Anti-pneumoconiosis effect of schisantherin A in PMA-induced A549 cells and SiO2/TiO2nanoparticles-induced acute pulmonary injury in mice.

There has been significant global interest in respiratory health driven by the coronavirus disease (COVID-19) and severe environmental pollution. This study explored the potential of schisantherin A (SchA), a compound derived from Schisandra chinensis, to protect against acute pneumoconiosis. We assessed the effects of SchA on phorbol 12-myristate 13-acetate (PMA)-stimulated A549 alveolar epithelial cells and SiO2/TiO2-induced pulmonary injury in mice. In A549 cells, SchA significantly decreased pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin (IL)-8 levels. SchA-mediated reduction in inflammatory mediators was associated with the downregulation of PMA-stimulated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling activation. In SiO2/TiO2-induced lung-injured mice, SchA administration significantly reduced MUC5AC production in lung tissue. SchA administration significantly downregulated the overexpression of NK-κB and the subsequent production of COX-2, iNOS, and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasomes. It significantly suppressed expected increases in total cell numbers and pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and IL-1ß in the bronchoalveolar lavage fluid (BALF) in SiO2/TiO2-stimulated mice. In contrast, the SiO2/TiO2-mediated decrease in IL-10 levels was significantly improved by SchA treatment. These fundamental results can be used to develop potential treatments involving SchA for acute pneumoconiosis.

Nootkatone (NK), a grapefruit-derived aromatic compound, inhibited lipid accumulation by regulating JAK2-STAT signaling and antioxidant response in adipocyte.

Nootkatone (NK) is an aromatic compound derived from grapefruit. This study aimed to investigate the inhibitory effect of NK on lipid accumulation and its underlying mechanism in adipocytes. NK effectively inhibited adipogenic lipid storage by downregulating C/EBPα and PPARγ, while upregulating KLF2, an early inhibitory factor, downregulating C/EBPß, an early promoting factor. In addition, NK inhibited the JAK2-STAT signaling pathway by decreasing the phosphorylation of STAT3 and STAT5 in the early adipogenic stage. NK significantly reduced ROS generation while elevating antioxidant enzymes such as catalase and glutathione peroxidase. It activated NRF2-HO-1 signaling, responsible for antioxidant response, by increasing protein levels. Furthermore, NK regulated adipokines, increasing adiponectin and visfatin, while downregulating resistin. Collectively, NK inhibited adipogenic lipid accumulation through the suppression of JAK2-STAT signaling and the augmentation of antioxidant response. This study highlights the potential of NK as an edible agent to alleviate obesity and its associated metabolic diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01522-2.

Lactobacillus brevis M2-Fermented Whey Protein Hydrolysate Increases Slow-Wave Sleep via GABAA Receptors in Rodent Models.

In this study, we investigated the effects of whey protein hydrolysate (WPH) fermented with Lactobacillus brevis on sleep behavior and GABAergic mechanisms in rodent models. Fermentation converted the glutamate in WPH to high (3.15 ± 0.21 mg/mL) levels of γ-aminobutyric acid (GABA). Fermented WPH (WP-SF) enhanced sleep duration in mice by increasing GABA content in the brain. The increase in sleep duration induced by WP-SF resulted from an increase in delta wave activity during non-rapid eye movement sleep, and its sleep-promoting effect in a caffeine-induced insomnia model was characterized by an increase in delta waves. WP-SF increased GABAergic receptors at both mRNA and protein levels. Cotreatment with GABAA receptor antagonists abolished the sleep-promoting effects of WP-SF, indicating that WP-SF shares binding sites with antagonists on GABAA receptors. Collectively, WP-SF effectively increased sleep duration by enhancing delta wave activity through GABAergic activation; thus, it is suggested as a functional food-grade ingredient for promoting sleep.

Lactitol Alleviates Loperamide-Induced Constipation in Sprague Dawley Rats by Regulating Serotonin, Short-Chain Fatty Acids, and Gut Microbiota.

