The process of apoptotic cell clearance by phagocytes, known as efferocytosis, plays an essential role in maintaining homeostasis. Defects in efferocytosis can lead to inflammatory diseases such as atherosclerosis and autoimmune disorders. Therefore, the maintenance and promotion of efferocytosis are considered crucial for preventing these diseases. In this study, we observed that resveratrol, a representative functional food ingredient, and its glycoside, piceid, promoted efferocytosis in both human THP-1 macrophages differentiated with phorbol 12-myristate 13-acetate and peritoneal macrophages from thioglycolate-elicited mice. Resveratrol and piceid significantly increased mRNA expression and protein secretion of MFG-E8 in THP-1 macrophages. Furthermore, the activation of efferocytosis and the increment in MFG-E8 protein secretion caused by resveratrol or piceid treatment were canceled by MFG-E8 knockdown in THP-1 macrophages. In conclusion, we have demonstrated for the first time that resveratrol and piceid promote efferocytosis through the upregulation of MFG-E8 excretion in human THP-1 macrophages.
OBJECTIVE: The aim of this study was to determine the associations between dietary diversity and risk of dyslipidemia in Japanese workers. METHODS: The cross-sectional study included 1399 participants aged 20-63 years and the longitudinal study included 751 participants aged 20-60 years in 2012-2013 (baseline) who participated at least once from 2013 to 2017 with cumulative participation times of 4.9 times. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity score (DDS) was determined using the Quantitative Index for Dietary Diversity. Dyslipidemia was diagnosed when at least one of the following conditions was met: hypertriglyceridemia, high LDL-cholesterol, low HDL-cholesterol, high non-HDL-cholesterol, and a history of dyslipidemia. Multivariable logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for dyslipidemia with control of confounding factors in cross-sectional analysis. Generalized estimating equations were used for calculating the ORs (95% CI) for dyslipidemia in the follow-up period according to the DDS at baseline with control of confounding factors in longitudinal analysis. RESULTS: Cross-sectional analysis showed that the highest DDS reduced the odds of dyslipidemia in men (OR [95% CI] in Tertile 3: 0.67 [0.48-0.95], p value = 0.023). In longitudinal analysis, a moderate DDS reduced the risk of dyslipidemia (OR [95% CI] in Tertile 2: 0.21 [0.07-0.60], p value = 0.003) in women. CONCLUSIONS: The results of cross-sectional analysis in this study suggest that the higher diversity of diet might reduce the presence of dyslipidemia in men and the results of longitudinal analysis suggest that a moderate DDS might reduce the risk of dyslipidemia in women. Further studies are needed since the results of cross-sectional and longitudinal analyses in this study were inconsistent.
OBJECTIVE: To evaluate change in higher-level functional capacity of older Japanese individuals during the COVID-19 pandemic. METHODS: Four hundred older Japanese individuals completed an online questionnaire in early May 2021. Participants were asked retrospectively about their higher-level functional capacity and lifestyle before and during the COVID-19 pandemic. Higher-level functional capacity was determined as total score on the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). Total TMIG-IC score ranges from 0 to 13. A decline in higher-level functional capacity was defined as a decrease in TMIG-IC score of more than 2 points during the COVID-19 pandemic. Changes in higher-level functional capacity during the COVID-19 pandemic were assessed by paired t-test and a general linear model. RESULTS: Decreased TMIG-IC scores were found in 43 (21.5%) men and 61 (30.5%) women. Among those with higher-level functional capacity, scores for total TMIG-IC and Social Role decreased significantly in both sexes (all p<0.005). CONCLUSION: The findings suggest an association of the COVID-19 pandemic with a decrease in higher-level functional capacity, especially in Social Role, among older adults living in Japan. J. Med. Invest. 71 : 66-74, February, 2024.
