Assessment of exposure to sulfuric acid in workers using cleaning equipment operated with lead-acid batteries.

Sulfuric acid, a constituent of lead-acid batteries, is an extremely hazardous substance, necessitating utmost caution. Unfortunately, many workers that utilize battery-operated equipment remain unaware of the potential exposure. This study aims to evaluate the potential exposure to sulfuric acid among workers employed by small companies associated with the operation of floor cleaning equipment powered by lead-acid batteries. Only cleaning equipment (hand-push and ride-on types) that required supplementation of lead-acid batteries with distilled water were targeted. Exposure measurement and analysis were performed according to the guidelines of NIOSH and including personal sampling and stationary sampling on the equipment. Exposure measurements indicated that workers were exposed to sulfuric acid. Additionally, the concentration level was slightly elevated in the stationary samples compared to personal samples. This study affirms that workers can experience exposure to sulfuric acid, even in the absence of direct handling of the substance. Consequently, there is a need to recognize and mitigate the potential risks.

E-Health Interventions for Older Adults With Frailty: A Systematic Review.

OBJECTIVE: : To systematically review the efficacy of e-Health interventions on physical performance, activity and quality of life in older adults with sarcopenia or frailty. METHODS: : A systematic review was conducted by searching the MEDLINE, Embase, Cochrane Library, CINHAL, Web of Science, and the Physiotherapy Evidence Database for experimental studies published in English from 1990 to 2021. E-Health studies investigating physical activity, physical performance, quality of life, and activity of daily living assessment in adults aged ≥65 years with sarcopenia or frailty were selected. RESULTS: : Among the 3,164 identified articles screened, a total of 4 studies complied with the inclusion criteria. The studies were heterogeneous by participant characteristics, type of e-Health intervention, and outcome measurement. Age criteria for participant selection and sex distribution were different between studies. Each study used different criteria for frailty, and no study used sarcopenia as a selection criteria. E-Health interventions were various across studies. Two studies used frailty status as an outcome measure and showed conflicting results. Muscle strength was assessed in 2 studies, and meta-analysis showed statistically significant improvement after intervention (standardized mean difference, 0.51; 95% confidence interval, 0.07-0.94; p=0.80, I2=0%). CONCLUSION: : This systematic review found insufficient evidence to support the efficacy of e-Health interventions. Nevertheless, the studies included in this review showed positive effects of e-Health interventions on improving muscle strength, physical activity, and quality of life in older adults with frailty.

Methyl lucidone inhibits airway inflammatory response by reducing TAK1 activity in human bronchial epithelial NCI-H292 cells.

Background: Methyl lucidone (ML), a methyl derivative of lucidone, has anti-inflammatory properties. However, the molecular mechanisms that reduce the inflammatory effect of ML in human lung epithelial cells remain unkown. This study aimed to elucidate the molecular mechanisms underlying the anti-inflammatory effect of ML. Methods: Four compounds (ML, methyl linderone, kanakugiol, and linderone) from Lindera erythrocarpa Makino were evaluated for their ability to reduce MUC5AC secretion levels in phorbol-12-myristate-13-acetate (PMA)-stimulated NCI-H292 cells using ELISA. The expression and secretion levels of inflammatory response-related proteins were analyzed using quantitative reverse transcription-PCR, ELISA, and western blotting. To determine whether ML directly regulates TGF-ß-activated kinase 1 (TAK1), we performed an in vitro kinase assay. Results: ML treatment effectively reduced the levels of inflammatory cytokines, including interleukin-1ß and TNF-α, increased by stimulation. Furthermore, ML downregulated the pathway cascade of both IκB kinase (IKK)/NF-κB and p38 mitogen-activated protein (MAP) kinase/CREB by inhibiting the upstream kinase TAK1. An in vitro kinase analysis confirmed that ML treatment significantly reduced the kinase activity of TAK1. Conclusion: ML pretreatment repressed the PMA-stimulated inflammation reaction by reducing the TAK1-mediated IKK/NF-κB and p38 MAP kinase/CREB signaling. These findings suggest that ML may improve respiratory health and can be used as a dietary supplement or functional food to prevent inflammatory lung diseases.

Garcinia mangostana Suppresses Triacylglycerol Synthesis in Hepatocytes and Enterocytes.

