Lactic Acid Bacteria Isolated from Human Breast Milk Improve Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid by Inhibiting NF-κB Signaling in Mice.

Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1ß. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1ß, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

Aggregation-induced emission (AIE) nanoparticles labeled human embryonic stem cells (hESCs)-derived neurons for transplantation.

Transplantation of differentiated neurons derived from either human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) is an emerging therapeutic strategy for various neurodegenerative diseases. One important aspect of transplantation is the accessibility to track and control the activity of the stem cells-derived neurons post-transplantation. Recently, the characteristics of organic nanoparticles (NPs) with aggregation-induced emission (AIE) have emerged as efficient cell labeling reagents, where positive outcomes were observed in long-term cancer cell tracing in vivo. In the current study, we designed, synthesized, and analyzed the biocompatibility of AIE-NPs in cultured neurons such as in mouse neuronal progenitor cells (NPCs) and hESC-derived neurons. Our data demonstrated that AIE-NPs show high degree of penetration into cells and presented intracellular long-term retention in vitro without altering the neuronal proliferation, differentiation, and viability. Furthermore, we have tracked AIE-NPs labeled neuronal grafts in mouse brain striatum in various time points post-transplantation. We demonstrated prolonged cellular retention of AIE-NPs labeled neuronal grafts 1 month post-transplantation in mouse brain striatum. Lastly, we have shown activation of brain microglia in response to AIE-NPs labeled grafts. Together, these findings highlight the potential application of AIE-NPs in neuronal transplantation.

Current Status of Stem Cell-Derived Therapies for Parkinson's Disease: From Cell Assessment and Imaging Modalities to Clinical Trials.

Curative therapies or treatments reversing the progression of Parkinson's disease (PD) have attracted considerable interest in the last few decades. PD is characterized by the gradual loss of dopaminergic (DA) neurons and decreased striatal dopamine levels. Current challenges include optimizing neuroprotective strategies, developing personalized drug therapy, and minimizing side effects from the long-term prescription of pharmacological drugs used to relieve short-term motor symptoms. Transplantation of DA cells into PD patients' brains to replace degenerated DA has the potential to change the treatment paradigm. Herein, we provide updates on current progress in stem cell-derived DA neuron transplantation as a therapeutic alternative for PD. We briefly highlight cell sources for transplantation and focus on cell assessment methods such as identification of genetic markers, single-cell sequencing, and imaging modalities used to access cell survival and function. More importantly, we summarize clinical reports of patients who have undergone cell-derived transplantation in PD to better perceive lessons that can be drawn from past and present clinical outcomes. Modifying factors include (1) source of the stem cells, (2) quality of the stem cells, (3) age of the patient, (4) stage of disease progression at the time of cell therapy, (5) surgical technique/practices, and (6) the use of immunosuppression. We await the outcomes of joint efforts in clinical trials around the world such as NYSTEM and CiRA to further guide us in the selection of the most suitable parameters for cell-based neurotransplantation in PD.

Amyloid precursor protein intracellular domain-dependent regulation of FOXO3a inhibits adult hippocampal neurogenesis.

The amyloid precursor protein (APP) intracellular domain (AICD) is a metabolic by-product of APP produced through sequential proteolytic cleavage by α-, ß-, and γ-secretases. The interaction between AICD and Fe65 has been reported to impair adult neurogenesis in vivo. However, the exact role of AICD in mediating neural stem cell fate remains unclear. To identify the role of AICD in neuronal proliferation and differentiation, as well as to clarify the molecular mechanisms underlying the role of AICD in neurogenesis, we first generated a mouse model expressing the Rosa26-based AICD transgene. AICD overexpression did not alter the spatiotemporal expression pattern of full-length APP or accumulation of its metabolites. In addition, AICD decreased the newly generated neural progenitor cell (NPC) pool, inhibited the proliferation and differentiation efficiency of NPCs, and increased cell death both in vitro and in vivo. Given that abnormal neurogenesis is often associated with depression-like behavior in adult mice, we conducted a forced swim test and tail suspension test with AICD mice and found a depression-like behavioral phenotype in AICD transgenic mice. Moreover, AICD stimulated FOXO3a transcriptional activation, which in turn negatively regulated AICD. In addition, functional loss of FOXO3a in NPCs derived from the hippocampal dentate gyrus of adult AICD transgenic mice rescued neurogenesis defects. AICD also increased the mRNA expression of FOXO3a target genes related to neurogenesis and cell death. These results suggest that FOXO3a is the functional target of AICD in neurogenesis regulation. Our study reveals the role of AICD in mediating neural stem cell fate to maintain homeostasis during brain development via interaction with FOXO3a.

