AICAR Induces Apoptosis and Inhibits Migration and Invasion in Prostate Cancer Cells Through an AMPK/mTOR-Dependent Pathway.

Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-ß-d-ribofuranoside), an AMP-activated protein kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Cell growth was performed by MTT assay and soft agar assay; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining and poly ADP ribose polymerase (PARP) cleavage western blot, while cell migration and invasion were evaluated by wound-healing assay and transwell assay respectively. Epithelial-mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. In addition, our results demonstrated that AICAR induces apoptosis, attenuates transforming growth factor (TGF)-ß-induced cell migration, invasion and EMT-related protein expression, and enhances the chemosensitivity to docetaxel in prostate cancer cells through regulating the AMPK/mTOR-dependent pathway. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.

Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia.

BACKGROUND: Inflammation has been found to be associated with many neurodegenerative diseases, including Parkinson's and dementia. Attenuation of microglia-induced inflammation is a strategy that impedes the progression of neurodegenerative diseases. METHODS: We used lipopolysaccharide (LPS) to simulate murine microglia cells (BV2 cells) as an experimental model to mimic the inflammatory environment in the brain. In addition, we examined the anti-inflammatory ability of corylin, a main compound isolated from Psoralea corylifolia L. that is commonly used in Chinese herbal medicine. The production of nitric oxide (NO) by LPS-activated BV2 cells was measured using Griess reaction. The secretion of proinflammatory cytokines including tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) by LPS-activated BV2 cells was analyzed using enzyme-linked immunosorbent assay (ELISA). The expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, IL-1ß and mitogen-activated protein kinases (MAPKs) in LPS-activated BV2 cells was examined by Western blot. RESULTS: Our experimental results demonstrated that corylin suppressed the production of NO and proinflammatory cytokines by LPS-activated BV2 cells. In addition, corylin inhibited the expression of iNOS and COX-2, attenuated the phosphorylation of ERK, JNK and p38, decreased the expression of NLRP3 and ASC, and repressed the activation of caspase-1 and IL-1ß by LPS-activated BV2 cells. CONCLUSION: Our results indicate the anti-inflammatory effects of corylin acted through attenuating LPS-induced inflammation and inhibiting the activation of NLRP3 inflammasome in LPS-activated BV2 cells. These results suggest that corylin might have potential in treating brain inflammation and attenuating the progression of neurodegeneration diseases.

Scratch wound closure of myoblasts and myotubes is reduced by inflammatory mediators.

Complex interactions exist between muscle repair processes and acute inflammatory responses that are initiated by exercise-induced muscle damage. The purpose of this study was to examine whether inflammatory mediators secreted by activated macrophages affect the migration of myogenic cells to the injury site. Migration was measured using a scratch wound closure assay in C2 C12 -derived myogenic cells incubated in activated macrophage-conditioned medium. Both myoblast and myotube migrations were significantly reduced in activated macrophage-conditioned medium compared with control medium. Furthermore, we demonstrated that the inhibitory effect on myoblast and myotube migrations was mediated, at least in part, by the two major cytokines secreted by activated macrophages, tumour necrosis factor (TNF)-α and interleukin (IL)-6. These findings suggest that the migration rate of myogenic cells may be reduced by inflammatory mediators. It may provide useful insights for future researches on the role of macrophages in the process of muscle repair and regeneration.

Salivary Immuno Factors, Cortisol and Testosterone Responses in Athletes of a Competitive 5,000 m Race.

