γ-Oryzanol suppresses COX-2 expression by inhibiting reactive oxygen species-mediated Erk1/2 and Egr-1 signaling in LPS-stimulated RAW264.7 macrophages.

Cyclooxygenase (COX)-2 produces prostanoids, which contribute to inflammatory responses. Nuclear factor (NF)-κB is a key transcription factor mediating COX-2 expression. γ-Oryzanol is an active component in rice bran oil, which inhibits lipopolysaccharide (LPS)-mediated COX-2 expression by inhibiting NF-κB. However, the inhibition of COX-2 expression by γ-oryzanol independently of NF-κB is poorly understood. We found that LPS upregulated Egr-1 expression at the transcriptional level. Forced expression of Egr-1 trans-activated the Cox-2 promoter independently of NF-κB. In contrast, silencing of Egr-1 abrogated LPS-mediated COX-2 expression. LPS produced reactive oxygen species (ROS), which, in turn, induced Egr-1 expression via the Erk1/2 MAPK pathway. ROS scavenging activity of γ-oryzanol suppressed Egr-1 expression by inhibiting the Erk1/2 MAPK pathway. Our results suggest that γ-oryzanol inhibits LPS-mediated COX-2 expression by suppressing Erk1/2-mediated Egr-1 expression. This study supports that γ-oryzanol may be useful for ameliorating LPS-mediated inflammatory responses.

Agrimonia pilosa Ledeb. aqueous extract improves impaired glucose tolerance in high-fat diet-fed rats by decreasing the inflammatory response.

BACKGROUND: Agrimonia pilosa Ledeb. is a medicinal plant with physiological activities such as anti-cancer, antioxidant, anti-inflammatory activities and in vitro anti-diabetic activity. However, the effects of aqueous extracts from A. pilosa on insulin-resistant rats have not yet been examined. We investigated the effects of aqueous extract from A. pilosa on impaired glucose metabolism induced by a high-fat diet in rats. METHODS: Male Sprague-Dawley rats were assigned to the following groups: normal-fat diet (NF, n = 9); high-fat diet (HF, n = 9); high-fat diet with 0.1% A. pilosa aqueous extract (HFA, n = 10). Experimental diets were administered for 16 weeks. At the end of the treatment, liver and fat tissues were isolated, and serum was collected for biochemical analysis. RESULTS: The HF group rats had a significantly higher liver weight than the NF group rats did, and increased hepatic lipid accumulation (p < 0.05); however, supplementation with A. pilosa decreased liver weight. Blood glucose levels in the HFA group were lower than levels measured in the HF group 30, 60, and 120 min after glucose administration (p < 0.05). In addition, dietary A. pilosa supplementation decreased tumor necrosis factor α and interleukin 6 levels, while increasing serum adiponectin concentrations (p < 0.05 vs. the HF group). These effects were accompanied by reduced hepatic and adipose tissue expression of inflammation-related genes such as Tnf and Il1b (p < 0.05). CONCLUSIONS: Our findings indicate that A. pilosa aqueous extract can ameliorate insulin resistance in high-fat diet-fed rats by decreasing the inflammatory response.

Anti-inflammatory effects of Salvia plebeia R. Br extract in vitro and in ovalbumin-induced mouse model.

BACKGROUND: Asthma is an increasing global health problem, and novel strategies to prevent or ameliorate the condition are needed. Here, the effects of 80 % ethanol extracts of Salvia plebeia R. Br. (SE) on an induced inflammatory response were investigated. RESULTS: Salvia plebeia R. Br. inhibited production of pro-inflammatory cytokines, such as TNF-α and IL-6, as well as nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. NO and pro-inflammatory cytokine production was suppressed more effectively by SE of the aerial parts (SE-A) than of the roots (SE-R) of S. plebeia. In BEAS-2B cells, both SE-A and SE-R inhibited the increase in production of the inflammatory cytokines IL-6 and IL-8. We also investigated the anti-asthmatic effects of SE in an ovalbumin (OVA)-induced BALB/c mouse model. SE-A treatment significantly reduced the number of airway eosinophils, IL-4 and IL-13 levels, mucus production, and inflammatory infiltration, as compared with the corresponding levels in the untreated, OVA-induced mice, and had similar effects to dexamethasone. CONCLUSIONS: Salvia plebeia ethanol extract ameliorated the induced inflammatory response in RAW 264.7 and BEAS-2B cells, with more effective inhibition noted for SE-A than for SE-R. SE-A treatment was effective in improving the histopathological changes in the lungs of asthma model mice via modulation of eosinophils and Th2 cytokines. These results suggest that SE-A can be considered as a therapeutic agent that can potentially relieve asthma.

