IL-6 In Rats Research Articles

The mechanism of the effects of Monascus jmbA rice on increased platelet count in Wistar rats infected with Dengue virus serotype 3.

BackgroundSeveral traditional medicines have been developed among communities as part of the efforts to improve thrombocytopenia in patients with Dengue virus infection (DVI). Among those efforts is the administration of Monascus jmbA rice (MJR), which is rice fermented with Monascus purpureus. The administration of MJR is believed to increase the platelet count in patients with DVI.AimThe objective of this study is to elucidate the mechanism of the effects of MJR on increased levels of platelets in DVI serotype 3 through changes in IL-3, IL-6, IL-11 and TNF-α.MethodsIt was a true experimental laboratory study using the randomized posttest only control group design. The study compared between groups of wistar rats were being treated only with group IVD wistar rats who experienced treatment followed by administration of MJR as well as groups of wistar rats without any treatment as a control group.ResultsThe increase in platelet count in the group treated with DVI + MJR was higher than that treated with only DVI and the difference was a significant (P<0.05). Increased levels of TNF-α in the group treated with DVI + MJR were lower than that treated with only DVI and the difference was significant (P<0.05). The significant levels of the causal relationship of TNF-α with IL-6, TNF-α with IL-11 and IL- 6 with platelets were 0.044 (P<0.05), 0.029 (P<0.05) and 0.041 (P<0.05), respectively.ConclusionMJR is capable of increasing platelet count through the role of TNF- α and IL-6 in Wistar rats infected with DVI serotype 3.

Effectiveness of oral irrigation with an extract of green microalga Nannochloropsis oculata as an anti-inflammatory in rats infected with Aggregatibacter actinomycetemcomitans

Abstract. Revianti S, Andriani D, Parisihni K, Wahjuningsih E, Widyastuti. 2020. Effectiveness of oral irrigation with an extract of green microalga Nannochloropsis oculata as an anti-inflammatory in rats infected with Aggregatibacter actinomycetemcomitans. Biodiversitas 21: 2977-2981. Aggressive periodontitis is strongly correlated with Aggregatibacter actinomycetemcomitans, a periodontopathic bacterium, which releases endotoxins and lipopolysaccharides (LPS). LPS acts as a stimulus to a variety of host cells that can promote the expression of pro-inflammatory cytokines, such as the tumor necrosis factor-α (TNF-α), in periodontal disease. The marine green microalga Nannochloropsis oculata has anti-inflammatory properties. This study aimed to examine the anti-inflammatory efficacy of oral irrigation with N. oculata extract against periodontitis induced by A. actinomycetemcomitans in a rat model. Twenty-four male Wistar rats were divided randomly into four groups (n = 6). First control group was without any treatment, the second to fourth groups were infected with A. actinomycetemcomitans and then orally irrigated with N. oculata extract at concentrations of 2.375%, 2.5%, and 2.625%. The mandibles of the euthanized rats were hemisected to measure the expression of TNF-α, interleukin-10 (IL-10, an anti-inflammatory cytokine), and osteoprotegerin (OPG) by immunohistochemistry. The first group (control) showed significantly higher expression of TNF-α and significantly lower expression of IL-10 and OPG compared to the other groups. Oral irrigation with N. oculata extracts reduced the expression of TNF-α and enhanced the expression of IL-10 and OPG in rats infected with A. actinomycetemcomitans. The effective concentration of N. oculata extract as an anti-inflammatory for oral irrigation was 2.375%.

High Fiber Diets Enhance Gene Expression and Il-10 Level on Hyperlipidemic Rats Model