The exercise-stress model can be a model of temporary immunosuppression that occurs after severe physical and psychological stress. It also allows for the study of interactions between the endocrine and the immune systems. This study examined changes in salivary hormonal and immune factors in athletes in response to physical and psychological stress in a 5,000 m running competition. Eighteen endurance-trained runners (9 males and 9 females) participated in this study. All participants completed a competitive 5,000 m race. Saliva samples were collected 10 min before (PRE) and 10 min after (POST) the competition. Saliva was analyzed for α-amylase activity, concentrations of salivary immunoglobulin A (SIgA), lactoferrin, cortisol, testosterone and total protein. Although the concentrations of salivary TP, SIgA, lactoferrin, cortisol and α-amylase activity were significantly increased immediately after a competitive 5,000 m race, the secretion rates of these factors were not significantly altered in both male and female groups. Additionally, basal levels of SIgA and α-amylase activity were significantly higher in female runners than in male runners. This gender difference still existed after the race. The secretion rates of testosterone decreased significantly after the race in the male, but not in the female group. Moreover, testosterone-to-cortisol (T/C) ratios were significantly lower post-competition compared to pre-competition in both male and female athletes. The T/C ratio had been used as a performance index for athletes. Whether there are correlations between these changes of their physiological characteristics and better running performance need further investigations.

Supplementation of L-glutamine enhanced mucosal immunity and improved hormonal status of combat-sport athletes.

BACKGROUND: Maintaining proper immune function and hormone status is important for athletes to avoid upper respiratory tract infection (URTI) and insufficient recovery, which is detrimental to sport performance and health. The aim of this study was to evaluate whether three-week supplementation of L-glutamine could benefit the mucosal immunity and hormonal status of combat-sport athletes as well as their rates of upper respiratory tract infection (URTI) and subjective feelings of well-being after intensive training. METHODS: Twenty-one combat-sport athletes from the National Taiwan University of Sport were recruited in this study. After intensive training, two groups of the participants were asked to consume powder form of 0.3 g/kg body weight of L-glutamine (GLU group) or maltodextrin (PLA group) with drinking water in a randomized design at the same time every day during 3 weeks. Saliva samples were collected to measure immunoglobulin A (IgA), nitric oxide (NO), testosterone (T) and cortisol (C) before and after three-week supplementation; moreover, Hooper's index questionnaires were completed for wellness assessment. The incidence and duration of URTI were recorded by using a health checklist throughout the entire study period. RESULTS: Supplementation of L-glutamine significantly enhanced the concentrations of IgA and NO in saliva; additionally, the incidence of URTI was significantly reduced. Regarding hormones, T concentration was significantly decreased in the PLA group, whereas C concentration was significantly increased, resulting in a significant decrease of T/C ratio. In contrast, the GLU group showed a significant increase of T/C ratio, while the mood scores of the Hooper's index questionnaire were higher in the PLA group. CONCLUSIONS: Three-week supplementation of L-glutamine after intensive training enhanced the mucosal immunity, improved hormonal status and reduced the rate of URTI of combat-sport athletes while feelings of well-being were also enhanced. Therefore, L-glutamine would be beneficial for the sports performance and recovery of athletes.

Concurrent Ingestion of Alkaline Water and L-Glutamine Enhanced Salivary α-Amylase Activity and Testosterone Concentration in Boxing Athletes.

Athletes often take sport supplements to reduce fatigue and immune disturbances during or after training. This study evaluated the acute effects of concurrent ingestion of alkaline water and L-glutamine on the salivary immunity and hormone responses of boxers after training. Twelve male boxing athletes were recruited in this study. During regular training, the participants were randomly divided into three groups and asked to consume 400 mL of alkaline water (Group A), 0.15 g/kg body weight of L-glutamine with 400 mL of water (Group G), and 0.15 g/kg of L-glutamine with 400 mL of alkaline water (Group A+G) at the same time each day for three consecutive weeks. Before and immediately after the training, saliva, heart rates, and the rate of perceived exertion were investigated. The activity of α-amylase and concentrations of lactoferrin, immunoglobulin A (IgA), testosterone, and cortisol in saliva were measured. The results showed that the ratio of α-amylase activity/total protein (TP) significantly increased after training in Group A+G but not in Group A or G, whereas the ratios of lactoferrin/TP and IgA/TP were unaffected in all three groups. The concentrations of salivary testosterone after training increased significantly in Group A+G but not in Group A or G, whereas the salivary cortisol concentrations were unaltered in all groups. In conclusion, concurrent ingestion of 400 mL of alkaline water and 0.15 g/kg of L-glutamine before training enhanced the salivary α-amylase activity and testosterone concentration of boxers, which would be beneficial for post-exercise recovery.