24-Methylenecycloartanyl ferulate, a major compound of γ-oryzanol, promotes parvin-beta expression through an interaction with peroxisome proliferator-activated receptor-gamma 2 in human breast cancer cells.

Parvin-ß is an adaptor protein that binds to integrin-linked kinase (ILK) and is significantly downregulated in breast tumors and breast cancer cell lines. We treated the breast cancer cell line MCF7 with 24-methylenecycloartanyl ferulate (24-MCF), a γ-oryzanol compound. We observed upregulation of parvin-ß (GenBank Accession No. AF237769) and peroxisome proliferator-activated receptor (PPAR)-γ2 (GenBank Accession No. NM_015869). Among γ-oryzanol compounds, only treatment with 24-MCF led to the formation of reverse transcription-PCR products of parvin-ß (650 and 500 bp) and PPAR-γ2 (580 bp) in MCF7 cells, but not in T47D, SK-BR-3, or MDA-MB-231 cells. 24-MCF treatment increased the mRNA and protein levels of parvin-ß in MCF7 cells in a dose-dependent manner. We hypothesized that there is a correlation between parvin-ß expression and induction of PPAR-γ2. This hypothesis was investigated by using a promoter-reporter assay, chromatin immunoprecipitation, and an electrophoretic mobility shift assay. 24-MCF treatment induced binding of PPAR-γ2 to a peroxisome proliferator response element-like cis-element (ACTAGGACAAAGGACA) in the parvin-ß promoter in MCF7 cells in a dose-dependent manner. 24-MCF treatment significantly decreased anchorage-independent growth and inhibited cell movement in comparison to control treatment with dimethyl sulfoxide. 24-MCF treatment reduced the levels of GTP-bound Rac1 and Cdc42. Evaluation of Akt1 inhibition by 24-MCF revealed that the half maximal effective concentration was 33.3 µM. Docking evaluations revealed that 24-MCF binds to the ATP-binding site of Akt1(PDB ID: 3OCB) and the compound binding energy is -8.870 kcal/mol. Taken together, our results indicate that 24-MCF treatment increases parvin-ß expression, which may inhibit ILK downstream signaling.

Characterization and quantification of γ-oryzanol in grains of 16 Korean rice varieties.

γ-Oryzanol, a mixture of ferulic acid esters of triterpene alcohols and sterols, is a nutritionally important group of rice secondary metabolites. A library of 27 γ-oryzanol was assembled from existing data and used to assist identification and quantification of γ-oryzanol isolated from 16 Korean rice varieties (11 white and 5 pigmented). γ-Oryzanol was analyzed with liquid chromatography with diode array detection and electrospray ionization mass spectrometry. Nineteen different γ-oryzanol were observed and identified as stigmasterol, campesterol and sitosterol or common and hydroxylated triterpene alcohols. In the 16 varieties, the total γ-oryzanol content averaged 43.8 mg/100 g (range, 26.7-61.6 mg/100 g), which Josaengheugchal exhibited the highest level (61.6 mg/100 g). The Korean rice varieties were classified based on qualitative and quantitative γ-oryzanol data by multivariate statistical analysis. Clusters of specialty rice varieties exhibited higher γ-oryzanol levels than those of common rice varieties.

Anti-obesity and immunomodulatory effects of Allium hookeri leaves cultivated with artificial light of different intensities on immune-depressed obese mice.

This study was conducted to evaluate the effects of Allium hookeri (AH) leaves cultivated with different light-emitting diode (LED) intensities (L: low, 100 µmol/m2/s; M: medium, 150 µmol/m2/s; H: high, 200 µmol/m2/s). Alliin concentration increased as light intensity increased in AH and showed the highest level at LED-H condition. The anti-obesity and immunomodulatory properties of AH were evaluated in a cyclophosphamide (CPA)-induced immunosuppressed obese animal model. C57BL/6 J mice were randomly divided into control (CON), high-fat diet (HFD) control (CON-H), negative control (NC), positive control (PC, ß-glucan, 50 mg/kg body weight (BW)), AH L, M, and H groups. The three kinds of AH extracts were orally administered to the mice at 300 mg/kg BW for 2 weeks. Except for CON and CON-H, all the other groups were intraperitoneally treated with CPA. Epididymal and abdominal fat weight decreased as LED intensity increased while spleen weight increased in the AH groups. Serum glucose decreased as LED intensity increased in the AH groups and H group showed the lowest level. Triglycerides, total, and LDL-cholesterol levels decreased while HDL-cholesterol level increased in the AH groups compared to the NC group. Moreover, AH effectively reduced serum ALT and AST levels and increased the total white blood cell count, particularly elevating lymphocyte and monocyte levels. Furthermore, NK cell activity was higher in the AH groups. These findings suggest that AH cultivated at optimal LED intensity could be used as a novel biomedicine and in pharmacotherapy to treat related diseases to improve public health without any toxicity.

