scholarly journals Formulation of Huangqin Decoction Influence Immune Function and Fecal Microbiome of Chicks Suffered Escherichia Coli O78 Challenge

2021 ◽  
Author(s):  
Junyan Wang ◽  
Rui Li ◽  
Yong Liu ◽  
Chensheng Gu ◽  
Haili Wang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Mortality Rate ◽  
Mrna Expression ◽  
Relative Abundance ◽  
Inflammatory Factors ◽  
Fecal Microbiome ◽  
E Coli ◽  
Liver Index ◽  
Tnf Α ◽  
Spleen Index

Abstract Ethnopharmacological relevance: Huangqin Decoction (HQD), a traditional Chinese medicine formula from the Shang Han Lun written by Zhang Zhongjing, has been used in China for nearly two thousand years. According to traditional Chinese medicine and a previous literature, HQD has the effect of clearing heat and removing toxin, antidiarrhea, and relieving pain. Therefore, HQD were used to prevent or cure many diseases, such as inflammation, diarrhea, malaria, and other acute or chronic gastrointestinal diseases. Materials and methods: HQD consist of four components: Scutellariae Radix (huangqin, HQ), Paeoniae Radix Alba (shaoyao, SY), Jujubae Fructus (dazao, DZ), Licorice (gancao, GC). A total of 80 1-day-old male Esa brown chicks were divided into eight groups (n=10): Control group (CG), model group (MG), Enrofloxacin group (ENR, 10 mg/kg·BW), HQD group (HQD, 500 mg/kg·BW), HQD-GC group (GC absent HQD, 500 mg/kg·BW), HQD-HQ group (HQ absent HQD, 500 mg/kg·BW), HQD-DZ group (DZ absent HQD, 500 mg/kg·BW) and HQD-SY group (SY absent HQD, 500 mg/kg·BW). The chicks, which were given HQD, herb absent HQD, or enrofloxacin orally at 19 days of age for 7 days, and then were intraperitoneally injected with inoculum of E. coli O78，fed continuously for 5 days as before. Results: It showed that E. coli O78 challenge decreased the average daily gain (ADG) and increased the mortality rate of chicks, increased the heart index and the liver index, decreased the bursal index, and had no effect on the spleen index. E. coli O78 challenge increased the serum lysozyme (LZM) and IL-1β, TNF-α, IL-10, IL-6, up-regulated the mRNA expression of TLR4, TLR5 and TLR15 in the spleen, and had no effect on the bursal compared with CG. E. coli O78 challenge increased the Operational Taxonomic Unit (OTU), increased the relative abundance of harmful bacteria Proteobacteria, and decreased the relative abundance of probiotics Bacteroidetes and Firmicutes at the phylum levels. E. coli O78 challenge increased the relative abundance of harmful bacteria Escherichia-Shigella and Pseudomonas at the genus levels. HQD supplementation showed higher ADG and reduced the mortality rate caused by E. coli O78 challenge, decreased the heart index and liver index, and increased the bursal index and spleen index. HQD supplementation decreased the serum LZM, IL-1β, TNF-α, IL-10, IL-6 levels, down-regulated the mRNA expression of TLR4, TLR5 and TLR15 in the spleen in E. coli O78 challenged chicks, and up-regulated the mRNA expression of TLR4, TLR5 and TLR15 in the bursal in that. At the phylum levels, HQD supplementation reversed the increased of OTUs, decreased the relative abundance of harmful bacteria Proteobacteria, increased the relative abundance of probiotics Bacteroidetes and Firmicutes. At the genus levels, HQD decreased the relative abundance of harmful bacteria Escherichia-Shigella and Pseudomonas. It means that HQD reversed the change of the gut microbiota structure. Compared with HQD, HQD-DZ and HQD-HQ increased the mortality rate. HQD-HQ decreased the ADG and liver index. HQD-GC decreased the spleen index. HQD-DZ, HQD-HQ, HQD-SY and HQD-GC increased the serum TL-6, but only the HQD-HQ and HQD-SY increased the serum TNF-α. All herb absent HQD did not activate the toll-like receptors signaling pathways in spleen and bursal of chicks. HQD-DZ and HQD-HQ increased the harmful bacteria Escherichia-Shigella, and HQD-DZ increased the harmful bacteria Proteobacteria levels. Conclusions: Dietary supplementation with HQD, by down-regulating the mRNA expression of TLR4, TLR5 and TLR15 in the spleen, further decreasing the serum LZM and IL-1β, TNF-α, IL-10, IL-6 levels, improves the immune function and reverse the change of fecal microbiome in chicks challenged with E. coli O78. About herb absent groups, the results shown that SY and DZ play a key role in reducing the level of inflammatory factors and keeping fecal microbiome balance respectively. what’s more, we highlighted that HQ is indispensable in HQD, HQ not only play a key role in reducing the level of inflammatory factors, but also keep the balance of fecal microflora.

