Antiinflammatory effect of the ethanolic extract of Korean native herb Potentilla rugulosa Nakai in Bisphenol-a-stimulated A549 cells.

Potentilla rugulosa Nakai (P. rugulosa) is a perennial herb in the Rosaceae family and found in the Korean mountains. Previously, our findings demonstrated that P. rugulosa contains numerous polyphenols and flavonoids exhibiting important antioxidant and anti-obesity bioactivities. Bisphenol A (BPA) is a xenoestrogen that was shown to produce pulmonary inflammation in humans. However, the mechanisms underlying BPA-induced inflammation remain to be determined. The aim of this study was to examine whether ethanolic extract of P. rugulosa exerted an inhibitory effect on BPA-induced inflammation utilizing an adenocarcinoma human alveolar basal epithelial cell line A549. The P. rugulosa extract inhibited BPA-mediated cytotoxicity by reducing levels of reactive oxygen species (ROS). Further, P. rugulosa extract suppressed the upregulation of various pro-inflammatory mediators induced by activation of the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, inhibition of the NF-κB and MAPK signaling pathways by P. rugulosa extract was found to occur via decrease in the transcriptional activity of NF-κB. Further, blockade of phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) was noted. Thus, our findings suggest that the ethanolic extract of P. rugulosa may act as a natural anti-inflammatory therapeutic agent.

Bidirectional Interactions between Green Tea (GT) Polyphenols and Human Gut Bacteria.

Green tea (GT) polyphenols undergo extensive metabolism within gastrointestinal tract (GIT), where their derivatives compounds potentially modulate the gut microbiome. This biotransformation process involves a cascade of exclusive gut microbial enzymes which chemically modify the GT polyphenols influencing both their bioactivity and bioavailability in host. Herein, we examined the in vitro interactions between 37 different human gut microbiota and the GT polyphenols. UHPLC-LTQ-Orbitrap-MS/MS analysis of the culture broth extracts unravel that genera Adlercreutzia, Eggerthella and Lactiplantibacillus plantarum KACC11451 promoted C-ring opening reaction in GT catechins. In addition, L. plantarum also hydrolyzed catechin galloyl esters to produce gallic acid and pyrogallol, and also converted flavonoid glycosides to their aglycone derivatives. Biotransformation of GT polyphenols into derivative compounds enhanced their antioxidant bioactivities in culture broth extracts. Considering the effects of GT polyphenols on specific growth rates of gut bacteria, we noted that GT polyphenols and their derivate compounds inhibited most species in phylum Actinobacteria, Bacteroides, and Firmicutes except genus Lactobacillus. The present study delineates the likely mechanisms involved in the metabolism and bioavailability of GT polyphenols upon exposure to gut microbiota. Further, widening this workflow to understand the metabolism of various other dietary polyphenols can unravel their biotransformation mechanisms and associated functions in human GIT.

Anti-inflammatory effects of Athyrium yokoscense extract via inhibition of the Erk1/2 and NF-κB pathways in bisphenol A-stimulated A549 cells.

Bisphenol A is an environmental endocrine disruptor that has similar functions to estrogen in humans. However, few studies have investigated pulmonary inflammation induced by BPA, and the effect of Athyrium yokoscense extract on this inflammatory response is unknown. In this study, we investigated this effect in A549 human alveolar epithelial cells. BPA at concentrations higher than 100 µM were cytotoxic to A549 cells at 24 and 48 h after treatment; however, AYE (100 µg/mL) had a protective effect against BPA-induced cytotoxicity. AYE also inhibited the generation of intracellular reactive oxygen species, expressions of cyclooxygenase-2 and extracellular signal-regulated kinase1/2 proteins, activities of phospholipase A2, COX-2, nuclear factor kappa-light-chain-enhancer of activated B cells, and proinflammatory mediators including prostaglandin E2, tumor necrosis factor-α, and interleukin-6 induced by BPA in A549 cells. This study demonstrated that BPA, which induces chronic lung disease, causes oxidative stress and inflammatory response in lung epithelial cell line, and found that AYE reduces BPA-induced oxidative stress and inflammatory response by down-regulating the Erk1/2 and NF-κB pathways.