Effects of anthocyanin supplementation on blood lipid levels: a systematic review and meta-analysis.

Introduction: Dyslipidemia is a major cardiovascular disease risk factor associated with increased mortality. The intake of plant food-derived bioactive compounds is associated with beneficial cardiovascular effects, including decreased blood lipid levels and cardiovascular risk. We aimed to evaluate the effects of anthocyanin intake on blood lipid levels by analyzing relevant randomized controlled trials. Methods: We searched the PubMed and Embase databases using the "Patient/Population, Intervention, Comparison, and Outcomes" format to determine whether anthocyanin supplementation intervention affected blood lipid levels compared with placebo supplementation in human participants. Results: A total of 41 studies with 2,788 participants were included in the meta-analysis. Anthocyanin supplementation significantly reduced triglyceride [standardized mean difference (SMD) = -0.10; 95% confidence interval [CI], -0.18, -0.01) and low-density lipoprotein-cholesterol (SMD = -0.16; 95% CI -0.26, -0.07) levels and increased high-density lipoprotein-cholesterol levels (SMD = 0.42; 95% CI 0.20, 0.65). Discussion: Anthocyanin supplementation significantly improved blood lipid component levels in the included studies. Larger, well-designed clinical trials are needed to further investigate the effects of anthocyanin intake on blood lipid levels and the safety of anthocyanin supplementation for treating dyslipidemia. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021257087, identifier: CRD42021257087.

Antioxidant and Immune Stimulating Effects of Allium cepa Skin in the RAW 264.7 Cells and in the C57BL/6 Mouse Immunosuppressed by Cyclophosphamide.

Allium cepa L. (onion) has been reported to have various pharmacological effects, such as preventing heart disease, and improving antimicrobial activity and immunological effects. The Republic of Korea produced 1,195,563 tons of onions (2022). The flesh of onion is used as food while the onion skin (OS) is thrown away as an agro-food by-product and is considered to induce environmental pollution. Thus, we hypothesize that increasing usage of OS as functional food material could help protect from the environment pollution. The antioxidant effects and immune-enhancing effects of OS were evaluated as functional activities of OS. In this study, OS showed high 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities and xanthine oxidase (XO) inhibitory activity. The antioxidant activities increased in a dose-dependent manner. The IC50 values of DPPH, ABTS radical scavenging activity, and XO inhibitory activity were 954.9 µg/mL, 28.0 µg/mL, and 10.7 µg/mL, respectively. Superoxide dismutase and catalase activities of OS in RAW 264.7 cells were higher than those of the media control. There was no cytotoxicity of OS found in RAW 264.7 cells. Nitric oxide and cytokines (IL-1ß, IL-6, IFN-γ, and TNF-α) concentrations in RAW 264.7 cells significantly increased in a dose dependent manner. Immune-stimulating effects of OS were evaluated in immunosuppressed mice induced by cyclophosphamide. White blood cell count and the B cell proliferation of splenocytes were higher in OS100 (OS extract 100 mg/kg body weight) and OS200 (OS extract 200 mg/kg body weight) groups than in the negative control (NC) group. Serum IgG and cytokine (IL-1ß and IFN-γ) levels were also higher in OS100 and OS200 groups than in the NC group. OS treatment increased NK cell activity compared with the NC group. The results suggested that OS can improve antioxidant and immune stimulating effects. The use of OS as functional supplement can reduce the agro-food by-product and it may contribute to carbon neutrality.

Supplementary Effects of Allium hookeri Extract on Glucose Tolerance in Prediabetic Subjects and C57BL/KsJ-db/db Mice.

