Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this study, 40 high fat diet (HFD) rats were supplemented with 100-300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.

Ramie leaf Extract Alleviates Bone Loss in Ovariectomized Rats-The Involvement of ROS and Its Associated Signalings.

Ramie leaf (Boehmeria nivea L.) has been traditionally used to treat gynecological and bone-related disorders. This study aims to evaluate the effect of Ramie leaf extracts (RLE) against osteoporosis in ovariectomized (OVX) rats. Female SD rats aged seven weeks were randomly assigned into five OVX and a sham-operated (sham) group. OVX subgroups include OVX, vehicle-treated OVX group; E2, OVX with 100 µg/kg 17ß-estradiol; and RLE 0.25, 0.5, and 1, OVX rats treated with 0.25, 0.5, and 1 g/kg/day RLE, respectively. Two weeks into the bilateral ovariectomy, all the rats were orally administered with or without RLE daily for 12 weeks. OVX rats administered with RLE showed higher bone density, relatively low tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and lower reactive oxygen species (ROS) within bone tissues compared to vehicle-treated OVX rats. Furthermore, supplementation of RLE improved bone mineral density (BMD) and bone microstructure in the total femur. RLE prevented RANKL-induced osteoclast differentiation and expression of osteoclastogenesis-related genes such as Cal-R, MMP-9, cathepsin K, and TRAP in RANKL-induced RAW264.7 cells. Moreover, RLE administration lowered the intracellular ROS levels by reducing NADPH oxidase 1 (NOX-1) and 4-hydroxynonenal (4HNE). These results suggest that RLE alleviates bone mass loss in the OVX rats by inhibiting osteoclastogenesis, where reduced ROS and its associated signalings were involved.

Lycium chinense Miller fruit extract lowers liver enzyme levels in subjects with mild hepatic dysfunction: a randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: In our previous study, we showed that Lycium chinense Miller fruit extract (LFE) exerted hepatoprotective effects in mice. In the current study, we examined the effect of LFE on liver enzyme levels in subjects with mild hepatic dysfunction. METHODS: A total of 90 subjects, aged 19 to 70 years old, with abnormal alanine aminotransferase (ALT) levels, were randomly placed into either an LFE (n = 45) treatment group or a placebo group (n = 45). During the 12-week clinical trial, subjects in each group received either LFE or placebo capsules, and were instructed to take four tablets per day (1760 mg/day). The primary outcome of the study was the changes of ALT and γ-glutamyltransferase (GGT) levels in each subject. The safety of LFE supplementation was assessed and adverse events were recorded. RESULTS: LFE supplementation for 12 weeks resulted in a significant reduction of ALT (P = 0.0498) and GGT (P = 0.0368) levels in comparison to the placebo. No clinically significant changes were observed in any safety parameters. CONCLUSION: These results suggest that LFE can be applied to subjects with mild hepatic dysfunction with no possible side effects. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service (CRIS) as no. KCT0003985.

Supplementation with Vitis vinifera Jingzaojing Leaf and Shoot Extract Improves Exercise Endurance in Mice.

Switching myofibers from the fast-glycolytic type to the slow-oxidative type is associated with an alleviation of the symptoms associated with various cardiometabolic diseases. This study investigates the effect of Vitis vinifera Jingzaojing leaf and shoot extract (JLSE), which is rich in phenolic compounds, on the regulation of skeletal muscle fiber-type switching, as well as the associated underlying mechanism. Male C57BL/6N mice were supplemented orally with vehicle or JLSE (300 mg/kg) and subjected to treadmill exercise training. After four weeks, mice in the JLSE-supplemented group showed significantly improved exercise endurance and mitochondrial oxidative capacity. JLSE supplementation increased the expression of sirtuin 6 and decreased Sox6 expression, thereby elevating the number of mitochondria and encouraging fast-to-slow myofiber switching. The results of our experiments suggest that JLSE supplementation reprograms myofiber composition to favor the slow oxidative type, ultimately enhancing exercise endurance.

