Levels Of Nuclear Factor Kappa Research Articles

Effect of Dendrobium officinale superfine powder on stomach Yin deficiency model mice induced by "spicy overeating"

Dendrobium officinale is a traditional Chinese medicine for nourishing Yin and benefiting stomach. Its superfine powder has many advantages, such as good dissolution, high utilization rate, strong integrity and easy to use. However, the researches on effect of D. officinale superfine powder on stomach Yin deficiency model are still not sufficient. In this experiment, we explored the effect of D. officinale superfine powder in mice model with stomach Yin deficiency caused by "spicy overeating", and provided certain reference value for its application in gastrointestinal diseases. Male ICR mice were randomly divided into normal group, model group, Yiweitang group, omeprazole group, and D. officinale superfine powder high, medium and low dose groups. The mixture of wine and pepper liquid was given by gavage administration for 30 d, and the corresponding drug was given for 60 d while the model was conti-nued. The body weight, food intake, water intake, fecal moisture content and particle number, foot temperature of mice were measured. The levels of serum gastrin(Gas), motilin(MTL) and somatostatin(SS) were measured by ELISA. Gastric histomorpho-logy was observed by HE staining. The expression levels of nuclear factor kappa B(NF-κB) and cyclooxygenase-2(COX-2) were determined by immunohistochemistry. The expression levels of B-cell lymphoma-2(Bcl-2) and Bcl-2 associated X protein(Bax) in gastric tissues were detected by Western blot. The results showed that D. officinale superfine powder could increase the food intake, water intake, fecal moisture content and particle number, reduce the foot temperature, improve the pathological changes of gastric mucosa, reduce the expression of NF-κB, COX-2 protein in gastric tissues, and increase the ratio of Bax/Bcl-2. D. officinale superfine powder can "nourish Yin and benefit the stomach", improve the syndrome of stomach Yin deficiency, such as "hunger but not want to eat, dry mouth but not want to drink, hand and feet hot, constipation", and reduce the damage of gastric mucosa. The mechanism may be related to regulating the secretion of gastrointestinal hormones, inhibiting the inflammation of gastric tissues and promoting the apoptosis of abnormal cells in gastric tissues.

Anti-inflammatory effect of phenylpropanoids from Dendropanax dentiger in TNF-α-induced MH7A cells via inhibition of NF-κB, Akt and JNK signaling pathways

The root of Dendropanax dentiger (Harms) Merr. has been used for centuries as an empirical treatment for rheumatoid arthritis (RA) in China without scientific validation. In our recent study, nineteen phenylpropanoids (1–19) with cyclooxygenase-2 inhibitory activities from the ethanol extract of D. dentiger roots, indicated to have a potential anti-RA effect. This study, evaluated the anti-RA effect of 19 phenylpropanoids on tumor necrosis factor (TNF)-α induced inflammation in MH7A cells and clarified their underlying mechanisms. As a result, 16 compounds remarkably suppressed nitric oxide (NO) production at a concentration of 40 μM in TNF-α-induced MH7A cells. Among them, pinoresinol (12) and dendrocoumarin A (1) were the most effective substances, which showed significant inhibitory effect on NO production, with IC50 values of 6.25 ± 0.42 and 7.87 ± 0.67 μM, respectively. Furthermore, pinoresinol and dendrocoumarin A remarkably decreased the levels of interleukin (IL)-2, 6, 8, and interferon-gamma (IFN-γ), as well as prominently reduced the phosphorylation protein levels of nuclear factor kappa B (NF-κB) p65, I-kappa-B-alpha (IkBα), protein kinase B (Akt), and c-Jun N-terminal kinase (JNK) by Western blot analysis. Taken together, our findings suggest that pinoresinol and dendrocoumarin A may offer new and safe anti-RA candidates by inhibiting NF-kB, Akt and JNK signaling pathways.

CQMUH-011 Inhibits LPS-Induced Microglia Activation and Ameliorates Brain Ischemic Injury in Mice

