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The chemical 4-amino-3-nitrophenol (4A3NP) is classified as an amino nitrophenol and is primarily utilized as an ingredient in hair dye colorants. In Korea and Europe, it is exclusively used in non-oxidative or oxidative hair dye formulations, with maximum allowable concentrations of 1% and 1.5%, respectively. Despite this widespread use, risk assessment of 4A3NP has not been completed due to the lack of proper dermal absorption data. Therefore, in this study, both the analytical method validation and in vitro dermal absorption study of 4A3NP were conducted following the guidelines provided by the Korea Ministry of Food and Drug Safety (MFDS). Before proceeding with the dermal absorption study, analytical methods were developed for the quantitation of 4A3NP through multiple reaction monitoring (MRM) via liquid chromatography-mass spectrometry (LC-MS) in various matrices, including swab wash (WASH), stratum corneum (SC), skin (SKIN, comprising the dermis and epidermis), and receptor fluid (RF). These developed methods demonstrated excellent linearity (R2 = 0.9962–0.9993), accuracy (93.5–111.73%), and precision (1.7–14.46%) in accordance with the validation guidelines.The dermal absorption of 4A3NP was determined using Franz diffusion cells with mini-pig skin as the barrier. Under both non-oxidative and oxidative (6% hydrogen peroxide (H2O2): water, 1:1) hair dye conditions, 1% and 1.5% concentrations of 4A3NP were applied to the skin at a rate of 10 μL/cm2, respectively. The total dermal absorption rates of 4A3NP under non-oxidative (1%) and oxidative (1.5%) conditions were determined to be 5.62 ± 2.19% (5.62 ± 2.19 μg/cm2) and 2.83 ± 1.48% (4.24 ± 2.21 μg/cm2), respectively.

During the off-season, soccer players in Korea attend the winter training season (WTS) to build running stamina for the next season. For young soccer players, proper recovery time is needed to prevent injury or muscle damage. In this study, urinary metabolites in young players after 1, 5, and 10 days of the WTS were analyzed using nuclear magnetic resonance spectroscopy (NMR) combined with multivariate analysis to suggest appropriate recovery times for improving their soccer skills. After NMR analysis of the urine samples obtained from young players, 79 metabolites were identified, and each group (1, 5, or 10 days after WTS) was separated from the before the WTS group in the target profiling analysis using partial least squares-discriminant analysis (PLS-DA). Of these, 15 metabolites, including 1-methylnicotinamide, 3-indoxylsulfate, galactarate, glutamate, glycerol, histamine, methylmalonate, maltose, N-phenylacetylglycine, trimethylamine, urea, 2-hydroxybutyrate, adenine, alanine, and lactate, were significantly different than those from before the WTS and were mainly involved in the urea, purine nucleotide, and glucose-alanine cycles. In this study, most selected metabolites increased 1 day after the WTS and then returned to normal levels. However, 4 metabolites, adenine, 2-hydroxybutyrate, alanine, and lactate, increased during the 5 days of recovery time following the WTS. Based on excess ammonia, adenine, and lactate levels in the urine, at least 5 days of recovery time can be considered appropriate.

Pyrogallol is an ingredient in hair dye. Its concentration in hair dye is managed at less than 2.0% in Korea. There have been no reports on the dermal absorption rate of pyrogallol. The two purposes of this study were to develop an analytical method and determine the dermal absorption rate of pyrogallol. An analytical method was developed and validated by high-performance liquid chromatography (HPLC) analysis of various matrices including swabs (SWAB), skin (SKIN, dermis + epidermis), stratum corneum (SC), and receptor fluid (RF). Linearity (r2 = 0.9993–0.9998), accuracy (92.1–108.2%), and precision (0.5–9.5%) met the validation criteria in guidelines. A Franz diffusion cell was used to determine the dermal absorption of pyrogallol using the skin of mini pigs. Pyrogallol (2.0%) was applied to the skin (10 μL/cm2). For the actual hair dye conditions, the skin was wiped with a swab 30 min after application. Twenty-four hours later, it was wiped with a swab again and the SC was collected using tape stripping. All samples were extracted with water and analyzed. RF was recovered at 0, 1, 2, 4, 8, 12, and 24 h. The total dermal absorption rate of pyrogallol was determined to be 26.0 ± 3.9%.

