Inflammatory Cytokines In Rats Research Articles

Qiliqiangxin Alleviates Imbalance of Inflammatory Cytokines in Patients with Dilated Cardiomyopathy: A Randomized Controlled Trial.

Qiliqiangxin (QLQX) capsule- a traditional Chinese medicine used for treating heart failure (HF), can modulate inflammatory cytokines in rats with myocardial infarction. However, its immune-regulating effect on dilated cardiomyopathy (DCM) remains unknown. The aim of this study was to investigate whether QLQX has a unique regulatory role in the imbalance of pro- and anti-inflammatory cytokines in patients with DCM. The QLQX-DCM is a randomized- double-blind trial conducted at 24 tertiary hospitals in China. A total of 345 patients with newly diagnosed virus-induced DCM were randomly assigned to receive QLQX capsules or placebo while receiving optimal medical therapy for HF. The primary endpoints were changes in plasma inflammatory cytokines and improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDd) over the 12-month treatment. At the 12-month follow-up, the levels of IFN-γ, IL-17, TNF-α, and IL-4 decreased significantly, while the level of IL-10 increased in both groups compared with baselines (all P<0.0001). Furthermore-these changes, coupled with improvements in LVEF, NT-proBNP and New York Heart Association (NYHA) functional classification, excluding the LVEDd in the QLQX group, were greater than those in the placebo group (all P<0.001). Additionally, compared with placebo, QLQX treatment also reduced all-cause mortality and rehospitalization rates by 2.17% and 2.28%, respectively, but the difference was not statistically significant. QLQX has the potential to alleviate the imbalance of inflammatory cytokines in patients with DCM, potentially leading to further improvements in cardiac function when combined with anti-HF standard medications.

Bushen Zhuyun Decoction Improves Endometrial Receptivity by Inhibiting NF-κB/NLRP3 Signaling Pathway.

Bushen Zhuyun Decoction (BSZY), a traditional Chinese herbal prescription has shown promising effects on gynecological infertility, but the mechanism for endometrial receptivity is still unclear. This study aimed to investigate the regulatory effects of BSZY on endometrial receptivity, which plays a key role in colonization of embryo, and its regulatory mechanisms associated with NF- κB/NLRP3 pathway. SD rats at reproductive age with affected endometrial receptivity was established using mifepristone (RU486), and the regulatory effects of BSZY on endometrial receptivity were evaluated by H&E staining, and changes in sex hormones by ELISA and Western blot. Moreover, human endometrial RL95-2 cells were treated with H2O2, and inflammatory cytokines in rats and RL95-2 cells were analyzed by ELISA. The activation of NF-κB/NLRP3 signaling pathway in RL95-2 cells were characterized using immunofluorescence and Western blot. Mitochondrial morphology and function in RL95-2 cells were observed by transmission electron microscope and cell mitochondrial stress test. BSZY increased uterine endometrial thickness and attenuate histopathological changes induced by RU486. BSZY can regulate endometrial estrogen receptor and progesterone receptor, and the levels of sex hormones and inflammatory cytokines in pregnant rats. BSZY-containing serum also showed strong anti-inflammatory and cytoprotective effects in vitro. In addition, BSZY-containing serum inhibited the activation of NF-κB/NLRP3 signaling pathway, and improve mitochondrial morphology and function in RL95-2 cells. BSZY can improve endometrial receptivity, potentially by improving mitochondrial morphology and function to inhibit the activation of NF-κB/NLRP3 signaling pathway in endometrial cells, thus regulate inflammation to improve endometrial receptivity.

Acupuncture at "Die E acupoint" alleviates inflammatory reaction via inhibiting TLR4/MyD88/NF-κB signaling in rats with allergic rhinitis.