Sophora flavescens Aiton methanol extract exerts anti-inflammatory effects via reduction of Src kinase phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens Aiton (Family: Leguminosae), an herbal plant, has been used in East Asian home remedies for centuries for treating ulcers, skin burns, fevers, and inflammatory disorders. In addition, the dried root of S. flavescens was also applied for antipyretic, analgesic, antihelmintic, and stomachic uses. AIM OF STUDY: Nonetheless, how this plant can show various pharmacological activities including anti-inflammatory responses was not fully elucidated. In this study, therefore, we aimed to investigate the curative effects of S. flavescens on inflammation and its molecular mechanism. MATERIALS AND METHODS: For reaching this aim, various in vitro and in vivo experimental models with LPS-treated RAW264.7 cells, HCl/EtOH-induced gastric ulcer, and LPS-triggered lung injury conditions were employed and anti-inflammatory activity of S. flavescens methanol extract (Sf-ME) was also tested. Fingerprinting profile of Sf-ME was identified via LC-MS analysis. Its anti-inflammatory molecular mechanism was also examined by immunoblotting analysis. RESULTS: Nitric oxide production and mRNA expression levels of iNOS, COX-2, IL-1ß, and TNF-α were decreased. Additionally, phosphorylation of Src in the signaling cascade was decreased, and activities of the transcriptional factor NF-κB were reduced as determined by a luciferase reporter assay. Moreover, in vivo, gastritis and lung injury lesions were attenuated by Sf-ME. CONCLUSION: Taken together, these findings suggest that Sf-ME could be a potential anti-inflammatory therapeutic agent via suppression of Src kinase activity and regulation of IL-1ß secretion.

Anti-Gastritis and Anti-Lung Injury Effects of Pine Tree Ethanol Extract Targeting Both NF-κB and AP-1 Pathways.

An ethanol extract (Pd-EE) of Pinus densiflora Siebold and Zucc was derived from the branches of pine trees. According to the Donguibogam, pine resin has the effects of lowering the fever, reducing pain, and killing worms. The purpose of this study is to investigate whether Pd-EE has anti-inflammatory effects. During in vitro trials, NO production, as well as changes in the mRNA levels of inflammation-related genes and the phosphorylation levels of related proteins, were confirmed in RAW264.7 cells activated with lipopolysaccharide depending on the presence or absence of Pd-EE treatment. The activities of transcription factors were checked in HEK293T cells transfected with adapter molecules in the inflammatory pathway. The anti-inflammatory efficacy of Pd-EE was also estimated in vivo with acute gastritis and acute lung injury models. LC-MS analysis was conducted to identify the components of Pd-EE. This extract reduced the production of NO and the mRNA expression levels of iNOS, COX-2, and IL-6 in RAW264.7 cells. In addition, protein expression levels of p50 and p65 and phosphorylation levels of FRA1 were decreased. In the luciferase assay, the activities of NF-κB and AP-1 were lowered. In acute gastritis and acute lung injury models, Pd-EE suppressed inflammation, resulting in alleviated damage.

Nontargeted Metabolomics as a Screening Tool for Estimating Bioactive Metabolites in the Extracts of 50 Indigenous Korean Plants.

Many indigenous Korean plants have been used in medicinal preparations and health-promoting foods. These plant species contain beneficial metabolites with various bioactivities, such as antioxidant and anti-inflammatory activities. Herein, we suggest a new screening strategy using metabolomics to explore the bioactive compounds in 50 Korean plants. Secondary metabolites were analyzed using UHPLC-LTQ-Orbitrap-MS/MS. The plant extracts were subjected to antioxidant and anti-inflammatory assays. We identified metabolites that contributed to bioactivities according to the results of bioassays and multivariate analyses. Using Pearson's correlation, phenolics (e.g., casuarictin, 3-O-methylellagic acid) showed positive correlation with antioxidant activity, while biflavonoids (e.g., amentoflavone, rosbustaflavone) were correlated with nitric oxide (NO) inhibition activity. To compensate for the limitation of this new strategy, we further validated these by investigating three parts (branches, fruits, leaves) of Platycladus orientalis which showed high activities on both bioassays. Unlike the above observation, we identified significantly different metabolites from different parts, which was not the results of bioassays. In these validation steps, interestingly, biflavonoids (e.g., robustaflavone, sciadopitysin) contributed to both activities in P. orientalis. The findings of this work suggest that new strategy could be more beneficial in the identification of bioactive plant species as well as that of their corresponding bioactive compounds that impart the bioactivity.

Evaluation of Metabolite Profiles of Ginseng Berry Pomace Obtained after Different Pressure Treatments and Their Correlation with the Antioxidant Activity.

