WGA-M001, a Mixture of Total Extracts of Tagetes erecta and Ocimum basilicum, Synergistically Alleviates Cartilage Destruction by Inhibiting ERK and NF-κB Signaling.

Tagetes erecta and Ocimum basilicum are medicinal plants that exhibit anti-inflammatory effects against various diseases. However, their individual and combined effects on osteoarthritis (OA) are unknown. Herein, we aimed to demonstrate the effects of T. erecta, O. basilicum, and their mixture, WGA-M001, on OA pathogenesis. The administration of total extracts of T. erecta and O. basilicum reduced cartilage degradation and inflammation without causing cytotoxicity. Although WGA-M001 contained lower concentrations of the individual extracts, it strongly inhibited the expression of pathogenic factors. In vivo OA studies also supported that WGA-M001 had protective effects against cartilage destruction at lower doses than those of T. erecta and O. basilicum. Moreover, its effects were stronger than those observed using Boswellia and Perna canaliculus. WGA-M001 effectively inhibited the interleukin (IL)-1ß-induced nuclear factor kappa-light-chain-enhancer of the activated B cell (NF-κB) pathway and ERK phosphorylation. Furthermore, RNA-sequence analysis also showed that WGA-M001 decreased the expression of genes related to the IL-1ß-induced NF-κB and ERK signaling pathways. Therefore, WGA-M001 is more effective than the single total extracts of T. erecta and O. basilicum in attenuating OA progression by regulating ERK and NF-κB signaling. Our results open new possibilities for WGA-M001 as a potential therapeutic agent for OA treatment.

Euglena gracilis (Euglena) powder supplementation enhanced immune function through natural killer cell activity in apparently healthy participants: A randomized, double-blind, placebo-controlled trial.

Euglena gracilis (Euglena) is a microalgae found in most freshwater environments that produces paramylon, an insoluble ß-1,3-glucan linked to human immunity. We hypothesized that Euglena powder has effects on immune function in apparently healthy adults. The study included male or female volunteers between the ages of 20 and 70 years who had white blood cell counts ranging from 4 × 103/µL to 10 × 103/µL, a "severe" rating on the stress questionnaire from the Korea National Health and Nutrition Examination Survey, and at least 2 upper respiratory infections with cold-like symptoms in the previous year. Participants received either a placebo or 700 mg of Euglena powder daily for 8 weeks. The study measured natural killer cell activity, cytokine concentrations, and blood lipid profiles to confirm the immune effect of Euglena consumption. In conclusion, Euglena improved immunological function through natural killer cell activity. Safety assessment showed no significant changes in vital signs or clinical chemistry indicators, and there were no adverse events associated with Euglena consumption. Euglena supplementation may help boost the immune systems of healthy individuals.

All-cause and cause-specific mortality risks associated with calcium supplementation with or without vitamin D: A nationwide population-based study.

BACKGROUND: Current evidence regarding the mortality outcomes associated with calcium supplementation with or without low-dose vitamin D is conflicting. OBJECTIVES: To investigate the effects of calcium supplementation with or without vitamin D on all-cause and cause-specific mortalities in a large-scale cohort. METHODS: This study used data from the Korean National Health Insurance System database and National Death Registry. A total of 27,846 participants aged >55 years who had taken calcium supplements with or without vitamin D for at least 90 days (calcium supplementation only [CaO], n = 6256; calcium supplementation in combination with vitamin D [CaD], n = 21,590) were matched in a 1:1 ratio to those who did not take calcium or vitamin D supplements (control group) using propensity scores. RESULTS: No difference in all-cause mortality risk was found between the CaO and control groups: (adjusted hazard ratio [HR] = 1.00; 95% confidence interval [CI]: 0.92-1.10). However, all-cause mortality was lower in the CaD group (HR = 0.85; 95% CI: 0.80-0.89) compared with that in the control group. Mortality risk associated with cardiovascular disease (CVD) was decreased in the CaD group when the daily vitamin D dose received was less than 1000 IU (HR = 0.72; 95% CI: 0.64-0.81). Subgroup analysis showed significant effect of vitamin D with calcium in individuals who were female, aged ≥65 years or had previous history of cancer or CVD. CONCLUSION: In combination with calcium, vitamin D supplementation provides better outcomes for all-cause mortality, particularly CVD-associated mortality, in a duration-dependent manner.

