Bone-on-a-chip simulating bone metastasis in osteoporosis.

Osteoporosis is the most common bone disorder, which is a highly dangerous condition that can promote bone metastases. As the current treatment for osteoporosis involves long-term medication therapy and a cure for bone metastasis is not known, ongoing efforts are required for drug development for osteoporosis. Animal experiments, traditionally used for drug development, raise ethical concerns and are expensive and time-consuming. Organ-on-a-chip technology is being developed as a tool to supplement such animal models. In this study, we developed a bone-on-a-chip by co-culturing osteoblasts, osteocytes, and osteoclasts in an extracellular matrix environment that can represent normal bone, osteopenia, and osteoporotic conditions. We then simulated bone metastases using breast cancer cells in three different bone conditions and observed that bone metastases were most active in osteoporotic conditions. Furthermore, it was revealed that the promotion of bone metastasis in osteoporotic conditions is due to increased vascular permeability. The bone-on-a-chip developed in this study can serve as a platform to complement animal models for drug development for osteoporosis and bone metastasis.

Effects of Endocrine-Disrupting Chemicals on Bone Health.

This comprehensive review critically examines the detrimental impacts of endocrine-disrupting chemicals (EDCs) on bone health, with a specific focus on substances such as bisphenol A (BPA), per- and polyfluoroalkyl substances (PFASs), phthalates, and dioxins. These EDCs, by interfering with the endocrine system's normal functioning, pose a significant risk to bone metabolism, potentially leading to a heightened susceptibility to bone-related disorders and diseases. Notably, BPA has been shown to inhibit the differentiation of osteoblasts and promote the apoptosis of osteoblasts, which results in altered bone turnover status. PFASs, known for their environmental persistence and ability to bioaccumulate in the human body, have been linked to an increased osteoporosis risk. Similarly, phthalates, which are widely used in the production of plastics, have been associated with adverse bone health outcomes, showing an inverse relationship between phthalate exposure and bone mineral density. Dioxins present a more complex picture, with research findings suggesting both potential benefits and adverse effects on bone structure and density, depending on factors such as the timing and level of exposure. This review underscores the urgent need for further research to better understand the specific pathways through which EDCs affect bone health and to develop targeted strategies for mitigating their potentially harmful impacts.

Parathyroid-on-a-chip simulating parathyroid hormone secretion in response to calcium concentration.

The parathyroid gland is an endocrine organ that plays a crucial role in regulating calcium levels in blood serum through the secretion of parathyroid hormone (PTH). Hypoparathyroidism is a chronic disease that can occur due to parathyroid defects, but due to the difficulty of creating animal models of this disease or obtaining human normal parathyroid cells, the evaluation of parathyroid functionality for drug development is limited. Although parathyroid-like cells that secrete PTH have recently been reported, their functionality may be overestimated using traditional culture methods that lack in vivo similarities, particularly vascularization. To overcome these limitations, we obtained parathyroid organoids from tonsil-derived mesenchymal stem cells (TMSCs) and fabricated a parathyroid-on-a-chip, capable of simulating PTH secretion based on calcium concentration. This chip exhibited differences in PTH secretion according to calcium concentration and secreted PTH within the range of normal serum levels. In addition, branches of organoids, which are difficult to observe in animal models, were observed in this chip. This could serve as a guideline for successful engraftment in implantation therapies in the future.

Bone Loss after Solid Organ Transplantation: A Review of Organ-Specific Considerations.

This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.

Association between exercise and risk of fractures in new-onset type 2 diabetes: a retrospective cohort study.

In this population-based retrospective cohort study, exercising before and after the diagnosis of type 2 diabetes was significantly associated with lower risk of fractures. This result suggested that exercising might be effective in reducing fracture risk. PURPOSE: Patients with diabetes have a significantly higher risk of fractures. We aimed to investigate the association between exercise and fracture risk in new-onset type 2 diabetes. METHODS: This retrospective cohort study using the Korean National Health Insurance Service database included 170,148 patients with new-onset type 2 diabetes who underwent two cycles of health checkup between 2009-2012 and 2011-2014. The patients were classified into four groups (non-exercising, newly exercising, previously exercising, and continuously exercising) and followed up until the date of fracture, death, or December 31, 2018. Hip fractures, vertebral fractures, and any fractures were defined using diagnostic codes. RESULTS: The proportions of non-exercising, newly exercising, previously exercising, and continuously exercising patients were 65.1%, 15.7%, 10.9%, and 8.3%, respectively. Continuously exercising patients showed the lowest risk for fractures, followed by newly exercising patients using the non-exercising group as a reference. The adjusted hazard ratios (95% confidence intervals) for hip fracture, vertebral fracture, and any fracture were 0.69 (0.50-0.94), 0.73 (0.63-0.84), and 0.90 (0.83-0.97), respectively, in the continuously exercising group and 0.76 (0.61-0.95), 0.85 (0.76-0.94), and 0.93 (0.88-0.98) in the newly exercising group. The risk was lower in patients who lost less than 5% of their body weight than in those who lost 5% or more. CONCLUSION: Exercising was associated with lower risk of fractures in newly diagnosed diabetes. However, exercise accompanied by excessive weight loss may not have a significant association with a lower risk of fractures.