Regulation of diacylglycerol acyltransferase (DGAT) and pancreatic lipase (PL) activities is important in the treatment of triacylglycerol (TG)-related metabolic diseases. Garcinia mangostana, also known as mangosteen, is a traditional medicine ingredient used in the treatment of inflammation in Southeast Asia. In this study, The ethanolic extract of G. mangostana peel inhibited human recombinant DGAT1 and DGAT2, and PL enzyme activities in vitro. The inhibitory activity of DGAT1 and DGAT2 enzymes of four representative bioactive substances in mangosteen was confirmed. In addition, G. mangostana was confirmed to suppress the serum TG levels in C57 mice by inhibiting the absorption and synthesis of TG in the gastrointestinal tract. Through this study, it was revealed that G. mangostana extract could be useful for the prevention and amelioration of TG-related metabolic diseases such as obesity and fatty liver.

Comparing the Effectiveness of Physical Rehabilitation Interventions for Post-Stroke Function and Mobility Recovery: A Meta-Analysis.

Various interventions to physical rehabilitation have been used after stroke, including musculoskeletal, neurophysiological, and motor learning interventions, with ongoing debates and controversies about their relative effectiveness. In this systematic review, we searched 3 international electronic databases (MEDLINE, Embase, and Cochrane Library) to identify relevant studies. We included only randomized controlled trials (RCTs) that directly compared motor relearning, neurophysiological, and musculoskeletal interventions for improving motor function in adult stroke patients. Risk of bias (RoB) assessment was performed using Cochrane's RoB tool, and meta-analysis was conducted using Revman 5.4 with a random effects model. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations method. The meta-analysis for immediate outcome for physical rehabilitation included 9 RCTs for balance, 10 RCTs for gait velocity, 7 RCTs for lower extremity motor function and 8 RCTs for performance of activities of daily living. There was no statistically significant different on improvement of balance, gait velocity, lower extremity motor function and performance of activity among physical rehabilitation interventions. Moderate-level evidence supports that no single intervention is superior. Clinicians and therapist should consider individual patient characteristics, preferences, and available resources when selecting the intervention for stroke rehabilitation.

Clinical Practice Guideline for Stroke Rehabilitation in Korea-Part 1: Rehabilitation for Motor Function (2022).

This clinical practice guideline (CPG) is the fourth edition of the Korean guideline for stroke rehabilitation, which was last updated in 2016. The development approach has been changed from a consensus-based approach to an evidence-based approach using the Grading of Recommendations Assessment Development and Evaluation (GRADE) method. This change ensures that the guidelines are based on the latest and strongest evidence available. The aim is to provide the most accurate and effective guidance to stroke rehabilitation teams, and to improve the outcomes for stroke patients in Korea. Fifty-five specialists in stroke rehabilitation and one CPG development methodology expert participated in this development. The scope of the previous clinical guidelines was very extensive, making it difficult to revise at once. Therefore, it was decided that the scope of this revised CPG would be limited to Part 1: Rehabilitation for Motor Function. The key questions were selected by considering the preferences of the target population and referring to foreign guidelines for stroke rehabilitation, and the recommendations were completed through systematic literature review and the GRADE method. The draft recommendations, which were agreed upon through an official consensus process, were refined after evaluation by a public hearing and external expert evaluation.

Black Ginseng Extract Exerts Potentially Anti-Asthmatic Activity by Inhibiting the Protein Kinase Cθ-Mediated IL-4/STAT6 Signaling Pathway.

Asthma is a chronic inflammatory lung disease that causes respiratory difficulties. Black ginseng extract (BGE) has preventative effects on respiratory inflammatory diseases such as asthma. However, the pharmacological mechanisms behind the anti-asthmatic activity of BGE remain unknown. To investigate the anti-asthmatic mechanism of BGE, phorbol 12-myristate 13-acetate plus ionomycin (PMA/Iono)-stimulated mouse EL4 cells and ovalbumin (OVA)-induced mice with allergic airway inflammation were used. Immune cells (eosinophils/macrophages), interleukin (IL)-4, -5, -13, and serum immunoglobulin E (IgE) levels were measured using an enzyme-linked immunosorbent assay. Inflammatory cell recruitment and mucus secretion in the lung tissue were estimated. Protein expression was analyzed via Western blotting, including that of inducible nitric oxide synthase (iNOS) and the activation of protein kinase C theta (PKCθ) and its downstream signaling molecules. BGE decreased T helper (Th)2 cytokines, serum IgE, mucus secretion, and iNOS expression in mice with allergic airway inflammation, thereby providing a protective effect. Moreover, BGE and its major ginsenosides inhibited the production of Th2 cytokines in PMA/Iono-stimulated EL4 cells. In EL4 cells, these outcomes were accompanied by the inactivation of PKCθ and its downstream transcription factors, such as nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), activator of transcription 6 (STAT6), and GATA binding protein 3 (GATA3), which are involved in allergic airway inflammation. BGE also inhibited the activation of PKCθ and the abovementioned transcriptional factors in the lung tissue of mice with allergic airway inflammation. These results highlight the potential of BGE as a useful therapeutic and preventative agent for allergic airway inflammatory diseases such as allergic asthma.