Excessive microglial activation-mediated neuroinflammation is closely involved in the pathogenesis of several neurological diseases. CQMUH-011, as a novel adamantane sulfonamide compound, has been shown anti-inflammatory properties in activated macrophages (RAW264.7). However, the role of CQMUH-011 in microglial activation-induced neuroinflammation and neuroprotective properties has yet to be elucidated. In the present study, we investigated the potential effects and mechanisms of CQMUH-011 on lipopolysaccharide (LPS)-stimulated primary microglia in vitro and transient middle cerebral artery occlusion (t-MCAO)–induced acute cerebral ischemia/reperfusion (I/R) injury in vivo. The results demonstrated that CQMUH-011 significantly suppressed the production of tumor necrosis factor (TNF)-α and interleukin (IL)-1β by LPS-stimulated primary microglia. In addition, CQMUH-011 inhibited the proliferation of activated microglia by arresting the cell cycle at the G1/S phase accompanied by downregulating the expression of cell cycle regulatory proteins such as proliferating cell nuclear antigen (PCNA) and cyclin D1. CQMUH-011 was seen to induce apoptosis in activated microglia by regulating the expression of Bax and Bcl-2. Furthermore, CQMUH-011 markedly attenuated the protein expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) as well as the phosphorylation levels of nuclear factor-kappa (NF-κB) subunit p65, inhibitory kappa B-alpha (IκBα), and mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK) and p38 kinases. In vivo, CQMUH-011 administration significantly improved neurological function and infarct volume, and ameliorated the inflammatory cytokines and microglia amount around the injury site of mice. In conclusion, these results suggested that CQMUH-011 has a notable anti-inflammatory effect and protects mice from I/R injure. Thus, CQMUH-011 may be a candidate drug for the treatment of cerebral ischemia patients.

Myricitrin attenuates hypoxic-ischemia-induced brain injury in neonatal rats by mitigating oxidative stress and nuclear factor erythroid 2-related factor 2/hemeoxygenase-1/antioxidant response element signaling pathway

Background: Neonatal hypoxic ischemia (HI) is an overwhelming infantile neurological disability causing extreme morbidity and mortality with limited therapies available. Objectives: In this study, we aimed to explore the neuroprotective efficacy of myricitrin and elucidate the mechanism of action of myricitrin through the regulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1)/antioxidant response element (ARE)-signaling pathways in neonatal rats. Materials and Methods: Seven-day-old neonatal rats were divided into four groups. Sham group served as the control group. After inducing HI through standard operation procedure, two groups of neonatal rats were intraperitoneally administered with 20 and 40 mg/kg bw of myricitrin twice a day for up to 1 week. At the end of the experiment, we assessed the brain infract area, edema, and motor coordination activity by using Rota Rod test. Furthermore, we measured the level of antioxidant enzymes and oxidative stress markers in the brain tissue samples. Real-time quantitative polymerase chain reaction was conducted to detect the inflammatory molecules expression including HO-1 being the activator of Nrf2 where further mediates the transcriptional activation of ARE. Subsequently, the hypothesis was further confirmed by the immunosorbent assay and Western blot analysis. Results: Myricitrin administration ameliorated HI-induced increase in infract volume and edema of the brain, as well as improved neurobehavioral impairments. Interestingly, myricitrin significantly reduced the level of nuclear factor kappa B (NF-κB) p65 and reduced the levels of nuclear fraction of Nrf2-ARE and cytosolic fraction of HO-1 enzyme activation. Conclusion: In summary, myricitrin improved the antioxidant defense mechanism and ameliorated the oxidative stress-associated neurological damage via modulating Nrf2/ARE-dependent HO-1 pathway in neonatal rats.

Potential effect of astragaloside IV on the lipopolysaccharide induced inflammation via the inactivation of NF-κB signaling pathway

Background: The host treats lipopolysaccharides (LPS) as a sign of microbial invasion by pathogenic Gram-negative bacteria. In lungs, LPS activates a cascade of inflammatory reactions leading to inflammation. Previous investigation suggests that astragaloside IV (AG) has an anti-inflammatory and antioxidant effect, but the potential mechanism of lung inflammation is still unknown. In this experimental study, we aimed to investigate the anti-inflammatory potential of AG against LPS-induced lung inflammation. Materials and Methods: In this study, we used Sprague Dawley rats for the experimental protocol. Animals were injected with LPS (10 mg/kg, b. w.) for the induction of lung inflammation and were subsequently administered with AG (1.25, 2.5, and 5 mg/kg). At the end of the experiment, acute phase response and lipid parameters were estimated. Pro-inflammatory cytokines and inflammatory mediators were also estimated. Furthermore, quantitative real-time polymerase chain reaction was used to estimate the inflammatory markers and expression of mRNA of apoptosis markers. Results: AG treatment significantly increased the survival rate as compared to LPS control. AG significantly (P < 0.001) altered the renal, hepatic, lipid, and antioxidant parameter at dose dependent manner. AG significantly (P < 0.001) decreased the level of malondialdehyde and reduced glutathione and increased he activity of superoxide dismutase. AG significantly (P < 0.001) decreased the level of nuclear factor kappa B (NF-κB). In addition, AG significantly (P < 0.001) down-regulated the expression of inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-1 β, tumor necrosis factor-α, IL-18 and upregulated the expression of IL-4 and IL-10. Conclusion: In summary, these findings indicate that AG effectively suppressed the LPS-induced inflammation through inactivation of NF-κB signaling pathway.