Allium hookeri (AH) has been used as a nutritional and medicinal food in Asia for many years. Our previous studies have described its anti-diabetic, anti-obesity, and anti-inflammatory activities in animal models and prediabetes. This study investigated whether AH could improve glycemia by modulating insulin secretion in prediabetic subjects through an in-depth study. Eighty prediabetic subjects (100 ≤ fasting plasma glucose < 140 mg/dL) were randomly assigned to a placebo (n = 40) group or an ethanol AH extract (500 mg/day, n = 40) group for 12 weeks. Dietary intake and physical activity, blood glucose (an oral glucose tolerance test for 120 min), insulin (insulin response to oral glucose for 120 min), area under the curve (AUC) of glucose or insulin after oral glucose intake, insulin sensitivity markers, C-peptide, adiponectin, glycated hemoglobin A1c (HbA1c) levels, hematological tests (WBC, RBC, hemoglobin, hematocrit, and platelet count), blood biochemical parameters (ALP, AST, total bilirubin, total protein, albumin, gamma-GT, BUN, creatinine, LD, CK, and hs-CRP), and urine parameters (specific gravity and pH) were examined at both baseline and 12 weeks after supplementation with placebo or AH capsules. Fifty-eight participants (placebo group: 20 men and 10 women; AH group: 13 men and 15 women) completed the study. AH supplementation moderately reduced postprandial blood glucose at 60 min (-6.14 mg/dL, p = 0.061), postprandial insulin levels at 90 min (-16.69 µU/mL, p = 0.017), the glucose AUC at 90 min (-412.52 mg*min/dL, p = 0.021), as well as the insulin AUC at 90 min (-978.77 µU*min/mL, p = 0.021) and 120 min (-1426.41 µU*min/mL, p = 0.015) when compared with the placebo group. However, there were no effects of AH on dietary intake and physical activity; HOMA index; HbAlc; C-peptide; or adiponectin, hematological-, blood biochemical-, and urinary markers. To confirm the effects of AH extract on blood glucose insulin sensitivity, C57BL/6J or C57BL/KsJ-db/db mice were used (n = 8/group). Body weight, fasting plasma glucose level, lipid profiles, liver and renal function, pancreatic histology, and insulin immunoreactivity were assessed. In the diabetic db/db mice, hyperglycemia, which was accompanied by an increase in insulin secretion in diabetic mice, was significantly reduced by AH treatment, resulting in the alleviation of ß-cell overcompensation and insulin resistance. We confirmed that AH supplementation can effectively control blood glucose and insulin levels by improving insulin sensitivity and may be a potential agent for glycemic control in subjects with prediabetes and type 2 diabetes mellitus.

Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts.

The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin, respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929-933 sequence of the ß1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner. According to subsequent experiments, we found that the YIGSR peptide strongly enhanced collagen type 1 synthesis without changing cell proliferation or cellular MMP-1 level. This YIGSR peptide-mediated collagen type 1 synthesis was modulated by FAK inhibitor and MEK inhibitor. This study clearly reveals that YIGSR peptide plays a novel function on the collagen type 1 synthesis of dermal fibroblasts and also suggests that YIGSR is a strong candidate peptide for the treatment of skin aging and wrinkles.

Estrogen-like activity of aqueous extract from Agrimonia pilosa Ledeb. in MCF-7 cells.

BACKGROUND: Postmenopausal women experience estrogen deficiency-related menopausal symptoms (e.g., hot flashes and mood swings) and a dramatic increase in the incidence of chronic diseases. Although estrogen-replacement therapy (ERT) can reduce mortality from cardiovascular disease and improve osteoporosis and menopausal symptoms, its side effects have limited recent use. This study investigated the estrogen-like activity of aqueous extract from Agrimonia pilosa Ledeb. METHODS: The estrogenic activity of A. pilosa was investigated by using several in vitro assays. The binding activity of A. pilosa on estrogen receptors was examined using a fluorescence polarization-based competitive binding assay. The proliferative activity of A. pilosa was also examined using MCF-7 cells. Furthermore, the effect of A. pilosa on the expression of 3 estrogen-dependent genes was assessed. RESULTS: Using liquid chromatography-mass spectrometry, the 3 major peaks of A. pilosa aqueous extract were identified as apigenin-hexose, luteolin-glucuronide, and apigenin-glucuronide. The aqueous extract induced the proliferation of estrogen receptor-positive MCF-7 cells (p < 0.05). A. pilosa-stimulated proliferation was blocked on adding the estrogen antagonist ICI 182,780. Moreover, A. pilosa treatment increased the mRNA expression of the estrogen-responsive genes pS2 and PR (p < 0.05). CONCLUSIONS: These results suggest A. pilosa can be used to improve estrogen deficiency-related menopausal symptoms or to treat diseases in postmenopausal women.

