Immunomodulatory effects of Ulva-derived polysaccharides, oligosaccharides, and residues in a murine model of delayed-type hypersensitivity.

Ulva, an edible green alga, contains sulfated polysaccharides and oligosaccharides that possess immunomodulatory and anti-inflammatory properties. The objective of this study was to investigate the anti-allergic effects of Ulva-derived samples of polysaccharides (UP), oligosaccharides (UO), and residues (UR) on delayed-type hypersensitivity (DTH) in mice. Oral treatment of mice with UP, UO, and UR (250 mg/kg body weight) daily noticeably improved the DTH reaction as evidenced by attenuation of footpad swelling and cell infiltration at the allergen-challenge site. Although the Ulva samples had limited impacts on the production of serum total IgG, decreased concentrations of allergen-specific IgG and IgG2a and an increased concentration of IgG1 were observed in the treated mice. Moreover, treatment with them suppressed allergen-induced IFN-γ and TNF-α secretion and elevated IL-4 secretion. However, none of the Ulva sample treatments could modulate the production of IL-10. Concordantly, the in situ data reveal that the Ulva sample treatments suppressed IFN-γ and TNF-α expression at the allergen-injection site. These findings collectively suggest the potential of UP, UO, and UR as functional food candidates for the management of delayed-type hypersensitivity.

Protective effect of Ganoderma lucidum-fermented crop extracts against hydrogen peroxide- or ß-amyloid-induced damage in human neuronal SH-SY5Y cells.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of stacked ß-amyloid peptides in the brain and associated with the generation of oxidative stress. So far, there is no cure for AD or a way to stop its progression. Although the neuroprotective effects of Ganoderma lucidum aqueous extract and G. lucidum-derived triterpenoids and polysaccharides have been reported, the influence of G. lucidum-fermented crops on AD still lacks clarity. METHODS: This study aimed to investigate the protective effect of G. lucidum-fermented crop extracts against hydrogen peroxide- or ß-amyloid peptide (Aß25-35)-induced damage in human neuroblastoma SH-SY5Y cells. RESULTS: Various extracts of G. lucidum-fermented crops, including extract A: 10% ethanol extraction using microwave, extract B: 70˚C water extraction, and extract C: 100˚C water extraction followed by ethanol precipitation, were prepared and analyzed. Extract B had the highest triterpenoid content. Extract C had the highest total glucan content, while extract A had the highest gamma-aminobutyric acid (GABA) content. The median inhibitory concentration (IC50, mg/g) for DPPH and ABTS scavenging activity of the fermented crop extracts was significantly lower than that of the unfermented extract. Pretreatment with these extracts significantly increased the cell viability of SH-SY5Y cells damaged by H2O2 or Aß25-35, possibly by reducing cellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Moreover, extract B markedly alleviated the activity of acetylcholinesterase (AChE), which is crucial in the pathogenesis of AD. CONCLUSION: These results clearly confirmed the effects of G. lucidum-fermented crop extracts on preventing against H2O2- or Aß25-35-induced neuronal cell death and inhibiting AChE activity, revealing their potential in management of AD.

Effects of Vigiis 101-LAB on a healthy population's gut microflora, peristalsis, immunity, and anti-oxidative capacity: A randomized, double-blind, placebo-controlled clinical study.

Vigiis 101-LAB capsules are produced from the fermentation of Lactobacillus paracasei subsp. paracasei NTU 101. We tested effects of Vigiis 101-LAB capsules I or II (5 or 10 billion CFU/day, respectively) on gut microflora in clinical trial I, and on peristalsis, immunity, and anti-oxidative capacity in clinical trial II, during a 4-week randomized, double-blind, placebo-controlled, adaptive-design study. In trial I, 36 subjects were divided into capsule I and placebo groups. After 4 weeks, Bifidobacterium spp. and Lactobacillus spp. counts were significantly higher in the feces of treatment subjects, with increases of 4.01- and 4.25-fold, respectively. In trial II, 52 subjects were divided into capsule II and placebo groups. After 4 weeks, the treatment group was found to have improved motility, decreased food transit time, and significantly increased immunoglobulin G, immunoglobulin M, and antioxidant activity. Thus, daily administration of Vigiis 101 capsule II can improve peristalsis, immunity, and anti-oxidative capacity.