The Effect of Azalea on Oxidative Stress, Immune Factors and Vasodilator Factor in Hypertensive Rats

To analyze the effects of azalea on oxidative stress, immune factors and vasodilator factors in hypertensive rats. 24 male Specific-pathogen-free grade spontaneous hypertension rats were divided into model group (normal saline), azalea group (50 mg/kg/d azalea), verapamil group (50 mg/kg/d verapamil) and 8 normal control group (normal saline) and observed the changes of tail artery systolic pressure of rats for 2-18 w after administration, superoxide dismutase, malondialdehyde were detected after 18 w The levels of nuclear factor kappa B, Smooth muscle alpha-actin and Smooth muscle alpha actin were detected by reverse transcription–polymerase chain reaction and Western blot. The systolic pressure of the caudal artery in azalea group and verapamil group was significantly lower than that in the model group (p<0.05). The levels of Malondialdehyde and reactive oxygen species in azalea group and verapamil group were significantly lower than that in the model group and Superoxide dismutase level was significantly higher than that in the model group (p<0.05). The levels of interleukin-6 and tumor necrosis factor-alpha in azalea group and verapamil group were significantly lower than those in the model group (p<0.05). The levels of Angiotensin α and endothelin-1 in azalea group and verapamil group were significantly lower than that in the model group and no and nitric oxide synthase levels were significantly higher than those in the model group (p<0.05). The expression of nuclear factor kappa light chain enhancer of activated B cells messenger Ribonucleic acid and protein in azalea group and verapamil group was significantly lower than that in model group and Smooth muscle alpha-actin messenger Ribonucleic acid and protein were significantly higher than that in model group (p<0.05). Azalea can significantly reduce the systolic pressure of hypertensive rats and protect the aortic injury. It may be related to the reduction of oxidative stress, regulation of immune factors and diastolic vasodilator factors, and regulation of nuclear factor kappa light chain enhancer of activated B cells, Smooth muscle alpha-actin expressions.

Dietary glucosinolates inhibit splenic inflammation in high fat/cholesterol diet-fed C57BL/6 mice.

BACKGROUND/OBJECTIVESObesity is associated with chronic inflammation. The spleen is the largest organ of the lymphatic system and has an important role in immunity. Obesity-induced inflammatory responses are triggered by Toll-like receptor (TLR)-myeloid differentiation primary response 88 (MyD88) pathway signaling. Phenethyl isothiocyanate (PEITC) and 3,3′-diindolylmethane (DIM), major dietary glucosinolates present in cruciferous vegetables, have been reported to produce anti-inflammatory effects on various diseases. However, the effects of PEITC and DIM on the obesity-induced inflammatory response in the spleen are unclear. The purpose of this study was to examine the anti-inflammatory effects of PEITC and DIM on the spleen and their mechanism in high fat/cholesterol diet (HFCD)-fed C57BL/6 mice.MATERIALS/METHODSWe established an animal model of HFCD-induced obesity using C57BL/6 mice. The mice were divided into six groups: normal diet with AIN-93G diet (CON), high fat diet (60% calories from fat) with 1% cholesterol (HFCD), HFCD with PEITC 30 mg/kg/day or 75 mg/kg/day (HFCD+P30, HFCD+P75), and HFCD with DIM 1.5 mg/kg/day or 7.5 mg/kg/day (HFCD+D1.5, HFCD+D7.5). Enzyme-linked immunosorbent assay was used to evaluate pro-inflammatory cytokine secretion. Western blot and quantitative polymerase chain reaction were used to analyze protein and mRNA levels of nuclear factor kappa B (NF-κB) p65, interleukin 6 (IL-6), cyclooxygenase 2 (COX-2), TLR2, TLR4, and MyD88 in spleen tissue.RESULTSSerum IL-6 levels were significantly higher in the HFCD group than in groups fed a HFCD with PEITC or DIM. Levels of NF-κB p65 protein and TLR2/4, MyD88, NF-κB p65, IL-6, and COX-2 mRNA were significantly higher in the HFCD group than in the CON group and were reduced by the PEITC and DIM supplements.CONCLUSIONSPEITC- and DIM-supplemented diets improved splenic inflammation by modulating the TLR2/4-MyD88 pathway in HFCD-fed mice. We suggest that dietary glucosinolates may at least partially improve obesity-induced inflammation of the spleen.