To observe effects of acupuncture at "Die E acupoint" on the protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB), transcription factor T-bet (T-bet), and GATA-binding protein-3 (GATA-3) in the nasal mucosa and the serum contents of related inflammatory cytokines in rats with allergic rhinitis, so as to explore the mechanism of acupuncture in treating allergic rhinitis. Twenty-four healthy SD rats were randomly divided into blank, model, acupuncture, and sham acupuncture groups, with 6 rats in each group. The rat model of allergic rhinitis was established by using ovalbumin induction. The rats in the acupuncture group received bilateral acupuncture at the "Die E acupoint" with a depth of 15-20 mm, while the rats in the sham acupuncture group received only sham acupuncture (light and shallow acupunture of the skin at the "Die E acupoint" ). Both interventions were performed once daily for a total of 6 days. Behavioral scores of rats in each group were recorded. Pathological changes of nasal mucosa were observed by H.E. staining. Serum contents of IgE, ovalbumin-specific IgE (OVA-sIgE), interferon(IFN)-γ, interleukin(IL)-4, IL-10 and IL-17 were measured by ELISA and the protein expression levels of T-bet, GATA-3, TLR4, MyD88 and NF-κB p65 in the nasal mucosa were detected by Western blot. After modeling, compared with the blank group, rats in the model group showed increased behavioral scores, serum IgE, OVA-sIgE, IL-4, and IL-17 contents, and nasal mucosal GATA-3, TLR4, MyD88, and NF-κB p65 protein expression levels (P<0.05), whereas the contents of serum IFN-γ, IL-10 and the protein expression level of T-bet in the nasal mucosa were decreased (P<0.05). Comparison between the EA and model groups showed that acupuncture intervention can decrease the behavioral scores of rats with allergic rhinitis, the contents of serum IgE, OVA-sIgE, IL-4, IL-17, and the protein expression levels of GATA-3, TLR4, MyD88, and NF-κB p65 in the nasal mucosa (P<0.05), and up-regulate the contents of serum IFN-γ, IL-10, and the nasal mucosal T-bet protein expression level. Sham acupuncture did not have a significant modulating effect on the above indicators. Inflammatory infiltration of nasal mucosa was seen in the model group and sham acupuncture, and the inflammatory reaction was milder in the acupuncture group. Acupuncture at "Die E acupoint" can alleviate the symptoms of allergic rhinitis and suppress the inflammation of nasal mucosa in rats, which may be related to inhibiting the TLR4/MyD88/NF-κB signaling and balancing the levels of cytokines of Th1/Th2 and Treg/Th17, and T-bet/GATA-3.

Humic Acid Derived from Agricultural Biomass Mitigates Alveolar Bone Loss and Modulates Systemic Inflammatory Cytokines in Rats with Periodontitis.

Humic acid (HA) is a bioproduct that can be extracted from different sources and has anti-inflammatory properties that have been little explored in the treatment and prevention of Periodontal Disease (PD). Thus, we aimed to investigate the effects of oral administration of HA on the progression of PD in rats. Twenty-four male Wistar rats were distributed into three experimental groups (Control/ Sham, PD, and PD + HA). HA was administered by gavage (80 mg/kg/day) for 28 days, and PD was induced 14 days after the beginning of treatment. Bone loss, bone topography, and surface elemental composition were analyzed. Circulating IL1-beta, TNF-alpha, and IL-10 levels were evaluated through Enzyme-Linked Immunosorbent Assay (ELISA). The animals treated with HA showed lower bone loss (p < 0.05). Calcium and phosphorus levels on the alveolar bone surface were lower in the PD group (p < 0.05) compared to the control group, whereas the animals treated with HA exhibited attenuation in this loss (p < 0.05). The animals treated with HA showed reduced TNF-alpha, IL1-beta, IL-10, and the TNF-alpha/IL-10 ratio compared to those with PD (p < 0.05). Treatment with HA attenuated the parameters of alveolar bone loss and modulated systemic inflammatory parameters in rats with ligature-induced PD.

Sodium Pentaborate Prevents Acetaminophen-Induced Hepatorenal Injury by Suppressing Oxidative Stress, Lipid Peroxidation, Apoptosis, and Inflammatory Cytokines in Rats.

Acetaminophen (N-acetyl-p-aminophenol, APAP, or paracetamol) is one of the drugs that may be damaging to the kidneys and liver when used in excess. In this context, it is vital to treat these side effects on the liver and kidneys with various antioxidants. Diseases have been treated using herbal and mineral remedies since ancient times. The mineral boron, found in rocks and water, is a crucial ingredient with multiple positive biological effects. The primary objective of this research is to determine whether or not boron has a protective effect against the toxicity generated by APAP in rats. Male Sprague-Dawley rats were pretreated orally with boron-source sodium pentaborate (B50 and B100 mg/kg) for 6 days by gastric gavage in order to counteract the toxicity caused by a single dose of APAP (1g/kg). APAP increased lipid peroxidation as well as serum BUN, creatinine concentrations, and serum activities of AST, ALP, and ALT by consuming GSH in liver and kidney tissues. In addition, the activity of antioxidative enzymes, including SOD, CAT, and GPx, was diminished. Inflammatory indicators such as TNF-α, IL-1β, and IL-33 were elevated in conjunction with APAP toxicity. In kidney and liver tissues, APAP dramatically increased the activity of caspase-3 and triggered apoptosis. Sodium pentaborate therapy on a short-term basis reduced biochemical levels despite these effects of APAP. This study showed that boron protects rats from the harmful effects of APAP by acting as an anti-inflammatory, antioxidant, and anti-apoptotic agent.