Two-Year Changes in Diabetic Kidney Disease Phenotype and the Risk of Heart Failure: A Nationwide Population-Based Study in Korea.

BACKGRUOUND: Diabetic kidney disease (DKD) is a risk factor for hospitalization for heart failure (HHF). DKD could be classified into four phenotypes by estimated glomerular filtration rate (eGFR, normal vs. low) and proteinuria (PU, negative vs. positive). Also, the phenotype often changes dynamically. This study examined HHF risk according to the DKD phenotype changes across 2-year assessments. METHODS: The study included 1,343,116 patients with type 2 diabetes mellitus (T2DM) from the Korean National Health Insurance Service database after excluding a very high-risk phenotype (eGFR <30 mL/min/1.73 m2) at baseline, who underwent two cycles of medical checkups between 2009 and 2014. From the baseline and 2-year eGFR and PU results, participants were divided into 10 DKD phenotypic change categories. RESULTS: During an average of 6.5 years of follow-up, 7,874 subjects developed HHF. The cumulative incidence of HHF from index date was highest in the eGFRlowPU- phenotype, followed by eGFRnorPU+ and eGFRnorPU-. Changes in DKD phenotype differently affect HHF risk. When the persistent eGFRnorPU- category was the reference, hazard ratios for HHF were 3.10 (95% confidence interval [CI], 2.73 to 3.52) in persistent eGFRnorPU+ and 1.86 (95% CI, 1.73 to 1.99) in persistent eGFRlowPU-. Among altered phenotypes, the category converted to eGFRlowPU+ showed the highest risk. In the normal eGFR category at the second examination, those who converted from PU- to PU+ showed a higher risk of HHF than those who converted from PU+ to PU-. CONCLUSION: Changes in DKD phenotype, particularly with the presence of PU, are more likely to reflect the risk of HHF, compared with DKD phenotype based on a single time point in patients with T2DM.

Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract.

Metformin as an oral glucose-lowering drug is used to treat type 2 diabetic mellitus. Considering the relatively high incidence of cardiovascular complications and other metabolic diseases in diabetic mellitus patients, a combination of metformin plus herbal supplements is a preferrable way to improve the therapeutic outcomes of metformin. Ginseng berry, the fruit of Panax ginseng Meyer, has investigated as a candidate in metformin combination mainly due to its anti-hyperglycemic, anti-hyperlipidemic, anti-obesity, anti-hepatic steatosis and anti-inflammatory effects. Moreover, the pharmacokinetic interaction of metformin via OCTs and MATEs leads to changes in the efficacy and/or toxicity of metformin. Thus, we assessed how ginseng berry extract (GB) affects metformin pharmacokinetics in mice, specially focusing on the effect of the treatment period (i.e., 1-day and 28-day) of GB on metformin pharmacokinetics. In 1-day and 28-day co-treatment of metformin and GB, GB did not affect renal excretion as a main elimination route of metformin and GB therefore did not change the systemic exposure of metformin. Interestingly, 28-day co-treatment of GB increased metformin concentration in the livers (i.e., 37.3, 59.3% and 60.9% increases versus 1-day metformin, 1-day metformin plus GB and 28-day metformin groups, respectively). This was probably due to the increased metformin uptake via OCT1 and decreased metformin biliary excretion via MATE1 in the livers. These results suggest that co-treatment of GB for 28 days (i.e., long-term combined treatment of GB) enhanced metformin concentration in the liver as a pharmacological target tissue of metformin. However, GB showed a negligible impact on the systemic exposure of metformin in relation to its toxicity (i.e., renal and plasma concentrations of metformin).

The effect of metabolic dysfunction-associated fatty liver disease and diabetic kidney disease on the risk of hospitalization of heart failure in type 2 diabetes: a retrospective cohort study.