Antioxidant and Immune Stimulating Effects of Allium hookeri Extracts in the RAW 264.7 Cells and Immune-Depressed C57BL/6 Mice.

We investigated the antioxidant and immune-enhancing effects of the extracts from Allium hookeri leaves and roots (AHL and AHR) in in vitro and in vivo models. Their antioxidant effects were determined by total phenolic content (TPC), DPPH and ABTS radical scavenging activities, and superoxide dismutase and catalase activities. The immunomodulatory effects were evaluated by nitric oxide (NO) production and cytokine concentrations produced from RAW 264.7, and by serum IgA and IgG levels, cytokine levels, and NK cell activities in the immunosuppressed C57BL/6 mice. AHL and AHR extracts improved antioxidant activities and productions of NO and cytokines without cytotoxicity in the RAW 264.7 cells. AHL and AHR groups showed significantly higher serum IgA and IgG levels, Th1 cytokine concentrations, splenocyte proliferations, and NK cell activities than the NC group which was not treated with AHL or AHR extract. AHR extract showed higher values than AHL extract in the factors evaluated in this study. The results show that they have high antioxidant and immunomodulatory effects and can be used as novel potential therapeutic candidates to treat related diseases and to improve public health.

Differences in dietary patterns related to metabolic health by gut microbial enterotypes of Korean adults.

Diet has a profound impact on the progression of metabolic syndrome (MetS) into various diseases. The gut microbiota could modulate the effect of diet on metabolic health. We examined whether dietary patterns related to MetS differed according to gut microbial enterotypes among 348 Korean adults aged 18-60 years recruited between 2018∼2021 in a cross-sectional study. The enterotype of each participant was identified based on 16S rRNA gut microbiota data. The main dietary pattern predicting MetS (MetS-DP) of each enterotype was derived using reduced-rank regression (RRR) models. In the RRR models, 27 food group intakes assessed by a semi-quantitative food frequency questionnaire and MetS prediction markers including triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio and homeostatic model assessment for insulin resistance (HOMA-IR) were used as predictor and response variables, respectively. The MetS-DP extracted in Bacteroides enterotype (B-type) was characterized by high consumption of refined white rice and low consumption of eggs, vegetables, and mushrooms. The MetS-DP derived among Prevotella enterotype (P-type) was characterized by a high intake of sugary food and low intakes of bread, fermented legumes, and fermented vegetables. The MetS-DP of B-type was positively associated with metabolic unhealthy status (OR T3 vs. T1 = 3.5; 95% CI = 1.5-8.2), comparing the highest tertile to the lowest tertile. Although it was not significantly associated with overall metabolic unhealthy status, the MetS-DP of P-type was positively associated with hyperglycemia risk (OR T3 vs. T1 = 6.2; 95% CI = 1.6-24.3). These results suggest that MetS-DP may differ according to the gut microbial enterotype of each individual. If such associations are found to be causal, personalized nutrition guidelines based on the enterotypes could be recommended to prevent MetS.

Anti-Diabetic Effects of Allium hookeri Extracts Prepared by Different Methods in Type 2 C57BL/J-db/db Mice.

This study was conducted to evaluate whether Allium hookeri can control diabetic symptoms. Aqueous extract (AE1: 100 mg/kg BW, AE2: 200 mg/kg BW) and ethanol extract (EE1: 100 mg/kg BW, EE2: 200 mg/kg BW) of A. hookeri were orally administrated to diabetic mice (C57BL/J-db/db) for 8 weeks. The negative (NC) and the positive (PC) control groups were treated with 0.9% saline and metformin (150 mg/kg BW), respectively. Glucose and lipid profile (triglyceride, total cholesterol (TC), LDL-C, and HDL-C) as biochemical parameters, toxicological factors such as liver/kidney functional parameters (ALT, AST, BUN, and Cr), and NK cell activity in blood were measured. Oral glucose tolerance test (OGTT) and histopathological examination were also conducted. Compared with the NC group, AE and EE decreased blood glucose, HbA1c, area under the curve (AUC) during OGTT, and leptin levels while increasing adiponectin levels. Serum lipid profiles and toxicological factors levels were reduced by the A. hookeri extract. Interestingly, HDL-C, glomerular mesangial expansion score in the kidney, and NK cell activity were effectively controlled in EE groups. Based on the results, EE is considered to be more effective in reducing high blood glucose, lipid profile, and related factor levels than AE, and is comparable to metformin in some biomarkers. It can be presumed that EE can more effectively control the major anomalies in the diabetic model than AE, and it may be used to prevent diabetic symptoms without toxicity in the Type 2 diabetic model.