Potent inhibition of human tyrosinase inhibitor by verproside from the whole plant of Pseudolysimachion rotundum var. subintegrum.

Affinity-based ultrafiltration-mass spectrometry coupled with ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry was utilised for the structural identification of direct tyrosinase ligands from a crude Pseudolysimachion rotundum var. subintegrum extract. False positives were recognised by introducing time-dependent inhibition in the control for comparison. The P. rotundum extract contained nine main metabolites in the UPLC-QTOF-MS chromatogram. However, four metabolites were reduced after incubation with tyrosinase, indicating that these metabolites were bound to tyrosinase. The IC50 values of verproside (1) were 31.2 µM and 197.3 µM for mTyr and hTyr, respectively. Verproside showed 5.6-fold higher efficacy than that of its positive control (kojic acid in hTyr). The most potent tyrosinase inhibitor, verproside, features a 3,4-dihydroxybenzoic acid moiety on the iridoid glycoside and inhibits tyrosinase in a time-dependent and competitive manner. Among these three compounds, verproside is bound to the active site pocket with a docking energy of -6.9 kcal/mol and four hydrogen bonding interactions with HIS61 and HIS85.

Clinical Practice Guidelines for Oropharyngeal Dysphagia.

OBJECTIVE: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one's physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. METHODS: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. RESULTS: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. CONCLUSION: This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Hydrogen-Bonding Trends in a Bithiophene with 3- and/or 4-Pyridyl Substituents.

To improve the charge-carrier transport capabilities of thin-film organic materials, the intermolecular electronic couplings in the material should be maximized. Decreasing intermolecular distance while maintaining proper orbital overlap in highly conjugated aromatic molecules has so far been a successful way to increase electronic coupling. We attempted to decrease the intermolecular distance in this study by synthesizing cocrystals of simple benzoic acid coformers and dipyridyl-2,2'-bithiophene molecules to understand how the coformer identity and pyridine N atom placement affected solid-state properties. We found that with the 5-(3-pyridyl)-5'-(4-pyridyl)-isomer, the 4-pyridyl ring interacted with electrophiles and protons more strongly. Synthesized cocrystal powders were found to have reduced average crystallite size in reference to the parent compounds. The opposite was found for the intermolecular electronic couplings, as determined via density functional theory (DFT) calculations, which were relatively large in some of the cocrystals.

Preoperative prediction of Ki-67 and p53 status in meningioma using a multiparametric MRI-based clinical-radiomic model.

Purpose: To investigate the utility of preoperative multiparametric magnetic resonance imaging (mpMRI)-based clinical-radiomic analysis combined with machine learning (ML) algorithms in predicting the expression of the Ki-67 proliferative index and p53 tumor suppressor protein in patients with meningioma. Methods: This multicenter retrospective study included 483 and 93 patients from two centers. The Ki-67 index was classified into high (Ki-67≥5%) and low (Ki-67<5%)-expressed groups, and the p53 index was classified into positive (p53≥5%) and negative (p53<5%)-expressed groups. Clinical and radiological features were analyzed using univariate and multivariate statistical analyses. Six ML models were performed with different types of classifiers to predict Ki-67 and p53 status. Results: In the multivariate analysis, larger tumor volumes (p<0.001), irregular tumor margin (p<0.001), and unclear tumor-brain interface (p<0.001) were independently associated with a high Ki-67 status, whereas the presence of both necrosis (p=0.003) and the dural tail sign (p=0.026) were independently associated with a positive p53 status. A relatively better performance was yielded from the model constructed by combined clinical and radiological features. The area under the curve (AUC) and accuracy of high Ki-67 were 0.820 and 0.867 in the internal test, and 0.666 and 0.773 in the external test, respectively. Regarding p53 positivity, the AUC and accuracy were 0.858 and 0.857 in the internal test, and 0.684 and 0.718 in the external test. Conclusion: The present study developed clinical-radiomic ML models to non-invasively predict Ki-67 and p53 expression in meningioma using mpMRI features, and provides a novel non-invasive strategy for assessing cell proliferation.

