Jin-Yuarn Lin

Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes.

This study investigated 27 selected terpenoid compounds, including 8 monoterpenoids, 7 sesqui-terpenoids, 3 di-terpenoids, 8 tri-terpenoids, and 1 tetra-terpenoid, for their Th1/Th2 immunomodulatory potential using mouse primary splenocytes. Changes in Th1 cytokines, including interleukin (IL)-2 and interferon (IFN)-γ, and Th2 cytokines, including IL-4, IL-5 and IL-10, secreted by terpenoid-treated splenocytes were measured using the ELISA method. The results showed that triptolide, a diterpenoid, was most cytotoxic, reflecting an IC50 value of 46nM. Eucalyptol, limonene, linalool, thymol, parthenolide, andrographolide, 18β-glycyrrhetinic acid, lupeol, ursolic acid and β-sitosterol showed a strong Th2-inclination and anti-inflammation potential in vitro. In addition, (-)-trans-caryophyllene, oridonin, triptolide, diosgenin, betulinic acid, escin, and β-sitosterol treatments significantly inhibited both IL-2 (Th1) and IL-10 (Th2) cytokine production at the same time, suggesting that these terpenoid compounds have an anti-inflammation potential through the inhibition of T-cell immune responses. Diosgenin treatments significantly increased IFN-γ secretion levels using mouse splenocytes, suggesting that diosgenin may be useful in treating a viral infection through the stimulation of IFN-γ production. Menthone, farnesol and oridonin treatments did not markedly increase IL-10/IL-2 (Th2/Th1) cytokine secretion ratios, suggesting that menthone, farnesol and oridonin may have a relative Th1-inclination property, compared to the other selected terpenoid compounds. The relative Th1-inclination property of menthone, farnesol and oridonin may be applied to improve Th2-skewed allergic diseases.

Anti-inflammatory and anti-apoptotic effects of strawberry and mulberry fruit polysaccharides on lipopolysaccharide-stimulated macrophages through modulating pro-/anti-inflammatory cytokines secretion and Bcl-2/Bak protein ratio

This study is the first to isolate strawberry (SP) and mulberry fruit polysaccharides (MP) and assess their anti-inflammatory and anti-apoptotic activities using lipopolysaccharide (LPS)-stimulated mouse primary macrophages. Pro-/anti-inflammatory cytokine levels secreted by LPS-stimulated macrophages cultured with SP and MP for 48 h were determined using ELISA method to evaluate anti-inflammatory effects of SP and MP. The Bcl-2/Bak (anti-/pro-apoptotic) protein levels in the cells were determined using Western blotting method to evaluate anti-apoptotic effects of SP and MP. The results showed that the maximum absorption peak of SP and MP appeared at 240 nm with a small shoulder around 280∼310 nm, suggesting that SP and MP might be glycoproteins. SP- and MP-treatment significantly (P<0.05) decreased pro-inflammatory cytokines including interleukin (IL)-1β and IL-6, whereas the anti-inflammatory cytokine IL-10 was markedly increased, suggesting that SP and MP have anti-inflammation potential via modulating pro-/anti-inflammatory cytokine secretion profiles. Both SP and MP modulated Bak and Bcl-2 protein levels in the cells, suggesting that the SP and MP protected LPS-stimulated macrophages from apoptotic cell death. A negative correlation between cytokine secretion levels and Bcl-2 protein levels suggested that pro-inflammatory IL-1β and IL-6 cytokines decreased Bcl-2 levels in the LPS-stimulated macrophages.

Characterisation of the pigment components in red cabbage (Brassica oleracea L. var.) juice and their anti-inflammatory effects on LPS-stimulated murine splenocytes

To determine anti-inflammatory effects of pigments from red cabbage, red cabbage (Brassica oleracea L. var.) juice was prepared, characterized by UV-vis absorption spectra, partially purified by Sephadex LH-20 column, analyzed by HPLC, and administered to lipopolysaccharide (LPS)-stimulated murine splenocyte cultures. The study showed that red cabbage juice (RC) exhibited anti-inflammatory effects against LPS-induced inflammation of splenocytes via increasing anti-inflammatory cytokine interleukin (IL)-10 and decreasing pro-inflammatory cytokine IL-6 secretions. The maximum absorption peaks of RC and its heated products, but not activated charcoal-adsorbed products, appeared at 280nm with a small shoulder around 310-330nm while there existed a minor peak at 560nm (range from 480 to 630nm), reflecting red cabbage juice included phenolics, flavonoids, and anthocyanins. The lyophilized powder of chromatographic fractions F2, F3, and F4 through Sephadex LH-20 column were rich in phenolics (5.9±0.2%, 4.4±0.0%, and 3.9±0.0%, respectively) and flavonoids (1.8±0.3%, 1.8±0.3%, and 1.1±0.3%, respectively). The results suggest that anti-inflammatory pigment compounds in red cabbage juice were heat stable. Further analysis of chromatograms from HPLC suggests malvidin glycosides including malvidin 3-glucoside (oenin), malvidin 5-glucoside and malvidin 3,5-diglucoside in red cabbage juice could inhibit IL-6 secretion of LPS-stimulated splenocytes.