Sulforaphane is an isocyanate abundantly present in cruciferous vegetables. In the present study, we aimed to investigate the effects of sulforaphane on secondhand smoking (SHS)-induced pulmonary damage in mice. Additionally, a metabolomic study was performed to identify biomarkers associated with pulmonary disease using proton nuclear magnetic resonance (1H-NMR) analysis. Male C57BL6J mice were divided into a control group, an SHS exposure group (positive control group, PC), and a sulforaphane treatment group exposed to secondhand smoke (SS) (n = 5 per group). The PC and SS groups were exposed to secondhand smoke in a chamber twice daily for four weeks. Mice in the SS group were orally administered sulforaphane (50 mg/kg) for four weeks during secondhand smoke exposure. Histopathological examination of the lungs revealed pulmonary damage in PC mice, including loss of bronchial epithelial cells, bronchial wall thickening, and infiltration of macrophages. In contrast, mice in the SS group showed little or no epithelial thickening, thereby exhibiting reduced lung damage. Mouse serum and lung tissues were collected and analyzed to determine changes in endogenous metabolites using 1H-NMR. After target profiling, we identified metabolites showing the same tendency in the serum and lung as biomarkers for SHS-induced pulmonary damage, including taurine, glycerol, creatine, arginine, and leucine. As a result of histopathological examination, sulforaphane might inhibit SHS-induced lung damage, and metabolite analysis results suggest potential biomarkers for SHS-induced pulmonary damage in mice.

The cosmetic industry has flourished in recent years. Accordingly, the safety of cosmetic ingredients is increasing. Bromochlorophene (BCP) is a commonly used cosmetic preservative. To evaluate the effects of BCP exposure, in vitro dermal absorption and in vivo pharmacokinetic (PK) studies were conducted using gel and cream formulations. The Franz diffusion cell system and rat dorsal skin were used for tests according to the Korea Ministry of Food and Drug Safety guidelines for in vitro skin absorption methods. After the dermal application (1.13 mg/cm2) of BCP in the gel and cream formulations, liquid chromatography–mass spectrometry (LC–MS/MS) was used to evaluate the amount of BCP that remained unabsorbed on the skin (WASH), and that was present in the receptor fluid (RF), stratum corneum (SC), and (epi)dermis (SKIN). The total dermal absorption rate of BCP was 7.42 ± 0.74% for the gel formulation and 1.5 ± 0.9% for the cream formulation. Total recovery in an in vitro dermal absorption study was 109.12 ± 8.79% and 105.43 ± 11.07% for the gel and cream formulations, respectively. In vivo PK and dermal absorption studies of BCP were performed following the Organization for Economic Cooperation and Development guidelines 417 and 427, respectively. When intravenous (i.v.) pharmacokinetics was performed, BCP was dissolved in glycerol formal and injected into the tail vein (n = 3) of the rats at doses of 1 and 0.2 mg/kg. Dermal PK parameters were estimated by the application of the gel and cream formulations (2.34 mg/kg of BCP as an active ingredient) to the dorsal skin of the rats. Intravenous and dermal PK parameters were analyzed using a non-compartmental method. The dermal bioavailability of BCP was determined as 12.20 ± 2.63% and 4.65 ± 0.60% for the gel and cream formulations, respectively. The representative dermal absorption of BCP was evaluated to be 12.20 ± 2.63% based on the results of the in vivo PK study.

The temporal metabolomes associated with Rubus coreanus (RC) vinegar production were delineated using mass spectrometry-based metabolomic analyses with multivariate studies. We observed a clustered pattern of 27 discriminant metabolites: 4 organic acids, 9 sugars and sugar derivatives, 2 alcohol and carboxylic acid, 6 esters, and 6 terpenes. The levels of organic acids and alcohols were steadily decreased throughout fermentation, whereas those of sugars and sugar derivatives, carboxylic acids, esters, and terpenes peaked at 6 days. Further, the in vivo nutraceutical potentials of RC vinegar were examined with its metabolomic implications for bone health in growing rat model. Intriguingly, the plasmatic metabolomes among treated rat groups were observed with lower levels of non-essential amino acids and lysophosphatidylcholines (LysoPCs) coupled with higher levels of fatty acids and bile acids. The plasmatic metabolomes complemented with bone morphometric and clinical parameters suggest the bone health ameliorating effects of RC vinegar.

Dermal absorption of chemicals is a key factor in risk assessment. This study investigated the effects of different amounts of application on dermal absorption and suggested an appropriate application dose for proper dermal absorption. Caffeine and testosterone were chosen as test compounds. An in vitro dermal absorption test was performed using a Franz diffusion cell. Different amounts (5, 10, 25, and 50 mg (or µL)/cm2) of semisolid (cream) and liquid (solution) formulations containing 1% caffeine and 0.1% testosterone were applied to rat and minipig (Micropig®) skins. After 24 h, the concentrations of both compounds remaining on the skin surface and in the stratum corneum, dermis and epidermis, and receptor fluid were determined using LC-MS / MS or HPLC. Dermal absorption of both compounds decreased with increasing amounts of application in both skin types (rat and minipig) and formulations (cream and solution). Especially, dermal absorptions (%) of both compounds at 50 mg (or µL)/cm2 was significantly lower compared to 5 or 10 mg (or µL)/cm2 in both rat and minipig skins. Therefore, a low dose (5 or 10 mg (or µL)/cm2) of the formulation should be applied to obtain conservative dermal absorption.