scholarly journals Post-treatment curcumin reduced ischemia–reperfusion-induced pulmonary injury via the Notch2/Hes-1 pathway

2019 ◽  
Vol 48 (4) ◽  
pp. 030006051989243
Author(s):  
HaiZou bo ◽  
XiaoSun feng
Keyword(s):  
Lung Injury ◽  
Mrna Expression ◽  
Ischemia Reperfusion ◽  
Limb Ischemia ◽  
Post Treatment ◽  
Inflammatory Factors ◽  
Pulmonary Injury ◽  
Pathological Changes ◽  
Sprague Dawley ◽  
Tnf Α

Objective To investigate the influence of curcumin on the Notch2/Hes-1 pathway after pulmonary injury induction via limb ischemia–reperfusion (I/R). Methods Adult male Sprague–Dawley rats were randomly divided into four groups (n = 30 each): sham, I/R, curcumin post-treatment (I/R+Cur), and inhibitor (I/R+DAPT). Hind-limb ischemia was induced for 4 hours, followed by reperfusion for 4 hours. After ischemia, curcumin (200 mg/kg) or DAPT (0.5 µm) was injected intraperitoneally in the I/R+Cur or I/R+DAPT group, respectively. PaO2 was examined after 4 hours of reperfusion. Pathological changes in the lung and the apoptotic index (AI) were examined. Lung malondialdehyde (MDA), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β levels, the wet/dry (W/D) ratio, semi-quantitative score of lung injury (SSLI), and Notch2 protein and Hes-1 mRNA expression were also examined. Results In the I/R group, inflammatory changes were observed, AI increased, and MDA, SSLI, W/D, TNF-α, IL-1β, Notch2, and Hes1-mRNA expression increased, while PaO2 decreased compared with the Sham group. Pathological changes in the I/R+Cur group were reversed. All indexes in the I/R+DAPT and I/R+Cur group were similar. Conclusion Curcumin post-treatment reduced I/R-induced lung injury in rats. Its mechanism may be related to the inhibition of Notch2/Hes-1 signaling pathway and the release of inflammatory factors.

scholarly journals Keel Fracture Causes Stress and Inflammatory Responses and Inhibits the Expression of the Orexin System in Laying Hens

Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 804 ◽  
Author(s):  
Haidong Wei ◽  
Chun Li ◽  
Hongwei Xin ◽  
Shuang Li ◽  
Yanju Bi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Laying Hens ◽  
Inflammatory Responses ◽  
Abdominal Muscle ◽  
Inflammatory Factors ◽  
Prostaglandin E ◽  
Inflammatory Factor ◽  
Tnf Α ◽  
Cox 2 ◽  
The Brain