Neuroprotective effect of chrysin on isoniazid-induced neurotoxicity via suppression of oxidative stress, inflammation and apoptosis in rats

Isoniazid (INH) is among the most important anti-tuberculosis agents widely prescribed. However, its clinical use is restricted due to its severe side effects associated with neurotoxicity. The aim of the present study was to investigate the neuroprotective effects of chrysin (CR), a natural antioxidant, against INH-induced neurotoxicity in rats. The rats were treated orally with INH (400 mg/kg body weight) alone or with CR (25 and 50 mg/kg body weight) for 7 consecutive days. INH administration significantly increased brain lipid peroxidation and resulted in a significant decrease in antioxidant biomarkers including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH). INH treatment also increased levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), glial fibrillary acidic protein (GFAP) and activities of p38α mitogen-activated protein kinase (p38α MAPK) while decreasing levels of neural cell adhesion molecule (NCAM). Double immunofluorescence expressions of c-Jun N-terminal kinase (JNK) and Bcl-2 associated X protein (Bax) in brain tissues were increased after INH administration. Furthermore, INH increased mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (Gclm), glutamate cysteine ligase catalytic subunit (Gclc), NF-κB, TNF-α, interleukin-1β (IL-1β), interleukin-6 (IL-6) and GFAP in rat brain tissues. Co-treatment with CR increased anti-oxidant capacity as well as regulated inflammation and apoptosis in brain. Additionally, molecular docking results showed that CR had the potential to interact with the active sites of TNF-α and NFκ-B. In conclusion, CR improved INH-induced brain oxidative damage, inflammation and apoptosis, possibly through their antioxidant properties.

Silymarin alleviates docetaxel-induced central and peripheral neurotoxicity by reducing oxidative stress, inflammation and apoptosis in rats.

Docetaxel (DTX) is a chemotherapeutic agent used in the treatment of various malignancies but is often associated with central and peripheral neurotoxicity. The aim of this study was to investigate the neuroprotective effect of silymarin (SLM) against DTX-induced central and peripheral neurotoxicities in rats. Rats received 25 and 50mg/kg body weight SLM orally for seven consecutive days after receiving a single injection of 30mg/kg body weight DTX on the first day. SLM significantly decreased brain lipid peroxidation level and ameliorated brain glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in DTX-administered rats. SLM attenuated levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), glial fibrillary acidic protein (GFAP) and activity of p38α mitogen-activated protein kinase (p38α MAPK) whereas caused an increase in levels of neural cell adhesion molecule (NCAM) in the brain and sciatic nerve of DTX-induced rats. In addition, SLM improved the histological structure of the brain and sciatic nerve tissues and decreased the expression of c-Jun N-terminal kinase (JNK) in the sciatic nerve whereas increased cyclic AMP response element binding protein (CREB) expression in the brain induced by DTX. Additionally, SLM markedly up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and B-cell lymphoma-2 (Bcl-2) and downregulated the expression of Bcl-2 associatedXprotein (Bax) in the brain and sciatic nerve tissues of DTX-induced rats. Our results show that SLM can protect DTX-induced brain and sciatic nerve injuries by enhancing the antioxidant defense system and suppressing apoptosis and inflammation.

Anti-inflammatory effect of traditional Chinese medicine preparation Penyanling on pelvic inflammatory disease