Effect of Ginseng Extracts on the Improvement of Osteopathic and Arthritis Symptoms in Women with Osteopenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Ginsenosides are active compounds that are beneficial to bone metabolism and have anti-osteoporosis properties. However, very few clinical investigations have investigated the effect of ginseng extract (GE) on bone metabolism. This study aims to determine the effect of GE on improving bone metabolism and arthritis symptoms in postmenopausal women with osteopenia. A 12-week randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 90 subjects were randomly divided into a placebo group, GE 1 g group, and GE 3 g group for 12 weeks based on the random 1:1:1 assignment to these three groups. The primary outcome is represented by bone metabolism indices consisting of serum osteocalcin (OC), urine deoxypyridinoline (DPD), and DPD/OC measurements. Secondary outcomes were serum CTX, NTX, Ca, P, BsALP, P1NP, OC/CTX ratio, and WOMAC index. The GE 3 g group had a significantly increased serum OC concentration. Similarly, the GE 3 g group showed a significant decrease in the DPD/OC ratio, representing bone resorption and bone formation. Moreover, among all the groups, the GE 3 g group demonstrated appreciable improvements in the WOMAC index scores. In women with osteopenia, intake of 3 g of GE per day over 12 weeks notably improved the knee arthritis symptoms with improvements in the OC concentration and ratios of bone formation indices like DPD/OC.

Efficacy and Safety of Sesame Oil Cake Extract on Memory Function Improvement: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Pilot Study.

The goal of treatment for mild cognitive impairment (MCI) is to reduce the existing clinical symptoms, delay the progression of cognitive impairment and prevent the progression to Alzheimer's disease (AD). At present, there is no effective drug therapy for AD treatment. However, early intake of dietary supplements may be effective in alleviating and delaying the MCI. This study aims to evaluate the effects of sesame oil cake extract (SOCE) supplementation on cognitive function in aged 60 years or older adults with memory impairment. A total of 70 subjects received either SOCE (n = 35) or placebo (n = 35) for 12 weeks based on random 1:1 assignment to these two groups. Cognitive function was evaluated by a computerized neurocognitive function test (CNT), and changes in the concentrations of plasma amyloid ß (Aß) proteins and urine 8-OHdG (8-hydroxy-2'-deoxyguanosine) were investigated before and after the experiment. Verbal learning test index items of the CNT improved markedly in the SOCE group compared to the placebo group (p < 0.05). Furthermore, plasma amyloid-ß (1-40) and amyloid-ß (1-42) levels in the SOCE group decreased significantly compared to that in the placebo group (p < 0.05). There was no statistically significant difference in urine 8-OHdG between the two groups (p > 0.05). Collectively, intake of SOCE for 12 weeks appears to have a beneficial effect on the verbal memory abilities and plasma ß-amyloid levels of older adults with memory impairment.

Effect of processed aloe vera gel on immunogenicity in inactivated quadrivalent influenza vaccine and upper respiratory tract infection in healthy adults: A randomized double-blind placebo-controlled trial.

BACKGROUND: Aloe vera is a functional food with various pharmacological functions, including an immune-modulating effect. Until now, A. vera has never been studied as an adjuvant in influenza vaccine, and its effects on upper respiratory tract infection (URI) are unknown. PURPOSE: The objective of our study was to investigate the effect of processed A. vera gel (PAG) on immunogenicity of quadrivalent inactivated influenza vaccine and URI in healthy adults. STUDY DESIGN: A randomized, double-blind, placebo-controlled clinical trial was performed. METHODS: This study was conducted in 100 healthy adults at a single center from September 2017 to May 2018. Subjects were randomly divided into a PAG group (n = 50) and a placebo group (n = 50). The enrolled subjects were instructed to ingest the study drug for 8 weeks. The participants received a single dose of quadrivalent inactivated influenza vaccine after taking the study drug for the first 4 weeks of the study. The primary endpoint was seroprotection rate against at least one viral strain at 4 weeks post-vaccination. Other outcomes were seroprotection rate at 24 weeks post-vaccination, seroconversion rate, geometric mean fold increase (GMFI) at 4 and 24 weeks post-vaccination, seroprotection rate ratio and geometric mean titer ratio (GMTR) at 4 weeks post-vaccination between PAG and placebo groups, and incidence, severity, and duration of URI. RESULTS: The European Committee for proprietary medicinal products (CPMP) evaluation criteria were met at least one in the PAG and placebo groups for all strains. However, there was no significant difference in the seroprotection rate at 4 weeks post-vaccination against all strains in both PAG and placebo groups. Among secondary endpoints, the GMFI at 4 weeks post-vaccination for the A/H3N2 was significantly higher in the PAG than in placebo group. The GMTR as adjuvant effect was 1.382 (95% CI, 1.014-1.1883). Kaplan-Meier curve analysis showed a reduction in incidence of URI (p = 0.035), and a generalized estimating equation model identified a decrease in repeated URI events (odds ratio 0.57; 95% CI, 0.39-0.83; p = 0.003) in the PAG group. CONCLUSIONS: Oral intake of PAG did not show a significant increase in seroprotection rate from an immunogenicity perspective. However, it reduced the number of URI episodes. A well-designed further study is needed on the effect of PAG's antibody response against A/H3N2 in the future.