The objective of this study was to examine the impact of lactitol on constipation caused by loperamide in Sprague Dawley rats, with a particular emphasis on its underlying mechanisms and potential health advantages. The lactitol effectively improved fecal parameters, intestinal tissue structure, and the expression of constipation-related gene expression and proteins. Lactitol alleviated fecal weight and water content altered by loperamide and enhanced gastrointestinal transit. The administration also restored mucosal and muscular layer thickness. Mechanistically, lactitol upregulated the mRNA expression and/or protein levels of mucins (MUC2 and MUC4), occludin, claudin-1, and zonula occludens, indicating improved intestinal barrier function. Lactitol positively regulated the composition of cecal microbiota, leading to an increased relative abundance of Bifidobacterium, Lactobacillus, and Romboutsia. Conversely, lactitol decreased the relative abundance of Prevotella, Aerococcus, Muribaculum, Blautia, and Ruminococcus. This study demonstrated the potential of lactitol to relieve constipation by modulating the gut microbiota. These findings suggest that lactitol is an alternative to traditional laxatives and has potential as a health-promoting food sweetener.

Improvement of sleep duration and quality through GABAA receptor by whey protein hydrolysate containing DIQK as the active main compound.

This study characterized the sleep activity, sleep mechanism, and active peptides of whey protein hydrolysates selected through behavioral analysis of fruit-flies (Drosophila melanogaster). Sleep-inducing whey protein (WP) hydrolysate was selected through fruit fly behavior analysis, and sleep activity was measured using a pentobarbital model and electroencephalographic analysis. The mechanism of action was confirmed using a γ-aminobutyric acid (GABA) receptor antagonist, and the active peptide was identified using liquid chromatography-mass spectroscopy. Whey protein hydrolysate, prepared using Alcalase and Prozyme (WP-AP), increased sleep time in a dose-dependent manner. WP-AP significantly increased not only sleep time but also slow-wave sleep and showed an insomnia-alleviating effect in a caffeine-induced insomnia mouse model. In addition, the gene and protein expression levels of GABA sub-type A (GABAA) receptors increased in the brains of mice orally administered with WP-AP. Through peptide analysis, the mixture of DIQK, VPPF peptide, and GABA contained in WP-AP was estimated to exhibit sleep activity, and due to its high content, DIQK was speculated to be the main sleep -inducing ingredient. These results indicate that WP-AP has the potential to be used as a new ingredient to improve sleep quality.

Lactobacillus brevis-Fermented Gamma-Aminobutyric Acid Ameliorates Depression- and Anxiety-Like Behaviors by Activating the Brain-Derived Neurotrophic Factor-Tropomyosin Receptor Kinase B Signaling Pathway in BALB/C Mice.

This study investigated the effects of Lactobacillus brevis-fermented gamma-aminobutyric acid (LB-GABA) on depressive and anxiety-like behaviors with the underlying molecular mechanism in a chronic stress model of BALB/c mice. LB-GABA attenuates both neuronal cell death and the increase of monoamine oxidase activity induced by hydrogen peroxide. Behavioral tests revealed that GABA significantly increased sucrose preference and reduced immobility time in both tail suspension and forced swimming tests. LB-GABA increased exploration of the open arms in the elevated plus maze and restored activity in the open field. Moreover, LB-GABA lowered stress hormone and inflammatory mediator levels. Mechanistically, LB-GABA increased protein levels of BDNF and TrkB, activating downstream targets (AKT, ERK, and CREB), crucial for neuronal survival and plasticity. Furthermore, LB-GABA protected hippocampal neurons from stress-induced cell death and increased serotonin and dopamine levels. Overall, LB-GABA has the potential to alleviate stress-induced depression and anxiety-like symptoms and neuroinflammation by activating the BDNF-TrkB signaling pathway.

Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide-induced oxidative stress.