Silver Nanoparticles Biofabricated from Cinnamomum zeylanicum Reduce IL-6, IL-18, and TNF-ɑ in Female Rats with Polycystic Ovarian Syndrome.

Polycystic ovarian, or stein leventhal, syndrome (PCOS) is an inflammatory disorder resulting in metabolic dysregulation and ovarian dysfunction as well as women's infertility. Management of PCOS requires multiple approaches. This experimental study was sought to assess the influence of Cinnamomum zeylanicum (CZ) derived silver particles (AgNPs) on inflammatory cytokines in rats with PCOS. In this experimental study, AgNPs were synthesized using CZ bark extract, and characterized by the scanning electron microscope (SEM) and atomic force microscope (AFM). Thirty female rats, rattus norvegicus, were grouped into five groups (6 animals/group). The experimental groups were vehicle control group (received 0.2 ml corn oil only), PCOS (received estradiol valerate of 4 mg/kg only), PCOS group received CZ extract (200 mg/kg), PCOS group received metformin (50 mg/kg) and PCOS group received AgNPs (3.53 mg/kg). After 30 days of treatment, serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukins-18 (IL-18), and 6 (IL-6) were measured using ELISA. Significant elevation (P<0.05) was noted in TNF-α, IL-6, and IL-18 levels of the PCOS group when compared with findings in the control group (TNF-α: 250.4 ± 32.5 vs. 164.3 ± 34.4 ng/L, IL-6: 169.8 ± 9.4 vs. 77.0 ± 9.3 pg/ml, and IL-18: 45.9 ± 5.5 vs. 35.3 ± 4.1 ng/L). Importantly, AgNPs decreased all three inflammatory biomarkers in the treated group when compared with the PCOS group (TNF-α: 173.9 ± 31.2 vs. 250.4 ± 32.5 ng/L, IL-6: 133.7 ± 9.3 vs. 169.8 ± 9.4 pg/ml, and IL-18: 36.1 ± 6.2 vs. 45.9 ± 5.5 ng/L). CZ-derived AgNPs may have an anti-inflammatory effect in PCOS rats by decreasing the concentrations of inflammatory cytokines TNF-α, IL-6 and IL-18.

Nephroprotective effects of 4-4(hydroxyl-3 methoxyphenyl)-2-butane against sodium tellurite induced acute kidney dysfunction by attenuating oxidative stress and inflammatory cytokines in rats

The aim of this study was to elucidate the protective action mechanism of 4-4(hydroxyl-3-methoxyphenyl)-2-butane against Sodium tellurite (ST) induced nephrotoxicity in rats. ST is a hazardous substance used in metallurgical and glassware industries, but its renal toxicities have not been well established before. Rats were distributed into four groups, six rats contain in each group. Normal control group given only vehicles only, toxic group given ST 8.5 mg/kg p o, treated groups given ST and 4-(hydroxyl-3-methoxyphenyl)-2-butane(100 mg/kg bwt), and positive control given only treatment drug 4-(hydroxyl-3-methoxyphenyl)-2-butane (100 mg/kg bwt) daily for 14 days. ST administration increases an alteration in biochemical, oxidative stress, cytokines markers, and morphological changes in toxic group. When it was treated with 4-(hydroxyl-3- methoxyphenyl)-2-butane significantly (p < 0.5) restores all these changes such as biochemical markers, antioxidant, inflammatory cytokines, and histopathological improvements in treated group as compared to toxic group. No significant (p > 0.05) changes have been seen in positive control as compared to normal control. In conclusion, 4(hydroxyl-3 methoxyphenyl)-2-butane successfully defended the kidney from oxidative stress, inflammatory cytokines and necrosis against ST intoxication. Thus, significant improvements were reflected and confirms with the improvement in histopathological changes.

Immunomodulatory Effects of Bio-Clean II on T-Helper 4 and Cytotoxic T-Lymphocytes in Rats Exposed to Purified Bacterial Lipopolysaccharide