Diplacone Isolated from Paulownia tomentosa Mature Fruit Induces Ferroptosis-Mediated Cell Death through Mitochondrial Ca2+ Influx and Mitochondrial Permeability Transition.

The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)/glutathione peroxidase-4 (GPx4) and iron-dependent lipid peroxidation. Diplacone (DP), a geranylated flavonoid compound found in Paulownia tomentosa fruit, has been identified to have anti-inflammatory and anti-radical activity. In this study, the potential anticancer activity of DP was explored against A549 human lung cancer cells. It was found that DP induced a form of cytotoxicity distinct from apoptosis, which was accompanied by extensive mitochondrial-derived cytoplasmic vacuoles. DP was also shown to increase mitochondrial Ca2+ influx, reactive oxygen species (ROS) production, and mitochondrial permeability transition (MPT) pore-opening. These changes led to decreases in mitochondrial membrane potential and DP-induced cell death. DP also induced lipid peroxidation and ATF3 expression, which are hallmarks of ferroptosis. The ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 were effective in counteracting the DP-mediated ferroptosis-related features. Our results could contribute to the use of DP as a ferroptosis-inducing agent, enabling studies focusing on the relationship between ferroptosis and the immunogenic cell death of cancer cells.

Verproside, the Most Active Ingredient in YPL-001 Isolated from Pseudolysimachion rotundum var. subintegrum, Decreases Inflammatory Response by Inhibiting PKCδ Activation in Human Lung Epithelial Cells.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease which causes breathing problems. YPL-001, consisting of six iridoids, has potent inhibitory efficacy against COPD. Although YPL-001 has completed clinical trial phase 2a as a natural drug for COPD treatment, the most effective iridoid in YPL-001 and its mechanism for reducing airway inflammation remain unclear. To find an iridoid most effectively reducing airway inflammation, we examined the inhibitory effects of the six iridoids in YPL-001 on TNF or PMA-stimulated inflammation (IL-6, IL-8, or MUC5AC) in NCI-H292 cells. Here, we show that verproside among the six iridoids most strongly suppresses inflammation. Both TNF/NF-κB-induced MUC5AC expression and PMA/PKCδ/EGR-1-induced IL-6/-8 expression are successfully reduced by verproside. Verproside also shows anti-inflammatory effects on a broad range of airway stimulants in NCI-H292 cells. The inhibitory effect of verproside on the phosphorylation of PKC enzymes is specific to PKCδ. Finally, in vivo assay using the COPD-mouse model shows that verproside effectively reduces lung inflammation by suppressing PKCδ activation and mucus overproduction. Altogether, we propose YPL-001 and verproside as candidate drugs for treating inflammatory lung diseases that act by inhibiting PKCδ activation and its downstream pathways.

Gender-specific trends in cigarette smoking and lung cancer incidence: A two-stage age-stratified Bayesian joinpoint model.

BACKGROUND: Previous studies have explored population-level smoking trends and the incidence of lung cancer, but none has jointly modeled them. This study modeled the relationship between smoking rate and incidence of lung cancer, by gender, in the U.S. adult population and estimated the lag time between changes in smoking trend and changes in incidence trends. METHODS: The annual total numbers of smokers, by gender, were obtained from the database of the National Health Interview Survey (NHIS) program of the Centers for Disease Control and Prevention (CDC) for the years 1976 through 2018. The population-level incidence data for lung and bronchus cancers, by gender and five-year age group, were obtained for the same years from the Surveillance, Epidemiology, and End Results (SEER) program database of the National Cancer Institute. A Bayesian joinpoint statistical model, assuming Poisson errors, was developed to explore the relationship between smoking and lung cancer incidence in the time trend. RESULTS: The model estimates and predicts the rate of change of incidence in the time trend, adjusting for expected smoking rate in the population, age, and gender. It shows that smoking trend is a strong predictor of incidence trend and predicts that rates will be roughly equal for males and females in the year 2023, then the incidence rate for females will exceed that of males. In addition, the model estimates the lag time between smoking and incidence to be 8.079 years. CONCLUSIONS: Because there is a three-year delay in reporting smoking related data and a four-year delay for incidence data, this model provides valuable predictions of smoking rate and associated lung cancer incidence before the data are available. By recognizing differing trends by gender, the model will inform gender specific aspects of public health policy related to tobacco use and its impact on lung cancer incidence.