High dose vitamin C supplementation increases the Th1/Th2 cytokine secretion ratio, but decreases eosinophilic infiltration in bronchoalveolar lavage fluid of ovalbumin-sensitized and challenged mice.

Vitamin C is traditionally regarded to be beneficial for asthma, however the benefit is still controversial. In the present study, high dose vitamin C was supplemented to ovalbumin (OVA)-sensitized and challenged mice to evaluate the effects of dietary vitamin C on allergic asthma. In this study, the experimental mice were divided into four groups, including nonsensitized control, dietary control, positive control (cured ip with dexamethasone), and high dose vitamin C supplementation (130 mg of vitamin C/kg bw/day by gavage for 5 weeks). Differential leukocyte counts, levels of inflammatory mediators, as well as type 1 T-helper lymphocytes (Th1)-type and type 2 T-helper lymphocytes (Th2)-type cytokines in the bronchoalveolar lavage fluid (BALF) were determined. The results showed that both high dose vitamin C supplementation and dexamethasone treatments significantly (P < 0.05) decreased eosinophilic infiltration into BALF. High dose vitamin C supplementation significantly increased the secretion ratio of interferon (IFN)-gamma/interleukin (IL)-5 cytokines. This study suggests that high dose vitamin C supplementation might attenuate allergic inflammation in vivo via modulating the Th1/Th2 balance toward the Th1 pole during the Th2-skewed allergic airway inflammation and decreasing eosinophilic infiltration into BALF.

Purification, partial characterization and anti-inflammatory characteristics of lotus (Nelumbo nucifera Gaertn) plumule polysaccharides

A novel lotus plumule polysaccharide (LPPS) was purified, characterised and cultured with RAW264.7 macrophages to evaluate its anti-inflammatory characteristics. LPPS was purified using Sepharose 6B gel filtration and dissolved into two major components, fraction-1 (F1) and fraction-2 (F2). The molecular weights of native F1 and F2 were approximately distributed at >2,000 and 25.7kDa, respectively. The total protein and carbohydrate constituent ratios in LPPS, F1, and F2 were 30.0±0.9% vs. 70.0±0.9%, 30.1±2.6% vs. 69.9±2.6%, and 96.5±6.1% vs. 3.5±6.1% (w/w), respectively, suggesting that F1 may be a major proteo-polysaccharide component and F2 a glycoprotein constituent in LPPS. Pro-/anti-inflammatory (IL-6/IL-10) cytokine secretion ratios by lipopolysaccharide-stimulated RAW264.7 macrophages were significantly decreased by F1 and F2 treatments, particularly by F2, in a dose-dependent manner under a preventive experimental model. This study suggests that purified components, F1 and F2 from LPPS, have strong anti-inflammatory effects on LPS-induced inflamed macrophages in a preventive manner.

Dietary perilla oil lowers serum lipids and ovalbumin-specific IgG1, but increases total IgE levels in ovalbumin-challenged mice