Allomyrina dichotoma larval extract attenuates intestinal barrier disruption by altering inflammatory response and tight junction proteins in lipopolysaccharide-induced Caco-2 cells.

Intestinal epithelial cells form a barrier between the intestinal lumen and host connective tissues and play an important role in maintaining intestinal nutrient homeostasis. This study investigated effects of Allomyrina dichotoma (rhinoceros beetle) larval extract (ADLE) on the intestinal barrier damage and explored mechanisms for reversing intestinal barrier dysfunction in lipopolysaccharide (LPS)-stimulated Caco-2, human intestinal epithelial cells. LPS reduced intestinal epithelial barrier function by increasing transepithelial electrical resistance, and this effect was significantly attenuated by ADLE treatment. ADLE also significantly countered the inhibition of tight junction-related protein expression in both LPS-induced Caco-2 cells and intestine from HFD-induced mice. Moreover, ADLE significantly decreased expression and production of inflammatory factors, such as iNOS, cox-2, nitric oxide, and cytokines induced by LPS stimulus. Reduction in phosphorylation of adenosine monophosphate-activated protein kinase was averted by ADLE treatment in LPS treated INS-1 cells. Finally, reactive oxygen stress level was decreased and ATP production was increased by ADLE treatment. ADLE appears to display gut health-promoting effects by reducing inflammation and inducing tight junction proteins in Caco-2 cells. Therefore, ADLE might be useful for preventing or treating intestine cell damage in inflammatory bowel disease.

Development and application of an antibody that binds to interleukin-1ß of various mammalian species for the treatment of inflammatory diseases.

Inflammation is provoked by host immune reactions to pathogenic or tissue injury and is arbitrated by cytokines. Among the pro-inflammatory cytokines, the tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) are main mediators of inflammation. The production of these pro-inflammatory cytokines is mainly triggered in macrophages by harmful stimuli including microbial pathogens, irritants, and toxic cellular components, and plays key roles in the palpation of the inflammatory response. Among the therapeutic antibodies for the treatment of inflammation, those targeting TNF-α (including adalimumab and infliximab) are frequently used in clinical settings. Although IL-1ß is a key cytokine for the onset of inflammatory diseases, such as inflammatory bowel disease (IBD) and type 2 diabetes (T2DM), few therapeutic antibodies exist for this cytokine, with the exception of canakinumab. Canakinumab binds to human IL-1ß, but does not bind to murine IL-1ß, which hampers its experimental use. Therefore, inflammation-therapeutic antibodies that bind to IL-1ß of various mammals are needed. In this study, we report the development of an antibody that bound to IL-1ß of various mammalian species and exhibited therapeutic effects in inflammatory diseases.

IL-10 Expression-Inducing Gut Bacteria Alleviate High-Fat Diet-Induced Obesity and Hyperlipidemia in Mice.

In the present study, we examined the effects of interleukin (IL)-10 expression-inducing bacteria Bifidobacterium adolescentis HP1, Lactobacillus mucosae HP2, and Weissella cibaria HP3 on high-fat diet (HFD)-induced obesity and liver steatosis in mice. Oral gavage of HP1, HP2, and HP3 reduced HFD-induced bodyweight gain, triglycerides, and total cholesterol levels in the blood and liver. They also suppressed HFD-induced colitis and the fecal δ,γ-Proteobacteria population. Of the tested bacteria, HP2, which most potently inhibited IL-10 expression, also suppressed HFD-induced bodyweight gain, liver steatosis, and colitis most effectively. These findings suggest that IL-10 expression-inducing gut bacteria can suppress obesity and liver steatosis.

Amelioration of colitis in mice by Leuconostoc lactis EJ-1 by M1 to M2 macrophage polarization.