Anthocyanins attenuate endothelial dysfunction through regulation of uncoupling of nitric oxide synthase in aged rats.

Endothelial dysfunction is one of the main age-related arterial phenotypes responsible for cardiovascular disease (CVD) in older adults. This endothelial dysfunction results from decreased bioavailability of nitric oxide (NO) arising downstream of endothelial oxidative stress. In this study, we investigated the protective effect of anthocyanins and the underlying mechanism in rat thoracic aorta and human vascular endothelial cells in aging models. In vitro, cyanidin-3-rutinoside (C-3-R) and cyanidin-3-glucoside (C-3-G) inhibited the d-galactose (d-gal)-induced senescence in human endothelial cells, as indicated by reduced senescence-associated-ß-galactosidase activity, p21, and p16INK4a . Anthocyanins blocked d-gal-induced reactive oxygen species (ROS) formation and NADPH oxidase activity. Anthocyanins reversed d-gal-mediated inhibition of endothelial nitric oxide synthase (eNOS) serine phosphorylation and SIRT1 expression, recovering NO level in endothelial cells. Also, SIRT1-mediated eNOS deacetylation was shown to be involved in anthocyanin-enhanced eNOS activity. In vivo, anthocyanin-rich mulberry extract was administered to aging rats for 8 weeks. In vivo, mulberry extract alleviated endothelial senescence and oxidative stress in the aorta of aging rats. Consistently, mulberry extract also raised serum NO levels, increased phosphorylation of eNOS, increased SIRT1 expression, and reduced nitrotyrosine in aortas. The eNOS acetylation was higher in the aging group and was restored by mulberry extract treatment. Similarly, SIRT1 level associated with eNOS decreased in the aging group and was restored in aging plus mulberry group. These findings indicate that anthocyanins protect against endothelial senescence through enhanced NO bioavailability by regulating ROS formation and reducing eNOS uncoupling.

A randomized, double-blind, placebo-controlled crossover clinical trial to evaluate the anti-diabetic effects of Allium hookeri extract in the subjects with prediabetes.

BACKGROUND: Allium hookeri is widely consumed as a vegetable and herbal medicine in Asia. A. hookeri has been reported anti-inflammatory, anti-obesity, osteoblastic, anti-oxidant, and anti-diabetic effects in animal studies. We investigated the anti-diabetic effects of A. hookeri aqueous extract (AHE) in the Korean subjects. METHODS: Prediabetic subjects (100 ≤ fasting plasma glucose (FPG) < 126 mg/dL) who met the inclusion criteria were recruited for this study. The enrolled subjects (n = 30) were randomly divided into either an AHE (n = 15, 486 mg/day) or placebo (n = 15) group. Outcomes were measurements of FPG, glycemic response to an oral glucose tolerance test (OGTT), insulin, C-peptide, hemoglobin A1c (HbA1c), total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol. The t-test was used to assess differences between the groups. A p-value < 0.05 was considered statistically significant. RESULTS: Eight weeks after AHE supplementation, HbA1c level was significantly decreased in the AHE group compared with the placebo group. No clinically significant changes in any safety parameter were observed. CONCLUSION: The findings suggest that AHE can be effective in reducing HbA1c, indicating it as an adjunctive tool for improving glycemic control. TRIAL REGISTRATION: The study protocol was retrospectively registered at www.clinicaltrials.gov ( NCT03330366 , October 30, 2017).

