Lower vitamin D levels in the breast milk is associated with atopic dermatitis in early infancy.

BACKGROUND: Our previous study showed that the discontinuation of breastfeeding could improve atopic dermatitis (AD) symptoms in exclusively breastfed infants. As vitamins A and D are influential on the immune system, we aimed to analyze the association of vitamin A and D levels in breast milk (BM) with AD. METHODS: We enrolled two- to four-month-old exclusively breastfed infants. The objective SCORing Atopic Dermatitis (objSCORAD) was evaluated. The lipid layer of BM was extracted and analyzed by liquid chromatography for vitamin A and D levels. Medical charts were reviewed for the clinical course of AD. RESULTS: Forty-five AD patients and 45 healthy controls were enrolled. The objSCORAD was 20.54 ± 1.73 (shown as mean ± SEM) in the AD group. The sex, parental atopy history, nutrient intake of mothers, and vitamin A levels in BM were not significantly different between the two groups. The 25-(OH) D3 level in BM was significantly lower in the AD group than in the control group (1.72 ± 0.30 and 3.95 ± 0.64 ng/mL, respectively; P = .001). The 25-(OH) D3 level negatively correlated with objSCORAD (P = .003). The only factor that is significantly associated with persistent AD is the objSCORAD in infancy (P = .003) after adjusting for age, sex, parental atopy history, and 25-(OH) D3 level by multiple regression. CONCLUSION: Vitamin D levels in BM for exclusively breastfed infants were negatively associated with objSCORAD. Lower vitamin D levels in BM might be a risk factor for infantile AD.

Hyperimmune colostrum alleviates rheumatoid arthritis in a collagen-induced arthritis murine model.

Our aging population and the accompanying decline in immune function is a growing concern that may be addressed by finding natural methods to enhance the immunocompetence of our elderly. Bovine milk and colostrum from cows that have been immunized have been shown to provide additional immunoglobulins and other bioactive molecules that enhance immune function. The purpose of this study was to investigate the ability of hyperimmune bovine colostrum to alleviate the symptoms of rheumatoid arthritis in a murine model. The collagen-induced arthritis DBA/1J murine model was used for this study. Mice were fed colostrum from immunized cows at either 5 or 10 mg/mouse per day or controls for 49 d. The data showed that the colostrum-fed groups had significantly lower total swelling scores and significantly lower collagen-specific antibody (IgG2a), inflammation-associated antibody (total IgG), and the inflammatory cytokines tumor necrosis factor α, IL-2, IL-6, and IFN-γ. The results strongly suggest that colostrum from immunized cows may have anti-inflammatory activity in a mouse model of rheumatoid arthritis.

Ethanol Extract of Perilla frutescens Suppresses Allergen-Specific Th2 Responses and Alleviates Airway Inflammation and Hyperreactivity in Ovalbumin-Sensitized Murine Model of Asthma.

This study was to investigate the effects of different fractions of Perilla frutescens (Pf) leaves extracted by water or ethanol on asthma. BALB/c mice sensitized intraperitoneally and challenged with ovalbumin (OVA) were divided into six groups. Each group of mice was tube-feeding with 0 (control), 80 µg (PfWL), or 320 µg (PfWH) water extracts or 80 µg (PfEL) or 320 µg (PfEH) ethanol extracts of perilla leaves daily for 3 weeks. A negative control group (PBS) was neither sensitized nor treated with Pf. The effects of perilla leave extracts on allergic immune response were evaluated. The results showed that OVA-specific IL-5 and IL-13 secretions from OVA-stimulated splenocytes were significantly suppressed in the ethanol extract groups PfEL and PfEH. Serum level of anti-OVA IgE tended to be lower in the PfEH group. The inflammatory mediators, such as eotaxin and histamine, and total cells, particularly eosinophils in bronchoalveolar lavage fluid (BALF), were also decreased in the PfEL and the PfEH groups. Therefore, the PfEL and the PfEH groups had significantly lower methacholine-induced hyperresponsiveness (AHR). In conclusion, ethanol extracts, rather than water extract, of perilla leaves could significantly suppress Th2 responses and airway inflammation in allergic murine model of asthma.