Introduction: Bio-Clean II has been previously shown to boost immunity, fight viral infection, and possesses anti-inflammatory properties by regulating the serum level of inflammatory cytokines in rats exposed to purified bacterial lipopolysaccharide (LPS). In this study, we investigated the immunomodulatory effect of Bio-Clean II on T-Helper 4 and Cytotoxic T-Lymphocytes in rats exposed to purified bacterial LPS. Materials and Methods: A total of 36 male Wistar rats weighing 150g±50g (mean±SD) were purchased and randomly assigned to six (6) groups of 6 rats each. Group 1, 2, 3, 5 and 6 were induced with a single dose of 5mg/Kg of purified LPS® (E. coli 0127:B8, Sigma-Aldrich, St. Louis, USA), administered through intraperitoneal route using 1ml sterile needle and syringe, except for group 4 which served as the zero control (given water and feed only throughout the experiment). Group 1 served as the inflammation control. Group 2 which served as the positive control received 50mg/Kg/bid Diclofenac +500mg/kg/bid of Ciprofloxacin. Group 3 which served as the negative control received sterile phosphate buffer saline (PBS). While rats in group 5 and group 6 were treated orally with the herbal remedy “Bio-Clean II” for 7 days and 14 days, respectively. After which, the rats were sacrificed and a cardiac blood specimen was taken from each rat by terminal bleeding from the heart. CD4 and CD8 Cell counts were evaluated using Fluorescence photomicroscopy and ELISA techniques, respectively. Results: The outcome of this investigation shows that treatment with Bio-Clean II resulted in a significant (P&lt;0.05) increase in CD4 cell count in duration-dependent manner, 7 days (8.40±1.44 Cells/ul) and 14 days (18.40±2.66 Cells/ul), respectively, when compared to the inflammation control (4.80±1.16 Cells/ul). There was also a significant (P&lt;0.05) decrease in CD8 cell count of the Bio-Clean II treated groups: 7 days (27.67±1.32ng/ml) and 14 days (17.44±1.00ng/ml) when compared to the inflammation control (32.93±2.52ng/ml). Conclusion: Bio-Clean Il caused significant alterations in the CD4 and CD8 counts of rats exposed to purified lipopolysaccharide. The outcome of this study, underscores the potential role of Bio-Clean Il in the treatment of bacterial inflammatory diseases, however, the molecular mechanism behind this action warrants for further investigation.

Immunomodulatory Effects of Bio-Clean II on Some Inflammatory Cytokines in Rats Exposed to Purified Bacterial Lipopolysaccharide

Bacterial inflammatory diseases have continued to be a major threat to public health. The aim of this study is to determine the effects of Bio-Clean II on serum levels of some selected cytokines in rats exposed to purified bacterial lipopolysaccharide (LPS). A total of 36 male Wistar rats weighing 150g±50g (mean±SD) were purchased and randomly assigned to six (6) groups of 6 rats each. Group 1, 2, 3, 5 and 6 were induced with a single dose of 5mg/Kg of purified LPS® (E.coli 0127:B8, Sigma-Aldrich, St. Louis, USA), administered through intraperitoneal route using 1ml sterile needle and syringe, except for group 4 which served as the zero control (given water and feed only throughout the experiment). Group 1 served as the inflammation control. Group 2 which served as the positive control received 50 mg diclofenac/kg [bid] and 500 mg ciprofloxacin/kg [bid] (positive control) in place of the Bio-Clean. Group 3 which served as the negative control received sterile phosphate buffer saline (PBS). While rats in group 5 and group 6 were treated orally with the herbal remedy “Bio-Clean II” for 7 days and 14 days, respectively. After which, the rats were sacrificed and a cardiac blood specimen was taken from each rat by terminal bleeding from the heart. The serum levels of Interleukin-6 (IL-6), Interleukin-10 (IL-10), Interferon-Gamma (IFN-γ), and Tissue Necrosis Factor-Alpha (TNF-α) were determined using ELISA technique. The outcome of this investigation shows that treatment with the Bio-Clean II resulted in a significant decrease (p=0.000*) in the serum level of IL-6, IFN-γ and TNF-α, but a significant (p=0.000*) increase in the serum level of IL-10 (in a duration-dependent manner) in rats exposed to LPS when compared to the inflammation control group. The outcome of this study suggests that Bio-Clean could find some use in the future for the alleviation of bacterial inflammatory diseases through modulations of host inflammatory responses to pathogens.

Epifriedelinol Ameliorates DMBA-Induced Breast Cancer in Albino Rats by Regulating the PI3K/AKT Pathway.

We evaluated the protective effect of epifriedelinol against breast cancer and postulated an underlying mechanism. Breast cancer was induced by a single dose of 50 mg/kg 7,12-Dimethylbenanthracene (DMBA), and rats were treated with 100 or 200 mg/kg (i.p.) epifriedelinol for 4 weeks. We then evaluated the effect of epifriedelinol on tumor growth, oxidative stress and serum inflammatory cytokine levels in DMBA-induced breast cancer. Protein and mRNA levels were determined using western blotting and quantitative reverse transcription polymerase chain reaction, respectively. The tumor volume and weight were significantly (p < 0.01) decreased in the epifriedelinol-treated group compared to the negative control group. Epifriedelinol decreased the altered levels of oxidative stress and serum inflammatory cytokines in rats with DMBA-induced breast cancer. Protein levels of PI3K, AKT and mTOR and mRNA levels of PI3K, AKT, Map3k1, Erbb2 and Pdk1 were decreased in the mammary tissue of epifriedelinol-treated rats with DMBA-induced breast cancer. Apoptosis was significantly induced in the epifriedelinol-treated group compared to the negative control group. In conclusion, epifriedelinol ameliorates DMBA-induced breast cancer by regulating the PI3K/AKT pathway.