Effects of Porphyra tenera Supplementation on the Immune System: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

OBJECTIVE: The purpose of this study was to determine if Porphyra tenera extract (PTE) has immune-enhancing effects and is safe in healthy adults. METHODS: Subjects who met the inclusion criteria (3 × 103 ≤ peripheral blood leukocyte level ≥ 8 × 103 cells/µL) were recruited for this study. Enrolled subjects (n = 120) were randomly assigned to either the PTE group (n = 60) and were given 2.5 g/day of PTE (as PTE) in capsule form or the placebo group (n = 60) and were given crystal cellulose capsules with the identical appearance, weight, and flavor as the PTE capsules for 8 weeks. Outcomes were assessed based on measuring natural killer (NK) cell activity, cytokines level, and upper respiratory infection (URI), and safety parameters were assessed at baseline and 8 weeks. RESULTS: Compared with baseline, NK cell activity (%) increased for all effector cell-to-target cell ratios in the PTE group after 8 weeks; however, changes were not observed in the placebo group (p < 0.10). Subgroup analysis of 101 subjects without URI showed that NK cell activity in the PTE group tended to increase for all effector cell/target cell (E:T) ratios (E:T = 12.5:1 p = 0.068; E:T = 25:1 p = 0.036; E:T = 50:1 p = 0.081) compared with the placebo group. A significant difference between the two groups was observed for the E:T = 25:1 ratio, which increased from 20.3 ± 12.0% at baseline to 23.2 ± 12.4% after 8 weeks in the PTE group (p = 0.036). A significant difference was not observed in cytokine between the two groups. CONCLUSION: PTE supplementation appears to enhance immune function by improving NK cell activity without adverse effects in healthy adults.

Lemon balm and dandelion leaf extract synergistically alleviate ethanol-induced hepatotoxicity by enhancing antioxidant and anti-inflammatory activity.

We investigated the effect of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (LD) on ethanol (EtOH)-mediated liver injury and explored the underlying mechanisms. Administration of LD synergistically reduced relative liver weight and decreased the levels of serum biomarkers of hepatic injury. Histopathological and biochemical analyses indicated that LD synergistically attenuated hepatic accumulation of triacylglycerides (TGs) and restored the levels of mRNAs related to fatty acid metabolism. In addition, LD significantly reduced EtOH-induced hepatic oxidative stress by attenuating the reduction in levels of nuclear factor E2-related factor 2 (Nrf2) mRNA and enhancing antioxidant activity. Moreover, LD decreased the EtOH-mediated increase in levels of hepatic tumor necrosis factor-α (TNF-α) mRNA. In vitro, LD significantly scavenged free radicals, increased cell viability against tert-butylhydroperoxide (tBHP), and transactivated Nrf2 target genes in HepG2 cells. Furthermore, LD decreased levels of pro-inflammatory mediators in lipopolysaccharide-stimulated Raw264.7 cells. Therefore, LD shows promise for preventing EtOH-mediated liver injury. PRACTICAL APPLICATIONS: There were no approved therapeutic agents for preventing and/or treating alcoholic liver diseases. In this study, a 2:1 (w/w) mixture of lemon balm and dandelion leaf extract (DL) synergistically ameliorated EtOH-induced hepatic injury by inhibiting lipid accumulation, oxidative stress, and inflammation. Our findings will enable the development of a novel food supplement for the prevention or treatment of alcohol-mediated liver injury.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Assessing the Effects of Angelica Gigas Nakai Extract on Blood Triglycerides.

Angelica gigas Nakai, Korean dang-gui, has long been widely used in traditional treatment methods. There have been a number of studies of the health effects of A. gigas and related compounds, but studies addressing effects on blood triglycerides (TG) are lacking. To investigate the effects of A. gigas Nakai extract (AGNE) on TG in Korean subjects, we carried out a 12-week, randomized, double-blind, placebo-controlled clinical trial. Subjects who met the inclusion criterion (130 mg/dL ≤ fasting blood TG ≤ 200 mg/dL) were recruited for this study. One hundred subjects were assigned to the AGNE group (n = 50) or the placebo group (n = 50), who were given 1 g/day of AGNE (as a gigas Nakai extract 200 mg/d) in capsules and the control group for 12 weeks. Outcomes were efficacy TG, lipid profiles, atherogenic index, and safety parameters were assessed initially for a baseline measurement and after 12 weeks. After 12 weeks of supplementation, TG and very low-density lipoprotein cholesterol (VLDL-C) concentration and TG/HDL-C ratio in the AGNE group were significantly reduced compared to the placebo group (p < 05). No significant changes in any safety parameter were observed. These results suggest that the ingestion of AGNE may improve TG and be useful to manage or prevent hypertriglyceridemia.