COVID-19 , Humans , COVID-19/epidemiology , Female , Male , Aged , Japan/epidemiology , Aged, 80 and over , Retrospective Studies , Pandemics , Surveys and Questionnaires , Life Style , Geriatric Assessment
PURPOSE: To clarify the association between dietary diversity and inflammatory status in Japanese workers. METHODS: Of 1,460 men and women aged 20-64 years in 2010 (baseline), those who were followed-up at least once between 2011 and 2018 were included in this study; 1,433 participants and 745 participants were included in the cross-sectional and longitudinal analyses, respectively. Dietary intake was assessed using a food frequency questionnaire at baseline, and the dietary diversity score was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). High-sensitivity C-reactive protein (hs-CRP) was taken to indicate inflammatory status at the baseline and follow-up surveys. In the cross-sectional analysis using baseline data, a generalized linear model was used to calculate adjusted means and 95% confidence intervals (CIs) for hs-CRP according to the QUANTIDD score. In the longitudinal analysis, generalized estimating equations were used to calculate the adjusted mean (95% CI) for hs-CRP in follow-up according to the QUANTIDD score at baseline. RESULTS: In the cross-sectional analysis, the hs-CRP concentration in male participants was significantly lower in those who had a high QUANTIDD score (adjusted mean [95% CI]: 0.074 [0.009-0.140] mg/dL in the lower group vs. 0.038 [-0.029-0.105] mg/dL in the higher group, p-value = 0.034). In the longitudinal analysis, the hs-CRP concentration of male participants also tended to be lower in those with higher QUANTIDD scores (p-value = 0.103). In both the cross-sectional and longitudinal analyses in women, there was no significant difference between the lower and higher QUANTIDD score groups. CONCLUSION: These findings suggest that, in male Japanese workers, higher dietary diversity might be important for maintaining a low inflammatory status.
Immune checkpoint therapy has been shown to be an effective therapy for many types of tumors. Much attention has been paid to the development of an effector target would be helpful for immune checkpoint therapy. Genistein has been shown to have an anti-tumor effect both in vitro and in vivo. In this study, we examined the effect of genistein on immune checkpoint blockade therapy against B16F1 melanoma tumors. Mice treated with genistein or anti-programmed death (PD)-1 antibody showed a significant decrease in tumor growth. However, treatment with genistein had no effect on or attenuated the efficacy of immune checkpoint therapy. The percentages of T cell receptor (TCR)ß+CD4+ and TCRß+CD8+ cells and the concentrations of interferon-γ and tumor necrosis factor-α in tumor tissue were not different among the experimental groups. A significant difference was also not found in microbe composition. Interestingly, a high expression level of PD-ligand (L)1 closely reflected the outcome of therapy by genistein or anti-PD-1 antibody. The study showed that a combination of genistein treatment does not improve the effect of immune blockade therapy. It also showed that a high PD-L1 expression level in tumors is a good prediction maker for the outcome of tumor therapy.
This study assessed the validity of dietary balance scores (DBSs) by investigating the association between DBSs and nutrient adequacy (NA) in two Japanese populations. The participants were 65 community-dwelling Japanese from Tokushima Prefecture and 2,330 community-dwelling Japanese from Aichi Prefecture. Based on food frequency questionnaires or 3-day dietary records, we obtained 18 food groups. The NA score integrates nine beneficial nutrients and two nutrients that should be limited. We calculated four different DBSs: DBS1 consisted of five food groups (score range:0?20), DBS2 consisted of nine food groups (score range:0?36), DBS3 consisted of eight food groups (score range:0?32), and DBS4 consisted of 10 food groups (score range:0?40). Both the Spearman rank correlation coefficient with NA and the area under the receiver operating characteristic curve (AUC-ROC) for the nine beneficial nutrients were then estimated to test the performance of each DBS in predicting nutrient intake. The results showed that DBS1 and DBS4 were positively correlated with NA, while the AUC-ROC showed that DBS4 could moderately discriminate individuals with adequate intake levels of all nine nutrients. These findings suggest DBSs (especially DBS4) are useful in assessing dietary balance in middle-aged and older community-dwelling Japanese. J. Med. Invest. 70 : 377-387, August, 2023.