Dysregulation of immune responses to environmental antigens by the intestine leads to the chronic inflammatory disease, inflammatory bowel disease (IBD). Recent studies have thus sought to identify a dietary component that can inhibit lipopolysaccharide (LPS)-induced nuclear factor-kappa beta (NF-κB) signaling to ameliorate IBD. This study assessed if the lactic acid bacteria (LAB) from kimchi, suppresses the expression of tumor necrosis factor-alpha (TNF-α) in peritoneal macrophages induced by LPS. Leuconostoc lactis EJ-1, an isolate from LAB, reduced the expression of interleukin-6 (IL-6) and IL-1ß in peritoneal macrophages induced by LPS. The study further tested whether EJ-1 alleviates colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. TNBS significantly increased myeloperoxidase (MPO) expression, macroscopic colitis scores, and colon shortening. Oral administration of L. lactis EJ-1 resulted in an inhibited in TNBS-induced loss in body weight, colon shortening, MPO activity, and NF-κB and inducible nitric oxide synthase expression; it also led to a marked reduction in cyclooxygenase-2 expression. L. lactis EJ-1 also inhibited the TNBS-induced expression of TNF-α, IL-1ß, and IL-6; however, it induced the expression of IL-10. The M2 macrophage markers arginase I, IL-10, and CD206 were elevated by EJ-1. Collectively, these results suggest that EJ-1 inhibits the NF-κB signaling and polarizes M1- to M2-macrophage transition, which help in ameliorating colitis.

Lactobacillus sakei S1 Improves Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid by the Inhibition of NF-κB Signaling in Mice.

Lactobacillus sakei S1 strongly inhibits the expression of interleukin (IL)-6 and IL-1ß in lipopolysaccharide-induced peritoneal macrophages by a mechanism for which lactic acid bacteria from kimchi that inhibit tumor necrosis factor-alpha (TNF-κ) were isolated. Therefore, we further evaluated the protective effect of this strain on the colitis mouse model induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS significantly elevated myeloperoxidase (MPO) expression, macroscopic scores, and colon shortening. Oral L. sakei S1 administration resulted in reduction of TNBS-induced loss in body weight, colon shortening, MPO activity, expression of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB). L. sakei S1 inhibited the expression of inflammatory cytokines IL-1ß, IL-6 and TNF-κ, induced by TNBS, but enhanced IL-10 expression. L. sakei S1 showed resistance to artificial digestive juices and adherence to intestinal epithelial Caco-2 cells. Thus, L. sakei S1 may inhibit the NF-κB pathway and be used in functional food to treat colitis.

Upregulation of caveolin-1 and its colocalization with cytokine receptors contributes to beta cell apoptosis.

Caveolin-1 (cav-1), the principal structural and signalling protein of caveolae, is implicated in various signalling events, including apoptotic cell death in type 2 diabetes. However, the precise role of beta cells in apoptosis has not been clearly defined. In this study, we investigated the involvement of cav-1 in cytokine-induced beta cell apoptosis and its underlying mechanisms in the rat beta cell line, INS-1 and isolated islets. Treatment of cytokine mixture (CM, TNFα + IL-1ß) significantly increased the mRNA and protein expression of cav-1, and resulting in increased formation of caveolae. We found that IL-1 receptor 1 and TNF receptor localized to plasma membrane lipid rafts in the control cells and CM treatment recruited these receptors to the caveolae domain. After cav-1 siRNA transfection, CM-dependent NF-κB activation was reduced and consequently downregulated the mRNA expression of iNOS and IL-1ß. Finally, decreased cell viability by CM treatment was ameliorated in both INS-1 cells and isolated islets treated with cav-1 siRNA. These results suggest that increased cav-1 expression and recruitment of cytokine receptors into caveolae contribute to CM-induced beta cell apoptosis.

Lactobacillus plantarum NK3 and Bifidobacterium longum NK49 Alleviate Bacterial Vaginosis and Osteoporosis in Mice by Suppressing NF-κB-Linked TNF-α Expression.

Excessive expression of TNF-α worsens bacterial vaginosis (BV) and osteoporosis. Therefore, to understand whether probiotics could alleviate vaginosis and osteoporosis, we isolated anti-inflammatory Lactobacillus plantarum NK3 and Bifidobacterium longum NK49 from kimchi and human fecal lactic acid bacteria collection and examined their effects on Gardnerella vaginalis (GV)-induced vaginosis and ovariectomy-induced osteoporosis in female mice. Oral gavage of NK3 and/or NK49 significantly alleviated GV-induced vaginosis; these inhibited NF-κB activation and TNF-α expression in the vagina and uterus, and decreased the GV population in the vagina. Furthermore, treatment with NK3 and/or NK49 alleviated ovariectomy-induced osteoporosis and obesity; these increased blood calcium, phosphorus, and osteocalcin levels and suppressed body weight. GV-induced vaginosis and ovariectomy increased colonic myeloperoxidase activity, TNF-α expression, and fecal Proteobacteria population. NK3 and/or NK49 treatments reduced TNF-α expression and NF-κB activation in the colon. NK3 and NK49 treatment also restored GV- or ovariectomy-disrupted gut microbiota composition. In conclusion, NK3 and NK49 may simultaneously alleviate BV and osteoporosis by suppressing NF-κB-linked TNF-α expression through the regulation of gut microbiota population.