Triterpenoids and Polysaccharide Fractions of Ganoderma tsugae Exert Different Effects on Antiallergic Activities.

This study was to investigate antiallergic effects of triterpenoids (Gt-TRE) and polysaccharide (Gt-PS) extracts from Ganoderma tsugae, using mast cell line RBL-2H3, T cell line EL4, primary T cells, and transfected RAW264.7 macrophage cells. The results showed that histamine secreted from activated RBL-2H3 mast cells was significantly suppressed by Gt-TRE but not Gt-PS. Interleukin- (IL-) 4 secreted from activated EL4 cells was significantly suppressed by Gt-TRE but not Gt-PS. Further primary CD4(+) T cells cultures also confirmed that Gt-TRE (5 ~ 50 µg/mL) significantly suppressed Th2 cytokines IL-4 and IL-5 secretions but had no effect on Th1 cytokines IL-2 and interferon (IFN)-γ. Gt-PS did not affect IL-4 and IL-5 secretions until higher doses (400, 500 µg/mL) and significantly suppressed IFNγ secretions but enhanced IL-2 at these high doses. The reporter gene assay indicated that Gt-TRE inhibited but Gt-PS enhanced the transcriptional activity of NF-κB in activated transfected RAW264.7 cells and transfected EL4 cells. IL-4 secreted by this transfected EL-4 cells was also significantly decreased by Gt-TRE but not by Gt-PS, suggesting that these two fractions may exert different effects on NF-κB related cytokines expression. These data suggested that triterpenoids fraction of Ganoderma tsugae might be the main constituents to alleviate allergic asthma.

Concentration variation and molecular characteristics of soluble (1,3;1,6)-ß-D-glucans in submerged cultivation products of Ganoderma lucidum mycelium.

(1,3)-ß-D-Glucans with (1,6)-ß-D-glucosyl branches are bioactive polysaccharides in fruiting bodies and mycelia of Ganoderma lucidum, a mushroom used in traditional Chinese medicine. Submerged cultivation of mycelium is one of the more efficient means of generating polysaccharides from this fungus. Twelve mycelium samples examined in this study demonstrated the quantitative and qualitative molecular characteristics of soluble (1,3;1,6)-ß-D-glucans. It was observed that the concentration of soluble (1,3;1,6)-ß-D-glucan varied substantially from 1.3 to 79.9 mg/dL. (1,3;1,6)-ß-D-Glucans also preserved their molecular characteristics with degrees of branching (DB) of 0.21-0.36 and molecular masses of 10(5)-10(6) g/mol for those samples with substantial quantities of ß-D-glucan. Using the high aggregating tendency of these molecules, (1,3;1,6)-ß-D-glucans were successfully purified via fractional precipitation with 35% (v/v) ethanol. (1,3;1,6)-ß-D-Glucan was proposed as a putative bioactive marker for immunomodulation because it was the most abundant polysaccharide in G. lucidum mycelium products to stimulate macrophage RAW 264.7 cells to release TNF-α.

Dietary factors regulate cytokines in murine models of systemic lupus erythematosus.

Cytokines play the active roles in the pathogenesis of systemic lupus erythematosus (SLE) and contribute significantly to the immune imbalance in this disease. Conservative therapeutic approaches, such as dietary modifications have been shown to have some beneficial impact on the disease activity of the SLE. Over the past years, accumulating evidences have supported a major role for specific dietary factors, including calorie restriction, n-3/n-6 fatty acids, vitamin A, vitamin D, vitamin E, phytoestrogens or herbal medicine in the regulation of cytokines involved in SLE development. Although there are many reviews that discuss the issue of nutrition and immunity, there are relatively few articles that focus on the regulation of cytokines by dietary factors. This concise review will summarize those animal studies that investigated not only the outcome of autoantibody production and proteinuria, but also cytokines production. However, the field of dietary factors in the immunomodulation of SLE is still in its infancy. More clinical studies are needed to confirm the preliminary results and advance the knowledge in this field. Lifestyle modification and adjustments in diet are important and encouraged to be suggested as an adjuvant therapy for SLE.