Ethnopharmacological relevancePenyanling is made up of Smilacis Glabrae Rhizoma (SG, from Smilar glabra Roxb.), Angelicae Sinensis Radix (AS, from Angelica sinensis (Oliv.) Diels), Salviae Miltiorrhizae Radix et Rhizoma (SM, from Salvia miltiorrhiza Bunge), Sargentodoxae Caulis (SC, from Sargentodoxa cuneata (Oliv.) Rehd.et Wils.), Linderae Radix (LR, from Lindera aggregata (Sims) Kosterm.), Paeoniae Radix Rubra (PR, from Paeonia lactiflora Pall.), Sparganii Rhizoma (SR, from Sparganium stoloniferum (Graebn.) Buch.-Ham.), Corydalis Rhizoma (CoR, from Corydalis yanhusuo W. T. Wang), Cyperi Rhizoma (CyR, from Cyperus rotundus Linn.), Glycyrrhizae Radix et Rhizoma (GR, from Glycyrrhiza uralensis Fisch.), and Patrinia Scabiosaefolia (PS, from Patrinia scabiosaefolia Fisch. ex Trev.) recorded in Chinese Pharmacopoeia. It has been used on pelvic inflammatory disease (PID) for more than twenty years.Aim of the study: This study was carried out to illustrate its pharmacological action and clarify its substantial composition. Materials and methodsThe anti-inflammatory effects of Penyanling were studied on a PID rat model and a lipopolysaccharides (LPS)-stimulated THP-1 cell line. Histological changes and levels of inflammatory factors in the uterine tube of the PID rat were examined. Levels of nuclear factor-kappa B (NF-κB) in the nuclear of THP-1 cells and NF-κB, IκB-α, and FPR2 in the cytoplasm were tested by Western blot analysis. Substances within Penyanling were scanned with liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-Q-TOF-MS). The contents of total flavonoids, phenolics, and saponins were quantified. ResultsThe anti-inflammatory effects of Penyanling were observed on PID rats, such as suppressing the infiltrations of lymphocytes and neutrophils in the uterine tube, decreasing the release of interleukin (IL)-1β, IL-6, IL-8, and monocyte chemotactic protein (MCP)-1, and promoting the production of lipoxin A4 (LXA4). On the other hand, Penyanling regulated the activity of NF-κB signal pathway on the LPS-stimulated THP-1 cell line, which suggested the potential mechanism of its anti-inflammatory effect. Besides, it could promote the expression of formyl peptide receptor 2 (FPR2), which suggested its effect on enhancing the resolution of inflammation. Seventy-six substances were identified by their accurate molecular weights, mass fragment patterns, retention times, and standards if available. Most of these substances were flavonoids, phenolics, saponins, and alkaloids. The contents of total flavonoids, phenolics, and saponins within Penyanling were 0.186, 1.371, and 4.321 mg/mL, respectively. ConclusionPenyanling showed an anti-inflammatory effect on PID, and its potential mechanism involved suppressing NF-κB signal pathway and promoting the resolution of inflammation. The main substances within it were flavonoids, phenolics, saponins, and alkaloids.

The protective effect of Morin against ifosfamide-induced acute liver injury in rats associated with the inhibition of DNA damage and apoptosis

Morin is a flavonoid and broadly found in white berry and cranberry branch. Ifosfamide (IFOS) is known as an anticancer and cytotoxic drug especially on the liver. This study aimed to explore the potential protective effects of Morin against IFOS-induced liver toxicity in rats. The model group of rats received a single injection of IFOS (500 mg/kg; i.p.) at day 2, whereas the protective groups of rats were given two different doses of Morin (100 and 200 mg/kg; given by gavage) at days 1 and 2. All animals were then culled 24 h post-IFOS injection. We observed that IFOS caused liver injury, oxidative stress, inflammation, DNA damage, and apoptosis. However, Morin decreased the levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT) (p < 0.05). While Morin contributed to the recovery of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) levels, Morin decreased the levels of malondialdehyde (MDA) induced by IFOS in the liver (p < 0.05). Besides, the levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and P53 measured by ELISA test were reduced via Morin administration (p < 0.05). Lastly, the mRNA transcript levels of Bax, Apaf-1, Bcl-2, Bcl-xL, and inducible nitric oxide synthase (iNOS) determined by RT-PCR were down-regulated in the Morin groups (p < 0.05). These results indicate that Morin plays a protective role by reducing oxidative stress, inflammation, and apoptosis in the IFOS-induced liver injury in rats.

Neuroprotective effect of Umbelliferone against Cerebral ischemia/Reperfusion induced neurological deficits: in-vivo and in-silico studies

Inflammatory pathway is the significant marker of neuro-inflammation and plays a significant role in the expansion of cerebral ischemia/reperfusion injury. Umbelliferone (UF), 7-hydroxy coumarin, has been already proved for its anti-inflammatory and anti-oxidative effects against ischemic brain injury in the rodent model, but its underlying pharmacological mechanism for neuro-protection remain unclear. In this study, we try to explore the neuro-protective effect of umbelliferone against ischemia/Reperfusion induced neurological deficits in rats and explore the underlying mechanism. Inserting thread into the middle cerebral artery was used to induce the ischemic stroke model. The rats were treated with the umbelliferone (5, 10 and 20 mg/kg) for 14 days prior to the ischemic stroke. At the end of the experimental study, brain infarction volume, neurological score, brain edema, pro-inflammatory cytokines, inflammatory mediator were estimated in the region of brain and serum. The mRNA expression of Toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88), Fas and FasL were also estimated at the end of the study. Dose dependently treatment of umbelliferone down-regulated the neurological score, brain infarction, inflammatory mediator (TNF-α, IL-1β, IL-6, COX-2, NF-kB and PGE2) in the serum and brain tissue as compared to I/R induced control group rats. Umbelliferone also reduced the expression of TRL4, MyD88, Fas and FasL as compared to I/R control group rats. Umbelliferone also decreased the level of nuclear factor kappa B (NF-kB) compared to MACO control group rats. Collectively, the obtained result showed that the umbelliferone protected the brain against the ischemic injury in the rats through the inhibition of inflammatory pathway. Communicated by Ramaswamy H. Sarma

Anti-atherosclerotic effects of Lactobacillus plantarum ATCC 14917 in ApoE-/- mice through modulation of proinflammatory cytokines and oxidative stress.