Diet , East Asian People , Aged , Humans , Middle Aged , Diet/methods , Energy Intake , Independent Living , Japan , Nutrients
We examined the effects of polymethoxyflavonoids (PMFs) on T helper (Th) 17 cell differentiation in vitro and in vivo. Five different PMFs including nobiletin (NOB), sudachitin (SUD), demethoxysudachitin, heptamethoxyflavone and natsudaidain were used for the in vitro study, and effects of those flavonoids on Th17 responses were investigated. NOB and heptamethoxyflavone significantly suppressed the proliferation response, but SUD, demethoxysudachitin and natsudaidain did not suppress the proliferation response. All of the five flavonoids decreased IL-17A production. Mice with experimentally induced autoimmune encephalomyelitis were used as an in vivo Th17 differentiation model. We focused on two flavonoids, NOB and SUD, and examined the effects of those flavonoids. NOB significantly suppressed Th17 cell proliferation and cytokine responses, but SUD only decreased proliferation responses. The results suggest that the suppressive effect of NOB on Th17 response in vivo is stronger than that of SUD. J. Med. Invest. 70 : 166-170, February, 2023.
Encephalomyelitis, Autoimmune, Experimental , Flavonoids , Mice , Animals , Flavonoids/pharmacology , Cytokines , Th17 Cells , Cell Differentiation , Mice, Inbred C57BL
BACKGROUND AND OBJECTIVES: We examined how food choice motives and dietary habits changed during the COVID-19 pandemic. METHODS AND STUDY DESIGN: Four hundred elderly Japanese completed an online questionnaire in early May in 2021. Participants were retrospectively asked about their intake of food groups and food choice motives before and during the COVID-19 pandemic. Dietary diversity was determined using the dietary variety score calculated from the food frequency questionnaire with 10 food groups. The importance of each of the nine food choice motives for elderly people was assessed. Each scores ranged from 1 to 5. Changes in food choice motives and dietary behaviors during the COVID-19 pandemic were assessed using the paired t-test and a general linear model. RESULTS: Among the food choice motives, scores for the importance of weight control, physical well-being and economical efficiency significantly increased in both sexes (all p<0.05). Dietary diversity score was lower during the COVID-19 pandemic than that before the pandemic in women (p=0.019), but there was no difference in men. In the multivariate adjustment model, physical well-being and economical efficiency were shown to have significant positive associations with the COVID-19 pandemic in women (p=0.034 and 0.009, respectively). In contrast, eating out was shown to have a significant inverse association with the COVID-19 pandemic in women (p=0.009). CONCLUSIONS: The findings suggest that the COVID-19 pandemic was associated with an increase in some food choice motives and a decrease in the frequency of eating out among elderly female Japanese.
COVID-19 , Pandemics , Aged , COVID-19/epidemiology , Diet , Feeding Behavior , Female , Humans , Internet , Japan/epidemiology , Male , Retrospective Studies , Surveys and Questionnaires
Sudachitin is a polymethoxylated flavone found in the peel of Citrus sudachi, a unique specialty citrus fruit in Tokushima Prefecture, Japan. Previous reports have demonstrated that sudachitin has anti-inflammatory and metabolic regulatory activities. However, to the best of our knowledge, no studies have explored whether sudachitin can act as an antitumor therapeutic agent by regulating metabolic functions in the tumor microenvironment. In the present study, cell proliferation and cytotoxicity assays were used to determine whether sudachitin inhibited the in vitro growth of liver cancer and pancreatic carcinoma, cholangiocarcinoma and colorectal cancer cells and to compare its toxicity against normal fibroblasts and induced cancer-associated fibroblasts (CAFs). Using lactate assays and reverse transcription-quantitative PCR, the effects of sudachitin on glycolysis in CAFs were investigated. The effects of CAFs on malignant tumor cells were evaluated in vitro using cell proliferation, wound healing and invasion assays. As result, sudachitin inhibited various types of tumor cells with different half-maximal inhibitory concentrations. Treatment with 50 µM sudachitin for 48 h suppressed tumor and CAFs proliferation but was not cytotoxic against normal fibroblasts. This dose also inhibited glycolysis in CAFs and, thus, diminished their pro-tumorigenic activities. Overall, the present study revealed that sudachitin has promise as a safe and widely available natural antitumor adjuvant.