Effects of garlic extract on inflammatory cytokines in rats with type 1 and type 2 diabetes

Background and purposeOne of the most important complications of diabetes mellitus (DM) is liver damage. Hyperglycemia-induced inflammation is a major cause of diabetic complications. Therefore, compounds with hypoglycemic properties can be useful in controlling the complications of diabetes. The purpose of the current report was to evaluate the impact of garlic extract on inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and transforming growth factor-β2 (TGF-β2) proteins levels in serum and liver tissue of diabetic rats. Experimental approachA total of thirty-six male Wistar rats were accidentally assigned to six classes: C: untreated group, D1: type 1 diabetes group (induced with streptozotocin, STZ), D1 + G: type 1 diabetes + garlic group (rats with diabetes type 1 that received garlic extract), D2: type 2 diabetes group (induced with STZ + niacinamide), D2 + G: type 2 diabetes + garlic group (rats with diabetes type 2 that received garlic extract), and G: garlic group (healthy rats that treated with garlic extract). After a period of five weeks, blood and tissue sections of animal's liver were obtained for serum and liver cytokines levels evaluation using specific ELISA kits. Findings/resultsThe serum and liver tissue TNF-α, IL-1β and TGF-β2 proteins concentrations were increased significantly in both groups with diabetes type 1 and type 2 compared with the untreated group (p < 0.01). The serum and liver tissue concentrations of the cytokines were attenuated in the diabetic rats treated with garlic extract (p < 0.05). Conclusion and implicationsThese findings indicated that garlic extract could act as potential medicinal purpose for diabetic complications through its beneficial effects in prevention of inflammation.

Parasympathetic innervation contributes to the increase of survival rate and anti-inflammatory effect of electroacupuncture at "Ciliao"(BL32) in rats with lethal endotoxemia

To observe the effect of electroacupuncture (EA) at "Ciliao" (BL32) on the survival rate and serum inflammatory cytokine levels in rats with lethal endotoxemia, and to explore its parasympathetic mechanism in suppressing severe systemic inflammation. A total of 82 male SD rats were used in the present study. In the first part of this study, 40 rats were randomized into model and EA-BL32 groups (n=20/group). The endotoxemia model was established by intraperitoneal injection of lethal amount of lipopolysaccharide (LPS, 10 mg/kg). EA (30 Hz, 6 mA) was applied to bilateral BL32 for 30 min before and after LPS injection. The survival rate in 7 days was then recorded. In the second part of this study, 42 rats were randomized into normal control, model, EA-BL32, EA-BL32+cervical vagotomy, EA-BL32+truncal (subdiagrammatical) vagotomy and EA-BL32+pelvic neurectomy groups (n=7/group). The endotoxemia model was established by intraperitoneal injection of LPS (6 mg/kg) 30 min after the neurectomy. Rats of the control group received intraperitoneal injection of 6 mg/kg saline. EA with the same parameters mentioned above was applied to bilateral BL32 for 30 min before and after LPS injection. Blood sample was collected from the abdominal aorta 3 h after LPS injection for detecting the levels of TNF-α, IL-1β and IL-6 by ELISA. ① The EA survival rate was 25% in the model group and 60% in the EA -BL32group, being significantly improved after EA (P<0.05). ② The contents of serum TNF-α, IL-1β and IL-6 were significantly higher in the model group than those in the control group (P<0.000 1). After EA intervention, and compared with the model group, the levels of TNF-α, IL-1β and IL-6 were significantly decreased in the EA-BL32, EA-BL32+cervical vagotomy, EA-BL32+truncal vagotomy and EA-BL32+pelvic neurectomy groups (P<0.000 1，P<0.01). After neurectomy and compared to the EA-BL32 group, the contents of TNF-α and IL-6 in the EA+cervical vagotomy and EA+pelvic neurectomy groups, IL-1β in the EA+pelvic neurotomy group were significantly higher (P<0.0000 1, P<0.05), suggesting an elimination of EA effects after neurectomy. No significant differences were found among the 3 neurectomy groups in the levels of TNF-α, IL-1β and IL-6 (P>0.05). EA of BL32 can improve the survival rate and attenuate the level of inflammatory cytokines in rats with lethal endotoxemia, which is closely related to the intact of parasympathetic pathway including the vagus nerve and pelvic nerve.