Atherosclerosis is a chronic inflammatory disease mediated by monocyte infiltration and cholesterol deposition into the subendothelial area, resulting in foam cell development. Probiotics are live bacteria that are beneficial for health when administered orally in adequate amounts. In this study, 8-week-old atherosclerosis-prone apolipoprotein E-deficient (ApoE-/-) mice were fed with or without Lactobacillus plantarum ATCC 14917 per day for 12 weeks. Serum was collected to analyse the lipid profile, oxidative status and proinflammatory cytokines. The heart was isolated to quantify the atherosclerotic lesion size in the aortic arch. Quantitative real-time polymerase chain reaction was performed to determine the expression levels of tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-1β in the aorta. The proteins extracted from the aorta were used for Western blot analysis to assess the expression levels of nuclear factor kappa B (NF-κB) and inhibitor of NF-κB (IκBα). The composition of gut microbiota was also examined through high-throughput sequencing. Results showed that the daily consumption of L. plantarum ATCC 14917 had no effect on body weight and lipid profile. L. plantarum ATCC 14917 treatment significantly inhibited atherosclerotic lesion formation. In addition, the oxLDL, MDA, TNF-α and IL-1β levels were significantly reduced, whereas the SOD level was induced in the bacteria + high-fat diet group. Furthermore, the administration of L. plantarum ATCC 14917 significantly attenuated IκBα protein degradation and inhibited the translocation of P65 subunits of NF-κB. L. plantarum ATCC 14917 treatment also modulated the composition of gut microbiota in ApoE-/- mice. Our findings showed that L. plantarum ATCC 14917 supplementation decreases the progression of atherosclerotic lesion formation by alleviating the inflammatory process and lowering oxidative stress.

Saroglitazar attenuates renal fibrosis induced by unilateral ureteral obstruction via inhibiting TGF-β/Smad signaling pathway

Obstructive nephropathy is a common clinical case that causes chronic kidney disease and ultimately progresses to end-stage renal disease. The activation of peroxisome proliferator-activated receptor-α (PPAR-α) reduces tubulointerstitial fibrosis and inflammation associated with obstructive nephropathy. AimsThis study was carried out to investigate the potential effect of saroglitazar, dual PPAR-α/γ agonist, in alleviating renal fibrosis induced by unilateralureteral obstruction (UUO). Main methodsTwenty-four male Sprague Dawley rats were haphazardly divided into four groups of six rats each, including sham operated group, vehicle- or saroglitazar-treated UUO and saroglitazar groups. Rats received oral gavage of saroglitazar (3 mg/kg/day) for 13 days. On day 14, all rats were sacrificed; blood and renal tissues were collected. Key findingsSaroglitazar inhibited UUO-induced oxidative stress; it decreased the elevated levels of MDA and nitric oxide and increased levels of GSH and SOD in renal tissue. Moreover, saroglitazar repressed UUO-induced inflammation; it decreased the renal levels of nuclear factor kappa B (NF-κB) and interleukin-6 (IL-6). Furthermore, saroglitazar inhibited the accumulation of extracellular matrix via decreasing collagen, hydroxylproline and matrix metalloproteinase-9 (MMP-9) levels. Saroglitazar also decreased the expression of both the alpha smooth muscle actin (α-SMA) and tumor growth factor-beta (TGF-β). These effects were in parallel with reduction in mothers against decapentaplegic homolog 3 (smad3) expression and plasminogen activator inhibitor-1 (PAI-1) levels. SignificanceCollectively, the protective impact of saroglitazar might be attributed to its antioxidant, anti-inflammatory and anti-fibrotic effects against UUO-induced tubulointerstitial fibrosis through its regulatory effect on TGF-β1/Smad3 signaling pathway.

Baicalin alleviates deoxynivalenol-induced intestinal inflammation and oxidative stress damage by inhibiting NF-κB and increasing mTOR signaling pathways in piglets