The validity of dietary variety score (DVS) using a short-form questionnaire has not been investigated using dietary diversity based on a quantitative distribution of consumed foods in older Japanese. We examined the association between DVS and objective dietary diversity using a Quantitative Index for Dietary Diversity (QUANTIDD) based on the quantitative distribution of foods consumed by older Japanese community dwellers. The subjects were 65 older Japanese community dwellers aged 60?79 years. We used two kinds of scores for assessment of dietary diversity. At first, dietary diversity was determined using DVS calculated from answers to a questionnaire about frequencies of intake of 10 food groups. Second, dietary intake was assessed using a 3-day dietary record with photographs, and dietary diversity was determined using QUANTIDD. The relationships between DVS and QUANTIDD were assessed using partial correlation coefficients controlling for confounders. The correlation coefficient between DVS and QUANTIDD was moderate (r=0.212-0.458). After controlling for confounders, those correlation coefficient between DVS and QUANTIDD remained moderate. The findings suggest that there was a moderate relationship between DVS and QUANTIDD, and DVS using a short-form questionnaire may be useful for assessing dietary diversity in older Japanese community dwellers. J. Med. Invest. 69 : 31-37, February, 2022.
Diet , Food , Aged , Eating , Humans , Japan , Surveys and Questionnaires
The essential oil of Citrus sudachi (sudachi oil) is extracted from the peel of sudachi, a citrus plant. We investigated the effect of sudachi oil on immune function in both in vitro antigen (Ag) induced lymphocyte activation and in vivo Ag-specific immune response. In the in vitro study, the proliferative activity of splenocytes upon Ag-specific and non-specific stimulation was suppressed by treatment with sudachi oil in a dose-dependent manner. In addition, the expression level of Ag-presentation-related molecules and their Ag-presenting function on dendritic cells were suppressed by sudachi oil. To examine how sudachi oil regulates an Ag-specific immune response in vivo, mice were immunized with ovalbumin and the immune response of the mice was investigated. Ag-specific proliferation response of splenocytes from mice treated with sudachi essential oil was significantly suppressed. The results indicate that sudachi oil suppresses T cell and dendritic cell functions in vitro and Ag-specific T cell induction in vivo.
Citrus , Oils, Volatile , Mice , Animals , Lymphocyte Activation , Oils, Volatile/pharmacology , T-Lymphocytes , Ovalbumin , Mice, Inbred BALB C
Multiple sclerosis is an organ-specific autoimmune disease that targets the myelin antigen in the central nervous system. Nobiletin is a dietary polymethoxylated flavonoid found in citrus fruits. In this study, we investigated how nobiletin affects the disease state and immune responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis mice. Nobiletin was administered orally from 14 days before immunization until the end of the experiment, and clinical scores were determined. The production levels of interleukin-17A and interferon-γ were measured in a culture supernatant of splenocytes stimulated with myelin oligodendrocyte glycoprotein. In addition, flow cytometric analysis was performed to examine the effect of nobiletin on T cell differentiation in vitro. Admin-istration of nobiletin significantly decreased the clinical score and interleukin-17A production in splenocytes. Furthermore, in vitro analysis showed that nobiletin significantly suppressed Th17 cell differentiation and interleukin-17A production in a dose-dependent manner. The results suggest that nobiletin attenuates experimental autoimmune encephalomyelitis severity through modulation of Th17 cell differentiation.
Caveolin-1 is a major protein of the caveolae structure in vascular endothelial cell membrane. Phosphorylation of caveolin-1 is one of the initial events leading to exacerbation of vascular permeability caused by oxidative stress. Although quercetin is known to be an anti-atherosclerosis factor that acts as a dietary antioxidant, little is known about its role in the regulation of caveolin-1 phosphorylation. In this study, we investigated the inhibitory effect of quercetin on hydrogen peroxide-induced caveolin-1 phosphorylation in human umbilical vein endothelial cells. Quercetin inhibited caveolin-1 phosphorylation in cells pretreated with quercetin for 24âh and then exposed to hydrogen peroxide. However, quercetin 3-O-ß-glucuronide, a conjugated metabolite of quercetin, did not exert this inhibitory effect. Exposure to hydrogen peroxide increased vascular permeability and reduced mRNA expression of the intercellular adhesion protein, vascular endothelial cadherin (VE-cadherin). By contrast, pretreatment with quercetin suppressed the increase in vascular permeability and decreased VE-cadherin expression. These results indicate that deconjugated quercetin can play a role in the prevention of altered vascular permeability under oxidative stress by suppressing caveolin-1 phosphorylation. Thus, dietary quercetin may be beneficial for the maintenance of endothelial cell function.