Validation of soy isoflavone intake and its health effects: a review of the development of exposure biomarkers.

BACKGROUND/OBJECTIVES: It is difficult to consistently demonstrate the health effects of soy isoflavones owing to the multitude of factors contributing to their bioavailability. To accurately verify these health effects, dietary isoflavone intake should be measured using a biologically active dose rather than an intake dose. This concept has been expanded to the development of new exposure biomarkers in nutrition research. This review aims to provide an overview of the development of exposure biomarkers and suggest a novel research strategy for identifying the health effects of soy isoflavone intake. MATERIALS/METHODS: We cover recent studies on the health effects of soy isoflavones focusing on isoflavone metabolites as exposure biomarkers. RESULTS: Compared to non-fermented soy foods, fermented soy foods cause an increased concentration of isoflavones in the biofluid immediately following ingestion. The correlation between exposure biomarkers in blood and urine and the food frequency questionnaire was slightly lower than that of corresponding 24-h dietary recalls. Urinary and blood isoflavone levels did not show a consistent association with chronic disease and cancer risk. CONCLUSION: It is crucial to understand the variable bioavailabilities of soy isoflavones, which may affect evaluations of soy isoflavone intake in health and disease. Further studies on the development of valid exposure biomarkers are needed to thoroughly investigate the health effects of isoflavone.

Allium hookeri Extracts Improve Scopolamine-Induced Cognitive Impairment via Activation of the Cholinergic System and Anti-Neuroinflammation in Mice.

Allium hookeri (AH) is a medicinal food that has been used in Southeast Asia for various physiological activities. The objective of this study was to investigate the activation of the cholinergic system and the anti-neuroinflammation effects of AH on scopolamine-induced memory impairment in mice. Scopolamine (1 mg/kg body weight, i.p.) impaired the performance of the mice on the Y-maze test, passive avoidance test, and water maze test. However, the number of error actions was reduced in the AH groups supplemented with leaf and root extracts from AH. AH treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. AH significantly improved the cholinergic system by decreasing acetylcholinesterase activity, and increasing acetylcholine concentration. The serum inflammatory cytokines (IL-1ß, IL-6, and IFN-γ) increased by scopolamine treatment were regulated by the administration of AH extracts. Overexpression of NF-κB signaling and cytokines in liver tissue due to scopolamine were controlled by administration of AH extracts. AH also significantly decreased Aß and caspase-3 expression but increased NeuN and ChAT. The results suggest that AH extracts improve cognitive effects, and the root extracts are more effective in relieving the scopolamine-induced memory impairment. They have neuroprotective effects and reduce the development of neuroinflammation.

Effects of Platycodon grandiflorum on Gut Microbiome and Immune System of Immunosuppressed Mouse.

Platycodon grandiflorum (PG) is a perennial plant that has been used as a traditional remedy to control immune-related diseases. PG was steamed and dried to improve its taste (PGS). The aim of the study was to investigate the effects of PG and PGS (PG-diets) on the gut microbiome and immune system. We treated PG-diets to immunosuppressed mice via cyclophosphamide (CPA) injection. After two weeks of the supplement, we evaluated specific genera related to body weight and serum immunoglobulin levels and analyzed 16S rRNA sequencing and metagenomics statistical analysis. PG-diets groups showed an increased abundance of microorganisms in immunodeficient mice compared to the control group (NC). Moreover, Akkermansia significantly decreased in response to the CPA in the NC group at the genus level, whereas its abundance increased in the PG-diets groups. We also found that the modulation of the gut microbiome by PG-diets was correlated with body weight, IgA, and IgM levels. The results demonstrate that PG-diets may improve the health benefits of immunosuppressed mice by altering the gut microbiome, though not much difference was found between PG and PGS treatments. Finally, this is the first study showing the effects of PGS-diets on the gut microbiome and immune system as a potential nourishing immunity supplement.