BACKGROUND: Diabetes mellitus is a major risk factor for heart failure. A recent consensus statement recommended annual cardiac biomarker testing (e.g. natriuretic peptide or high-sensitivity cardiac troponin) for all patients with diabetes. We aimed to identify patients at a higher risk of hospitalization for heart failure among patients with type 2 diabetes to prioritize those who would require screening. METHODS: Overall, 1,189,113 patients who underwent two medical health checkup cycles (2009-2012 and 2011-2014) and had stable diabetic kidney disease (DKD) phenotype in the Korean National Health Insurance Service database were included in this study. After excluding those with concurrent proteinuria (PU) and reduced estimated glomerular filtration rate, three groups (no-DKD, PU+DKD, and PU-DKD) were identified. A fatty liver index of ≥ 60 was defined as metabolic dysfunction-associated fatty liver disease (MAFLD). Patients were followed up until December 2018 or until outcomes developed. The Cox proportional hazard model was used to compare the risk of hospitalization for heart failure across groups. RESULTS: During an average of 6.6 years of follow-up, 5781 patients developed hospitalization for heart failure. After adjusting for covariates, the risk of hospitalization for heart failure was highest in the PU+DKD group [HR 3.12, 95% CI (2.75-3.55)], followed by the PU-DKD group [HR 1.85, 95% CI (1.73-1.99)] using the no-DKD group as the reference category. The risk of hospitalization for heart failure was comparable regardless of MAFLD status in patients who already had DKD. However, in the no-DKD group, the risk of hospitalization for heart failure was 1.4 times higher in patients with MAFLD than in those without [HR 1.41, 95% CI (1.31-1.52)]. CONCLUSIONS: In lines with the international consensus statement, we suggest that annual cardiac biomarker testing should be conducted at least in patients with DKD and/or MAFLD.

Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database.

The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.

The Identification and Quantitative Analysis of Unusual Keto-Carotenoids in Ripe Fruits of Maclura tricuspidate and Its Potential as a Valuable Source of Cryptocapsin.

Ripe fruits of Maclura tricuspidata (MT) are used as food material and a natural colorant in Korea. Although MT fruits have a deep red color due to carotenoid-like pigments, their chemical nature has not been explored in detail so far. The present study aimed at elucidating the chemical structures and composition of carotenoids in MT fruits and changes at different maturity stages. Two carotenoids from saponified MT fruit extract were isolated using repeated silica gel column chromatography. Based on interpretations of spectroscopic data, these compounds were determined as keto-carotenoids, i.e., capsanthin (3,3'-dihydroxy-ß,κ-caroten-6'-one) and cryptocapsin (3'-hydroxy-ß,κ-caroten-6'-one), and the contents of individual carotenoids were quantified with HPLC based on calibration curves obtained from authentic standards. The contents of capsanthin and cryptocapsin in the sample of saponified MT fruits were 57.65 ± 1.97 µg/g and 171.66 ± 4.85 µg/g as dry weight base (dw). The majority of these keto-carotenoids in the MT fruits were present in esterified forms with lauric, myristic or palmitic acid rather than in their free forms. The results also showed that esterification of these compounds occurred starting from early stage (yellow-brownish stage) of maturation. Considering the high cryptocapsin content, MT fruits can be applied as a potentially valuable source of cryptocapsin for food and medicinal application as well as a source of provitamin A.

The risk of Parkinson's disease according to diabetic kidney disease status in a Korean population.

INTRODUCTION: Type 2 diabetes is a risk factor for Parkinson's disease (PD). Recently, it has been reported that proteinuria without reduced estimated glomerular filtration rate (eGFR) can increase the risk of PD development. The objective of this study was to evaluate the risk of PD among Korean adults with type 2 diabetes stratified by proteinuria (PU) and eGFR levels. METHODS: Using the Korean National Health Insurance Service database, a total of 2,217,326 patients with type 2 diabetes who underwent regular health check-ups from 2009 to 2012 were included. These patients were classified into four groups (no-diabetic kidney disease (DKD) (PU-GFR-), proteinuric DKD with normal eGFR (PU+GFR-), nonproteinuric DKD (PU-GFR+), and proteinuric DKD with reduced eGFR (PU+GFR+) and followed up until 2018. PD was defined using International Classification of Diseases, 10th revision. RESULTS: The prevalence of PU-GFR-, PU+GFR-, PU-GFR+, or PU+GFR+ phenotype was 83.3%, 5.0%, 10.1%, or 1.6%, respectively. During a median follow-up of 7.2 years, 16,079 participants developed PD. Hazard ratios for PD were 1.10 (95% confidence interval [CI]: 1.01-1.21, p = 0.0091), 1.15 (95% CI: 1.09-1.21, p < 0.0001), and 1.23 (95% CI: 1.09-1.39, p < 0.0001) for participants in PU+GFR-, PU-GFR+, and PU+GFR+ groups relative to those in the PU-GFR- group, respectively. Effects of DKD on PD were more pronounced in those aged less than 65 years. CONCLUSION: Reduced eGFR and/or proteinuria might be independent risk factors for boosting PD development among patients with type 2 diabetes. More attention should be paid to PD in patients with DKD, even in a younger aged population.