Lactobacillus paracasei subsp. paracasei NTU 101 lyophilized powder improves loperamide-induced constipation in rats.

Constipation is a condition of the digestive system characterized by formation of hard feces that are difficult to eliminate. It has emerged as a new problem that is commonly encountered by many people and lifestyle changes have been unsuccessful in providing a solution. This study aimed to investigate the effects of Lactobacillus paracasei subsp. paracasei NTU 101 on loperamide-induced constipated rats and on gastrointestinal tract function. Sprague-Dawley rats were administered loperamide (2 mg/kg BW) twice daily as well as 1.3, 2.6, and 13.0 mg/kg BW/rat/d of NTU 101 powder. The control, positive control, and NTU 101 powder groups (0.5, 1, 5×) showed improved intestinal mobility with a statistically significant increase of 12.4%, 14.7%, 12.5%, 13.4%, and 15.1%, respectively (p < 0.05); the fecal water content was also significantly increased by 11.7%, 9.0%, 10.0%, 9.3%, and 11.0%, respectively (p < 0.05), compared to the loperamide group. Furthermore, NTU 101 increased the Bifidobactrium spp. and decreased the Clostridium perfringens content in feces; it increased short-chain fatty acid levels, reduced fecal pH value, enhanced the thickness of the colonic mucosa, and increased the number of mucin-producing goblet cells and interstitial cells of Cajal. Thus, NTU 101 powder was found to alleviate loperamide-induced constipation and improve gastrointestinal tract function.

Therapeutic effects of Lactobacillus paracasei subsp. paracasei NTU 101 powder on dextran sulfate sodium-induced colitis in mice.

Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) whose exact cause is still unclear. Disruption of the intestinal microflora is considered one of the main causes of the disease. Lactobacillus paracasei subsp. paracasei NTU 101 (NTU 101) is a multifunctional strain that has been shown in previous studies to possess anti-inflammatory properties and to exert a modulatory effect on intestinal bacteria associated with certain pathogenic mechanisms of IBD. In the current study, we investigated the effects of NTU 101 on dextran sulfate sodium (DSS)-induced colitis in a mouse model. Colitis was induced in male C57BL/6 mice (total number n = 60) via dissolved DSS in drinking water on days 15-21 of the experiment. The effects of continuous 25 d feeding (days 0-25) of either a half or a full dose [2.3 × 109 colony-forming units (CFU)/kg body weight (BW)/d and 4.5 × 109 CFU/kg BW/d, respectively] of NTU 101 was evaluated. Lactobacillus rhamnosus BCRC 16000 (BCRC 16000) and L. paracasei subsp. paracasei BCRC 14023 (BCRC 14023) strains were given to control groups. The results indicated that NTU 101 powder improved anti-oxidant capacity, reduced pro-inflammatory cytokine levels, increased anti-inflammatory cytokine levels, and slightly ameliorated body weight loss in DSS-treated mice during the final days of the study. This indicated that NTU 101 powder can relieve the clinical symptoms of DSS-induced colitis in mice.

A randomized, double-blind clinical study of the effects of Ankascin 568 plus on blood lipid regulation.