Effects of stem cell-derived exosomes on neuronal apoptosis and inflammatory cytokines in rats with cerebral ischemia-reperfusion injury via PI3K/AKT pathway-mediated mitochondrial apoptosis

Objective This study aimed to investigate the effects of stem cell-derived exosomes (SC-Exos) on learning, memory, and neuronal apoptosis in rats with cerebral ischemia-reperfusion injury and to determine whether SC-Exos exert their effects via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway-mediated mitochondrial pathways of apoptosis. Materials and methods Eighty rats were randomly allocated to control, model, SC-Exos, and PI3K inhibitor groups. A model of focal cerebral ischemia-reperfusion was established using the improved Longa method. Expression of interleukin-1α (IL-1α), interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were compared in the brains and serum of each group. The expressions of Bcl-2, Bax, cleaved-caspase-3, cleaved-caspase-9, cytochrome C (CytC), PI3K, and AKT-related genes and proteins were evaluated by real-time quantitative polymerase chain reaction and western blotting. Results The SC-Exos-group exhibited more novel entries, less latency for the novel arm, and fewer entries into the starting arm and other arms than the model group (p<.05). Lower expression of the inflammatory cytokines IL-1α, IL-2, and TNF-α and higher expression of IFN-γ were observed in the SC-Exos group than in the model group. TdT-mediated dUTP nick end labeling (TUNEL) assay showed that lower neural cell apoptosis rate and expression of Bax, cleaved-caspase-3, cleaved-caspase-9, CytC, PI3K, and AKT mRNA and proteins and higher expression of Bcl-2 mRNA and protein were observed in the SC-Exos group than in the model group (p<.05). Conclusions SC-Exos can significantly ameliorate brain injury caused by cerebral ischemia-reperfusion. The mechanism may be a novel therapeutic target for ischemia-reperfusion injury.

Anti-inflammatory Effect of Aloe vera Extract on Inflammatory Cytokines of Rats Fed with a High-Fat Diet (HFD)

Background: Cytokines are glycoprotein compounds with an important role in inducing and regulating inflammation. Objectives: The present study aimed to measure the effect of Aloe vera alcoholic extracts on inflammatory cytokines in rats fed with a high-fat diet. Methods: Forty adult male Wistar rats were purchased and randomly categorized into five groups, including two control groups (control and control fed a high-fat diet (HFD) and three experimental groups (high-fat diet + 150 mg/kg Aloe vera, high fat diet + 300 mg/kg Aloe vera, and high-fat diet + 600 mg/kg Aloe vera). The rats in the experimental groups received high-fat emulsion and three doses of Aloe vera for 60 days in the form of gavage. Following blood sampling, serum concentrations of tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), interleukin 6 (IL-6), and interferon-γ (INF-γ) were measured. Statistical analysis was administered using SPSS-20 software by ANOVA test. Mean comparisons were conducted via Duncan’s multiple range test at the 0.05 level of significance. Results: The findings showed that a high-fat diet (HFD) could increase the concentrations of inflammatory factors TNF-α and TGF-β (P &lt; 0.05). Moreover, an increase in the concentration of inflammatory factor IL-6 was observed at P &lt; 0.01. No significant effects were observed in the mean concentration of INF-γ in the study groups. The use of Aloe vera gel extract considerably reduced inflammatory factors TNF-α, TGF-β, and IL-6 in the Aloe vera extract-receiving groups. Conclusions: In general, the results of the present study revealed that Aloe vera alcoholic extract reduced inflammatory factors in the rats fed with a high-fat diet.

Inhibitory effect of roflumilast on experimental periodontitis.

Phosphodiesterase-4 (PDE4) has been identified as a valid therapeutic target in several inflammatory diseases. In this study, we assessed PDE4 in gingival tissue from patients with chronic periodontitis and evaluated the therapeutic effects of the PDE4 inhibitor, roflumilast, in an experimental rat model of periodontitis. Gingival tissue specimens from 20 healthy subjects and 20 patients with periodontitis were collected, and the mRNA expression levels of PDE4, interleukin (IL)-1β, and IL-6 were assessed. Ninety rats were divided randomly into three groups (30 per group): non-ligature group, ligature-induced periodontitis group (L), and ligature-induced periodontitis with roflumilast administered group (5mg/kg/d) (L+R). Rats were euthanized on days 3, 8, and 14. Alveolar bone resorption was analyzed using microcomputed tomography. Inflammation and osteoclast number were analyzed histologically. Finally, the mRNA expression levels of PDE-4, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and nuclear factor kappa B (NF-κB) were assessed in the rat gingival tissue. The mRNA expression levels of PDE4, IL-1β, and IL-6 in the gingiva were significantly higher in patients with periodontitis compared with healthy individuals (P<0.05). Alveolar bone loss, degree of inflammation, number of TRAP-positive multinucleated osteoclasts, and mRNA expression levels of IL-1β, IL-6, TNF-α, NF-κB, and PDE4 in the L+R group were significantly lower than those in the L group (P<0.05). PDE4 expression was increased in the gingiva of patients with periodontitis. Roflumilast may decrease alveolar bone loss and the expression of inflammatory cytokines in rats with ligature-induced periodontitis.