Keel fracture has negative effects on the health and welfare of laying hens. We investigated effects of keel fracture on stress, inflammation, and the orexin system in laying hens. Ninety 17-week-old Lohmann white laying hens were palpated and euthanatized at 42 weeks old, and marked as normal keel (NK)/fractured keel (FK) from absence/presence of keel fracture. Serum, brain, liver, and abdominal-muscle samples were collected from 10 NK and 10 FK hens to determine the stress and inflammatory responses and the activity of orexin systems by corticosterone content, expression of heat shock proteins (TNF-α 60, 70, 90), and inflammatory factors (tumor necrosis factor (TNF)-α, nuclear factor-kappa Bp65 (NF-κBp65), inducible nitric oxide synthase (iNOS), prostaglandin E synthases (PTGEs), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β)), orexin (ORX), and orexin-receptor 1/2 (ORXR1/ORXR2). The FK hens had higher serum corticosterone content, Hsps, and inflammatory factor mRNA expression levels than NK hens, although levels of iNOS in the liver and TNF-α in the muscle were similar. Protein levels of Hsp70 and Hsp90 in the brain and liver, iNOS and COX-2 in the liver, NF-κBp65, iNOS, and COX-2 in the brain of FK hens were increased compared with NK hens. Furthermore, FK hens had lower mRNA expression of ORX, ORXR1, and ORXR2 than NK hens. Therefore, keel fracture causes stress and inflammation, and inhibits the expression of the orexin system in laying hens.

scholarly journals PSV-8 Enriched environment improves the resistance to transport stress in laying hens via modulating the heat shock protective response and inflammation

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 225-225
Author(s):  
Runxiang Zhang ◽  
Chun Li ◽  
Haidong Wei ◽  
Jianhong Li ◽  
Jun Bao
Keyword(s):  
Heat Shock ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Laying Hens ◽  
Enriched Environment ◽  
Inflammatory Factors ◽  
Prostaglandin E ◽  
Protective Response ◽  
Tnf Α ◽  
Transport Stress

Abstract Enriched environment can promote the adaptability of animals to cope with the complex environments. To evaluate how enriched environment experience can help laying hens resist to transport stress, a total of 432 18-week-old laying hens were randomly divided into two treated groups of which one group was housed in conventional battery cages (CC, 24 replicate cages, 3 birds/cage) and the other was in furnished cages (FC, 24 repeated cages, 15 birds/cage). At their 64 weeks of age, one hen per replicate was selected for 4h transportation. The spleen of hens was collected before transportation, after the transportation and 48h for recovery. The expression of heat shock proteins (HSPs), heat shock factors (HSFs) and inflammatory factors were measured. The serum from those birds was collected to detect inflammatory cytokines levels. Variance analysis showed that the expression of most of the detected HSPs and HSFs indicators were decreased after transportation and then elevated later. The mRNA expression of HSP10, 40, 60, 70, 90 and 110, HSF2 and HSF3 and the protein expression of HSP 60, 70 and 90 were higher in FC group than CC after the transportation and recovery (P < 0.05). Moreover, the hens housed in FC group had the lower mRNA expression of pro-inflammatory factors of nuclear transcription factor (NF-κB), cyclooxygenase-2 (COX-2) and prostaglandin E synthase (PTGEs) before and after the transportation compared to CC group (P < 0.05). The mRNA expression of inflammatory cytokines of interleukin-2 (IL-2), -6 (IL-6) and tumor necrosis factor (TNF-α) and serum concentration of IL-1β and TNF-α in FC hens were lower than CC after the transportation (P < 0.05), respectively. Therefore, by regulating the heat shock protective response and inflammatory cytokines expression, the enriched environment can reduce the stress damage of laying hens and improve the resistance to transport stress.

scholarly journals Antimicrobial Peptide MPX Against Escherichia Coli O157:H7 Infection and Inhibiting inflammation, Enhancing Epithelial Barrier and Promoting Nutrient Absorption in the Intestine

2020 ◽  
Author(s):  
Xue qin Zhao ◽  
Lei Wang ◽  
Chun ling Zhu ◽  
Xiao jing Xia ◽  
Shou ping Zhang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptide ◽  
Bacterial Infections ◽  
Intestinal Barrier ◽  
Animal Husbandry ◽  
New Drugs ◽  
Inflammatory Factors ◽  
Intestinal Diseases ◽  
E Coli ◽  
Tnf Α