Hyperlipidemia and inflammation play important roles in the development and progression of atherosclerosis. Atherosclerosis is regarded as an inflammatory response of blood vessels to injury at the start of atherosclerotic plaque formation, which then leads to cardiovascular events. Edible fungi of the Monascus species have been used as traditional Chinese medicines in East Asia for several centuries. The fermented products of Monascus purpureus NTU 568 possess a number of functional secondary metabolites including the anti-inflammatory pigments monascin and ankaflavin. Compounds derived from M. purpureus have been shown to have hypolipidemic effects. We aimed to evaluate the effects of M. purpureus NTU 568 fermentation product an extract (Ankascin 568 plus) containing monascin and ankaflavin on blood lipids in volunteers with borderline high levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) by conducting a 12-week randomized, double-blind, placebo-controlled, adaptive-design study. This study enrolled 40 subjects aged 18-65 years from a population of patients with TC and LDL-C levels of ≥180 mg/dL and 130-190 mg/dL, respectively. Measured endpoints included lipid profile, liver, kidney and thyroid function, electrolyte balance, creatinine phosphokinase, and fasting blood glucose. After 4 weeks of treatment (500 mg Ankascin 568 plus/day), the changes in the lipid levels showed that the active products had a more favorable effect than the placebo. Compared to the baseline, statistically significant decreases of 11.9% and 19.0% were observed in TC and LDL-C levels, respectively (p < 0.05 for all pairs). This study demonstrated that subjects administered one 500 mg capsule of Ankascin 568 plus for more than 4 weeks exhibited a significant reduction in serum TC and LDL-C levels. Therefore, Ankascin 568 plus may be a potentially useful agent for the regulation of blood lipids and the treatment of coronary artery diseases.

A randomized, double-blind clinical study to determine the effect of ANKASCIN 568 plus on blood glucose regulation.

Diabetes is the fourth major cause of death in Taiwan. High blood glucose can lead to macrovascular diseases, small vessel diseases (retinopathy, kidney disease), and neuropathy. This study aimed to investigate whether Monascus-fermented products (ANKASCIN 568 plus) can regulate blood glucose and blood lipids. This study enrolled 39 patients with a fasting blood glucose level between 100 mg/dL and 180 mg/dL, and a glycated hemoglobin (HbA1c) level of <9%. All patients were randomly divided into placebo (n=20) and experimental (n=19) groups. Each patient received two placebo capsules (maltodextrin) or ANKASCIN 568 plus capsules daily for 12 weeks. The patients were screened during follow-up 4 weeks after the administration of sample or placebo had been discontinued. Blood and urine samples were collected at the initial, 6th week, 12th week, and 16th week. The anthropometric indicators of blood pressure, fasting plasma glucose level, postprandial plasma glucose level, insulin level, insulin resistance, blood lipid changes, and liver, kidney, and thyroid function indices were measured. After 6 weeks, changes in fasting blood glucose, low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) levels showed that ANKASCIN 568 plus had a more favorable effect than the placebo. Compared to baseline, a statistically significant decrease of 8.5%, 10.3%, and 7.5% was observed in fasting blood glucose, LDL-C and, TC levels, respectively (p<0.05 for all pairs). Therefore, ANKASCIN 568 plus produced by Monascus purpureus NTU 568 fermentation may be a potentially useful agent for the regulation of blood glucose and blood lipids and for treatment of coronary artery diseases.

A Randomized, Double-Blind Clinical Study on Blood Pressure Reduction and Blood Lipid Profile Amelioration on Treatment with Ankascin 568.

Hypertension and cardiovascular complications are the leading causes of death worldwide. Antihypertensive drugs often cause various side effects, and improper use of antihypertensive medications can result in irreparable damage. Edible fungi of the Monascus species have been used as traditional Chinese medicines in Southeast Asia for several centuries. The fermented products of Monascus purpureus NTU 568 (ANKASCIN 568) possess a number of functional secondary metabolites including the anti-inflammatory pigments monascin (MS) and ankaflavin (AK). In this study, a double-blind, placebo-controlled clinical trial was performed in which patients with mild to moderate hypertension were randomly assigned to receive placebo or two 500-mg capsules of Ankascin 568 for 8 weeks. The effects of this treatment on the regulation of blood pressure (BP) were then examined. The results showed that systolic blood pressure (SBP) decreased from 141.6 ± 12.0 to 133.9 ± 14.4 mmHg (P < 0.05), and diastolic blood pressure (DBP) decreased from 91.7 ± 8.1 to 84.8 ± 7.4 mmHg (P < 0.05). Moreover, Ankascin 568 treatment effectively reduced serum triglycerides and total cholesterol (TC), increased high-density lipoprotein cholesterol (HDL-C), and reduced low-density lipoprotein cholesterol (LDL-C) levels, thereby improving the serum lipid profile. Additionally, administration of Ankascin 568 did not cause significant rhabdomyolysis nor impaired the metabolic or physiological functions of the liver or kidney. In conclusion, patients administered Ankascin 568 for 8 weeks exhibited significant in reduction of SBP, serum TC and LDL-C levels, which should contribute to better cardiovascular health.