Phytoestrogenic compounds in alfalfa sprout (Medicago sativa) beyond coumestrol.

Coumestrol has long been known as the phytoestrogenic compound in alfalfa. However, it has been demonstrated that the ethyl acetate extract of alfalfa sprout (AEA) attenuated the disease severity and increased survival and life span of autoimmune-prone MRL-lpr/lpr mice. Coumestrol, on the contrary, decreased the survival. This study thus aimed to isolate and identify phytoestrogenic compounds other than coumestrol in AEA. AEA was fractionated and separated by successive silica gel chromatography and preparative HPLC. The activity of collected fractions was tracked by a transactivation assay for ERα and ERß, respectively. In addition to coumestrol, liquiritigenin, isoliquiritigenin, loliolide, and (4S,6S)- and (4R,6S)-4-hydroxy-6-pentadecyltetrahydropyr-2-one were isolated and chemically identified. Except for loliolide, these compounds showed higher transactivation via ERß than via ERα. The maximal activation via ERα of coumestrol reached 80% that of 1 nM 17ß-estradiol (E(2)), whereas the activations of the remaining five compounds as well as AEA ranged from 8 to 49%. In addition, isoliquiritigenin, loliolide, and (4S,6S)- and (4R,6S)-4-hydroxy-6-pentadecyltetrahydropyr-2-one, but not coumestrol, preferentially inhibited 1 nM E(2) induced ERα activation, compared to that ERß activation. The selectivity of these phytoestrogens might account for the difference between the effects of AEA and coumestrol in autoimmune-prone MRL-lpr/lpr mice observed previously.

Inhibitory Effects of Ethyl Acetate Extract of Andrographis paniculata on NF-κB Trans-Activation Activity and LPS-Induced Acute Inflammation in Mice.

This study was to investigate anti-inflammatory effect of Andrographis paniculata (Burm. f.) Nees (Acanthaceae) (AP). The effects of ethyl acetate (EtOAc) extract from AP on the level of inflammatory mediators were examined first using nuclear factor kappa B (NF-κB) driven luciferase assay. The results showed that AP significantly inhibited NF-κB luciferase activity and tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), macrophage inflammatory protein-2 (MIP-2) and nitric oxide (NO) secretions from lipopolysaccharide (LPS)/interferon-γ stimulated Raw264.7 cells. To further evaluate the anti-inflammatory effects of AP in vivo, BALB/c mice were tube-fed with 0.78 (AP1), 1.56 (AP2), 3.12 (AP3) and 6.25 (AP4) mg kg(-1) body weight (BW)/day in soybean oil, while the control and PDTC (pyrrolidine dithiocarbamate, an anti-inflammatory agent) groups were tube-fed with soybean oil only. After 1 week of tube-feeding, the PDTC group was injected with 50 mg kg(-1) BW PDTC and 1 h later, all of the mice were injected with 15 mg kg(-1) BW LPS. The results showed that the AP1, AP2, AP3 and PDTC groups, but not AP4, had significantly higher survival rate than the control group. Thus, the control, AP1, AP2, AP3 and PDTC groups were repeated for in vivo parameters. The results showed that the AP and PDTC groups had significantly lower TNF-α, IL-12p40, MIP-2 or NO in serum or peritoneal macrophages and infiltration of inflammatory cells into the lung of mice. The AP1 group also had significantly lower MIP-2 mRNA expression in brain. This study suggests that AP can inhibit the production of inflammatory mediators and alleviate acute hazards at its optimal dosages.

Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian).