This study aimed to investigate the neuroprotective effects of whey protein hydrolysate (WPH) containing the pentapeptide leucine-aspartate-isoleucine-glutamine-lysine (LDIQK). Whey protein hydrolysate (50, 100, and 200 µg/mL) demonstrated the ability to restore the viability of HT22 cells subjected to 300 µM hydrogen peroxide (H2O2)-induced oxidative stress. Furthermore, at a concentration of 200 µg/mL, it significantly reduced the increase in reactive oxygen species production and calcium ion (Ca2+) influx induced by H2O2 by 46.1% and 46.2%, respectively. Similarly, the hydrolysate significantly decreased the levels of p-tau, a hallmark of tauopathy, and BCL2 associated X (BAX), a proapoptosis factor, while increasing the protein levels of choline acetyltransferase (ChAT), an enzyme involved in acetylcholine synthesis, brain-derived neurotrophic factor (BDNF), a nerve growth factor, and B-cell lymphoma 2 (BCL2, an antiapoptotic factor. Furthermore, it increased nuclear factor erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1(HO-1) signaling, which is associated with the antioxidant response, while reducing the activation of mitogen-activated protein kinase (MAPK) signaling pathway components, namely phosphor-extracellular signal-regulated kinases (p-ERK), phosphor-c-Jun N-terminal kinases (p-JNK), and p-p38. Column chromatography and tandem mass spectrometry analysis identified LDIQK as a compound with neuroprotective effects in WPH; it inhibited Ca2+ influx and regulated the BAX/BCL2 ratio. Collectively, WPH containing LDIQK demonstrated neuroprotective effects against H2O2-induced neuronal cell damage, suggesting that WPH or its active peptide, LDIQK, may serve as a potential edible agent for improving cognitive dysfunction.

Protective Effects of Whey Protein Hydrolysate, Treadmill Exercise, and Their Combination against Scopolamine-Induced Cognitive Deficit in Mice.

In this study, the potential of whey protein hydrolysate (WPH) and treadmill exercise to prevent cognitive decline was investigated, along with their neuroprotective mechanisms. Cognitive dysfunction was induced in mice with 1 mg/kg of scopolamine, followed by the administration of WPH at 100 and 200 mg/kg and/or treadmill exercise at 15 m/min for 30 min five days per week. Both WPH administration and treadmill exercise significantly improved the memory of mice with scopolamine-induced cognitive impairment, which was attributed to several key mechanisms, including a reduction in oxidative stress based on decreased levels of reactive oxygen species and malondialdehyde in the brain tissue and an increase in acetylcholine by increasing choline acyltransferase and decreasing acetylcholine esterase levels. Exercise and WPH also exerted neuroprotective effects by inhibiting the hyperphosphorylation of tau proteins, enhancing the expression of the brain-derived neurotrophic factor, and inhibiting apoptosis by reducing the Bax/Bcl2 ratio in conjunction with the downregulation of the mitogen-activated protein kinase pathway. Moreover, the impact of WPH and treadmill exercise extended to the gut microbiome, suggesting a potential link with cognitive improvement. These findings suggest that both WPH intake and treadmill exercise are effective strategies for mitigating cognitive impairment, providing promising avenues for treating neurodegenerative diseases.

Enzyme Activity and Lipogenesis Inhibition by Fermented Grain Using Natural Enzymes.

This study aims to compare the effects of three enzyme-rich foods, including one fermented (grain enzyme) and two non-fermented foods (enzyme foods 1 and 2), by investigating their antioxidant, anti-inflammatory, and anti-adipogenic properties. Grain enzyme exhibited the highest radical scavenging activity and was rich in antioxidant components, including total polyphenol and total flavonoid contents. Grain enzyme and enzyme foods 1 and 2 inhibited nitric oxide production by 27, 34, and 17%, respectively, at a concentration of 200 µg/mL in LPS-stimulated macrophages. Among the tested enzymes, grain enzyme demonstrated the strongest inhibition on the expression of inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX-2), and interleukin (IL)-1ß, while Enzyme Food 2 exhibited the most significant suppression of IL-6 mRNA levels. Furthermore, Grain Enzyme demonstrated a stronger inhibitory effect compared to Enzyme Food 1 and 2. Grain Enzyme decreased the mRNA expression of peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP)α, and fatty acid-binding protein (FABP)4 by 28, 21, and 30%, respectively, at a concentration of 400 µg/mL. In summary, fermented grain enzymes outperformed non-fermented enzymes in suppressing inflammation and adipogenesis. This study highlights the anti-inflammatory and anti-adipogenic effects of grain enzyme, suggesting its potential as a valuable dietary supplement for managing metabolic disorders.