The Cognitive Function and Taekwondo-Specific Kick Performance of Taekwondo Athletes at Different Hydration Statuses.

PURPOSE: Successful participation in taekwondo (TKD) requires athletes to possess quick decision-making abilities and demonstrate technical proficiency during competition. Dehydration, occurring during both training and competition, is widely recognized to have various negative effects. METHODS: This study investigated the impact of different levels of dehydration on cognitive function, as measured by the Vienna Test System, and the specific performance of kicking techniques among TKD athletes. Using a randomized crossover design, 12 participants were involved in the study. Before and after 1 hour of training at 80% of maximal heart rate, participants were weighed and provided urine samples. All participants were randomly assigned to 3 different hydration conditions: the euhydrated (EUH) group had unrestricted access to fluid consumption, while the hypohydrated (HYP) and severely HYP (S-HYP) groups experienced reductions of 2.0% and 4.0% of their initial body weight, respectively. RESULTS: The EUH group exhibited better reaction speed in reaction-time test-form S1 than the HYP and S-HYP groups. Notably, the EUH group demonstrated a significantly higher success rate in the front-side kick (EUH 98%, HYP 90%, S-HYP 88%; P < .05). However, the success rates of back roundhouse kick and free head kick were similar among the 3 statuses. Furthermore, postexercise heart rates were found to be significantly higher in the HYP and S-HYP groups compared with the EUH group. CONCLUSIONS: This study provides insight into the negative effects of dehydration on cognitive function and TKD-specific performance. It is recommended that TKD athletes maintain optimal hydration levels during training and competition to ensure optimal performance.

The COVID-19 vaccine did not affect the basal immune response and menstruation in female athletes.

The COVID-19 pandemic restricted the regular training and competition program of athletes. Vaccines against COVID-19 are known to be beneficial for the disease; however, the unknown side effects of vaccines and postvaccination reactions have made some athletes hesitant to get vaccinated. We investigated the changes in inflammatory responses and menstrual cycles of female athletes before and after vaccination. Twenty female athletes were enrolled in this study. Blood was collected from each subject before the first COVID-19 vaccination and after the first and second vaccinations. Laboratory data, including white blood cell, neutrophil, lymphocyte, and platelet counts, and inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), PLR (platelet lymphocyte ratio), RPR (red cell distribution width to platelet ratio), SII (systemic immune-inflammation index), and NeuPla (neutrophil-platelet ratio), were analyzed statistically. The menstrual changes before and after vaccination and the side effects were collected by questionnaires. No significant changes in the laboratory data were found after the first and second shots when compared to those at prevaccination: white blood cell, neutrophil, lymphocyte, platelet, NLR, PLR, SII, RPR, and NeuPla (p > 0.05). In addition, there were no significant changes in the menstruation cycle or days of the menstrual period (p > 0.05). All side effects after vaccination were mild and subsided in 2 days. The blood cell counts, inflammatory markers, and menstruation of female athletes were not affected by COVID-19 vaccines.

Resting salivary levels of IgA and cortisol are significantly affected during intensive resistance training periods in elite male weightlifters.

The aim of this study was to investigate the cumulative effects of intensive resistance training on salivary immunoglobulin A (SIgA) and cortisol responses in elite male weightlifters. Eleven elite male Taiwanese weightlifters were trained through 3 training stages before a national weightlifting competition, and this was followed by a 2-week recovery stage. Resting saliva samples were collected once in each of the 4 stages. Salivary concentrations of total protein (TP), SIgA, lactoferrin, and cortisol were measured. The results showed that (a) salivary TP concentrations were not significantly affected; (b) resting levels of SIgA, the ratio of SIgA to TP (SIgA/TP), cortisol, and the ratio of cortisol to TP (cortisol/TP) were significantly higher in the training stages than in the recovery stage; (c) a positive correlation was revealed between the ratios of SIgA/TP and cortisol/TP; and (d) the resting salivary lactoferrin concentrations and the ratio of lactoferrin to TP (lactoferrin/TP) were significantly lower in stage 1 than in the recovery stage. The findings in this study suggest that prolonged, intensive resistance training exerts cumulative effects on SIgA and cortisol responses in elite weightlifters.