Taxonomic Composition and Diversity of the Gut Microbiota in Relation to Habitual Dietary Intake in Korean Adults.

We investigated associations of habitual dietary intake with the taxonomic composition and diversity of the human gut microbiota in 222 Koreans aged 18-58 years in a cross-sectional study. Gut microbiota data were obtained by 16S rRNA gene sequencing on DNA extracted from fecal samples. The habitual diet for the previous year was assessed by a food frequency questionnaire. After multivariable adjustment, intake of several food groups including vegetables, fermented legumes, legumes, dairy products, processed meat, and non-alcoholic beverages were associated with major phyla of the gut microbiota. A dietary pattern related to higher α-diversity (HiαDP) derived by reduced rank regression was characterized by higher intakes of fermented legumes, vegetables, seaweeds, and nuts/seeds and lower intakes of non-alcoholic beverages. The HiαDP was positively associated with several genera of Firmicutes such as Lactobacillus, Ruminococcus, and Eubacterium (all p < 0.05). Among enterotypes identified by principal coordinate analysis based on the ß-diversity, the Ruminococcus enterotype had higher HiαDP scores and was strongly positively associated with intakes of vegetables, seaweeds, and nuts/seeds, compared to the two other enterotypes. We conclude that a plant- and fermented food-based diet was positively associated with some genera of Firmicutes (e.g., Lactobacillus, Ruminococcus, and Eubacterium) reflecting better gut microbial health.

Effects of Capsicum annuum supplementation on the components of metabolic syndrome: a systematic review and meta-analysis.

Metabolic syndrome (MetS) has increasingly gained importance as the main risk factor for cardiovascular diseases and type II diabetes mellitus. Various natural compounds derived from plants are associated with beneficial effects on the incidence and progression of MetS. This study aimed to evaluate the effects of Capsicum annuum on factors related to MetS by assessing randomized controlled trials (written in English). We searched the online databases of PubMed, Embase, Google scholar, and Cochrane Library up to April 2020. 'Patient/Population, Intervention, Comparison and Outcomes' format was used to determine whether intervention with C. annuum supplementation compared with placebo supplementation had any effect on the components of MetS among participants. We considered standardized mean differences (SMD) with 95% confidence intervals (CI) as effect size measures using random-effects model. Analysis of the included 11 studies (n = 609) showed that C. annuum supplementation had significant effect on low density lipoprotein-cholesterol [SMD = - 0.39; 95% CI - 0.72, - 0.07; P = 0.02; prediction interval, - 1.28 to 0.50] and marginally significant effect on body weight [SMD = - 0.19; 95% CI - 0.40, 0.03; P = 0.09]. However, larger and well-designed clinical trials are needed to investigate the effects of C. annuum on MetS.

Agrimonia pilosa Ledeb. Ameliorates Hyperglycemia and Hepatic Steatosis in Ovariectomized Rats Fed a High-Fat Diet.

Estrogen deficiency is associated with obesity, dyslipidemia, and increased insulin resistance in postmenopausal women. An efficient therapeutic agent prevents or improves postmenopausal conditions induced by estrogen deficiency. Here, we investigated the effects of aqueous Agrimonia pilosa Ledeb. extract on glucose and lipid metabolism in ovariectomized rats fed a high-fat diet (HFD). Female Sprague-Dawley rats were sham-operated or ovariectomized, and 3 weeks later were assigned to the following groups: sham-operated + HFD (S); ovariectomized + HFD (OVX); and ovariectomized + HFD with 0.5% A. pilosa aqueous extract (OVX + 0.5A) groups. Ovariectomy significantly increased body weight and dietary intake relative to the S group. However, A. pilosa treatment did not significantly affect weight gain or dietary intake. Blood triacylglycerol, total cholesterol, and low-density lipoprotein cholesterol levels tended to decrease in the A. pilosa-supplemented group. Blood glucose levels were significantly lower in the OVX + 0.5A group than those in the OVX group. Blood adiponectin and insulin concentrations increased significantly after A. pilosa treatment in the ovariectomized group. A. pilosa supplementation tended to decrease liver weights and prevented lipid accumulation. These effects correlated with reduced hepatic expression of lipogenesis-related genes (fatty acid synthase, acetyl-coenzyme A carboxylase alpha, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase). Therefore, A. pilosa may improve metabolic disorders in ovariectomized rats.