Abstract Background: Escherichia coli can cause intestinal diseases in humans and livestock, destroy the intestinal barrier, exacerbate systemic inflammation, and seriously threaten human health and animal husbandry development. The antimicrobial peptide MPX is extracted from venom and possesses good antibacterial activity against gram-negative bacteria. The aim of this study was to investigate whether MPX could be effective against E. coli infection. Results: In this study, the CCK-8 and lactic dehydrogenase results showed that MPX exhibited no toxicity in IPEC-J2 cells even at a concentration of 128 µg/mL. Furthermore, MPX notably suppressed the levels of IL-2, IL-6, TNF-α, myeloperoxidase and LDH induced by E. coli and reduced inflammation by inhibiting the p-p38-, TLR4- and p-p65-dependent pathways. In addition, MPX improved the expression of ZO-1, occludin, and claudin and enhanced the wound healing ability of IPEC-J2 cells. The therapeutic effect of MPX was evaluated in a murine model, and the results showed that MPX could protect mice against lethal infection with E. coli, improve the survival rate of the mice, and reduce the colonization of E. coli in organs and feces. H&E staining showed that MPX increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum, and the effect of MPX was better than that of enrofloxacin. The SEM and TEM results showed that MPX effectively ameliorated the damage caused by E. coli to the jejunum and increased the number and length of microvilli. In addition, real-time PCR revealed that MPX decreased the expression of IL-2, IL-6, and TNF-α in the jejunum and colon. Furthermore, immunohistochemistry and immunofluorescence studies revealed that MPX could reduce the expression of p-p38 and p-p65 in the jejunum, thereby reducing the secretion of inflammatory factors. Moreover, MPX increased the mRNA and protein expression of ZO-1, occludin and MUC2 in the jejunum and colon, improved the function of the intestinal barrier and promoted the absorption of nutrients. Conclusion: This study suggests that MPX may be an effective therapeutic agent against E. coli infection and other intestinal diseases, laying the foundation for the development of new drugs for bacterial infections.

scholarly journals Artemisinin Protects Porcine Mammary Epithelial Cells against Lipopolysaccharide-Induced Inflammatory Injury by Regulating the NF-κB and MAPK Signaling Pathways

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1528
Author(s):  
Wenfei Zhang ◽  
Liang Xiong ◽  
Jiaming Chen ◽  
Zhezhe Tian ◽  
Jiaxin Liu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathways ◽  
Mammary Epithelial Cells ◽  
Nuclear Factor Κb ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factors ◽  
Tnf Α ◽  
Expression Abundance ◽  
Anti Inflammatory

Artemisinin performs a variety of biological functions, such as anti-cancer, anti-inflammatory, anti-viral, and anti-oxidant effects. However, the effects of artemisinin on sow mastitis have not been studied. The results of the current study showed that mRNA expression abundance and content of the inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were significantly increased when using 50 μg/mL LPS to stimulate pMECs for 24 h (p < 0.05). Pretreatment with 20 μM artemisinin weakened LPS-induced inflammatory damage in pMECs and decreased mRNA expression abundance and the content of inflammatory factors (IL-1β, IL-6, and TNF-α) in pMECs (p < 0.05). Mechanistically, artemisinin inhibited LPS-induced activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. In summary, the pretreatment of pMECs with artemisinin showed enhanced anti-inflammatory activity against LPS-induced inflammation.

scholarly journals Platelet-Rich Plasma Combined with Alendronate Reduces Pain and Inflammation in Induced Osteoarthritis in Rats by Inhibiting the Nuclear Factor-Kappa B Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Feng Xin ◽  
Haihong Wang ◽  
Feng Yuan ◽  
Yunzhi Ding ◽  
Christina Pabelick
Keyword(s):  
Mrna Expression ◽  
Signaling Pathway ◽  
Platelet Rich Plasma ◽  
Cruciate Ligament ◽  
Cartilage Destruction ◽  
Inflammatory Factors ◽  
Tnf Α ◽  
Collagen Ii ◽  
Safranin O