Andrographis paniculata (Burm. f.) Nees (Acanthaceae) is a medicinal plant used in many countries. Its major constituents are diterpenoids, flavonoids and polyphenols. Among the single compounds extracted from A. paniculata, andrographolide is the major one in terms of bioactive properties and abundance. Among the andrographolide analogues, 14-deoxy-11,12-didehydroandrographolide is immunostimulatory, anti-infective and anti-atherosclerotic; neoandrographolide is anti-inflammatory, anti-infective and anti-hepatotoxic; 14-deoxyandrographolide is immunomodulatory and anti-atherosclerotic. Among the less abundant compounds from A. paniculata, andrograpanin is both anti-inflammatory and anti-infective; 14-deoxy-14,15-dehydroandrographolide is anti-inflammatory; isoandrographolide, 3,19-isopropylideneandrographolide and 14-acetylandrographolide are tumor suppressive; arabinogalactan proteins are anti-hepatotoxic. The four flavonoids from A. paniculata, namely 7-O-methylwogonin, apigenin, onysilin and 3,4-dicaffeoylquinic acid are anti-atherosclerotic.

Inhibitory effects of Angelica sinensis ethyl acetate extract and major compounds on NF-kappaB trans-activation activity and LPS-induced inflammation.

AIM OF THE STUDY: Previous study showed that the ethyl acetate (EtOAc) fraction from Angelica sinensis (Oliv.) Diels (Apiaceae) (AS) inhibited nitric oxide (NO) and prostaglandin E(2) secretions in vitro. This study was to evaluate anti-inflammatory activity of AS EtOAc extract and its major compounds in vivo and in vitro. MATERIALS AND METHODS: NF-kappaB luciferase activity and pro-inflammatory cytokine secretions from lipopolysaccharide (LPS) plus interferon (IFN)-gamma-stimulated RAW 264.7 cells pre-treated with EtOAc extract or compounds were analyzed. For further in vivo study, BALB/c mice were tube-fed with 1.56 (AS1 group), 6.25 (AS2 group) mg/kg body weight/day in 100 microl soybean oil, while the control and PDTC (pyrrolidine dithiocarbamate, an anti-inflammatory agent) groups were tube-fed with 100 microl soybean oil/day only. After 1 week of tube-feeding, the PDTC group was injected with 50 mg/kg BW PDTC and 1 h later, all of the mice were injected with 15 mg/kg BW LPS. The pro-inflammatory cytokine levels and lifespan of LPS-challenged mice were determined. RESULTS: The results showed that AS EtOAc extract significantly inhibited NF-kappaB luciferase activity and TNF-alpha, IL-6, macrophage inflammatory protein-2 (MIP-2) and NO secretions from LPS/IFN-gamma-stimulated RAW 264.7 cells. The AS1 and PDTC groups, but not AS2, had significantly higher survival rate than the control group. This was characterized by the inhibition of the serum TNF-alpha and IL-12p40 levels after LPS injection (p<0.05). The major compounds of AS, ferulic acid and Z-ligustilide, also significantly decreased NF-kappaB luciferase activity, which may contribute to the anti-inflammatory activity of AS. CONCLUSIONS: Low dose of AS EtOAc extract that inhibits the production of inflammatory mediators alleviates acute inflammatory hazards and protect mice from endotoxic shock.

Anti-inflammatory activity of new compounds from Andrographis paniculata by NF-kappaB transactivation inhibition.