Fermented Red Ginseng Alleviates Cyclophosphamide-Induced Immunosuppression and 2,4,6-Trinitrobenzenesulfonic Acid-Induced Colitis in Mice by Regulating Macrophage Activation and T Cell Differentiation.

A variety of products have been developed with red ginseng (RG, the steamed roots of Panax ginseng Meyer). To clarify the immunomodulating effects of water-extracted RG (wRG), 50% ethanol-extracted RG (eRG), enzyme-treated eRG (ERG) and probiotic-fermented eRG (FRG), we examined their immunopotentiating and immunosuppressive effects in mice with cyclophosphamide (CP)-induced immunosuppression (CI) or 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis (TC). Oral administration of RG in CI mice significantly increased blood IFN- γ levels. Treatment with RG also increased the tumoricidal effects of CI mouse splenic cytotoxic T (Tc) and NK cells against YAC-1 cells. Treatment with RGs, in particular FRG and wRG, significantly increased Th1 cell differentiation. Treatment with RG except wRG increased Treg cell differentiation. However, wRG alone increased IL-6 and IL-17 expression in the colon of CI mice. Furthermore, RG alleviated colitis in TC mice. FRG most potently suppressed TNBS-induced colon shortening, NF- κ B activation and TNF- α and IL-17 expression and increased IL-10 expression. RGs inhibited TNF- α expression and increased IL-10 expression in lipopolysaccharide-stimulated primary macrophages in vitro while the differentiation of splenic T cells into type 1 T (Th1) and regulatory T (Treg) cells was increased by FRG in vitro. In conclusion, FRG can alleviate immunosuppression and inflammation by inhibiting macrophage activation and regulating Th1 and Treg cell differentiation.

Evidence for interplay among antibacterial-induced gut microbiota disturbance, neuro-inflammation, and anxiety in mice.

The aim of the present study was to determine whether there is the mechanistic connection between antibacterial-dependent gut microbiota disturbance and anxiety. First, exposure of mice to ampicillin caused anxiety and colitis and increased the population of Proteobacteria, particularly Klebsiella oxytoca, in gut microbiota and fecal and blood lipopolysaccharide levels, while decreasing lactobacilli population including Lactobacillus reuteri. Next, treatments with fecal microbiota of ampicillin-treated mouse (FAP), K. oxytoca, or lipopolysaccharide isolated from K. oxytoca (KL) induced anxiety and colitis in mice and increased blood corticosterone, IL-6, and lipopolysaccharide levels. Moreover, these treatments also increased the recruitment of microglia (Iba1+), monocytes (CD11b+/CD45+), and dendritic cells (CD11b+/CD11c+) to the hippocampus, as well as the population of apoptotic neuron cells (caspase-3+/NeuN+) in the brain. Furthermore, ampicillin, K. oxytoca, and KL induced NF-κB activation and IL-1ß and TNF-α expression in the colon and brain as well as increased gut membrane permeability. Finally, oral administration of L. reuteri alleviated ampicillin-induced anxiety and colitis. These results suggest that ampicillin exposure can cause anxiety through neuro-inflammation which can be induced by monocyte/macrophage-activated gastrointestinal inflammation and elevated Proteobacteria population including K. oxytoca, while treatment with lactobacilli suppresses it.

Tyndallized Lactobacillus plantarum HY7712 Restores Whole-Body γ-Irradiation-Impaired Th Cell Differentiation in Mice.

In the present study, we investigated the effect of tyndallized HY7712 (tHY7712) on the expression of Th cell specific transcription factors and cytokines in whole-body γ-irradiated mice. Oral administration of tHY7712 strongly recovered the γ-irradiation-suppressed expression of helper T (Th) cell- and regulatory T cell-related transcription factors and cytokines, such as T-bet, Foxp3, IFN-γ, TNF-α, and IL-10, and suppressed Th2 cell-associated transcription factor and cytokine GATA3 and IL-5, respectively. Furthermore, compared with the control, tHY7712 treatment also restored γ-irradiation-impaired natural killer and cytotoxic T cell activities against YAC-1 tumor cells to 97.8% and 98.6%, respectively.

Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus La-14 Attenuate Gardnerella vaginalis-Infected Bacterial Vaginosis in Mice.

Oral administration of a probiotic mixture (PM; Respecta®) consisting of Lactobacillus rhamnosus HN001 (L1), Lactobacillus acidophilus La-14 (L2), and lactoferrin RCXTM results in colonization of these probiotics in the vagina of healthy women. Therefore, we examined whether vaginal colonization of the PM ingredients L1 and L2 could attenuate bacterial vaginosis (BV). BV was induced in mice via ß-estradiol-3-benzoate-induced immunosuppression and intravaginal inoculation with Gardnerella vaginalis (GV). Inflammatory markers were analyzed using enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, and flow cytometry. Oral or intravaginal administration of PM resulted in colonization of L1 and L2 in the vagina. Oral or intravaginal administration of L1, L2, or PM significantly inhibited GV-induced epithelial cell disruption, myeloperoxidase activity, NF-κB activation, and IL-1ß and TNF-α expression (p < 0.05). Administration of these probiotics also inhibited IL-17 and RORγt expression but increased IL-10 and Foxp3 expression. Of these probiotics, L2 most effectively attenuated GV-induced BV, followed by L1 and PM. Oral administration was more effective against GV-induced BV than intravaginal administration. L1 and L2 also significantly inhibited the adherence of GV to HeLa cells (a human cervical cancer cell line) and GV growth in vitro. In addition, L1 and L2 inhibited lipopolysaccharide-induced NF-κB activation in macrophages and the differentiation of splenocytes into Th17 cells in vitro, but increased their differentiation into Treg cells. Our study suggests that L1, L2, and PM attenuated GV-induced vaginosis by regulating both vaginal and systemic innate and adaptive immune responses rather than direct competition or killing of GV in the vagina.

Irisolidone attenuates ethanol-induced gastric injury in mice by inhibiting the infiltration of neutrophils.

SCOPE: This study was designed to determine whether irisolidone and its glycoside kakkalide, which are the major constituents of the flower of Pueraria lobata (Kudzu) can attenuate ethanol-induced gastritic injury in mice. METHODS AND RESULTS: Irisolidone and kakkalide inhibited IL-8 secretion and NF-κB activation in lipopolysaccharide-stimulated KATO III cells. Therefore, we investigated their protective effects against ethanol-induced gastric injury in mice. Pretreatment with kakkalide or irisolidone decreased the area of hemorrhagic ulcerative lesions caused by ethanol and suppressed stomach myeloperoxidase activity, CXCL4 secretion, and NF-κB activation. The ameliorating effect of irisolidone was more potent than that of kakkalide. CONCLUSION: Irisolidone may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, particularly neutrophils, through the regulation of CXCL-4 or IL-8 secretion.

Lactobacillus sakei K17, an inducer of IL-10 expression in antigen-presenting cells, attenuates TNBS-induced colitis in mice.

To understand the anti-colitic effects of probiotics that up-regulate interleukin (IL)-10 expression in dendritic cells (DCs) and macrophages, we isolated Lactobacillus sakei K17, which potently induced IL-10 expression in DCs and peritoneal macrophages in vitro, among the lactic acid bacteria strains collected from kimchi and investigated its anti-inflammatory effect in mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Oral administration of K17 (2 × 109 CFU·mouse-1·day-1) in mice with TNBS-induced colitis suppressed colon shortening and myeloperoxidase activity, as well as infiltration of CD86+ cells into the colon. Treatment with K17 also increased TNBS-suppressed expression of tight junction proteins and IL-10, but inhibited activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases and expression of tumor necrosis factor α and IL-17. Its effect was comparable with that of sulfasalazine (50 mg/kg), a positive commercial ant-colitic drug. Furthermore, treatment with K17 (1 × 105 CFU/mL) potently inhibited lipopolysaccharide (LPS)-stimulated NF-κB activation in DCs and peritoneal macrophages and restored tight junction protein expression in LPS-stimulated Caco-2 cells. These findings suggest that Lactobacillus sakei K17 may ameliorate colitis by up-regulating the expression of IL-10 and tight junction proteins and inhibiting NF-κB activation.

Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia.