BACKGROUND/OBJECTIVES: To clarify the effects of intake of legumes and isoflavones on all-cause mortality in middle-aged and older Japanese. SUBJECT/METHODS: The subjects were 2136 randomly chosen community-dwelling Japanese men and women aged 40-79 years who participated in a first-wave survey (1997-2000; baseline). The subjects were followed from baseline to December 31, 2017 (mean period of 16.6 ± 4.2 years). Intake of legumes, soybeans, and isoflavones at baseline was assessed using a 3-day dietary record with photographs. The relationships of intake amounts of legumes and isoflavones to mortality were assessed using Cox proportional hazards regression controlling for age, sex, education, employment, body mass index, smoking habits, medical histories, drinking, and energy intake. RESULTS: There were 491 deaths during the follow-up period. We found inverse associations of the intake of total soy products and intake of each of the isoflavones with all-cause mortality (p for trend < 0.05) in subjects aged < 60 years: the multivariate-adjusted hazard ratios (95% confidence intervals) for all-cause mortality in the highest intake group (third tertile) of total soy products and total isoflavones were 0.32 (0.13-0.78) and 0.35 (0.17-0.73), respectively, compared with the reference group (first tertile). In contrast, there were no significant associations of intake amounts of legumes, soybeans, and isoflavones with all-cause mortality in subjects aged 60 years or older. CONCLUSIONS: The findings suggest that a higher intake of isoflavones might decrease the risk of all-cause mortality, especially in middle-aged Japanese.
Isoflavones , Soy Foods , Adult , Aged , Diet , Diet Records , Female , Humans , Isoflavones/pharmacology , Japan/epidemiology , Male , Middle Aged , Glycine max
The aim of this study was to clarify the characteristics of lifestyle and health awareness according to dietary diversity in a Japanese worksite population. The participants were 1,312 men and women aged 20 to 63 years who were living in Tokushima Prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The characteristics of lifestyle and health awareness according to quartiles of the QUANTIDD score were assessed using the chi-square test and a general linear model. The higher the QUANTIDD score was, the larger were the proportions of participants who knew the appropriate amount of dietary intake and participants who referred to nutritional component information when choosing andâ/âor buying food. Among participants with higher QUANTIDD scores, the proportion of participants who considered their current diet was good was high in women, whereas the proportion of participants who wanted to improve their diet in the future was high in men. Those results indicate that higher dietary diversity was related to better characteristics of lifestyle and awareness of health. J. Med. Invest. 67 : 255-264, August, 2020.
Diet , Life Style , Adult , Awareness , Cross-Sectional Studies , Female , Health , Humans , Male , Middle Aged , Young Adult
We investigated the effects of Polygonum tinctorium Lour (PTL), a plant commonly known as indigo, on biological parameters in an animal model of high-fat diet-induced obesity. Wistar rats fed a high-fat diet and treated with PTL showed lower serum levels of triglycerides and total cholesterol levels and a higher serum levels of HDL cholesterol than those in Wistar rats fed a high-fat diet without PTL treatment. The weight of mesenteric fat in PTL-treated rats was decreased compared to that in control rats not treated with PTL. In addition, energy metabolic rate in the dark period, but not in the light period, in PTL-treated rats was higher than that in control rats. Although a significant difference was not observed, body weight in PTL-treated rats tended to be decreased compared to that in control rats. The results show that PTL improves serum lipid profiles in Wistar rats with high-fat diet-induced obesity. J. Med. Invest. 67 : 158-162, February, 2020.
Diet, High-Fat , Lipids/blood , Polygonum , Animals , Body Weight , Energy Metabolism/drug effects , Male , Polygonum/chemistry , Polyphenols/pharmacology , Rats , Rats, Wistar
BACKGROUND AND OBJECTIVES: The aim of this study was to determine the associations of dietary diversity with prevalences of allergic diseases. METHODS AND STUDY DESIGN: The participants were 1,317 men and women aged 20 to 63 years who were living in Tokushima Prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics and current medical histories of allergic diseases using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The ORs and 95% CIs for each of the allergic diseases with a 1 standard deviation (SD) increase in the QUANTIDD score were estimated, controlling for age, family history of allergic diseases, education, smoking, drinking, physical activity, energy intake and BMI. RESULTS: Higher dietary diversity showed significant inverse dose-response relationships with allergic diseases and allergic rhinitis in women. Multivariate-adjusted ORs (95% CI) for allergic diseases and allergic rhinitis with 1 SD increase in the QUANTIDD score were 0.77 (95% CI: 0.60-0.98, p=0.037) and 0.69 (95% CI: 0.53-0.90, p=0.007), respectively, in women. There were no significant associations between dietary diversity and allergic diseases in men. CONCLUSIONS: The results indicate that there is an inverse association between higher dietary diversity and allergic rhinitis in Japanese female workers.