Previous studies showed that the ethyl acetate (EtOAc) fraction of Andrographis paniculata (AP) possessed anti-inflammatory activity. This study further isolated these active compounds from bioactivity-guided chromatographic fractionation and identified eight pure compounds. Reporter gene assay indicated that 5-hydroxy-7,8-dimethoxyflavone (1), 5-hydroxy-7,8-dimethoxyflavanone (2), a mix of beta-sitosterol (3a) and stigmasterol (3b), ergosterol peroxide (4), 14-deoxy-14,15-dehydroandrographolide (5), and a new compound, 19-O-acetyl-14-deoxy-11,12-didehydroandrographolide (6a), significantly inhibited the transcriptional activity of NF-kappaB in LPS/IFN-gamma stimulated RAW 264.7 macrophages (P < 0.05). The two most abundant compounds, 14-deoxy-11,12-didehydroandrographolide (7) and andrographolide (8), had less inhibitory activity but exerted greater inhibitory activity by hydrogenation, oxidation, or acetylation to become four derived compounds, 9, 10, 11, and 12. All of the compounds significantly decreased TNF-alpha, IL-6, macrophage inflammatory protein-2 (MIP-2), and nitric oxide (NO) secretions from LPS/IFN-gamma stimulated RAW 264.7 cells. Compounds 5, 11, and 12 exerted the strongest inhibitory effect on NF-kappaB-dependent transactivation in the RAW 264.7 cell, with IC(50) values of 2, 2.2, and 2.4 microg/mL, respectively, providing encouraging results for bioactive compound development.

Ethyl acetate extracts of alfalfa (Medicago sativa L.) sprouts inhibit lipopolysaccharide-induced inflammation in vitro and in vivo.

This study aimed to investigate if food components that exert anti-inflammatory effects may be used for inflammatory disorders by examining alfalfa sprout ethyl acetate extract (ASEA). The cytokine profile and life span of BALB/c mice with acute inflammation after intra-peritoneal (ip) injection of 15 mg/kg BW lipopolysaccharide (LPS) were determined. The results showed that the life span of LPS-induced inflammatory mice were negatively correlated with serum levels of TNF-alpha, IL-6, and IL-1beta at 9 hr after LPS-injection, which indicated that suppressing these cytokines in the late phase of inflammation may be beneficial for survival. The in vitro experiment then showed that ASEA significantly reduced IL-6 and IL-1beta production and the NF-kappaB trans-activation activity of mitogen-stimulated RAW264.7 cells. To further evaluate the anti-inflammatory effects of ASEA in vivo, BALB/c mice were tube-fed with 25 mg ASEA/kg BW/day in 50 microl sunflower oil, while the control and PDTC (pyrrolidine dithiocarbamate, an anti-inflammatory agent) groups were tube-fed with 50 microl sunflower oil/day only. After one week of tube-feeding, the PDTC group was injected with 50 mg/kg BW PDTC and one hour later, all of the mice were injected with 15 mg/kg BW LPS. The results showed that the ASEA and PDTC groups had significantly lower serum TNF-alpha, IL-6, and IL-1beta levels at 9 hr after LPS challenge, and significantly higher survival rates than the control group. This study suggests that ASEA supplementation can suppress the production of pro-inflammatory cytokines and alleviate acute inflammatory hazards.

The production of nitric oxide and prostaglandin E2 in peritoneal macrophages is inhibited by Andrographis paniculata, Angelica sinensis and Morus alba ethyl acetate fractions.

AIM OF THE STUDY: Traditional Chinese medicine herbs (TCMHs) are used in medicines as well as in daily dietary supplements in Asia. In this study, we employed pNF-kappaB-Luc or pIFN-gamma-Luc and BALB/c mice peritoneal macrophages or splenocytes to investigate both the immune and inflammatory effects of six selected plant species. MATERIALS AND METHODS: Specifically, we used ethyl acetate fractions of Astragalus membranaceus (Fisch.) Bunge var. mongholicus (Bunge) Hsiao (Fabaceae) (AM), Andrographis paniculata (Burm. f.) Nees (Acanthaceae) (AP), Angelica sinensis (Oliv.) Diels (Apiaceae) (AS), Eucommia ulmodes Oliv. (Eucommiaceae) leaves (EU leaves), Isatis indigotica Fort. (Brassicaceae) (II) and Morus alba L. (Moraceae) (MA). RESULTS: We found that ethyl acetate fractions of AP, AS and MA significantly decreased NF-kappaB luciferase activity and also the secretion of NO and PGE(2) in LPS/IFN-gamma stimulated mouse peritoneal macrophages (p<0.05). In contrast, they did not affect IFN-gamma luciferase activity or IFN-gamma production in concanavalin A (Con A)-activated mouse splenocytes. Our results indicated that the anti-inflammatory properties of these plant extracts might be resulted from the inhibition of pro-inflammatory mediators (e.g., NO and PGE(2)), at least in part via suppression of a signaling pathway such as NF-kappaB. CONCLUSIONS: Collectively, we have found that three potent bioactive TCMH species exerted significant NF-kappaB inhibitory activity and acted in a cell type dependent fashion.