Horticulture therapy affected the mental status, sleep quality, and salivary markers of mucosal immunity in an elderly population.

Horticultural therapy (HT) has been reported to be beneficial to mental and physical health. This study investigated the effects of HT on the psychological status and mucosal immunity of elderly individuals. Twenty-four participants aged 70-93 were recruited from residential facilities and adult day-care services. Six different HT activities were designed and guided by licensed instructors who performed saliva collection and helped the participants complete the questionnaires before and after each activity. The sleep quality scores were collected during the 6 weeks of HT activities. Saliva was collected and analyzed to determine the concentrations of immunoglobulin A (IgA), lactoferrin, chromogranin A (CgA), α-amylase (AA) and total protein (TP). Comparisons of the questionnaire scores between preactivity and postactivity showed that feelings of satisfaction and happiness were significantly enhanced after each activity. In addition, sleep quality was significantly improved after the 6-week course of HT activities. Regarding mucosal immunity, the preactivity IgA and IgA/TP were significantly increased at week 3 and week 6; in addition, the ratio of lactoferrin/TP was significantly decreased at week 6 compared to week 1. The postactivity AA and CgA levels were significantly enhanced at weeks 2, 3 and 5 compared to the corresponding preactivity levels. In conclusions, HT activities significantly improved the happiness, satisfaction, well-being and sleep quality of the elderly. Moreover, mucosal immunity proteins, including IgA, lactoferrin, CgA and AA, were significantly increased.

Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players.

There is interest in whether nicotine could enhance attention in sporting performance, but evidence on the acute effect of nicotine on physical response and sports performance in baseball players remains scant. This was an observational study to examine whether nicotine gum chewed before exercise could provide acute effects on physiological responses and sport performance. Accordingly, heart rate variability (HRV), saliva cotinine concentration and α-amylase activity, cognitive function, muscle strength, and baseball-hitting performance were measured. Thirteen healthy male non-smoker baseball players were recruited. Conducting two sequences with 7-day intervals, they chewed nicotine gum (nicotine group) or flavor-matched placebo gum (placebo group) for 30 min. HRV and saliva analyses were conducted before gum consumption (S1), after gum consumption (S2), and after test completion (S3). Cognitive, muscle strength, and baseball-hitting performance tests were performed after nicotine or placebo gum chewing. The outcomes of all assessed variables were compared within and between the groups. Significant changes in HRV, α-amylase, testosterone, and cortisol were observed in the nicotine group at S2 and S3 (p < 0.05). Compared with the placebo group, the nicotine group exhibited enhanced motor reaction times, grooved pegboard test (GPT) results on cognitive function, and baseball-hitting performance, and small effect sizes were noted (d = 0.47, 0.46 and 0.41, respectively). Nicotine could induce changes in endocrine and sympathetic nerve activity and enhance cognitive function and baseball-hitting performance. However, no increase in muscle strength was observed after nicotine intake.

Low Vitamin D Status Relates to the Poor Response of Peripheral Pulse Wave Velocity Following Acute Maximal Exercise in Healthy Young Men.