Extremely Low Activity of Serum Alanine Aminotransferase Is Associated with Long-Term Overall-Cause Mortality in the Elderly Patients Undergoing Percutaneous Coronary Intervention after Acute Coronary Syndrome.

Background and Objectives: Recent studies revealed that the extremely low activity of serum alanine aminotransferase (ALT) is associated with frailty and contributes to increased mortality after acute physical stress. We aimed to investigate whether the extremely low activity of serum ALT (<10 U/L) at the time of diagnosis can be used to predict overall-cause mortality in elderly patients that underwent percutaneous coronary intervention (PCI) after acute coronary syndrome (ACS) diagnosis. Materials and Methods: A retrospective medical record review was performed on 1597 patients diagnosed with ACS who underwent PCI at a single university hospital from February 2014 to March 2020. The associations between the extremely low activity of serum ALT and mortality were assessed using a stepwise Cox regression (forward: conditional). Results: A total of 210 elderly patients were analyzed in this study. The number of deaths was 64 (30.5%), the mean survival time was 25.0 ± 18.9 months, and the mean age was 76.9 ± 7.6 years. The mean door-to-PCI time was 74.0 ± 20.9 min. The results of stepwise Cox regression analysis showed that the extremely low activity of serum ALT (adjusted hazard ratio: 5.157, 95% confidence interval: 3.001-8.862, p < 0.001) was the independent risk factor for long-term overall-cause mortality in the elderly who underwent PCI after ACS diagnosis. Conclusions: The extremely low activity of serum ALT at ACS diagnosis is a significant risk factor for increased long-term overall-cause mortality in the elderly who underwent PCI after ACS diagnosis. It is noteworthy that a simple laboratory test at the time of diagnosis was found to be a significant risk factor for mortality.

Deep learning-based personalised outcome prediction after acute ischaemic stroke.

BACKGROUND: Whether deep learning models using clinical data and brain imaging can predict the long-term risk of major adverse cerebro/cardiovascular events (MACE) after acute ischaemic stroke (AIS) at the individual level has not yet been studied. METHODS: A total of 8590 patients with AIS admitted within 5 days of symptom onset were enrolled. The primary outcome was the occurrence of MACEs (a composite of stroke, acute myocardial infarction or death) over 12 months. The performance of deep learning models (DeepSurv and Deep-Survival-Machines (DeepSM)) and traditional survival models (Cox proportional hazards (CoxPH) and random survival forest (RSF)) were compared using the time-dependent concordance index ([Formula: see text] index). RESULTS: Given the top 1 to all 60 clinical factors according to feature importance, CoxPH and RSF yielded [Formula: see text] index of 0.7236-0.8222 and 0.7279-0.8335, respectively. Adding image features improved the performance of deep learning models and traditional models assisted by deep learning models. DeepSurv and DeepSM yielded the best [Formula: see text] index of 0.8496 and 0.8531 when images were added to all 39 relevant clinical factors, respectively. In feature importance, brain image was consistently ranked highly. Deep learning models automatically extracted the image features directly from personalised brain images and predicted the risk and date of future MACEs at the individual level. CONCLUSIONS: Deep learning models using clinical data and brain images could improve the prediction of MACEs and provide personalised outcome prediction for patients with AIS. Deep learning models will allow us to develop more accurate and tailored prognostic prediction systems that outperform traditional models.

Benzene exposure assessment of printing workers treating petroleum-based cleaner in South Korea.

This study was conducted to check whether benzene is contained inside the petroleum-based cleaning agent used in the printing industry and measure whether it is actually exposed to the air. Benzene was analyzed inside the cleaning agent and air exposure evaluation was done by area sampling. Risk assessment was performed using the Chemical Hazard Risk Management (CHARM) technique. Most products contained benzene based on the results obtained from this study. As a result of collecting air samples and checking whether the workers were exposed to benzene actually, benzene was detected in three samples. As a result of the risk assessment, most of printing businesses scored more than four points. Benzene was detected in all petroleum-based cleaning products. In addition, benzene was detected in some of air samples. Considering the fact that even small exposure level of benzene is dangerous to worker health and most of the printing businesses in South Korea operate on a small scale with fewer than five employees so the health management system is poor, it is necessary to prepare appropriate measures to prevent work diseases provoked by benzene exposure.