Effects of triterpenoid-rich extracts of Ganoderma tsugae on airway hyperreactivity and Th2 responses in vivo.

BACKGROUND: Airway inflammation and Th2 responses play central roles in allergic asthma. We have previously reported that Ganoderma tsugae supplementation could attenuate airway inflammation in the murine model. Since it remains unclear which part of the G. tsugae exerts this effect on allergic asthma in vivo, this study was meant to investigate if triterpenoid extracts have anti-inflammatory effects on airway responses and regulatory effects on Th2 responses. METHODS: BALB/c mice sensitized intraperitoneally and challenged with ovalbumin (OVA) were treated with either triterpenoid-rich extracts (TRE) of G. tsugae or prednisolone for 2 weeks. The effects of TRE on bronchial airway hyperresponsiveness (AHR), airway inflammation, serum antigen-specific antibody levels, and cytokine secretions from splenocytes were evaluated. RESULTS: TRE supplementation significantly decreased AHR and reduced the total infiltrating leukocytes and eosinophils, as well as the levels of inflammatory mediators, such as interleukin (IL)-4, IL-5 and eotaxin in bronchoalveolar lavage fluid when compared with those of the control group. Lung histology also showed less cell recruitment and lung damage. TRE supplements suppressed IL-5 secretions from OVA-stimulated splenocytes, but did not affect the cell number of splenocytes, which was also reduced by prednisolone. Although OVA-specific immunoglobulin E levels were not significantly different among the groups, a lower level of OVA-specific immunoglobulin G1, another Th2-related antibody, was found in TRE and prednisolone treatment. CONCLUSIONS: TRE of G. tsugae exert anti-inflammatory effects on airway responses and attenuate Th2 responses without the overall immunosuppression effects in allergic murine models of asthma.

Ganoderma tsugae in vivo modulates Th1/Th2 and macrophage responses in an allergic murine model.

We have reported that Ganoderma tsugae supplementation alleviates bronchoalveolar inflammation in an airway sensitization and challenge model with female BALB/c mice. However, the effects of G. tsugae supplementation in vivo on serum antibody levels, splenocyte and peritoneal microphage immune responses have not yet been determined. In this study, serum antibody levels, cytokines and splenocyte chemical mediators and peritoneal macrophage cultures from ovalbumin (OVA)-sensitized and -challenged mice were examined after continuously consuming G. tsugae supplementation diets for 5 weeks. The results showed that OVA sensitization and challenge significantly (P<0.05) decreased the spontaneous production of IL-2 (Th1) cytokine, but significantly (P<0.05) increased spontaneous and OVA-stimulated IL-4 (Th2) production in splenocyte cultures from experimental mice. OVA administration significantly decreased both spontaneous and LPS/IFN-gamma-stimulated IL-1beta and IL-6 levels in peritoneal macrophage cultures from experimental mice. However, dietary supplementation with G. tsugae significantly increased spontaneous IL-2 level, but slightly decreased spontaneous IL-4 level in cultured splenocyte supernatants in the experimental groups. G. tsugae supplementation enhanced pro-inflammatory cytokines IL-1beta and IL-6 production in cultured peritoneal macrophages. However, the nitric oxide level from cultured peritoneal macrophages and serum OVA-specific IgE and IgG(2a) antibody levels was not significantly affected. These results suggest that OVA sensitization and challenge induced a Th2-skewed splenocyte response and decreased peritoneal macrophage cytokine secretion. G. tsugae supplementation in vivo modulated the Th1/Th2 balance and enhanced macrophage immune responses. However, the supplementation diet could not fully reverse the Th2-skewed responses to level of Th1-skewed responses.