Yeast-Hydrolysate-Derived 1-Methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic Acid Inhibits Fat Accumulation during Adipocyte Differentiation.

This study aimed to investigate the impact of yeast hydrolysate (YH) on lipogenesis, elucidate its mechanistic action, and identify the active compounds responsible for its anti-adipogenic effects. YH (2 mg/mL) significantly reduced Oil Red O-stained lipids. YH (2 mg/mL) also downregulated C/EBPß and upregulated KLF2, both of which are early adipogenic factors. Moreover, YH (2 mg/mL) decreased C/EBPα, PPARγ, FABP4, FAS, ACC, and HMGCR mRNA expression. Additionally, YH significantly downregulated SEBP1c and SREBP2 and their target genes, which govern fatty acid and cholesterol metabolism; however, 2 mg/mL YH had a greater suppressive effect on SREBP1c than on SREBP2. YH (2 mg/mL) also significantly reduced the mRNA level of G6PD and malic enzyme, which are enzymes that synthesize NADPH for lipid synthesis, compared with the control. Furthermore, 1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid (MTCA) was identified as the active compound with anti-adipogenic effects using solvent fractionation and chromatographic analysis of YH, and 1.1 µg/mL MTCA significantly downregulated SREBP1c/SREBP2 mRNAs by 47.8% and 69.2%, respectively, along with the target genes FAS, ACC, and HMGCR by 79.0%, 77.0%, and 40.9%, respectively. Collectively, YH effectively suppressed adipogenic lipid storage by downregulating SREBP- and NADPH-synthesizing genes. These findings suggest that YH containing MTCA has the potential to act as an anti-obesity agent.

Schisandra chinensis-derived gomisin C suppreses lipid accumulation by JAK2-STAT signaling in adipocyte.

Gomisin C is a lignan isolated from the fruit of Schisandra chinensis. The current study aimed to investigate the effect of gomisin C on lipid accumulation in adipocytes and its underlying mechanism. Gomisin C effectively inhibited lipid accumulation by downregulating adipogenic factors such as PPARγ and C/EBPα. Gomisin C-mediated suppression of lipid accumulation occurred in the early adipogenic stage; C/EBPß was downregulated by 55%, while KLF2 was upregulated by 1.5-fold. Gomisin C significantly reduced the production of reactive oxygen species but upregulated antioxidant enzymes, including catalase, SOD1, and Gpx at the mRNA level. Gomisin C regulated NRF2-KEAP1 pathway by increasing NRF2 and decreasing KEAP1, in protein abundance. Furthermore, gomisin C suppressed the JAK2-STAT signaling pathway by decreasing phosphorylation. Taken together, gomisin C reduced early adipogenesis and ROS production by inhibiting the JAK2-STAT signaling pathway but activating the NRF2-KEAP1 signaling pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01263-8.

Dibenzoylmethane ameliorates adiposity-mediated neuroinflammatory response and inflammation-mediated neuronal cell death in mouse microglia and neuronal cells.

Dibenzoylmethane (DBM), a licorice-derived component, has numerous health benefits. The current study aimed to investigate the effect of DBM on adiposity-induced neuroinflammatory/oxidative response and microglial activation-induced neuronal cell damage. For this research, BV2 and HT22 cells were cultured using adipcyte- and microglia-conditioned media, respectively. DBM effectively suppressed lipopolysaccharide-induced productions in inducible nitric oxide synthase and cyclooxygenase2. Interleukin (IL)-6, monocyte chemoattractant protein-1, IL-1ß, and tumor necrosis factor-α levels were also downregulated by DBM. In adipocyte-conditioned medium (ACM)-cultured BV2 cells, DBM effectively decreased ACM-induced generation of nitric oxide, reactive oxygen species, and inflammatory cytokines by activating nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling and reducing nuclear factor kappa-light-chain-enhancer of activated B cells. In BV2-conditioned medium (BVM)-cultured neuron cells, DBM recovered the BVM-induced reduction of neuronal cell viability, thereby regulating B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), and cleaved caspase-3 protein expression. Taken together, DBM suppressed adiposity-induced inflammation/oxidative responses and inflammation-induced neuronal cell death.