Mulberry Extract Attenuates Endothelial Dysfunction through the Regulation of Uncoupling Endothelial Nitric Oxide Synthase in High Fat Diet Rats.

Dyslipidemia is associated with endothelial dysfunction, which is linked to nitric oxide (NO) biology. The coupling of endothelial NO synthase with cofactors is a major step for NO release. This study is aimed to investigate the vascular pharmacology effects of mulberry in rat thoracic aorta and human vascular endothelial cells. In vitro, we investigated the protective effects of the mulberry extract and its main component cyanidin-3-rutinoside (C-3-R), against oxidized low-density lipoprotein (ox-LDL)-induced endothelial nitric oxide synthase (eNOS) uncoupling. Whereas ox-LDL significantly decreased NO levels in endothelial cells, mulberry extract, and C-3-R significantly recovered NO levels and phospho-eNOS Thr495 and Ser1177 expression. In vivo, mulberry was administered to 60% of high-fat diet (w/w)-fed Sprague Dawley (SD) rats for six weeks, in which endothelium-dependent relaxations were significantly improved in organ bath studies and isometric tension recordings. Consistently, aortic expressions of phospho-eNOS and nitrotyrosine were increased. Mulberry also raised serum NO levels, increased phosphorylation of eNOS, and reduced nitrotyrosine and intracellular reactive oxygen species (ROS) in aortas, showing that mulberry preserves endothelium-dependent relaxation in aortas from high-fat diet rats. We suggest that this effect is mediated through enhanced NO bioavailability, in which the regulation of ROS and its reduced eNOS uncoupling are involved.

Immunomodulatory effects of a mycelium extract of Cordyceps (Paecilomyces hepiali; CBG-CS-2): a randomized and double-blind clinical trial.

BACKGROUND: Cordyceps is a traditional Chinese herb that produces various biopharmaceutical effects, including immune-enhancing effects. In this study, we prepared a Cordyceps mycelium culture extract (Paecilomyces hepiali, CBG-CS-2) to confirm its efficacy in enhancing the immune system and to evaluate its safety in healthy adults. METHODS: Healthy adults were divided into the intervention group (n = 39), who were given 1.68 g/day of CBG-CS-2 in capsules, and the control group (n = 40) for 8 weeks. The activities of natural killer (NK) cells and serum levels of monocyte-derived mediators were assessed initially for a baseline measurement and after 8 wks. RESULTS: The CBG-CS-2 group showed a significant 38.8 ± 17.6% enhancement from the baseline of NK cell cytotoxic activity relative to the placebo group after the administration of the capsules for 8 wks. (P < 0.019). CONCLUSION: The results suggest that the immune system functions well with CBG-CS-2 supplementation, perhaps with less accompanying inflammation. Thus, CBG-CS-2 is safe and effective for enhancing cell-mediated immunity in healthy adults. TRIAL REGISTRATION: This study was registered at Clinical Trials.gov ( NCT 02814617 ).