Noni fruit extract ameliorates alcohol-induced hangover symptoms by reducing the concentrations of alcohol and acetaldehyde in a Sprague Dawley rat model and a human intervention study.

Various studies have reported that Noni shows various health effects. This study aimed to assess the ability of Noni fruit extract to serve as a single active functional ingredient for the alleviation of hangover symptoms in Sprague Dawley rats and healthy subjects in a single-dose, randomized, double-blind, crossover, placebo-controlled study. The rats were orally administered Noni fruit extract at 50 or 100 mg per kg body weight (B.W.) and HOVENIA. The blood ethanol (EtOH) and acetaldehyde concentrations were significantly lower in the 100 mg per kg B.W. group than in the EtOH group. Alcohol dehydrogenase and aldehyde dehydrogenase activity tended to increase in the 100 mg kg-1 B.W. group. In the human study, 30 subjects received either a placebo or Noni fruit extract (1 g). The Noni fruit extract group showed significantly faster time point at which the maximum concentration (Tmax) of alcohol than in the placebo group. In addition, blood acetaldehyde levels and diarrhea at 40 and 720 min after alcohol intake and the area under the curve between 40 and 60 min of acetaldehyde were significantly decreased in the Noni fruit extract group compared to the placebo group. According to the QUalitative INteraction Trees, subjects who were ≤36 years old who consumed more alcohol (>15 drinks per week) and had a higher total hangover score (>27.5 and 33) presented significantly lower blood acetaldehyde levels and less severe hangover symptoms. These results indicate that Noni fruit extract has the potential to improve hangover symptoms by decreasing alcohol and acetaldehyde levels.

Cardiovascular risks associated with calcium supplementation in patients with osteoporosis: a nationwide cohort study.

AIMS: This study aimed to evaluate the real effects of calcium supplementation on cardiovascular outcomes within a population-based cohort. METHODS AND RESULTS: From a nationwide health screening database in South Korea, a total of 11 297 patients with osteoporosis who had taken calcium supplementation with or without vitamin D for at least 90 days [total calcium group; calcium supplementation only (CaO), n = 567; calcium supplementation in combination with vitamin D (CaD), n = 10 730] were matched at a 1:1 ratio to patients who had not taken calcium supplements (control group) by using propensity scores. The overall mean age was 59.9 ± 8.8 years and the percentage of women was 87.9% in our study population. Over a median follow-up of 54 months, the incidence rate of composite cardiovascular diseases (CVDs) per 1000 person-years was not different between the groups: 9.73 in the total calcium group and 8.97 in the control group [adjusted hazard ratio (HR): 1.12; 95% confidence interval (CI): 0.99-1.28; P = 0.08]. However, calcium supplementation without vitamin D was associated with an increased risk of composite CVD (HR: 1.54; 95% CI: 1.17-2.04; P < 0.01), especially non-fatal myocardial infarction (HR: 1.89; 95% CI: 1.23-2.91; P < 0.01), compared with no calcium supplementation. CONCLUSION: Our population-based study supported that taking calcium supplementation combined with vitamin D did not appear to be harmful to cardiovascular health, but reminded that calcium supplementation without vitamin D should be used carefully even in populations with low dietary calcium intake.

A Systems Biological Approach to Understanding the Mechanisms Underlying the Therapeutic Potential of Red Ginseng Supplements against Metabolic Diseases.