Purpose. Osteoarthritis (OA) is one of the common degenerative diseases of the joint in the world. This study was designed to explore the effect of platelet-rich plasma (PRP) combined with alendronate (ALN) on OA. Methods. We induced OA model by anterior cruciate ligament transection (ACLT) method in rats and treating chondrocytes by IL-1β in vitro. PRP and/or ALN were used to treat induced rats and chondrocytes. Hematoxylin and eosin (H&E) and Safranin O staining were used to observe the structures of cartilage. The mRNA expression of Collagen II, MMP-13, and inflammatory factors (IL-18, IL-1β, and TNF-α) in the cartilage and chondrocytes of rats was determined by qRT-PCR. The expression of NF-κB pathway-related proteins (p-p65, p65, IκBα, and p-IκBα) in the cartilage and chondrocytes of rats was determined by Western blot. The proliferation of chondrocytes was detected by MTT assay. Results. Treatment with PRP, ALN, or PRP combined with ALN decreased the degree of cartilage destruction, the mRNA expression of MMP-13 and inflammatory factors (IL-18, IL-1β, and TNF-α), and the protein expression of p-IκBα/IκBα and p-p65/p65, increased Collagen II expression, and the threshold of tender and thermal pain in OA rats. Meanwhile, ALN, PRP, or ALN combined with PRP reversed the inhibiting effect of phorbol myristate acetate (PMA, an NF-κB agonist) on cell proliferation and cartilage matrix metabolism. Among them, the effects of ALN combined with PRP were most obvious. Conclusion. PRP combined with ALN delayed OA progression by inhibiting the NF-κB signaling pathway.

scholarly journals In vivo Therapeutic Effects and Mechanisms of Hydroxyasiaticoside Combined With Praziquantel in the Treatment of Schistosomiasis Induced Hepatic Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Huilong Fang ◽  
Ling Yu ◽  
Da You ◽  
Nan Peng ◽  
Wanbei Guo ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mrna Expression ◽  
Hepatic Fibrosis ◽  
Inflammatory Factors ◽  
Control Group ◽  
Therapeutic Effects ◽  
Type I ◽  
Expression Levels ◽  
Tnf Α ◽  
Mrna Expression Levels

Schistosomiasis has been a fatal obstinate disease that threatens global human health, resulting in the granulomatous inflammation and liver fibrosis.Objective:The aim of this study was to evaluate the therapeutic effects and mechanisms of hydroxyasiaticoside combined with praziquantel in the treatment of schistosomiasis-induced liver fibrosis.Methods:Mice were randomly distributed into four experimental groups: normal control group, model group, praziquantel group, praziquantel + hydroxyasiaticoside group. Except for the normal control group, they were infected with Schistosomia cercariae through the abdominal skin to induce liver fibrosis. In the intervention group, mice were administered with the respective drugs by gavage after 8 weeks of infection. At the end of the treatment, mice were sacrificed to collect blood for the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. Moreover, the liver was excised, weighed, and liver indices were calculated. Histopathological examination was performed to assess liver morphology. Besides, the expression of collagen type I and III in liver was determined; the mRNA expression levels of IL-6 and TNF-α in liver tissues were measured using Real-time PCR while ELISA and western blotting were performed on liver tissue homogenate to determine the protein expression of IL-6 and TNF-α.Results:The combination of praziquantel and hydroxyasiaticoside lowered the pathological scores of schistosomiasis-induced hepatic fibrosis, the liver indice, serum AST and ALT levels, improved liver morphology, downregulated the expression levels of hepatic type I and III collagen, inhibited the mRNA expression levels of pro-inflammatory factors (IL-6 and TNF-α) in the liver of mice relative to the praziquantel alone.Conclusion:The combination of hydroxyasiaticoside and praziquantel is a potential therapeutic option for schistosomiasis-induced hepatic fibrosis. Notably, this combination noticeably suppresses the protein and mRNA expression levels of pro-inflammatory factors (TNF-α and IL-6) in the liver.

scholarly journals Supplementation With Chinese Medicinal Plant Extracts From Lonicera hypoglauca and Scutellaria baicalensis Mitigates Colonic Inflammation by Regulating Oxidative Stress and Gut Microbiota in a Colitis Mouse Model

2022 ◽  
Vol 11 ◽  
Author(s):  
Fan Wan ◽  
Mengyu Wang ◽  
Ruqing Zhong ◽  
Liang Chen ◽  
Hui Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Mrna Expression ◽  
Relative Abundance ◽  
Scutellaria Baicalensis ◽  
Chronic Inflammatory Bowel Disease ◽  
Colonic Inflammation ◽  
Medicinal Plant Extracts ◽  
Tnf Α