Betelnut polyphenols provide protection against high-altitude hypoxia in rats

To investigate the protective effects of betelnut polyphenols on the vital organs against high-altitude hypoxia in rats. We compared low-, medium-, and high- dose betelnut polyphenols (400, 800, and 1600 mg/kg, respectively) and rhodiola the effects of against high-altitude hypoxia in Wistar rats. The rats were kept in normal condition and given the drugs daily for 3 days before transfer to a facility at the altitude of 4010 m, where the rats were kept for 5 consecutive days for hypoxic exposure. The rats were then euthanized for measuring arterial blood gas and assessing liver, lung, brain and cardiac pathologies with HE staining. SOD activity, MDA content and GSH content in the organs were measured, and serum levels of inflammatory factors were detected using a protein microarray. Acute exposure to hypoxia significantly reduced blood oxygen saturation of the rats (P < 0.05), caused damages in the liver, lung, brain and myocardium, lowered SOD activity and GSH content and increased MDA content in the vital organs, and increased serum levels of TIMP-1, MCP-1, ICAM-1, and L-selectin (P < 0.05). Treatment with betelnut polyphenols significantly improved blood oxygen saturation, alleviated organ damages, decreased MDA content and increased SOD activity and GSH content in the tissues, and significantly lowered serum levels of inflammatory cytokines in rats with acute exposure to high-altitude hypoxia (P < 0.05). Betelnut polyphenols provides protection of the vital organs against acute high-altitude hypoxia in rats by enhancing the antioxidant capacity and reducing inflammatory response.

Effects of Different Chromium Compounds on Hematology and Inflammatory Cytokines in Rats Fed High-Fat Diet.

The aim of the study was to determine how a high-fat diet supplemented with various forms of chromium affects hematological and immune parameters of the blood of rats. The rats received a standard diet or a high-fat diet supplemented with chromium at 0.3 mg/kg body weight (BW) in the form of chromium(III) picolinate, chromium(III)-methionine or nano-sized chromium. Selected hematological parameters were determined in the blood of the rats, including total white blood cell (WBC) count, leukogram, red blood cell (RBC) count, hemoglobin level (HGB), hematocrit (HCT), platelet count (PLT) and platelet percentage (PCT), as well as immune parameters: levels of immunoglobulins A and E (IgA and IgE), interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor α (TNF-α); activity of ceruloplasmin (Cp); and levels of caspase 3 and 8 (Casp3 and Casp8). Feeding rats a high-fat diet increased blood markers of induction of inflammation, ie pro-inflammatory cytokines IL-6 and TNF-α, and also significantly increased IgE. The diet had no effect on the blood count, except for an increase in the number of neutrophils. The chromium compounds tested, particularly Cr-Met and Cr-NPs, stimulated the immune system of the rats, as indicated by increased concentrations of IgA, IgE, IL-2, IL-6, TNF-α, and Cp. Given the increase in inflammatory mediators induced by chromium, it should not be used to mitigate the effects of a high-fat diet. Moreover, chromium picolinate and chromium nanoparticles were shown to increase the content of caspase 3 and 8 in the blood of rats, which indicates a pro-apoptotic effect. The effects of the use of chromium nanoparticles include reductions in the WBC count and in the thrombocyte count (leuko- and thrombopenia). Taking account these data the use of chromium as dietary supplement should be reconsidered.

Induction of analgesia using atorvastatin in experimental diabetic neuropathy through NMDA receptor and inflammatory cytokines inhibition