Low and high levels of alpha-tocopherol exert opposite effects on IL-2 possibly through the modulation of PPAR-gamma, IkappaBalpha, and apoptotic pathway in activated splenocytes.

OBJECTIVE: We previously demonstrated that a high dose of alpha-tocopheryl succinate inhibits interleukin-2 (IL-2) mRNA and production in autoimmune-prone MRL/lpr mice. In the present study, we investigated the regulation of alpha-tocopherol (alphaTOC) on IL-2 gene expression by examining the mRNA of IL-2, inhibitor kappaBalpha (IkappaBalpha), and peroxisome proliferator-activated receptor-gamma (PPARgamma). METHODS: Messenger RNA expression in active splenocytes of BALB/c mice was investigated with reverse transcriptase polymerase chain reaction. RESULTS: Levels of IL-2 mRNA in phorbol 12-myristate 13-acetate/ionomycin activated splenocytes and cytokine in T-helper-1 cells were increased by 50 microM of alphaTOC but decreased by 1 mM of alphaTOC. In addition, the IkappaBalpha gene expression significantly increased by the high dose (>or=500 microM) of alphaTOC, suggesting an inhibition on nuclear factor-kappaB pathway for activation of IL-2 expression. PPARgamma mRNA level in activated splenocytes was upregulated by 1 mM of alphaTOC. PPARgamma mRNA level in unstimulated splenocytes was upregulated by alphaTOC in a dose-dependent manner, suggesting that alphaTOC might enhance the PPARgamma signaling pathway. High-dose alphaTOC induced apoptosis of splenocytes and inhibited phytohemagglutinin-stimulated T-cell proliferation. Conversely, the proliferative response of splenocytes was enhanced by 5 microM of alphaTOC. Low-dose (50 microM) alphaTOC increased IL-2 expression, which may have been due to the absence of downregulation of PPARgamma and IkappaBalpha on the IL-2 gene. CONCLUSION: The results indicated that low and high doses of alphaTOC exert opposite effects on IL-2, possibly through modulation of PPARgamma, IkappaBalpha, and apoptosis pathways. The present findings support our previous observation of opposite effects of low- and high-dose vitamin E on survival of MRL/lpr mice.

Ganoderma tsugae supplementation alleviates bronchoalveolar inflammation in an airway sensitization and challenge mouse model.

Ganoderma tsugae (a Chinese mushroom Songshan lingzhi) cultivated in Taiwan is extensively used in Chinese traditional medicine to treat different diseases. To determine whether G. tsugae has anti-inflammatory effects on bronchoalveolar inflammation in vivo, we investigated the anti-inflammatory effects of G. tsugae products, YK01 and YK07, on bronchoalveolar inflammation using an airway sensitization and challenge mouse model. Female BALB/c mice were weekly sensitized by intraperitoneal injection of ovalbumin (OVA) three times and challenged with aerosolized OVA twice. Differential cell counts of infiltrating leukocytes, inflammatory mediators, cytokines in bronchoalvelor lavage fluid (BALF) of OVA-challenged mice were examined after continuously consuming G. tsugae diets for 5 weeks. We found that supplementation of G. tsugae significantly decreased total infiltrating leukocytes and lymphocyte percentage in BALF in the experimental groups. Supplementation of G. tsugae also significantly reduced inflammatory mediators in BALF including histamine, prostaglandin E2, eotaxin, and protein levels, however the levels of pro-inflammatory cytokines, interleukin (IL)-1beta and IL-6, in BALF did not significantly change. These results suggest that both G. tsugae supplementation diets YK01 and YK07 might alleviate bronchoalveolar inflammation via decreasing the infiltration of inflammatory cells and the secretion of inflammatory mediators into the local tissues of lungs and airways. Further, these results indicate that the relief of bronchoalveolar inflammation in an airway sensitization murine model provides a possible therapeutic application for G. tsugae in allergic asthma.