Colitis, a chronic inflammatory bowel disease, is characterized by bloody diarrhea and inflammation in the colon. Lonicera hypoglauca (“Shanyinhua” in Chinese) and Scutellaria baicalensis (“Huangqin” in Chinese) are two traditional Chinese medicinal plants rich in polyphenols, such as chlorogenic acid (CGA) and baicalin (BA), with the effects of anti-inflammation and antioxidation. However, it remains unknown whether extracts from L. hypoglauca and S. baicalensis (LSEs) could mitigate colonic inflammation. In the present study, ICR mice (22.23 ± 1.65 g) were allocated to three groups treated with chow diet without (CON) or with dextran sulfate sodium (DSS) (CON+DSS) in water or LSE supplementation in diet with DSS (LSE+DSS), and then inflammatory and oxidative parameters and colonic microbiota were detected. The results showed that LSE (500 mg/kg) treatment mitigated DSS-induced colitis symptoms and restored the shortened colon length, the increased disease activity index (DAI), and the damaged intestinal barrier. In serum, LSE supplementation significantly decreased levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and increased IL-10 level. Meanwhile, superoxide dismutase (SOD) and catalase (CAT) were increased, and malondialdehyde (MDA) and reactive oxygen species (ROS) levels were decreased. In the colon tissue, qPCR results showed that LSE supplementation dramatically downregulated the transcriptional expression of IL-1β, IL-6, TNF-α, and MDA and upregulated the expression of SOD1, CAT, and IL-10. Additionally, the damaged gut barriers occludin and zonula occludens-1 (ZO-1) in the CON+DSS group were enhanced with LSE supplementation. Furthermore, LSE treatment regulated the gut microbial communities with higher relative abundance of Dubosiella and Ruminococcus torques group and lower relative abundance of Bacteroides and Turicibacter. Moreover, the contents of short-chain fatty acids (SCFAs) as products of gut microbiota were also increased. Correlation analysis showed that the mRNA expression of SOD1 was negatively correlated with TNF-α (r = -0.900, P &lt; 0.05); the mRNA expression of IL-6 (r = -0.779, P &lt; 0.05) and TNF-α (r = -0.703, P &lt; 0.05) had a dramatically negative correlation with Dubosiella. In conclusion, LSE supplementation could effectively ameliorate inflammation by modulating oxidative stress and gut microbiota in a colitis mouse model.

Hyperlipidemia Could Activate Platelet and Induce the Production of Plasma Inflammatory Factors in Rabbits, Which Lead to Atherosclerosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5369-5369
Author(s):  
Shuangfeng Xie ◽  
Songmei Yin ◽  
Danian Nie ◽  
Yiqing Li ◽  
Xiuju Wang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Platelet Activation ◽  
Inflammatory Mediator ◽  
Inflammatory Factors ◽  
Tnf Α ◽  
Significant Difference ◽  
Set Up ◽  
High Level ◽  
Necrosis Factor ◽  
Time Point