Curcuma phaeocaulis Inhibits NLRP3 Inflammasome in Macrophages and Ameliorates Nanoparticle-Induced Airway Inflammation in Mice.

The activation of NLRP3 results in the assembly of inflammasome that regulates caspase-1 activation and the subsequent secretion of bioactive interleukin (IL)-1ß. Excessive activation of the NLRP3 inflammasome is mechanistically linked to diverse pathophysiological conditions, including airway inflammation. Here, we discovered that Curcuma phaeocaulis can suppress caspase-1 activation and processing of pro-IL-1ß into mature cytokine in macrophages stimulated with NLRP3 inflammasome activators, such as SiO2 or TiO2 nanoparticles. Furthermore, in the bronchoalveolar lavage fluids of animals administered the nanoparticles, the in vitro effects of C. phaeocaulis translated into a decrease in IL-1ß levels and cell infiltration. Demethoxycurcumin (DMC) and curcumin were found to be responsible for the inflammasome inhibitory activity of C. phaeocaulis. Interestingly, in contrast to the previously reported higher antioxidant- and NFκB-inhibitory activities of curcumin, DMC exhibited approximately two-fold stronger potency than curcumin against nanoparticle induced activation of NLRP3 inflammasome. In the light of these results, both compounds seem to act independently of their antioxidant- and NFκB-inhibitory properties. Although how C. phaeocaulis inhibits nanoparticle-activated NLRP3 inflammasome remains to be elucidated, our results provide a basis for further research on C. phaeocaulis extract as an anti-inflammatory agent for the treatment of disorders associated with excessive activation of NLRP3 inflammasome.

Roles of anti- and pro-oxidant potential of cinnamic acid and phenylpropanoid derivatives in modulating growth of cultured cells.

Cinnamic acid (CiA) and phenylpropanoid derivatives are widely distributed in plant foods. In this study, anti- and pro-oxidant properties of the derivatives and their roles in modulating cell growth were investigated. Ferulic acid, sinapinic acid, caffeic acid (CaA), and 3,4-dihydroxyhydrocinnamic acid (DHC) showed strong radical scavenging activities. They, except DHC, also performed considerable inhibitory effects on lipid peroxidation and reduced levels of intracellular reactive oxygen species (ROS). CaA and DHC, however, produced substantial amount of H2O2 with oxidative degradation in culture conditions. CaA and DHC (> 400 µM) showed potent cytotoxic effects which were abolished by superoxide dismutase/catalase; they significantly enhanced cell growth ROS-dependently at low levels (~ 100 µM). CiA derivatives without bearing hydroxyl group did not show any appreciable antioxidant activities. The results indicate that CiA derivatives with ortho-dihydroxyl group had strong anti- and pro-oxidant properties, which also play an important role in modulating cell growth. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01042-x.

Lactiplantibacillus plantarum K8-based paraprobiotics prevents obesity and obesity-induced inflammatory responses in high fat diet-fed mice.

This study was conducted to investigate the effect of the paraprobiotics, lactic acid bacteria lysates (LAB-P) prepared from Lactiplantibacillus plantarum K8, on obesity and obesity-induced inflammatory responses in high-fat diet (HFD)-fed mice. LAB-P (100 mg/kg) significantly decreased the HFD-induced increase in weight by approximately 20% compared to that in the HFD control. This result was accompanied by a decrease in adipose weight/size. The white adipose tissue weight of epididymis, subcutaneous inguinal region, and mesentery were decreased by 36%, 20%, and 40%, respectively, in LAB-P (100 mg/kg)-administered mice. The size of the epididymal white adipose tissue-derived adipocytes was reduced by 41%. The LAB-P-mediated reduction in adipose tissues was associated with downregulation of adipogenic factors, such as peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα). In addition, LAB-P administration reduced total cholesterol and low-density lipoprotein levels by 23% and 42%, respectively, with a 55% reduction in lactate dehydrogenase levels. Stromal vascular fraction-derived adipose tissue macrophages were favorably regulated by LAB-P administration; the expression of CD11c, an inflammatory marker, was reduced by 30%, and that of CD206, an anti-inflammatory marker, was increased by 9-fold. These results were shown to correlated with the inhibition of proinflammatory cytokines (IL-1ß and IL-6) and downregulation of NF-κB expression. Furthermore, LAB-P administration suppressed HFD-induced fatty liver by activating AMPKα, an energy metabolic sensor. This study indicates that LAB-P effectively prevents HFD-induced obesity and obesity-induced inflammatory responses and serves a valuable basic work for utilizing LAB-P as functional food ingredient to preventing obesity and treating obesity-associated inflammatory diseases.