This study was conducted to evaluate the intestinal protective effects of baicalin (BAI) in deoxynivalenol (DON)-treated piglets. A total of 320 weaned piglets were randomly allotted to 1 of 4 treatments with 8 replication pens per treatment and 10 piglets per pen. The treatments were basal diet (NC), basal diet + 0.1% baicalin (BAI), basal diet + 4 mg/kg DON (DON), and basal diet + 4 mg/kg DON + 0.1% BAI (DON + BAI). The experiment was conducted for 14 days. BAI supplementation alleviated the impairment of growth performance and the disorder of serum biochemical parameters in DON-challenged piglets. BAI supplementation also alleviated DON-induced negative effects, decreasing protein and gene expression levels of pro-inflammatory cytokines in the serum and intestinal tissue and increasing antioxidant capacity in the serum. BAI increased villus height and villus height/crypt depth but decreased the protein expression levels of nuclear factor kappa B (NF-κB), as determined by immunohistochemical analysis, in the ileum and jejunum. Moreover, we found that BAI inhibited NF-κB and increased mTOR protein and gene expression levels in the serum and intestinal tissues. Collectively, BAI alleviates intestinal inflammatory and oxidative damage by inhibiting NF-κB and increasing mTOR signaling to modulate downstream inflammatory and oxidative responses after DON challenge.

Differential behavior of NF-κB, IκBα and EGFR during the renal carcinogenic process in an experimental model in vivo.

Renal cell carcinoma (RCC) is the most common type of cancer of the adult kidney. It is generally asymptomatic even at advanced stages, so opportune diagnosis is rare, making it almost impossible to study this cancer at its early stages. RCC tumors induced by ferric nitrilotriacetate (FeNTA) in rats histologically correspond to the human clear cell RCC subtype (ccRCC) and the exposure to this carcinogen during either one or two months leads to different early stages of neoplastic development. High levels of nuclear factor kappa B (NF-κB) and epidermal growth factor receptor (EGFR) as well as low levels of NF-κB inhibitor alpha (IκBα) are frequent in human RCC, but their status in FeNTA-induced tumors and their evolution along renal carcinogenesis is unclear. On this basis, in the present study NF-κB, IκBα and EGFR behavior was analyzed at different stages of the experimental renal carcinogenesis model. Similar to patients with RCC, neoplastic tissue showed high levels of p65, one of the predominant subunits of NF-κB in ccRCC and of EGFR (protein and mRNA), as well as a decrease in the levels of NF-κB's main inhibitor, IκBα, resulting in a classic oncogenic combination. Conversely, different responses were observed at early stages of carcinogenesis. After one month of FeNTA-exposure, NF-κB activity and EGFR levels augmented; but unexpectedly, IκBα also did. While after two months, NF-κB activity diminished, but EGFR and IκBα levels remained elevated. In conclusion, FeNTA-induced tumors and RCC human neoplasms are analogues regarding to the classic NF-κB, IκBα and EGFR behavior, and distinctive non-conventional combination of changes is developed at each early stage studied. The results obtained suggest that the dysregulation of the analyzed molecules could be related to different signaling pathways and therefore, to particular effects depending on the phase of the carcinogenic process.

Pre- and Neonatal Exposure to Lead (Pb) Induces Neuroinflammation in the Forebrain Cortex, Hippocampus and Cerebellum of Rat Pups.

Lead (Pb) is a heavy metal with a proven neurotoxic effect. Exposure is particularly dangerous to the developing brain in the pre- and neonatal periods. One postulated mechanism of its neurotoxicity is induction of inflammation. This study analyzed the effect of exposure of rat pups to Pb during periods of brain development on the concentrations of selected cytokines and prostanoids in the forebrain cortex, hippocampus and cerebellum. Methods: Administration of 0.1% lead acetate (PbAc) in drinking water ad libitum, from the first day of gestation to postnatal day 21, resulted in blood Pb in rat pups reaching levels below the threshold considered safe for humans by the Centers for Disease Control and Prevention (10 µg/dL). Enzyme-linked immunosorbent assay (ELISA) method was used to determine the levels of interleukins IL-1β, IL-6, transforming growth factor-β (TGF-β), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). Western blot and quantitative real-time PCR were used to determine the expression levels of cyclooxygenases COX-1 and COX-2. Finally, Western blot was used to determine the level of nuclear factor kappa B (NF-κB). Results: In all studied brain structures (forebrain cortex, hippocampus and cerebellum), the administration of Pb caused a significant increase in all studied cytokines and prostanoids (IL-1β, IL-6, TGF-β, PGE2 and TXB2). The protein and mRNA expression of COX-1 and COX-2 increased in all studied brain structures, as did NF-κB expression. Conclusions: Chronic pre- and neonatal exposure to Pb induces neuroinflammation in the forebrain cortex, hippocampus and cerebellum of rat pups.

Plumbagin inhibits tumor angiogenesis of gastric carcinoma in mice by modulating nuclear factor-kappa B pathway.