Hip Fracture Risk According to Diabetic Kidney Disease Phenotype in a Korean Population.

BACKGROUND: Diabetic kidney disease (DKD) is associated with an elevated risk of fractures. However, little is known about the association between proteinuric or non-proteinuric DKD and the risk of hip fracture. Thus, we investigated the incidence of hip fractures among Korean adults with type 2 diabetes mellitus (T2DM) stratified by DKD phenotype. METHODS: In this retrospective cohort study using the Korean National Health Insurance Service database, patients with T2DM who received at least one general health checkup between 2009 and 2012 were followed until the date of hip fracture, death, or December 31, 2018. We classified the DKD phenotype by proteinuria and estimated glomerular filtration rate (eGFR), as follows: no DKD (PU-GFR-), proteinuric DKD with normal eGFR (PU+GFR-), non-proteinuric DKD with reduced eGFR (PU-GFR+), and proteinuric DKD with reduced eGFR (PU+GFR+). RESULTS: The cumulative incidence of hip fractures was highest in the PU+GFR+ group, followed by the PU-GFR+ group and the PU+GFR- group. After adjustment for confounding factors, the hazard ratio (HR) for hip fracture was still highest in the PU+GFR+ group. However, the PU+GFR- group had a higher HR for hip fracture than the PU-GFR+ group (PU+GFR+ : HR, 1.69; 95% confidence interval [CI], 1.57 to 1.81; PU+GFR- : HR, 1.37; 95% CI, 1.30 to 1.46; PU-GFR+ : HR, 1.20; 95% CI, 1.16 to 1.24 using the PU-GFR- group as the reference category). CONCLUSION: The present study demonstrated that DKD was significantly associated with a higher risk of hip fracture, with proteinuria as a major determinant.

Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Stroke among Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients. METHODS: Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF). RESULTS: After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease. CONCLUSION: In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

Discordance in Bone Mineral Density between the Lumbar Spine and Femoral Neck Is Associated with Renal Dysfunction.

PURPOSE: Bone mineral density (BMD) determined by dual-energy X-ray absorptiometry is considered a gold standard for diagnosing osteoporosis. Some people show discordance in BMD values measured at the femur and that at the lumbar spine (LS). The aim of the present study was to investigate whether differences in BMD T-scores between the LS and femur neck (FN) are associated with renal dysfunction in the general population of Korea. MATERIALS AND METHODS: We analyzed national data for 17306 adults from the Korean National Health and Nutrition Examination Survey conducted between 2008 and 2011. BMD T-score differences between LS and FN (termed BMD offset) were calculated by subtracting FN T-scores from LS T-scores. Diminished renal function was defined as estimated glomerular filtration rates (eGFR) less than 60 mL/min/1.73 m². RESULTS: Among those aged ≥50 years, BMD offset was negatively associated with eGFR levels. Additionally, eGFR levels decreased linearly across increasing BMD offset quartiles. Men and women with an offset of >1.5 showed a 4.79-times and 2.51-times higher risk of renal dysfunction, respectively, compared to individuals with an offset of ≤0, after adjusting for age, body mass index, educational level, current smoking, and physical activity. In contrast, there was little evidence of an association between renal dysfunction and BMD offset in subjects aged <50 years. CONCLUSION: Discordance between LS and FN BMDs was significantly associated with renal dysfunction in subjects aged ≥50 years. When assessing bone health in older chronic kidney disease patients, physicians should consider the possibility of BMD discordance between LS and FN.

Identification of Novel Parishin Compounds from the Twig of Maclura tricuspidata and Comparative Analysis of Parishin Derivatives in Different Parts.