Tangeretin, a flavonoid from citrus fruit peels, has been proven to play an important role in anti-inflammatory responses and neuroprotective effects in several disease models, but further study is necessary for elucidating the detailed mechanisms of these effects. In this study, we examined the anti-inflammatory effect of tangeretin in lipopolysaccharide (LPS)-stimulated microglia. We first observed that tangeretin inhibited LPS-induced production of nitric oxide, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1ß, as well as LPS-induced mRNA expression of inducible nitric oxide synthases and cytokines. Additionally, we found that the activities, mRNA levels, and protein levels of matrix metalloproteinase (MMP)-3 and MMP-8 were inhibited, while the expression of tissue inhibitor of metalloproteinase-2 was enhanced by tangeretin in LPS-stimulated microglia. Further mechanistic study showed that tangeretin suppressed LPS-induced phosphorylation of mitogen-activated protein kinases and Akt. Also, tangeretin inhibited nuclear factor-κB by upregulating sirtuin 1 and 5'-adenosine monophosphate-activated protein kinase. We further demonstrated the antioxidant effect of tangeretin by showing that tangeretin inhibited reactive oxygen species production and p47(phox) phosphorylation, while enhancing the expression of heme oxygenase-1 and the DNA binding activity of nuclear factor-erythroid 2-related factor 2 to the antioxidant response element in LPS-stimulated microglia. Taken together, the results of the present study demonstrate that tangeretin possesses a potent anti-inflammatory and antioxidant effect in microglia.

Orally administrated Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent colitis by inhibiting the nuclear factor-kappa B signaling pathway via the regulation of lipopolysaccharide production by gut microbiota.

To evaluate the anti-inflammaging effect of lactic acid bacteria (LAB) on age-dependent inflammation, we first screened and selected a tumor necrosis factor (TNF)-α and reactive oxygen species (ROS)-inhibitory LAB, Lactobacillus pentosus var. plantarum C29, among the LABs isolated from fermented vegetables using LPS-stimulated mouse peritoneal macrophages. Oral administration of C29 (2 × 109 CFU/rat) for 8 weeks in aged Fischer 344 rats (age, 16 months) inhibited the expression of the inflammatory markers myeloperoxidase, inducible nitric oxide (NO) synthase, cyclooxygenase-2, pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-6 and the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein 1 (AP1), and mitogen-activated protein kinases (MAPKs). Treatment with C29 induced the expression of tight junction proteins ZO-1, occludin, and claudin-1, and reduced intestinal microbial LPS and plasmatic LPS levels and ROS, as well as the Firmicutes to Bacteroidetes ratio, which is significantly higher in aged rats than in young rats. C29 treatment also reduced plasmatic reactive oxygen species, malondialdehyde, C-reactive protein, and TNF-α, and suppressed expression of senescence markers p16 and p53 in the colon of the aged rats, but increased SIRT 1 expression. Based on these findings, we concluded that C29 treatment may suppress aging-dependent colitis by inhibiting NF-κB, AP1, and MAPK activation via the inhibition of gut microbiota LPS production and the induction of tight junction protein expression.

Amelioration of trinitrobenzene sulfonic acid-induced colitis in mice by liquiritigenin.

BACKGROUND AND AIM: The anti-inflammatory effects of liquiritigenin, a major flavonoid isolated from Glycyrrhizae uralensis, have been reported in many inflammation models. However, its protective effects have not been reported in a colitis model. This study investigated the anti-inflammatory effect and mechanism of liquiritigenin for trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. METHODS: Male mice imprinting control regions (ICR) were randomly divided into five groups: normal, TNBS-induced colitis, colitis treated with liquiritigenin at low dose (10 mg/kg) and high dose (20 mg/kg), or mesalazine (10 mg/kg). TNBS colitis induction was performed except for in the normal group, and they were treated with liquiritigenin or mesalazine except control group. The treatment effect was measured after three days treatment, by body weight, colon length, macroscopic score, histological score, levels of cytokines (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, and IL-10) in colon tissue as well as the nuclear factor kappa-light-chain-enhancer pathway of activated B cells (NF-κB) activation. RESULTS: Mice treated with high-dose liquiritigenin showed significant body weight gain, inhibition of colon shortening, protective effect on histological damages, and myeloperoxidase activity of colon tissue compared with the control group. Furthermore, mice treated with high-dose liquiritigenin experienced significantly suppressed tumor necrosis factor-α, IL-1ß, and IL-6 as well as enhanced IL-10 expression (all P < 0.05). High-dose liquiritigenin treatment group showed significant decreases in TNBS-induced phosphorylation of IKKß, p65, and IκB-α. CONCLUSION: Liquiritigenin may ameliorate TNBS-induced colitis in mice by suppressing expression of pro-inflammatory cytokines through NF-κB pathway.