BackgroundWe aimed to determine the mechanism of plumbagin on tumor growth of gastric carcinoma.MethodsSixty BALB/c mice were treated with 200 µL SGC-7901 cells to establish gastric carcinoma xenograft and randomly divided into four groups: model group, low dose of plumbagin group (2 mg/kg), medium dose of plumbagin group (4 mg/kg) and high dose of plumbagin group (6 mg/kg). The tumor volume and weight were measured every week, and the ratio of anti-tumor was analyzed. The contents of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR2) in serum and tumor tissues were tested by enzyme linked immunosorbent assay (ELISA), immunohistochemistry and Western blot, respectively. The microvessel density (MVD) in tumor tissues was evaluated by immunohistochemistry and Western blot. The levels of nuclear factor-kappa B (NF-κB) p-p65/NF-κB p65, p-inhibitor of NF-κB (IκB)α/IKBα, p-IκB kinase (IKK)/IKK in tumor tissues were also analyzed by Western blot.ResultsCompared with model group, plumbagin treatment significantly suppressed the growth of tumor (P<0.05). The inhibition rate was 50.32% in high dose group (6 mg/kg). Furthermore, we found that the expressions of VEGF, VEGRF2 and MVD were obviously decreased in plumbagin treatment groups when compared to model group (P<0.05). Importantly, plumbagin treatment could down-regulate the levels of NF-κB p-p65/NF-κB p65, p-IKK/IKK and p-IKBα/IKBα in tumor tissues.ConclusionsOur study indicated that plumbagin might be an effective drug in inhibiting the tumor angiogenesis of gastric cancer and the mechanism of anti-tumor may be associated with NF-κB pathway.

The Blockade of Store-Operated Calcium Channels Improves Decompression Sickness in Rats.

BackgroundPrevious investigations reveal that BTP2, a store-operated calcium channel blocker, has protective and anti-inflammatory properties in multiple inflammatory diseases. This study investigates whether BTP2 can protect against decompression sickness (DCS) in a rat model.MethodsBTP2 (2 mg/kg) was administered to male Sprague–Dawley rats 30 min before subjecting them to hyperbaric pressure. Control rats were not treated. After decompression, signs of DCS were examined, and samples of bronchoalveolar lavage fluid and lung tissue were obtained for evaluation.ResultsThe incidence and mortality of DCS were decreased significantly in rats treated with BTP2 compared to those treated with dimethyl sulfoxide. BTP2 significantly attenuated DCS-induced lung edema, histological evidence of lung inflammation, necroptosis, and apoptosis, while it decreased levels of tumor necrosis factor alpha, interleukin-6, and cytokine-induced neutrophil chemoattractant-1 in bronchoalveolar lavage fluid. In addition, BTP2 reduced the expression of nuclear factor of activated T cells and early growth response protein 3 in lung tissue. BTP2 also significantly increased the levels of inhibitor kappa B alpha and suppressed the levels of nuclear factor kappa B in lung tissue.ConclusionThe results suggest that BTP2 may has potential as a prophylactic therapy to attenuate DCS-induced injury.

Antioxidant activity and inhibitory effect on nitric oxide production of rang chuet (Thunbergia laurifolia Lindl.) leaf extracts in lipopolysaccharide-stimulated BV2 microglial cells

Background: Oxidative stress and neuroinflammation mediated by microglial activation play a significant role in the pathogenesis of neurodegenerative diseases. Therefore, negative regulators of microglial activation have been identified as potential therapeutic candidates for the treatment of such diseases. Objectives: The aim of this study was to investigate the effects of Thunbergia laurifolia Lindl. or Rang Chuet (RC) extracts on reactive oxygen species (ROS) and nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV2 microglia cells. Materials and Methods: BV2 cells were treated with LPS in the presence or absence of RC extract, and the levels of ROS and NO were measured using CM-H2DCFDA and Griess reagent assay, respectively. The nuclear levels of nuclear factor kappa B (NF-kB) p65 and the activation of Akt and the extracellular signal-regulated kinase 1/2 (ERK1/2) were detected using immunofluorescence and western blotting assay, respectively. Results: The treatment of BV2 cells with RC concentration-dependently suppressed the LPS-induced ROS production compared to the control group. RC treatment also significantly decreased LPS-induced NO production in a concentration-dependent manner. In addition, RC treatment also suppressed NF-kB p65 translocation and the activation of Akt and the ERK1/2 pathway in LPS-stimulated BV2 cells. Conclusion: Taken together, these results demonstrate that RC exerts anti-oxidative activity by suppressing ROS production and that it exerts antioxidative activity by suppressing NO in LPS-stimulated BV2 cells. The mechanisms by which RC suppresses NO and ROS production may occur through inhibition of Akt and the ERK1/2-mediated NF-κB pathway. The results suggest that RC may be useful in treating neurodegenerative diseases mediated by microglial cells.