Red ginseng has been widely used in health-promoting supplements in Asia and is becoming increasingly popular in Western countries. However, its therapeutic mechanisms against most diseases have not been clearly elucidated. The aim of the present study was to provide the biological mechanisms of red ginseng against various metabolic diseases. We used a systems biological approach to comprehensively identify the component-target and target-pathway networks in order to explore the mechanisms underlying the therapeutic potential of red ginseng against metabolic diseases. Of the 23 components of red ginseng with target, 5 components were linked with 37 target molecules. Systematic analysis of the constructed networks revealed that these 37 targets were mainly involved in 9 signaling pathways relating to immune cell differentiation and vascular health. These results successfully explained the mechanisms underlying the efficiency of red ginseng for metabolic diseases, such as menopausal symptoms in women, blood circulation, diabetes mellitus, and hyperlipidemia.

Antithrombotic Effect of Artemisia princeps Pampanini Extracts in Vitro and in FeCl3 -Induced Thrombosis Rats.

Extracts of several plants possess antithrombotic effects. Herein, we examined the antithrombotic effects of different extracts of Artemisia princeps Pampanini prepared using distilled water, hot distilled water, 70% ethanol, or subcritical water. The antithrombotic effects were determined using a co-culture system consisting of tumor necrosis factor-alpha (TNF-α)-treated EA.hy926 cells and THP-1 cells. In addition, the coagulation time of plasma collected from healthy volunteers was evaluated in terms of the prothrombin time and activated partial thromboplastin time. A carotid arterial thrombosis model was induced by ferric chloride in Sprague Dawley rats. The rats were treated with either sterile water or three different doses of the subcritical water extract for 2 weeks. The thrombus weight, gene expression of cell adhesion molecules, and histological characteristics were assessed. The results of in vitro studies revealed a significant inhibition in the adhesion of monocytes to EA.hy926 cells stimulated by TNF-α in the subcritical water extract-treated group. We also observed considerable suppression of the occlusion and mRNA expression of cell adhesion molecules in the in vivo experiments. This study suggests that Artemisia princeps Pampanini may have the potential to improve blood coagulation.

Differential responses of endothelial integrity upon the intake of microencapsulated garlic, tomato extract or a mixture: a single-intake, randomized, double-blind, placebo-controlled crossover trial.

This study investigated the effect of microencapsulated garlic and/or tomato on endothelial dysfunction induced by the PhenFlex test (PFT) in healthy male smokers. In a randomized, double-blind, placebo-controlled crossover trial, 41 healthy male smokers were randomly assigned to one of four groups to receive the test groups (in microencapsulated garlic powder, tomato extract and a mixture thereof) or the placebo group. Proteomic biomarkers related to endothelial integrity were measured in plasma. Microencapsulated garlic, tomato extract and the mixture affected endothelial integrity biomarkers differently. Garlic consumption increased prothrombin time and decreased SAA and IL-12. Tomato extract intake increased activated partial thrombin time and decreased d-dimer, SAA, sVCAM-1, IL-13 and MCP-3 levels. Consumption of the mixture increased sE-selectin and lowered D-dimer, SAA, IL-13 and IL-10 responses after PFT challenge for 6 h. The different responses became clearer under high compliance in the dietary restriction groups. This single-intake clinical trial addressed the different responses of biomarkers related to endothelial integrity.

L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial.