Supplementation with extract of Gynostemma pentaphyllum leaves reduces anxiety in healthy subjects with chronic psychological stress: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: The ethanol extract of Gynostemma pentaphyllum Makino leaves (EGP) has been reported recently to have anxiolytic effects on chronically stressed mice models. PURPOSE: We aimed to investigate the efficacy and safety of EGP on anxiety level in healthy Korean subjects under chronic stressful conditions. STUDY DESIGN: Double-blind, placebo-controlled trial. METHODS: This study was conducted with 72 healthy adults who had perceived chronic stress and anxiety with a score on the State-Trait Anxiety Inventory (STAI) from 40 to 60. Participants were randomly assigned to receive either EGP (200 mg, twice a day, N = 36) or placebo (N = 36). All participants were exposed to repetitive loads of stress by performing the serial subtraction task for 5 min every second day during the 8-week intervention. Primary outcome of Trait-STAI and secondary outcomes of State-STAI, total score of STAI, Hamilton Anxiety Inventory (HAM-A), Beck Anxiety Inventory (BAI), blood norepinephrine and adrenocorticotropic hormone (ACTH), salivary cortisol and alpha-amylase, cardiovascular autonomic nervous system (ANS) functional test, and heart rate variability (HRV) test were measured before and after intervention. RESULTS: After the 8-week intervention, the EGP significantly lowered the score of the Trait Anxiety Scale of the STAI (T-STAI) by 16.8% compared to the placebo (p = 0.041). The total score on the STAI decreased by 17.8% in the EGP group and tended to improve compared with that of the placebo group (p = 0.067). There were no significant differences in the changes in score of S-STAI, HAM-A, BAI, and other parameters from baseline between the two groups. There was no causal relationship between the ingestion of EGP and adverse drug reactions. CONCLUSION: We found that supplementation with EGP reduced "anxiety proneness" in subjects under chronic psychological stress, as shown by a decrease in the score of T-STAI and the tendency for decrease in the total score of STAI. This result suggests that EGP supplementation can be used as a regimen to safely reduce stress and anxiety; however, more studies are needed to establish the long-term safety and effectiveness.

Gypenoside UL4-Rich Gynostemma pentaphyllum Extract Exerts a Hepatoprotective Effect on Diet-Induced Nonalcoholic Fatty Liver Disease.

Nonalcoholic steatohepatitis (NASH) arises from nonalcoholic fatty liver disease (NAFLD) as a consequence of oxidative stress. Gynostemma pentaphyllum extract (GPE) is proven to be beneficial for patients suffering from NAFLD. However, the precise mechanism by which GPE confers these benefits remains largely unknown. The purpose of this study was to investigate the underlying mechanism and to determine whether supplementation with the newly discovered GPE gypenoside UL4 mitigates NASH progression. Male c57BL/6 mice were fed a normal chow diet, a methionine choline-deficient (MCD) diet, or an MCD diet supplemented with various doses of UL4-rich GPE for eight weeks. GPE supplementation suppressed oxidative stress induced by the MCD diet by increasing levels of sirtuin 6 and phase 2 anti-oxidant enzymes in mouse liver and HepG2 cells. Additionally, GPE supplementation prevented diet-induced hepatic fat accumulation, hepatocellular injury, inflammation, and fibrosis in mice fed the MCD diet. These results indicate the possible therapeutic potential of dietary supplementation of UL4-rich GPE in preventing the development of fatty liver and its progression to NASH.

Epigallocatechin-3-Gallate-Rich Green Tea Extract Ameliorates Fatty Liver and Weight Gain in Mice Fed a High Fat Diet by Activating the Sirtuin 1 and AMP Activating Protein Kinase Pathway.

The prevalence of metabolic diseases has risen globally in parallel with the obesity epidemic over the past few decades. Green tea has been reported to have metabolically beneficial effects on obesity; however, the mechanism by which green tea regulates lipid metabolism is not clearly understood. Male c57BL/6 mice were fed a normal chow diet, a high-fat diet (HFD), or an HFD supplemented with various doses of epigallocatechin gallate-rich green tea extract (GTE) for 12 weeks. GTE supplementation reduced body weight gain, prevented hepatic fat accumulation, decreased hypertriglyceridemia, and improved hyperglycemia and insulin resistance in HFD-fed mice. The underlying mechanisms of these beneficial effects of GTE might involve the upregulation of sirtuin 1 and AMP activated protein kinase (AMPK) and the downregulation of enzymes related to de novo lipogenesis. Consistent with the in vivo findings, GTE increased the expression and activity of sirtuin 1, enhanced the binding of sirtuin 1 to liver kinase B1 (LKB1) and subsequent deacetylation of LKB1, and reduced triglyceride accumulation in HepG2 cells. These results suggest the possible therapeutic potential of dietary epigallocatechin gallate-rich GTE supplementation for preventing the development and progression of hepatic steatosis and obesity.