Ginseng berry pomace (GBP) is a byproduct of ginseng berry processing and is rich in numerous bioactive components, including ginsenosides and their derivatives. The application of GBP as a beneficial biomaterial is currently limited. In this study, we aimed to evaluate their potential as a promising source of bioactive compounds using metabolite profiling. The GBP obtained after different ultra-high-pressure (UHP) treatments was analyzed by GC-TOF-MS and UHPLC-LTQ-Orbitrap-MS/MS. In multivariate analyses, we observed a clear demarcation between the control and UHP-treated groups. The results demonstrated that the relative abundance of primary metabolites and a few ginsenosides was higher in the control, whereas UHP treatment contained higher levels of fatty acids and sugars. Furthermore, GBPs were fractionated using different solvents, followed by UHPLC-LTQ-Orbitrap-MS/MS analyses. The heatmap revealed that phenolics (e.g., quercetin, kaempferol) and fewer polar ginsenosides (e.g., F4, Rh2) were abundant in the ethyl acetate fraction, whereas the levels of lignans (e.g., 7-hydroxysecoisolariciresinol, syringaresinol) and fatty acids (e.g., trihydroxy-octadecenoic acid, oxo-dihydroxy-octadecenoic acid) were high in chloroform. Correlation analysis showed that phenolics, less polar ginsenosides, and fatty acids were positively correlated with the antioxidant activity of GBP. Our study highlights GBP as a functional ingredient for the development of high-quality ginseng berry products.

Association of insulin resistance with near peak bone mass in the femur and lumbar spine of Korean adults aged 25-35: The Korean National Health and Nutrition Examination Survey 2008-2010.

OBJECTIVE: This study aimed to evaluate the relationship between insulin resistance and the bone mineral density (BMD) of femur and lumbar spine in Korean adults who are expected to exhibit near peak bone mass. METHODS: Data from the Korean National Health and Nutrition Examination Survey 2008-2010 were analyzed. A total of 2,750 participants aged 25-35 years were included. Insulin resistance was assessed using a homeostatic model assessment of insulin resistance (HOMA-IR) and serum fasting insulin. RESULTS: In a multivariate linear regression analysis, the HOMA-IR was significantly inversely associated with the BMD of the total hip (TH, ß = -0.052, P = 0.002), femoral neck (FN, ß = -0.072, P<0.001), femoral trochanter (FTr, ß = -0.055, P = 0.003), femoral intertrochanter (FITr, ß = -0.041, P = 0.015), and lumbar spine (LS, ß = -0.063, P = 0.001) among all study subjects after adjustment for gender, age, height, weight, whole body fat mass percentage, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, vitamin D, smoking, alcohol intake, physical activity, education level, and household income in both genders as well as labor, the use of oral contraceptives, and age at menarche in females. The serum fasting insulin was significantly inversely associated with the BMD of the TH (ß = -0.055, P = 0.001), FN (ß = -0.072, P<0.001), FTr (ß = -0.055, P = 0.003), FITr (ß = -0.045, P = 0.009), and LS (ß = -0.064, P = 0.001) among all subjects in a multivariate linear regression analysis. CONCLUSION: Our results suggest that insulin resistance may be independently and inversely associated with the near peak bone mass of the femur and lumbar spine.

Association Between Duration of Breast Feeding and Metabolic Syndrome: The Korean National Health and Nutrition Examination Surveys.

BACKGROUND: This study aimed to evaluate the association of the lifelong duration of breast feeding with metabolic syndrome (MetS) and its components in Korean parous women aged 19-50 years. MATERIALS AND METHODS: A total of 4724 participants from the Korean National Health and Nutritional Survey were included. Subjects were divided into four groups according to the duration of breast feeding: ≤5, 6-11, 12-23, or ≥24 months groups. The adjusted odds ratios (ORs) of MetS and its components were assessed according to the duration of breast feeding. RESULTS: Women who breastfed for 6-11 months had an OR of 0.67 (95% confidence interval [CI], 0.54-0.86) for elevated blood pressure (BP) compared with those who breastfed for ≤5 months after adjustment for possible confounders in a multivariable logistic regression analyses. Women who breastfed for 12-23 months were associated with an OR of 0.68 (95% CI, 0.54-0.86) for elevated BP, an OR of 0.78 (95% CI, 0.62-0.97) for elevated glucose, and an OR of 0.73 (95% CI, 0.56-0.95) for MetS compared with those who breastfed for ≤5 months in a multivariable logistic regression analyses. Women who breastfed for ≥24 months had an OR of 0.62 (95% CI, 0.52-0.84) for elevated glucose, an OR of 0.76 (95% CI, 0.60-0.96) for elevated triglycerides, and an OR of 0.70 (95% CI, 0.53-0.92) for MetS compared with those who breastfed for ≤5 months in a multivariable logistic regression analyses. CONCLUSIONS: Our results suggest that lifelong breast feeding for ≥12 months may be associated with lower risk for MetS.