Hypothyroid patients experience fatigue-related symptoms despite adequate thyroid hormone replacement. Thyroid hormone plays an essential role in carnitine-dependent fatty acid import and oxidation. We investigated the effects of L-carnitine supplementation on fatigue in patients with hypothyroidism. In total, 60 patients (age 50.0 ± 9.2 years, 3 males, 57 females) who still experienced fatigue (fatigue severity scale [FSS] score ≥ 36) were given L-carnitine (n = 30, 990 mg L-carnitine twice daily) or placebo (n = 30) for 12 weeks. After 12 weeks, although neither the FSS score nor the physical fatigue score (PFS) changed significantly, the mental fatigue score (MFS) was significantly decreased by treatment with L-carnitine compared with placebo (from 4.5 ± 1.9 to 3.9 ± 1.5 vs. from 4.2 ± 1.8 to 4.6 ± 1.6, respectively; P < 0.01). In the L-carnitine group, 75.0%, 53.6%, and 50.0% of patients showed improvement in the FSS score, PFS, and MFS, respectively, but only 20.0%, 24.0%, and 24.0%, respectively, did so in the placebo group (all P < 0.05). Both the PFS and MFS were significantly improved in patients younger than 50 years and those with free T3 ≥ 4.0 pg/mL by treatment with L-carnitine compared with placebo. Additionally, the MFS was significantly improved in patients taking thyroid hormone after thyroid cancer surgery. These results suggest that L-carnitine supplementation may be useful in alleviating fatigue symptoms in hypothyroid patients, especially in those younger than 50 years and those who have hypothyroidism after thyroidectomy for thyroid cancer (ClinicalTrials.gov: NCT01769157).

Effect of Rubus Occidentalis Extract on Metabolic Parameters in Subjects with Prediabetes: A Proof-of-concept, Randomized, Double-blind, Placebo-controlled Clinical Trial.

Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12-week, randomized, double-blind, placebo-controlled trial. Forty-four patients (age 59.0 ± 8.2 years, 70.5% females, HbA1c 5.8 ± 0.4%) were divided into placebo (n = 13), low-dose RO extract (LRE; n = 14), or high-dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75-g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (-28.1 ± 42.4 vs. +13.4 ± 52.6 mg/dL, p < 0.05). Homoeostasis model assessment-B was increased (+17.11 ± 10.69, +5.24 ± 4.10, and +0.86 ± 6.01 in HRE, LRE, and placebo, respectively, p < 0.05). Serum levels of monocyte chemoattractant protein-1 and oxidized low-density lipoprotein were significantly decreased by treatment in a dose-dependent manner (monocyte chemoattractant protein-1: -35.0 ± 21.2, +8.4 ± 18.1, and +24.2 ± 14.5; oxidized low-density lipoprotein: -19.7 ± 8.5, -13.1 ± 7.2, and -2.2 ± 11.0 in the HRE, LRE, and placebo, respectively, p < 0.05). The results support the beneficial effects of RO extract on the control of glycemia and vascular inflammation in prediabetic patients. (ClinicalTrials.gov: NCT01964703). Copyright © 2016 John Wiley & Sons, Ltd.

Cell penetrating peptide conjugated liposomes as transdermal delivery system of Polygonum aviculare L. extract.

In this study, Polygonum aviculare L. extract, which has superior antioxidative and cellular membrane protective activity, was loaded onto cell penetrating peptide (CPP) conjugated liposomes to enhance transdermal delivery. The physical characteristics of typical liposomes and CPP-conjugated liposomes containing P. aviculare extract were evaluated. The particle sizes of both liposomes were approximately 150 nm. Whereas the zeta potential of typical liposomes was -45 mV, that of CPP-conjugated liposomes was +42 mV. The loading efficiency of P. aviculare extract in both liposomes was calculated to be about 83%. Fluorescent-labeled liposomes were prepared to evaluate cellular uptake and skin permeation efficiency. Using flow cytometry, we found that CPP-conjugated liposomes improved cellular uptake of the fluorescent dye as compared with the typical liposomes. In addition, the skin permeation of CPP-conjugated liposomes was proved higher than that of typical liposomes by confocal laser scanning microscopy studies and Franz diffusion cell experiments. The improved cellular uptake and skin permeation of the CPP-conjugated liposomes were due to the cationic arginine-rich peptide. In vivo studies also determined that the CPP-conjugated liposomes were more effective in depigmentation and anti-wrinkle studies than typical liposomes. These results indicate that the CPP-conjugated liposomes could be effective for transdermal drug delivery of antioxidant and anti-aging therapeutics.