Zingiber species are members of the Zingiberaceae family, and are widely used for medicinal and food purposes. In this study aboveground and root parts of Zingiber mioga and Zingiber officinale were subjected to metabolite profiling by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) in order to characterize them by species and parts and also to measure bioactivities. Both primary and secondary metabolites showed clear discrimination in the PCA score plot and PLS-DA by species and parts. Tetrahydrocurcumin, diarylheptanoid, 8-gingerol, and 8-paradol were discriminating metabolites between Z. mioga and Z. officinale that were present in different quantities. Eleven flavonoids, six amino acids, six organic acids, four fatty acids, and gingerenone A were higher in the aboveground parts than the root parts. Antioxidant activities were measured and were highest in the root part of Z. officinale. The relatively high contents of tetrahydrocurcumin, diarylheptanoid, and galanganol C in the root part of Z. officinale showed highly positive correlation with bioactivities based on correlation assay. On the basis of these results, we can suggest different usages of structurally different parts of Zingiber species as food plants.

In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without caffeine. The levels of cholesterol, triglycerides (TGs), and free fatty acid, as well as the size of adipose tissue altered by HFD, were improved by caffeine consumption. To investigate the metabolites that affected the change of the clinical factors, the urine and serum of rats fed a normal diet (ND), HFD, and HFDC were analyzed using ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS), gas chromatography (GC-TOF-MS), and linear trap quadruple mass spectrometry (LTQ-XL-MS) combined with multivariate analysis. A total of 68 and 52 metabolites were found to be different in urine and serum, respectively. After being fed caffeine, some glucuronide-conjugated compounds, lysoPCs, CEs, DGs, TGs, taurine, and hippuric acid were altered compared to the HFD group. In this study, caffeine might potentially inhibit HFD-induced obesity and we suggest possible biomarker candidates using MS-based metabolite profiling.

Penicillium spp. are known to harbor a wide array of secondary metabolites with cryptic bioactivities. However, the metabolomics of these species is not well-understood in terms of different fermentation models and conditions. The present study involved metabolomics profiling and transcriptomic analysis of Penicillium expansum 40815 under solid-state fermentation (SSF) and submerged fermentation (SmF). Metabolite profiling was carried out using ultra-performance liquid chromatography quadruple time-of-flight mass spectrometry with multivariate analysis, followed by transcriptomic analyses of differentially expressed genes. In principal component analysis, the metabolite profiling data was studied under different experimental sets, including SSF and SmF. The significantly different metabolites such as polyketide metabolites (agonodepside B, rotiorin, verrucosidin, and ochrephilone) and corresponding gene transcripts (polyketide synthase, aromatic prenyltransferase, and terpenoid synthase) were primarily detected under SmF conditions. In contrast, the meroterpenoid compounds (andrastin A and C) and their genes transcripts were exclusively detected under SSF conditions. We demonstrated that the metabolite production and its corresponding gene expression levels in P. expansum 40815 were significantly influenced by the varying growth parameters and the immediate environment. This study further provides a foundation to produce specific metabolites by regulating fermentation conditions.

The study was aimed at exploring the curative effects of Rubus coreanus (RC) vinegar against postmenopausal osteoporosis by using ovariectomized rats as a model. The investigations were performed in five groups: sham, ovariectomized (OVX) rats without treatment, low-dose RC vinegar (LRV)-treated OVX rats, high-dose RC vinegar (HRV)-treated OVX rats and alendronate (ALEN)-treated OVX rats. The efficacy of RC vinegar was evaluated using physical, biochemical, histological and metabolomic parameters. Compared to the OVX rats, the LRV and HRV groups showed positive effects on the aforementioned parameters, indicating estrogen regulation. Plasma metabolome analysis of the groups using gas chromatography-time of flight mass spectrometry (GC-TOF-MS) and ultra-performance liquid chromatography quadrupole-TOF-MS (UPLC-Q-TOF-MS) with multivariate analysis revealed 19 and 16 metabolites, respectively. Notably, the levels of butyric acid, phenylalanine, glucose, tryptophan and some lysophosphatidylcholines were marginally increased in RC vinegar-treated groups compared to OVX. However, the pattern of metabolite levels in RC vinegar-treated groups was found similar to ALEN, but differed significantly from that in sham group. The results highlight the prophylactic and curative potential of dietary vinegar against postmenopausal osteoporosis. RC vinegar could be an effective natural alternative for the prevention of postmenopausal osteoporosis.