The primary objective of this study was to determine the effects of vitamin D levels on peripheral pulse wave velocity (pPWV) following acute maximal exercise in healthy young adults. Fifty male healthy adults from National Chung Cheng University participated in the study. Participants were divided into the 25-hydroxyvitamin D (25(OH)D) sufficiency group (n = 28, 25(OH)D ≥ 50 nmol/L) and deficiency group (n = 22, 25(OH)D < 50 nmol/L). The acute maximal exercise was performed using an incremental cycling test to exhaustion. Additionally, the pPWV and blood pressure were obtained at rest and 0, 15, 30, 45, 60 min after acute maximal exercise. The results show that 25(OH)D deficiency group had higher pPWV at post-exercise (5.34 ± 0.71 vs. 4.79 ± 0.81 m/s, p < 0.05), post-exercise 15 min (5.13 ± 0.53 vs. 4.48 ± 0.66 m/s, p < 0.05) and post-exercise 30 min (5.26 ± 0.84 vs. 4.78 ± 0.50 m/s, p < 0.05) than the sufficiency group. Furthermore, there was a significant inverse correlation between 25(OH)D levels and pPWV following acute maximal exercise. Our study demonstrated that low vitamin D status relates to the poor response of pPWV following maximal exercise in healthy young men. Vitamin D deficiency may increase the risk of incident cardiovascular events after acute exhaustive exercise, even in healthy and active adults.

Honokiol inhibits LPS-induced maturation and inflammatory response of human monocyte-derived dendritic cells.

Honokiol (HNK) is a phenolic compound isolated from the bark of houpu (Magnolia officinalis), a plant widely used in traditional Chinese and Japanese medicine. While substantial evidence indicates that HNK possesses anti-inflammatory activity, its effect on dendritic cells (DCs) during the inflammatory reaction remains unclear. The present study investigates how HNK affects lipopolysaccharide (LPS)-stimulated human monocyte-derived DCs. Our experimental results show that HNK inhibits the inflammatory response of LPS-induced DCs by (1) suppressing the expression of CD11c, CD40, CD80, CD83, CD86, and MHC-II on LPS-activated DCs, (2) reducing the production of TNF-α, IL-1ß, IL-6, and IL-12p70 but increasing the production of IL-10 and TGF-ß1 by LPS-activated DCs, (3) inhibiting the LPS-induced DC-elicited allogeneic T-cell proliferation, and (4) shifting the LPS-induced DC-driven Th1 response toward a Th2 response. Further, our results show that HNK inhibits the phosphorylation levels of ERK1/2, p38, JNK1/2, IKKα, and IκBα in LPS-activated DCs. Collectively, the findings show that the anti-inflammatory actions of HNK on LPS-induced DCs are associated with the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways.

Immunomodulatory effects of lactobacillus and Bifidobacterium on both murine and human mitogen-activated T cells.

BACKGROUND: Beneficial effects of probiotics have been reported for patients with allergic diseases and intestinal disorders. There is increasing interest in studying the role of different strains or combined probiotic administration on immunoregulation. In this study, we investigated whether probiotics modulate the immune response through regulating T cell proliferation and differentiation. METHODS: We examined the effect of probiotic I (a combination of Lactobacillus acidophilus and Bifidobacterium bifidus) and probiotic II (a combination of L. acidophilus and B. infantis) on cell survival and proliferation, the progression of the cell cycle, and the production of Th1/Th2 cytokines by mitogen-stimulated murine spleen cells and human peripheral blood mononuclear cells (PBMCs). RESULTS: Our experimental results showed that high concentrations (≥ 1 × 10(6) CFU/ml) of probiotic I or II inhibited mitogen-induced cell proliferation and arrested the cell cycle at the G0/G1 stage in both mitogen-stimulated spleen cells and PBMCs. In the results of low concentrations (<1 × 10(6) CFU/ml), probiotic I or II enhanced the production of IFN-γ but inhibited the production of IL-4. Our results indicated that high concentrations of probiotic I or II treatment could attenuate mitogen-induced overactive immune responses. On the other hand, low concentrations of probiotic I or II treatment could promote a shift in the Th1/Th2 balance toward Th1-skewed immunity. CONCLUSION: Dose selection is an important issue for probiotic studies. Our results indicated that probiotics have beneficial effects on regulating T cell-mediated immune responses by attenuating mitogen-induced overactive immune responses and promoting Th1 immune responses.

Different influences on tacrolimus pharmacokinetics by coadministrations of zhi ke and zhi shi in rats.