Exposure Assessment of Airborne Bacteria and Fungi in the Aircraft.

Objective: The exposure levels of disease-causing bacteria and germs were assessed on aircraft cleaning workers on multiple different aircrafts. Method: Five measuring points were selected depending on the aircraft types. Four aircraft cleaning agencies were selected for the test. Aircraft cleaning work was classified as intensive cleaning and general cleaning work. Ventilation in aircraft when sampling during the cleaning operation was categorized into forced ventilation and natural ventilation. The collection of airborne microorganisms was made through inertial impactors which were installed 1.5 meters above the bottom of the aircraft. The airborne bacteria and fungus growth badges were selected by Trytpic Soy Agar and Sabouraud Dextrose Agar. Results: The average concentrations of bacteria in the air were higher in the order of small, medium, and large airplanes. Rainy days had higher concentrations inside and outside the aircraft as compared to those in sunny days. Regarding ventilation, concentrations in natural ventilation were higher than concentrations in forced ventilation. According to the type of work, the concentrations in the intensive cleaning groups (cleaning one plane a day) were lower than those of the ordinary cleaning groups (cleaning several planes per day). Conclusion: The concentration levels of airborne bacteria and fungi in the aircraft surveyed were lower than the indoor environmental standards of Korea (800 cfu/m3 and 500 cfu/m3). The average concentrations of bacteria in the air and fungi in the air were highest in small aircraft owned by Company D.

Metabolites identification for major active components of Agastache rugosa in rat by UPLC-Orbitap-MS: Comparison of the difference between metabolism as a single component and as a component in a multi-component extract.

Agastache rugosa (fisch. & C.A. Mey.) Kuntze (A. rugosa) is used in traditional medicine in Korea since it has variety of medicinal activities, such as antioxidant, anti-inflammatory, anti-photoaging. Acacetin, tilianin, and rosmarinic acid are the active components of A. rugosa but their metabolites have not yet been fully identified. The purpose of this study was to identify the metabolites of A. rugosa after oral administration in Sprague-Dawley rats. For this study, active components (acacetin, tilianin, rosmarinic acid) and A. rugosa extract were dissolved in 0.5% carboxymethyl cellulose sodium solution respectively and treated by oral gavage at a dose of 50 mg/kg (for single compounds) and 200 mg/kg (for A. rugosa extract). For metabolite identification, plasma, urine, and fecal samples were collected after oral administration and analyzed using liquid chromatography coupled with Orbitrap mass spectrometry (UPLC-Orbitrap-MS) for data acquisition and metabolite identification. Metabolite identification was performed by considering the mass difference of the metabolites from the parent compounds and using their exact m/z and MS/MS fragments. The main biotransformation of the major components of A. rugosa was hydrolysis to acacetin, followed by demethylation, methylation, and conjugation. That of rosmarinic acid is methylated and conjugated. There were differences in metabolism between the treatment of single active components and extract; some sulfate-conjugated metabolites or metabolic intermediates were only detected in the treatment of single active components. The reason for this is thought to be the low content of the active components in the extract, which react competitively with the components present in the extract in the metabolic process. This study provides valuable evidence for a comprehensive understanding of the metabolism of A. rugosa.

Anti-Inflammatory Activity of Cajanin, an Isoflavonoid Derivative Isolated from Canavalia lineata Pods.

The bioactive components of Canavalia lineata (Thunb.) DC pods were investigated using bioactivity-guided isolation, and the chemical structures of flavonoids 1-3, isoflavonoid derivatives 4-11, and phenolic compounds 12 and 13 were identified by comparing NMR, MS, and CD spectral data with previously reported spectroscopic data. Compounds 1-13 were evaluated for their anti-inflammatory effects on LPS-stimulated RAW264.7 macrophages. Among these compounds, the isoflavonoid derivative cajanin (7) exhibited the most potent anti-inflammatory activity (IC50 of NO = 19.38 ± 0.05 µM; IC50 of IL-6 = 7.78 ± 0.04 µM; IC50 of TNF-α = 26.82 ± 0.11 µM), exerting its anti-inflammatory effects by suppressing the activation and nuclear translocation of the transcription factor NF-κB by phosphorylating IκB and p65. These results suggested that cajanin (7) may be a potential candidate for improving the treatment of inflammatory diseases.