Asthma/epidemiology , Dermatitis, Atopic/epidemiology , Diet/standards , Food/classification , Rhinitis, Allergic/epidemiology , Adult , Cross-Sectional Studies , Female , Humans , Japan/epidemiology , Male , Middle Aged , Risk Factors , Young Adult
We examined the effect of nobiletin (5,6,7,8,3',4'-hexamethoxyflavone) on immune response in ovalbumin (OVA)-immunized mice. Treatment with nobiletin increased OVA-specific IL-4 and IL-10 production. In addition, mice that received nobiletin showed higher levels of OVA-specific IgE, IgG and IgG1 production than did control mice. The antibody response to the thymus-independent antigen 2,4,6-trinitrophenyl-Ficoll was not different in the control and nobiletin groups, suggesting that nobiletin does not directly stimulate antibody production. An in vitro study showed that treatment with nobiletin enhanced the ability of antigen presentation of bone marrow-derived dendritic cells. The in vivo and in vitro results indicate that nobiletin regulates immune function.
Flavones/pharmacology , Immunity, Cellular , Immunity, Humoral , Ovalbumin/immunology , Animals , Bone Marrow Cells/drug effects , Bone Marrow Cells/immunology , Cells, Cultured , Cytokines/immunology , Cytokines/metabolism , Dendritic Cells/drug effects , Dendritic Cells/immunology , Ficoll/analogs & derivatives , Ficoll/immunology , Immunity, Cellular/drug effects , Immunity, Cellular/immunology , Immunity, Humoral/drug effects , Immunity, Humoral/immunology , Immunization , Mice , Mice, Inbred BALB C , Trinitrobenzenes/immunology
The aim of this study was to clarify the associations of family members living together with healthrelated behaviors in Japanese young workers. The participants were 300 men and women aged 20-39 years in 2015 who had a job. A web-based self-administered questionnaire on status of partnering and parenting, number of family members living together, dietary habits, drinking habit, smoking habit, self-rated health, employment status, working time and commuting time was conducted through Internet. Multiple logistic regression analysis and general linear models were used to assess the association of family members living together with healthrelated behaviors. The multivariate-adjusted odds ratio (95% confidence interval, p-value) for current drinking in unmarried participants living with their parents compared to unmarried participants living alone was 0.35 (0.13-0.93, p=0.036). The adjusted means of frequency of breakfast skipping and frequency of eating out showed a trend for inverse associations with the presence of a partner and children. However, those associations disappeared after adjustment for age of youngest child. The findings suggest that the presence of parents might affect drinking behavior and that age of youngest child living together might affect the frequency of breakfast skipping in young Japanese workers. J. Med. Invest. 66 : 141-147, February, 2019.
Alcohol Drinking , Health Behavior , Marital Status , Parents , Smoking , Adult , Cross-Sectional Studies , Family , Female , Humans , Male , Middle Aged
Scdachitin is a polymethoxyflavone (5,7,4'-trihydroxy-6,8,3-trimethoxyflavone) that is found in the peel of Citrus sudachi. We examined the effect of sudachitin on immune response in ovalbumin-immunized BALB/c mice. Treatment with sudachitin increased ovalbumin-specific IL-4 and IL-10 productions. In addition, mice that received sudachitin showed higher levels of ovalbumin-specific IgE, IgG1 and IgG l production than did control mice. The antibody response to the thymus-independent antigen 2,4,6-trinitrophenyl Ficoll was not different in the control and sudachitin groups, suggesting that sudachitin does not directly stimulate antibody production. An in vitro study showed that treatment of sudachitin enhanced the ability of antigen presentation in bone marrow-derived dendritic cells. Furthermore, CD11c+ cells that had been treated with sudachitin showed increased expression of co-stimulatory molecules. The results indicate that sudachitin regulates immune function both in vivo and in vitro.