Background: Diabetic neuropathy is a complication of diabetes causing damage to the nerves. Objectives: Considering the neuroprotective anti-inflammatory antioxidant characteristics of statins, the current study aimed at determining the effects of atorvastatin on diabetic neuropathy through assessing the involvement of N-methyl-D-aspartic acid (NMDA) receptor, factors of oxidative stress, and inflammatory cytokines in rats with diabetes. Methods: Male rats were randomly assigned into six groups of the saline- and atorvastatin-treated controls, and streptozotocin (STZ)-induced diabetic animals treated with vehicle, diabetic animals treated with morphine (5 mg/kg), and rats treated with atorvastatin (10 mg/kg/day for 10 weeks) alone or in combination with NMDA receptor agonist. The hot plate and formalin tests were carried out on the rats. Moreover, malondialdehyde level, catalase and superoxide dismutase activities, levels of interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the dorsal root ganglia (DRG) of the animals were measured. Finally, the expression of the NMDA receptor in DRG was investigated in the current study. Results: Diabetes resulted in analgesia in all tests, and pretreatment with atorvastatin exacerbated diabetes-induced analgesic effects in the hot plate and early phase of the formalin test (P≤0.01 and P≤0.05 in comparison to those reported for the diabetic vehicle-treated group, respectively). The injection of NMDA could reverse the atorvastatin-induced analgesia in the hot plate test (P≤0.05). Diabetes caused to increase the levels of IL-1β, IL-6, and TNF-α in DRG in comparison to those reported for the control group (P≤0.05). Furthermore, the pretreatment of rats using atorvastatin could significantly reverse the increase in TNF-α level (P≤0.05). Conclusions: Atorvastatin showed analgesic properties, which might be acting through NMDA receptors and reduction of inflammatory cytokines.

Combination of Huangqi Granule and Rosuvastatin Improves the Cardiac Function in Heart Failure

Using rat models of heart failure, we evaluated the effects of rosuvastatin and Huangqi granule alone and in combination on left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole, and left ventricular posterior wall thickness at end-systole. Results showed that left ventricular end-diastolic dimension, left ventricular end-systolic dimension in the rosuvastatin + Huangqi granule group were significantly decreased (P ‹ 0.01), while left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole were significantly increased (P ‹ 0.05). The serum IL-2, IFN-β, and TNF-α in rosuvastatin + Huangqi granule group were significantly lower than those in model group (P ‹ 0.05). However, the levels of S-methylglutathione and superoxide dismutase in rosuvastatin + Huangqi granule group were significantly higher, while nitric oxide was significantly lower than that in the model group (P ‹ 0.05). Also, compared to the model group, the apoptosis rate, and the autophagy protein LC3-II in the cardiomyocytes of rosuvastatin + Huangqi granule group was significantly decreased (P ‹ 0.01), while the level of p62 protein was significantly increased (P ‹ 0.01). The levels of AMPK and p-AMPK in cardiomyocytes were significantly lower in rosuvastatin + Huangqi granule group; however, the levels of mTOR and p-mTOR showed an opposite trend (P ‹ 0.05). To sum up, rosuvastatin + Huangqi granule could improve the cardiac function, decrease the level of oxidative stress, and inflammatory cytokines in rats with HF. The possible underlying mechanism might be inhibition of autophagy and reduced apoptosis in cardiomyocytes by regulating AMPK-mTOR signaling pathway.

Effects of lycopene on metabolism of glycolipid and inflammation in non-alcoholic fatty liver disease rats

To investigate the effects of lycopene on metabolism of glycolipid and inflammation in rats with non-alcoholic fatty liver disease. According to body weight, sixty male Sprague-Dawley rats were randomly divided into control group, non-alcoholic fatty liver model group, 20, 60 mg/kg lycopene intervention groups, with 15 rats in each group. The control group was fed normal diet, and the other 3 groups were fed high-fat and high-fructose diet for 4 weeks to establish the model of non-alcoholic fatty liver disease. After modeling, the intervention groups were fed lycopene of different doses by gavage. After 8 weeks of continuous feeding, the rats were sacrificed, the body weight and liver weight were weighed, and the liver index was calculated. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. Serum was collected, fasting blood glucose(FBG), fasting insulin(INS), and insulin resistance index(HOMA-IR) were calculated; Liver function indicators alanine aminotransferase(ALT), aspartate aminotransferase(AST) were measured; Serum triglycerides(TG), total cholesterol(TC), high density lipoprotein-cholesterol(HDL-C), low density lipoprotein-cholesterol(LDL-C) and levels of inflammatory cytokines interleukin-6(IL-6), interleukin-18(IL-18) and interleukin-1β(IL-1β) were measured. Compared with the control group, the liver weight and liver index in the model group increased by 27% and 24%, respectively; And steatosis occurred in the liver tissue; The levels of serum ALT, TG, TC, LDL-C, IL-6, IL-1β were significantly increased, the level of serum HDL-C was significantly decreased(P&lt;0. 05). Compared with the model group, liver weight, liver index, levels of serum ALT, TG, FBG, IL-6 and IL-1β were significantly lower in the 20, 60 mg/kg lycopene intervention groups(P&lt;0. 05), the INS and HOMA-IR index showed a downward trend; Liver tissue lesions were reduced to different degrees, and the effect was more significant in the 60 mg/kg lycopene group. Lycopene can improve non-alcoholic fatty liver disease by regulating glycolipid metabolism and reducing levels of inflammatory cytokines in rats.