Abstract Background: It had been proved by epidemiology and clinical trials that hypercholesterolemia (HC) and atherosclerosis (AS) had close relations. Lipid could take part in many pathological processes of the AS. Platelets played an important role in this process as an inflammatory mediator. We Chose Platelet aggregation maximum (PAG(M)) and plasma P-selectin as the index of platelet activation, try to explore the transfer of platelet activation and lymphocyte inflammatory reaction in atherosclerosis. Design: We set up the rabbit hyperlipidemia atherosclerosis model through 12 weeks’ hyper lipid feeding. PAG(M), concentrations of plasma P-selectin, Interleukin (IL)- 6, IL-1β, tumor necrosis factor (TNF)-α and mRNA expression of these factors in the lymphocyte were measured at 0 week, 6th week and 12th week time point. Results: At the 6th week time point of the hyper lipid feeding, the rabbit had elevated PAG(M) (68.12%±4.73% vs. 62.67%±3.13%; P=0.002, n=20). The PAG(M) was maintained in the high level at 12th week time point (68.83%±3.35% vs. 62.67%±3.13%; P=0.001, n=20). At the 6th week time point of the hyper lipid feeding, the rabbit had elevated plasma P-selectin, IL-6, IL-1β and TNF-α (6th week vs. 0 week, n=20, P-selectin P=0.005, IL-6 P=0.000, IL-1β P=0.001, TNF-α P=0.001). The expressions of IL-6/mRNA, IL-1β/mRNA and TNF-α/mRNA in lymphocytes were elevated too (6th week vs. 0 week, n=20, IL-6/mRNA P=0.000, IL-1β/mRNA P=0.002, TNF-α/mRNA P=0.000). At the 12th week time point, all of the parameters were maintained in the high level, while there had no significant difference between 12th week time point and 6th week time point. Conclusion: Hyperlipidemia could activate platelet. Increased PAG(M) and plasma P-selectin represented the platelet activation. Hyperlipidemia could induce the production of plasma IL-6, IL-1β and TNF-α. The increased plasma IL-6, IL-1β and TNF-α were partly from the lymphocyte secretion because The IL-1β/mRNA, IL-6/mRNA and TNF-α/mRNA expression of lymphocyte elevated. So in rabbit hyperlipidemia atherosclerosis model, platelet activation and inflammatory factors increasing was the main mechanism, while the lymphocyte took part in the inflammatory process.

scholarly journals Liraglutide exerts an anti-inflammatory action in obese patients with type 2 diabetes

2019 ◽  
Vol 57 (3) ◽  
pp. 233-240
Author(s):  
Liudmyla G. Savchenko ◽  
Nataliia I. Digtiar ◽  
Liudmyla G. Selikhova ◽  
Elvira I. Kaidasheva ◽  
Oksana A. Shlykova ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Sirtuin 1 ◽  
Inflammatory Factors ◽  
Photometric Method ◽  
Obese Patients ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Introduction. Liraglutide (L) is the analogue of human glucagon-like peptide 1 which stimulates glucose-dependent insulin secretion and can modify the level of inflammatory biomarkers. L can influence NF-kB inflammatory cascade, but the mechanisms of anti-inflammatory activities of L remain to be determined. In animal models L influenced an activity of Sirtuin 1(SIRT1). Moreover, recent evidences strongly suggest that SIRT1 up-regulation may serve as a potent therapeutic approach against development and progression of diabetic complications. The aim of this study was to investigate L effects directed on the pro-inflammatory NF-kB pathway and expression of SIRT1 in obese patients with type 2 diabetes mellitus (DM). Materials and Methods. 15 obese patients with type 2 diabetes were studied, all using metformin (1-2 g/day) and sulfonylurea (glimiperide). All patients received L 1.2 mg daily add-on to stable therapy for 6 weeks. Blood samples were collected before, 6 weeks after start of treatment and after an overnight fast 6 weeks after stopping L, mononuclear cells (MNC) were isolated. The mRNA expressions of TNF-α, TLR2, TLR4, NOD1, IL-2 and SIRT1 were measured in MNC by RT-PCR. Ceruloplasmin concentration was measured in plasma by photometric method. Results. In this add-on pilot clinical investigation we received new data that L can inhibit proinflammatory NF-kB pathway by increased SIRT1 expression in obese patients with type 2 DM improving metabolic profile. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, and plasma ceruloplasmin fell after 6 weeks of L. Expressions of IL-2 and NOD-1 were stable. There was a significant increase of SIRT1 mRNA expression. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, NOD1, SIRT1 and ceruloplasmin concentrations did not reverse to baseline levels after 6 weeks stopping of L treatment. IL-2 expression decreased in comparison with basic level. Conclusions. L has a potent anti-inflammatory effect as do GLP-1 agonists due to inhibition of NF-kB pathways and up-regulate SIRT1 expression, down-regulating pro-inflammatory factors including cytokines (TNF-α), extra- and intracellular receptors (TLR2, TLR4), and inflammation markers such as ceruloplasmin. Long lasting effects of L can be mediated by epigenetic regulation of NF-kB pathway by SIRT-1.

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