Centella asiatica extract protects against amyloid ß1-40-induced neurotoxicity in neuronal cells by activating the antioxidative defence system.

Centella asiatica ( léi gong gen) is a traditional medicinal herb with high antioxidant activity, which decreases amyloid-ß (Aß) deposition in the brain. At the same time, aggregated Aß-induced oxidative stress is the trigger in the pathogenesis of Alzheimer's disease (AD). Here, we investigated the ability of C. asiatica ethanol extract (CAE) to protect PC12 and IMR32 cells from Aß1-40-induced production of reactive oxygen species (ROS) and concomitant neurotoxicity. Aggregated Aß1-40 treatment resulted in reduced cell viability, which can be reversed by cotreatment with 25, 50, and 100 µg/mL CAE. Moreover, CAE eliminated the Aß1-40-mediated increase in ROS production. Thus, CAE-mediated protection against aggregated Aß1-40-induced neurotoxicity is attributable to modulation of the antioxidative defense system in cells, including the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and levels of glutathione and glutathione disulfide by CAE. This emphasizes the potential therapeutic and preventive value of CAE in the treatment of AD.

Effects of red mold dioscorea with pioglitazone, a potentially functional food, in the treatment of diabetes.

The prevalence of type 2 diabetes mellitus is increasing rapidly, and its treatment with pioglitazone is likely to induce rhabdomyolysis. We aimed to determine the effect of cotreatment with pioglitazone and red mold dioscorea (RMD) produced by Monascus purpureus NTU 568 on pancreas function in streptozotocin (STZ)-induced diabetic rats. In diabetic rats fed RMD, RMD with pioglitazone, and pioglitazone alone, insulin concentrations increased significantly by 18.6-40.4%, 64.0-100.0%, and 52.8%, respectively, compared with that in the diabetic group (p < 0.05). Oral glucose tolerance was impaired in the STZ-induced diabetic group within 4 weeks, however, oral glucose tolerance in rats treated with RMD or RMD with pioglitazone improved after 4 weeks, 6 weeks, and 8 weeks. Findings from this study might lend support to the use of RMD as a novel functional food for the prevention of diabetes.

Red mold dioscorea: a potentially safe traditional function food for the treatment of hyperlipidemia.

A study was undertaken to evaluate whether the interaction between Monascus-fermented products and lovastatin contributes to increased risk of rhabdomyolysis. Rhabdomyolysis is a potentially dangerous side effect of statin drugs. In this study with hyperlipidemic hamsters fed lovastatin only, lovastatin with 1-fold red mold dioscorea (RMD), and lovastatin, the functional components of red mold fermented products, HMG-CoA reductase inhibitors, did not exacerbate pre-existing diseases, and actually helped in improving existing disease conditions, respectively, as compared with the control. Administration of RMD, alone or in combination with lovastatin did not cause significant rhabdomyolysis as assessed by measuring the levels of creatinine phosphokinase. Further, we did not find any study that clearly implicates the involvement of RMD, which have long been considered a food product, in liver and kidney toxicity. RMD alone or in combination with lovastatin, does not increase the risk of rhabdomyolysis, even when administered at a high dosage (including HMG-CoA reductase inhibitors >75 mg/day/adult).