Fermented Gamma Aminobutyric Acid Improves Sleep Behaviors in Fruit Flies and Rodent Models.

The aim of this study was to investigate the effect of Lactobacillus brevis-fermented γ-aminobutyric acid (LB-GABA) on sleep behaviors in invertebrate and vertebrate models. In Drosophila melanogaster, LB-GABA-treated group showed an 8-9%-longer sleep duration than normal group did. LB-GABA-treated group also showed a 46.7% lower level of nighttime activity with a longer (11%) sleep duration under caffeine-induced arousal conditions. The LB-GABA-mediated inhibition of activity was confirmed as a reduction of total movement of flies using a video tracking system. In the pentobarbital-induced sleep test in mice, LB-GABA (100 mg/kg) shortened the time of onset of sleep by 32.2% and extended sleeping time by 59%. In addition, mRNA and protein level of GABAergic/Serotonergic neurotransmitters were upregulated following treatment with LB-GABA (2.0%). In particular, intestine- and brain-derived GABAA protein levels were increased by sevenfold and fivefold, respectively. The electroencephalography (EEG) analysis in rats showed that LB-GABA significantly increased non-rapid eye movement (NREM) (53%) with the increase in theta (θ, 59%) and delta (δ, 63%) waves, leading to longer sleep time (35%), under caffeine-induced insomnia conditions. LB-GABA showed a dose-dependent agonist activity on human GABAA receptor with a half-maximal effective concentration (EC50) of 3.44 µg/mL in human embryonic kidney 293 (HEK293) cells.

Brassinin, a brassica-derived phytochemical, regulates monocyte-to-macrophage differentiation and inflammatory responses in human monocytes and murine macrophages.

OBJECTIVES: The effects and molecular mechanisms of brassinin (BR), an indole phytoalexin from cruciferous vegetables, on monocyte-to-macrophage differentiation and inflammatory responses were investigated in this study. METHODS: Inflammatory responses from RAW264.7 cells and THP-1 were stimulated by lipopolysaccharide (1 µg/ml), and monocyte-to-macrophage differentiation of THP-1 was induced by phorbol myristate acetate (50 ng/ml). The production of inflammatory mediators was determined by ELISA, Western blot or real-time PCR. Reactive oxygen species were examined by DCFH-DA assay. KEY FINDINGS: Brassinin at 50 µm suppressed lipopolysaccharide-induced production of nitric oxide synthase, cyclooxygenase-2, prostaglandin E2 and reactive oxygen species by 90%, 69%, 52% and 41%, respectively, in RAW264.7 cells. In THP-1 cells, BR inhibited phorbol myristate acetate-induced monocyte-to-macrophage differentiation by suppressing cluster of differentiation molecule ß and CD36. In addition, BR suppressed translocation of nuclear factor 'kappa-light-chain-enhancer' of activated B cells (NF-κB) into the nucleus. However, BR activated the nuclear factor erythroid-derived 2-like 2 (Nrf2) and its target molecules hemoxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), with an increase in nuclear translocation of Nrf2. CONCLUSIONS: Brassinin suppressed monocyte-to-macrophage differentiation and inflammatory responses by differentially regulating Nrf2 and NF-κB signallings.

Anti-inflammatory action of herbal medicine comprised of Scutellaria baicalensis and Chrysanthemum morifolium.