Our previous studies indicated that alpha-linolenic acid (ALA)-rich perilla oil might alleviate bronchoalveolar inflammation. However, it failed to modulate the Th1/Th2 balance toward the Th1 pole during Th2-skewed allergic airway inflammation in mice. This study attempts to further investigate the effects of dietary perilla oil on serum lipids and immunoglobulin profiles using an ovalbumin (OVA)-challenged mouse model. The inbred female BALB/c mice were randomly divided into four groups and fed different AIN-76 feeds containing 5% corn oil (rich in linoleic acid, 18:2n-6 polyunsaturated fatty acids (PUFA), as a control diet), 5% perilla oil (rich in alpha-linolenic acid, 18:3n-3 PUFA) or 5% compound oil containing 50% corn oil and 50% perilla oil, respectively, for 35 consecutive days ad libitum. Experimental mice were sensitized by an intraperitoneal injection of alum-precipitated antigen containing ovalbumin on 7, 14 and 21 days after supply of the specified experimental diets. One week later, the mice were then challenged by aerosolized OVA. The results showed that dietary perilla oil administration significantly (P < 0.05) decreased the relative liver tissue weight (RTW) and serum lipid levels including triglycerides, total cholesterol, HDL- and LDL-cholesterol. However, the HDL/LDL ratio was also significantly lowered by dietary perilla oil. Dietary perilla oil markedly decreased serum OVA-specific IgG1 level and total IgA antibodies (Th2 antibodies). Unfortunately, it also increased non-specific serum IgE (Th2 antibody) levels. The results suggest that dietary perilla oil might have a moderately beneficial effect on asthmatic allergy via lowering serum lipids and OVA-specific IgG1, as well as total IgA levels. However, it failed to obviously modulate Th1/Th2 antibody levels via isotype switching of B cells from Th2 antibody to Th1 antibody.

Berberine, an isoquinoline alkaloid, inhibits streptozotocin-induced apoptosis in mouse pancreatic islets through down-regulating Bax/Bcl-2 gene expression ratio

Diabetes may cause apoptosis in pancreatic islets. Berberine is an isoquinoline alkaloid used for its pharmacological functions including anti-inflammation. However, the berberine effect on pancreatic islets is still not clear. This study is aimed at clarifying the protective mechanism in berberine against islet cell apoptosis. This study established in vitro experimental models using streptozotocin (STZ)-treated primary pancreatic islet cells from ICR mice to unravel the protective mechanism of berberine on islets. The Bax/Bcl-2 (pro-/anti-apoptotic) genes expression in the islets was determined using real-time quantitative polymerase chain reaction assay. The results showed that berberine administration at one time or before STZ-stimulation significantly (P<0.05) down-regulated the Bax/Bcl-2 genes expression ratio, compared to those in STZ-treatment alone group. Our results suggest that berberines anti-apoptotic effect on pancreatic primary islets is through down-regulating the Bax/Bcl-2 genes expression ratio in both concurrent and preventive manners.

Lotus (Nelumbo nucifera Gaertn) plumule polysaccharide protects the spleen and liver from spontaneous inflammation in non-obese diabetic mice by modulating pro-/anti-inflammatory cytokine gene expression

A novel lotus plumule polysaccharide (LPPS) was administered to non-obese diabetic (NOD) mice for 15weeks to evaluate the protective effects of LPPS on type 1 diabetes. After the 15-week feeding experiment, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 expressions in the spleen, liver and kidney of the experimental mice were measured using enzyme-linked immunosorbent assay or real-time quantitative polymerase chain reaction assay. The results showed that LPPS significantly (p<0.05) decreased the absolute weights of the enlarged spleens in the NOD mice in a dose-dependent manner, inhibited pro-inflammatory TNF-α and IL-6 cytokine production and decreased the secretion ratio of IL-6/IL-10 in splenocyte cultures. LPPS markedly decreased the relative expression of pro-/anti-inflammatory cytokine genes (TNF-α/IL-10 and IL-6/IL-10) in the livers of NOD mice. Our results suggest that LPPS protected the spleen and liver from spontaneous inflammation in NOD mice by modulating pro-/anti-inflammatory cytokine gene expression.

Lotus (Nelumbo nucifera Gaertn) plumule polysaccharide ameliorates pancreatic islets loss and serum lipid profiles in non-obese diabetic mice

To unravel possible protective effects of a newly isolated lotus plumule polysaccharide (LPPS) on type 1 diabetes (T1D), this study isolated LPPS and administered it to non-obese diabetic (NOD) female mice for 15 weeks. Oral glucose tolerance, serum ketone body, glucose, insulin, and lipid levels, as well as pancreatic islet cell numbers and the insulin secretion ability of the experimental mice were determined. The results showed that LPPS administration in vivo significantly (P<0.05) increased pancreatic islet cell numbers and slightly enhanced the basal insulin secretion ability compared to the control group. LPPS administration improved serum lipid profiles in the diabetic mice via relatively increasing serum high density lipoprotein-cholesterol, but decreasing low density lipoprotein-cholesterol and total cholesterol levels. The present study suggests that LPPS supplementation may ameliorate T1D progress and its complications through protecting pancreatic islets and modulating serum lipid profiles.