Parishin compounds are rare polyphenolic glucosides mainly found in the rhizome of the traditional Chinese medicinal plant, Gastrodia elata. These constituents are reported to have several biological and pharmacological activities. In the present study, two novel parishin derivatives not previously reported as plant-based phytochemicals were identified from a twig of Maclura tricuspidata (MT) and two new compounds were elucidated as 1-(4-(ß-d-glucopyranosyloxy)benzyl)-3-hydroxy-3-methylpentane-1,5-dioate (named macluraparishin E) and 1,3-bis(4-(ß-d-glucopyranosyloxy)benzyl)-3-hydroxy-3-methylpentane- 1,5-dioate (macluraparishin C), based on the experimental data obtained by UV-Visible (UV-Vis) spectroscopy, high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) and nuclear magnetic resonance (NMR) spectroscopy. Additionally, gastrodin, parishin A and parishin B were positively identified by spectroscopic evidence and the comparison of HPLC retention time with the corresponding authentic standards. Gastrodin, parishin A and parishin B, macluraparishin E and macluraparishin C were found to be the most abundant constituents in the MT twig. The compositions and contents of these constituents were found to vary depending on the different parts of the MT plant. In particular, the contents of parishin A, parishin B, macluraparishin C and macluraparishin E were higher in the twig, bark and root than in the leaves, xylem and fruit.

Inhibitory Effects of Luteolin 7-Methyl Ether Isolated from Wikstroemia ganpi on Tnf-A/Ifn-Γ Mixture-Induced Inflammation in Human Keratinocyte.

Plants of the genus Wikstroemia are traditionally used in China to treat various inflammatory diseases. The purpose of this study was to isolate the components of Wikstroemia ganpi (Siebold & Zucc.) Maxim., to evaluate their anti-atopic activities and to identify candidates with anti-atopic therapeutics. A total of 24 compounds were isolated by bioassay-guided separation, including one novel compound, which was tilianin 5-methyl ether. The anti-atopic activities of the isolated compounds were determined using TNF-α-treated RBL-2H3 cells and HaCaT cells. The mRNA expressions of IL-4, IL-6, GM-CSF, G-CSF and TRPV1 were reduced by luteolin 7-methyl ether. The study shows that the luteolin 7-methyl ether isolated from W. ganpi is a potential therapeutic agent for the treatment of atopic dermatitis.

Effects of Short-term Mobile Application Use on Weight Reduction for Patients with Type 2 Diabetes.

BACKGROUND: The increasing prevalence of type 2 diabetes mellitus (T2DM) has led to a significant health burden. Technological advancements have highlighted the benefits of digital therapeutics for chronic diseases. In this study, we aimed to investigate the effects of a mobile application on weight reduction in patients with T2DM. METHODS: A total of 48 patients with T2DM was included in this single-center, randomized, controlled trial. In addition to conventional treatment, participants in the intervention group used a mobile application-based self-management system for diet, exercise, and medication adherence. The primary outcome of this study was weight change after 3 months of intervention, and secondary outcomes were metabolic parameters. RESULTS: After 12 weeks, no significant differences in body weight change were observed between the intervention and control groups (P=0.229). However, a significant difference was found in waist circumference (WC) between the two groups, wherein the control group showed an increase in WC (from 95.00±8.89 cm to 95.76±9.72 cm), while the intervention group showed a reduction (from 91.93±6.25 cm to 90.75±6.01 cm) with a significant time by group interaction (P=0.016). Additionally, participants with good compliance exhibited a more evident reduction in WC (P=0.037). However, no significant differences were found in other metabolic parameters between the two groups. CONCLUSION: Lifestyle modification using short-term mobile applications effectively reduced WC, especially in patients with good adherence to the application. However, weight reduction was not achieved.

Haplopine Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in Mice and TNF-α/IFN-γ-Induced Inflammation in Human Keratinocyte.

This study aimed to investigate the anti-inflammatory, antioxidant, and anti-atopic dermatitis (AD) effects of haplopine, which is one of the active components in D. dasycarpus. Haplopine (12.5 and 25 µM) inhibited the mRNA expressions of inflammatory cytokines IL-6, TSLP, GM-CSF, and G-CSF and the protein expressions of IL-6 and GM-CSF in TNF-α/INF-γ-stimulated HaCaT cells. In H2O2-induced Jukat T cells, haplopine (25 and 50 µM) suppressed the productions of proinflammatory cytokines (IL-4, IL-13, and COX-2) and increased the mRNA and protein expressions of oxidative stress defense enzymes (SOD, CAT, and HO-1) in a concentration-dependent manner. In vivo, haplopine significantly attenuated the development of AD symptoms in 2,4-dinitrochlorobenzene (DNCB)-stimulated Balb/c mice, as evidenced by reduced clinical dermatitis scores, skin thickness measurements, mast cell infiltration, and serum IgE concentrations. These findings demonstrate that haplopine should be considered a novel anti-atopic agent with the potential to treat AD.