Various mixtures were prepared depending on the mixing ratio of Scutellaria baicalensis hot water extract (SB-HW), and Chrysanthemum morifolium ethanol extract (CM-E) and their anti-inflammatory activity were compared. Among them, SB-HW (80 µg/mL)/CM-E (120 µg/mL) or SB-HW (40 µg/mL)/CM-E (160 µg/mL) significantly inhibited LPS-stimulated NO and IL-6 levels in RAW 264.7 cells. The SB-HW (80 µg/mL)/CM-E (120 µg/mL) mixture, which was determined as active mixture, significantly reduced MUC5AC secretion in PMA and LPS-induced NCI-H292 cells. The active mixture also reduced the production of PGE2 and IL-8 in PMA-induced A549 cells. LC-MS/MS analysis showed that the active mixture was composed of high contents of flavone glycosides, such as baicalin and cynaroside. Western blot analysis indicated that the active mixture suppressed phosphorylation of ERK, JNK, and p38, associating with the inhibition of MAPK signaling. Taken together, our results suggest that the active mixture could be applied as a new anti-inflammatory herbal medicine. ABBREVIATIONS: JNK: c-Jun N-terminal kinases; COPD: chronic obstructive pulmonary disease; CM: Chrysanthemum morifolium; COX-2: cyclooxygenase-2; ERK: extracellular-signal-regulated kinase; IL-6: interleukin-6; IL-8: interleukin-8; IL-12: interleukin-12; LPS: lipopolysaccharide; MAPK: mitogen-activated protein kinase; NO: nitric oxide; NK- κB: nuclear factor kappa B; p38: p38 mitogen-activated protein kinases; PBS: phosphate buffered saline; PMA: phorbol-12-myristate-13-acetate; SB: Scutellaria baicalensis; PGE2: prostaglandin E2; TBST: Tris-buffered saline containing 0.1% Tween 20; TIC: total ion chromatogram; TNF-α: tumor necrosis factor-alpha.

Parthenolide inhibits lipid accumulation via activation of Nrf2/Keap1 signaling during adipocyte differentiation.

The effects of parthenolide (PL), a sesquiterpene lactone obtained from feverfew plant, on lipid accumulation and signaling pathway in adipocytes were investigated. PL significantly inhibited lipid accumulation and adipogenic factors during adipogenesis. In particular, PL exerted its inhibitory effects in early adipogenic stage by regulating the early adipogenic factors. In addition, PL regulated the expression of adipokines; leptin, retinol binding protein, and resistin mRNAs were downregulated, whereas adiponectin gene expression was increased. Furthermore, PL significantly reduced intracellular reactive oxygen species (ROS) production during adipogenesis. This PL-mediated regulation of ROS production was associated with the regulation of nuclear factor erythroid 2-related factor (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) pathway. PL effectively increased the abundance of Nrf2 and its target proteins, heme oxygenase-1 (HO-1) and NADPH dehydrogenase 1 (NQO1), by promoting the nuclear translocation of Nrf2, indicating that PL-mediated anti-adipogenic effects are associated with the Nrf2/Keap1 pathway.

Red ginseng extract regulates differentiation of monocytes to macrophage and inflammatory signalings in human monocytes.

This study was aimed to investigate the effect of red ginseng extract (RGE) on monocyte to macrophage differentiation and inflammatory signalings in THP-1 human monocytes. In HPLC analysis, RGE contained saponin level of 516 µg/mg (extract) with 14 ginsenosides. RGE effectively suppressed the monocyte-to-macrophage differentiation induced by phorbol 12-myristate 13-acetated (PMA) by inhibiting the THP-1 cell adhesion. This result is evidenced by the down-regulation of cluster of differentiation molecule ß (CD11ß) and CD36. RGE significantly reduced translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (78%), while cytosolic NF-κB was increased (53%), compared with LPS group. In addition, RGE significantly increased the protein abundance of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its target protein, hemoxygenase-1 (HO-1), but, Kelch-like ECH-associated protein 1 (KEAP1), a negative regulator of Nrf2, was greatly decreased by RGE. Furthermore, RGE effectively mediated the regulation of Nrf2 level in nucleus and cytoplasm of THP-1.