Tacrolimus, an immunosuppressant with narrow therapeutic window, has been used widely in transplant patients. Grapefruit juice and pomelo have been reported to increase the blood levels of tacrolimus. Zhi Ke and Zhi Shi, the ripe peels and unripe fruits of Citrus aurantium which is chemotaxonomically related to grapefruit and pomelo, are in wide use in clinical Chinese medicine. To investigate the possible interaction of these two Citrus herbs with tacrolimus, male Sprague-Dawley rats were orally given tacrolimus (1.5 mg/kg) with and without Zhi Ke and Zhi Shi decoctions in a cross-over design. Blood samples were withdrawn via cardiopuncture at specific time and quantitated by a microparticle enzyme immunoassay. In addition, to explore the mechanism of interaction, LS 180 cell line was used for the transport study of rhodamine 123, a typical substrate of P-glycoprotein (P-gp). The results showed that Zhi Shi significantly decreased the C(max) and AUC(0-t) of tacrolimus by 72.4% and 72.0%, respectively, whereas Zhi Ke did not affect tacrolimus pharmacokinetics. LS 180 cell line study indicated that Zhi Shi increased the efflux activity of P-gp, enabling us to explain the decreased oral bioavailability of tacrolimus caused by Zhi Shi. Hence, we suggest that Zhi Shi be contraindicated for transplant patients treated with tacrolimus to reduce the risk of allograft rejection.

Nicotine supplementation enhances simulated game performance of archery athletes.

BACKGROUND: Nicotine is beneficial to mood, arousal and cognition in humans. Due to the importance of cognitive functioning for archery athletes, we investigated the effects of nicotine supplementation on the cognitive abilities, heart rate variability (HRV), and sport performance of professional archers. METHODS: Eleven college archers were recruited and given 2 mg of nicotine supplementation (NIC group) and placebo (PLA group) in a crossover design. RESULTS: The results showed that at 30 min after the intake of nicotine gum, the "correct rejection" time in the NIC group was significantly lower than that of the PLA group (7.29 ± 0.87 vs. 8.23 ± 0.98 msec, p < 0.05). In addition, the NIC group completed the grooved pegboard test in a shorter time than the PLA group (48.76 ± 3.18 vs. 53.41 ± 4.05 s, p < 0.05), whereas motor reaction times were not different between the two groups. Saliva α-amylase activity was significantly lower after nicotine supplementation (p < 0.01) but increased immediately after the archery test in the NIC group (p < 0.05). In addition, nicotine supplementation significantly decreased HRV and increased the archery score (290.58 ± 10.09 vs. 298.05 ± 8.56, p < 0.01). CONCLUSIONS: Nicotine enhances the performance of archery athletes by increasing cognitive function and stimulating the sympathetic adrenergic system.

Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in Macrophages.

Zerumbone is a natural product isolated from the pinecone or shampoo ginger, Zingiber zerumbet (L.) Smith, which has a wide range of pharmacological activities, including anti-inflammatory effects. However, the effects of zerumbone on activation of the NLRP3 inflammasome in macrophages have not been examined. This study aimed to examine the effects of zerumbone on LPS-induced inflammatory responses and NLRP3 inflammasome activation using murine J774A.1 cells, murine peritoneal macrophages, and murine bone marrow-derived macrophages. Cells were treated with zerumbone following LPS or LPS/ATP treatment. Production of nitric oxide (NO) was measured by Griess reagent assay. The levels of IL-6, TNF-α, and IL-1ß secretion were analyzed by ELISA. Western blotting analysis was performed to determine the expression of inducible NO synthase (iNOS), COX-2, MAPKs, and NLRP3 inflammasome-associated proteins. The activity of NF-κB was determined by a promoter reporter assay. The assembly of NLRP3 was examined by immunofluorescence staining and observed by confocal laser microscopy. Our experimental results indicated that zerumbone inhibited the production of NO, PGE2 and IL-6, suppressed the expression of iNOS and COX-2, repressed the phosphorylation of ERK, and decreased the activity of NF-κB in LPS-activated J774A.1 cells. In addition, zerumbone suppressed the production of IL-1ß and inhibited the activity of NLRP3 inflammasome in LPS/ATP- and LPS/nigericin-activated J774A.1 cells. On the other hand, we also found that zerumbone repressed the production of NO and proinflammatory cytokines in LPS-activated murine peritoneal macrophages and bone marrow-derived macrophages. In conclusion, our experimental results demonstrate that zerumbone effectively attenuates the LPS-induced inflammatory response in macrophages both in vitro and ex vivo by suppressing the activation of the ERK-MAPK and NF-κB signaling pathways as well as blocking the activation of the NLRP3 inflammasome. These results imply that zerumbone may be beneficial for treating sepsis and inflammasome-related diseases.

Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation.

Piplartine (or Piperlongumine) is a natural alkaloid isolated from Piper longum L., which has been proposed to exhibit various biological properties such as anti-inflammatory effects; however, the effect of piplartine on sepsis has not been examined. This study was performed to examine the anti-inflammatory activities of piplartine in vitro, ex vivo and in vivo using murine J774A.1 macrophage cell line, peritoneal macrophages, bone marrow-derived macrophages and an animal sepsis model. The results demonstrated that piplartine suppresses iNOS and COX-2 expression, reduces PGE2, TNF-α and IL-6 production, decreases the phosphorylation of MAPKs and NF-κB and attenuates NF-κB activity by LPS-activated macrophages. Piplartine also inhibits IL-1ß production and suppresses NLRP3 inflammasome activation by LPS/ATP- and LPS/nigericin-activated macrophages. Moreover, piplartine reduces the production of nitric oxide (NO) and TNF-α, IL-6 and IL-1ß, decreases LPS-induced tissue damage, attenuates infiltration of inflammatory cells and enhances the survival rate. Collectively, these results demonstrate piplartine exhibits anti-inflammatory activities in LPS-induced inflammation and sepsis and suggest that piplartine might have benefits for sepsis treatment.

Identification of 3',4',5'-trimethoxychalcone analogues as potent inhibitors of Helicobacter pylori-induced inflammation in human gastric epithelial cells.

Efforts to identify potent small molecule inhibitors of Helicobacter pylori led to the evaluation of 23 3',4',5'-trimethoxychalcone analogues. Some of the compounds displayed potent antibacterial activity against H. pylori. Three most active and selective compounds 1, 7, and 13 also showed the bactericide activity against the reference as well as multidrug-resistant strains of H. pylori. Additionally, the aforementioned three compounds potentially inhibited the H. pylori adhesion and invasion to human gastric epithelial (AGS) cells. Furthermore, these selective compounds inhibited the H. pylori-induced gastric inflammation by reduced inflammatory mediator's nuclear factor kappa B activation, and the secretion of interleukin-8.

Oral administration of Lactobacillus salivarius inhibits the allergic airway response in mice.

Asthma is recognized throughout the world as a chronic airway inflammatory disease. In this study, we investigated the effect of probiotics in response to antigen challenge in an ovalbumin (OVA)-sensitized asthma model in BALB/c mice. Lactobacillus salivarius PM-A0006 was orally administered to mice before antigen challenge. After antigen challenge, serum OVA-specific antibody levels, airway responsiveness to methacholine, influx of inflammatory cells to the lung, and cytokine levels in bronchoalveolar lavage (BAL) fluid and splenocytes were assessed. Oral treatment with live L. salivarius PM-A0006 significantly attenuated the influx of eosinophils to the airway lumen and reduced the levels of serum OVA-specific IgE and eotaxin in BAL fluid of antigen-challenged animals. Furthermore, L. salivarius PM-A0006 also decreased allergen-induced airway hyperresponsiveness and elevated the levels of IFN-gamma. These results showed that oral treatment with L. salivarius PM-A0006 could have therapeutic potential in the treatment of allergic airway disease.