Association of B vitamins status and homocysteine levels in elderly Taiwanese.

To investigate the relationship between homocysteine (Hcy) and B vitamins status in the Taiwanese elderly population, an analysis was made of the plasma Hcy levels in elderly persons. The study sample was taken from the Elderly Nutrition and Health Survey in Taiwan (1999-2000) (Elderly NAHSIT) and included 1094 males and 1135 females aged 65-90 years. The results showed that average plasma Hcy was 13.3+/-0.6 micromol/ L for males and 10.6+/-0.7 micromol/L for females. The average plasma Hcy levels of males from all age groups were significantly higher than those of females, and significantly increased with age (P<0.0001). The overall prevalence of hyperhomocysteinemia (Hcy>15 micromol/L) was 23.4% for elderly males and 11.2% for elderly females, and this also increased with age (P<0.0001). In subjects with normal renal function, folate, vitamin B2, B6, and B12 status were significantly lower in males with hyperhomocysteinemia, while only folate and vitamin B12 were significantly lower in females with hyperhomocysteinemia. Further analysis suggested that folate, vitamin B6 or B12 insufficiency were associated with hyperhomocysteinemia in both sexes, while vitamin B2 insufficiency was significantly associated only in males. In elderly persons with adequate folate, vitamin B6, and B12 status, there was no significant association between vitamin B2 and hyperhomocysteinemia. This association occurred only in those who had concurrent poor folate, vitamin B6, or B12 status. The strength of the association between vitamin B12 insufficiency and hyperhomocysteinemia was not affected by simultaneous vitamin B2 or B6 insufficiency, but increased about 3-fold when combined with folate. This suggests that poor folate and vitamin B12 status has a synergistic effect on the risk of hyperhomocysteinema in the elderly, as did a poor folate and vitamin B6 status. Therefore, maintaining adequate vitamin B12 status and avoiding multiple B vitamin insufficiency, especially that of folate and vitamin B12 or B6, should be emphasized as an important measure for reducing plasma Hcy levels among elderly Taiwanese.

Opposite effects of low and high dose supplementation of vitamin E on survival of MRL/lpr mice.

OBJECTIVE: The purpose of this study is to investigate the effects of vitamin E supplementation on the autoimmune disease course in MRL/lymphoproliferative mice. METHODS: Three-month-old MRL/lymphoproliferative lpr female mice were fed an AIN-76 diet containing 50 mg/kg (control), 250 mg/kg (E5), 375 mg/kg (E7.5), or 500 mg/kg (E10) all-rac-alpha-tocopheryl acetate. Eight mice per group were killed for analysis after two months of experimental diets, and the rest of the mice were followed up to observe their proteinuria levels and life span. RESULTS: The data suggest that the life span of the E5 group was longer than the E10 group. Though alpha-tocopherol content in the plasma, liver, and kidneys increased in the mice fed the diet supplemented with vitamin E, the thiobarbituric acid reactive substance values in the liver and kidneys among these groups were not significantly different. IgM anti-ds-DNA and anticardiolipin antibodies were significantly higher in the E10 group than in those of the other groups. Phytohemagglutinin-stimulated interleukin (IL)-2 secretion was significantly lower, but concanavalinA-stimulated IL-4 and IL-10 production was significantly higher in the E10 group compared with the control group. The in vitro study also showed decreased IL-2 secretion and messenger RNA expression in phytohemagglutinin-stimulated splenocytes cultured in medium supplemented with high doses of vitamin E, but increased IL-2 with low doses of vitamin E. CONCLUSIONS: Our data suggest that low and high dose supplementation of vitamin E has the opposite effect on the survival of MRL/lpr mice. The inhibitory effect of Th1 from high vitamin E content may not be beneficial for those suffering from Th2 prone autoimmune diseases, such as systemic lupus erythematosus.