Angelica gigas Ameliorates Hyperglycemia and Hepatic Steatosis in C57BL/KsJ-db/db Mice via Activation of AMP-Activated Protein Kinase Signaling Pathway.

The prevention and management of type 2 diabetes mellitus has become a major global public health challenge. Decursin, an active compound of Angelica gigas Nakai roots, was recently reported to have a glucose-lowering activity. However, the antidiabetic effect of Angelica gigas Nakai extract (AGNE) has not yet been investigated. We evaluated the effects of AGNE on glucose homeostasis in type 2 diabetic mice and investigated the underlying mechanism by which AGNE acts. Male C57BL/KsJ-db/db mice were treated with either AGNE (10 mg/kg, 20 mg/kg, and 40 mg/kg) or metformin (100 mg/kg) for 8 weeks. AGNE supplementation (20 and 40 mg/kg) significantly decreased fasting glucose and insulin levels, decreased the areas under the curve of glucose in oral glucose tolerance and insulin tolerance tests, and improved homeostatic model assessment-insulin resistant (HOMA-IR) scores. AGNE also ameliorated hepatic steatosis, hyperlipidemia, and hypercholesterolemia. Mechanistic studies suggested that the glucose-lowering effect of AGNE was mediated by the activation of AMP activated protein kinase, Akt, and glycogen synthase kinase-3[Formula: see text]. AGNE can potentially improve hyperglycemia and hepatic steatosis in patients with type 2 diabetes.

In vitro Stimulation of NK Cells and Lymphocytes Using an Extract Prepared from Mycelial Culture of Ophiocordyceps sinensis.

Ophiocordyceps sinensis is a natural fungus that has been valued as a health food and used in traditional Chinese medicine for centuries. The fungus is parasitic and colonizes insect larva. Naturally occurring O. sinensis thrives at high altitude in cold and grassy alpine meadows on the Himalayan mountain ranges. Wild Ophiocordyceps is becoming increasingly rare in its natural habitat, and its price limits its use in clinical practice. Therefore, the development of a standardized alternative is a great focus of research to allow the use of Ophiocordyceps as a medicine. To develop an alternative for wild Ophiocordyceps, a refined standardized extract, CBG-CS-2, was produced by artificial fermentation and extraction of the mycelial strain Paecilomyces hepiali CBG-CS-1, which originated from wild O. sinensis. In this study, we analyzed the in vitro immune-modulating effect of CBG-CS-2 on natural killer cells and B and T lymphocytes. CBG-CS-2 stimulated splenocyte proliferation and enhanced Th1-type cytokine expression in the mouse splenocytes. Importantly, in vitro CBG-CS-2 treatment enhanced the killing activity of the NK-92MI natural killer cell line. These results indicate that the mycelial culture extract prepared from Ophiocordyceps exhibits immune-modulating activity, as was observed in vivo and this suggests its possible use in the treatment of diseases caused by abnormal immune function.

Immune-Modulating Activity of Extract Prepared from Mycelial Culture of Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes).

Ophiocordyceps sinensis is a natural fungus that has been valued as a health food and traditional Chinese medicine for centuries. The fungus is parasitic and colonizes insect larva. Naturally occurring O. sinensis thrives at high altitude in cold and grassy alpine meadows on the Himalayan mountain ranges. Wild O. sinensis is becoming increasingly rare in its natural habitats, and its price is out of reach for clinical practice. For these reasons, development of a standardized alternative is a great focus of research to allow the use of O. sinensis as a medicine. To develop an alternative for wild O. sinensis, a refined standardized extract, CBG-CS-2, was produced by artificial fermentation and extraction of the mycelial strain Paecilomyces hepiali CBG-CS-1, which originated from wild O. sinensis. In this study, we analyzed the in vivo immune-modulating effect of CBG-CS-2 in mice. Oral administration of CBG-CS-2 supported splenocyte stimulation and enhanced Th1-type cytokine expression from the splenocytes. Importantly, the same treatment significantly enhanced the natural killer cell activity of the splenocytes. Finally, oral administration of CBG-CS-2 enhanced the potential for inflammatory responses. Together, these findings indicate that the mycelial culture extract prepared from O. sinensis exhibited immune-modulating activity and suggest its possible use in the treatment of diseases caused by abnormal immune function.