. Higher doses showed greater effectiveness in accelerating the clearance of these substances.Conclusions: The findings suggest that WON-21 may facilitate faster elimination of ethanol and acetaldehyde, potentially alleviating hangover symptoms. Combined with its known antioxidant, anti-inflammatory, and enzyme-activating properties, WON-21 may offer therapeutic benefits for managing alcohol-induced hangovers.

Skin aging and inflammatory skin lesions are exacerbated by reactive oxygen species (ROS) generated in the mitochondria of human dermal fibroblasts (HDFs). These oxidative stressors degrade the extracellular matrix (ECM), promote inflammation, and accelerate skin aging. Antioxidants that suppress reactive oxygen species (ROS) production play a crucial role in mitigating these effects. This study investigated the protective effects of Centipeda minima (CMX) and its active constituent, brevilin A, against tumor necrosis factor-alpha (TNF-α)-induced oxidative stress and ECM degradation in normal human dermal fibroblasts (NHDFs). Both CMX and brevilin A significantly inhibited TNF-α-induced elevations in ROS, nitric oxide (NO), and prostaglandin E₂ (PGE₂) levels, thereby reducing oxidative stress and inflammatory responses. Additionally, they effectively suppressed matrix metalloproteinase-1 (MMP-1) expression and restored the procollagen I α1 (COLIA1) levels, indicating their potential to preserve ECM integrity. Mechanistically, brevilin A selectively inhibited ERK phosphorylation in the mitogen-activated protein kinase (MAPK) pathway, suggesting its role in regulating collagen degradation and inflammation. These findings highlight that CMX and brevilin A are promising natural agents for protection against skin aging and inflammation. However, further in vivo studies are necessary to validate their efficacy and explore their potential applications in dermatological formulations.

Aim This study aimed to qualitatively identify the ranges of the factors involved in the tablet compression process for ivabradine Sustained Release (SR) tablets. Materials and Methods A full factorial design of experiments study was used to identify three factors (pre- and main-compression force and paddle rotation time) involved in the compression process of ivabradine SR tablets. For robust tableting, three responses (content uniformity, friability, and dissolution) were evaluated as critical quality attributes via analysis of variance using Design Expert software. Results The main compression force significantly influenced dissolution (1 hr, p <0.0001; 3 hr, p <0.0001; and 8 hr, p=0.0002). Precompression and paddle rotation time slightly influenced friability (p=0.0510) and content uniformity (p=0.0968). These results showed that paddle rotation time (0.27-1.37 sec), pre-compression (1.5 kN), and main compression (7.7-9.2 kN) influenced the tablet compression process of the optimal ivabradine SR tablet. Conclusion In summary, robust ranges of three factors for tableting were successfully evaluated. It can be concluded that the ranges of tablet compression leading to high quality (low friability and content uniformity, and optimal dissolution) for tableting were successfully observed by the DoE approach.

Chronic neurodegenerative diseases are typically associated with oxidative stress conditions leading to neuronal cell death. We aimed to investigate the neuroprotective effect of three pyranocoumarins (decursin, decursinol angelate, and decursinol) targeting oxidative stress factors. Decursin (also known as dehydro-8-prenylnaringenin) is a prenylated coumarin compound consisting of a coumarin ring system with a prenyl group attached to one of the carbons in the ring. As a secondary metabolite of plants, pyranocoumarin decursin from Angelica gigas Nakai presented protective effects against glutamate-induced oxidative stress in HT22, a murine hippocampal neuronal cell line. Decursinol (DOH) is a metabolite of decursin, sharing same coumarin ring system but a slightly different chemical structure with the prenyl group replaced by a hydroxyl group (-OH). In our findings, DOH was ineffective while decursin was, suggesting that this prenyl structure may be important for compound absorption and neuroprotection. By diminishing the accumulation of intracellular reactive oxygen species as well as stimulating the expression of HO-1, decursin triggers the self-protection system in neuronal cells. Additionally, decursin also revealed an anti-apoptotic effect by inhibiting chromatin condensation and reducing the forming of annexin-V-positive cells.

Centipeda minima (CMX) has been widely investigated using network pharmacology and clinical studies for its effects on hair growth via the JAK/STAT signaling pathway. Human hair follicle papilla cells exhibit hair regrowth through the expression of Wnt signaling-related proteins. However, the mechanism of action of CMX in animals has not been elucidated fully. This study examined the effect of induced hair loss and its side-effects on the skin, and observed the mechanism of action of an alcoholic extract of CMX (DN106212) on C57BL/6 mice. Our results showed that DN106212 was more effective in promoting hair growth than dimethyl sulfoxide in the negative control and tofacitinib (TF) in the positive control when mice were treated with DN106212 for 16 days. We confirmed that DN106212 promotes the formation of mature hair follicles through hematoxylin and eosin staining. We also found that the expression of vascular endothelial growth factor (Vegfa), insulin-like growth factor 1 (Igf1), and transforming growth factor beta 1 (Tgfb1) is related to hair growth using PCR. DN106212-treated mice had significantly higher expression of Vegfa and Igf1 than TF-treated ones, and inhibiting the expression of Tgfb1 had similar effects as TF treatment. In conclusion, we propose that DN106212 increases the expression of hair growth factors, promotes the development of hair follicles, and promotes hair growth. Although additional experiments are needed, DN106212 may serve as an experimental basis for research on natural hair growth-promoting agents.

Etomidate, with efficacy similar to that of propofol, has been used as a propofol substitute because propofol is a designated narcotic drug, and an increase in the frequency of illegal distribution and misuse has been reported in Korea. Previous analytical studies on etomidate used blood and urine. For long‐term use and timing estimation, a method for etomidate analysis using hair should be developed. Therefore, in this study, an analytical method using LC–MS/MS was developed to determine etomidate and its major metabolite in hair. Human hair samples were segmented after washing to eliminate possible contaminants on the hair and stirred with methanol. The LC–MS/MS conditions were optimized, and the chromatographic separation time was 10 min. Selectivity, linearity, limit of detection, limit of quantification, precision, accuracy, recovery, process efficiency, matrix effect, and stability were evaluated to validate the analytical method. The calibration curves ranged from 0.25 to 50 pg/mg for etomidate and 2–250 pg/mg for etomidate acid; the coefficients of determination were higher than 0.997. The intra‐ and inter‐assay precision results for all the compounds were <15% and satisfied at recovery, process efficiency, matrix effect, and stability. In addition, this method was applied to the hair of 4 rats which are administered with etomidate to evaluate. The etomidate concentrations in the rat hair ranged from 2.60 to 8.50 pg/mg, and the etomidate acid concentrations were 2.06–7.13 pg/mg. Thus, this method can be used as basic data for monitoring etomidate in hair.