Hyperlipidemia induces inflammation by increasing proinflammatory cytokines and reducing anti-inflammatory cytokines. Short chain fatty acids from fiber fermented by intestinal bacteria can reduce inflammation. The aim of this study is to evaluate the benefits of high fiber diet on IL-10 gene expression and IL-10 levels in white adipose tissue in rats with high fat and fructose diet. Twenty-five male Wistar rats, were divided into 5 groups: 1) normal (N); 2) Hyperlipidemia (HL); 3) Hyperlipidemia with fiber 1.04 g/rat/day (HL1); 4) Hyperlipidemia with fiber 2.07 g/rat/day (HL2), and 5) Hyperlipidemia with fiber 3.11 g/rat/day (HL3). The rats were considered hyperlipidemia, if their plasma triglyceride levels were &gt; 70.79 mg/dL. High fat and fructose diet contain high fructose and trans-fat, while intervention diet for T1, T2, and T3 contain a total fiber of 6.88%, 13.77% and 20.65%, respectively. Serum IL-10 analysis using ELISA method was done before and after intervention, and IL-10 gene expression was analyzed using qPCR method after intervention. High trans-fat and fructose diet decrease IL-10 levels, while high-fiber diet can significantly increase the gene expression and levels of IL-10 in hyperlipidemia rats (p&lt;0.05). High-fiber diet can improve inflammation through increase the gene expression and levels of IL-10.

Iridoid glycosides from Morinda officinalis How. exert anti-inflammatory and anti-arthritic effects through inactivating MAPK and NF-\u03baB signaling pathways

BackgroundThe root of Morinda officinalis How. (MO, the family of Rubiaceae) has long been used to treat inflammatory diseases in China and other eastern Asian countries, and iridoid glycosides extracted from MO (MOIG) are believed to contribute to this anti-inflammatory effect. However, the mechanism underlying the anti-inflammatory and anti-arthritic activities of MOIG has not been elucidated. The aim of the present study was to determine how MOIG exerted anti-inflammatory and anti-arthritic effects in vivo and in RAW 264.7 macrophages.MethodsMOIG were enriched by XDA-1 macroporous resin. The maximum feasible dose method was adopted to evaluate its acute toxicity. The analgesic effect of MOIG was evaluated by acetic acid writhing test and the anti-inflammatory effect was evaluated by cotton-pellet granuloma test in rats and air pouch granuloma test in mice. The anti-arthritic effect was evaluated by establishing an adjuvant arthritis model induced by Complete Freund’s Adjuvant (CFA). The viability of the cultured RAW 264.7 macrophages was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was evaluated by measuring NO, IL-1β, IL-6 and TNF-α levels in LPS-stimulated RAW 264.7 cells. The protein level of inflammatory responsive genes was evaluated by Western blot analysis.ResultsMOIG had no significant toxicity at maximum feasible dose of 22.5 g/kg. MO extracts and MOIG (50,100 and 200 mg/kg) all evoked a significantly inhibitory effects on the frequency of twisting induced by acetic acid in mice compared with the model control group. Administration of MO extracts and MOIG markedly decreased the dry and wet weight of cotton pellet granuloma in rats and air pouch granuloma in mice. MOIG significantly attenuated the paw swelling and decreased the arthritic score, weight loss, spleen index, and the serum level of inflammatory factors IL-1β, IL-6 and IL-17a in CFA-induced arthritic rats. MOIG inhibited the production of inflammatory cytokines in LPS-stimulated RAW264.7 cells, and the expressions of iNOS, COX-2 and proteins related to MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 macrophages.ConclusionMOIG exerted anti-inflammatory and anti-arthritic activities through inactivating MAPK and NF-κB signaling pathways, and this finding may provide a sound experimental basis for the clinical treatment of rheumatoid arthritis with MOIG.

Hepatoprotective effects and mechanisms of Ixeris denticulate water extract on liver cirrhosis in experimental rat

BackgroundTo explore the protective effect and mechanisms of Ixeris denticulate water extract (IDWE) in the development of liver cirrhosis in experimental rat.MethodsSixty rats were randomly divided into five groups: control group, model group and IDWE (2, 4 and 8 g/kg) treatment groups. Alanine transferase (ALT), aspartate transaminase (AST), albumin (ALB), tumor necrosis factor-alpha (TNF-α), Interleukin (IL)-6 and IL-8 in serum and superoxide dismutase (SOD), malondialdehyde (MDA) in liver tissue were evaluated, respectively. The liver index, liver morphology and liver histopathological analysis were detected as a supportive data. The liver protein expression of Bcl-2 and Bax were assessed by western blot, and NF-κB p65 protein expression was determined by immunohistochemistry analysis.ResultsThe result showed that a significantly decrease in the levels of serum AST, ALT and serum inflammatory factors TNF-α, IL-6 and IL-8 in IDWE-treated rats. The levels of serum ALB and SOD in liver tissue were markedly increased after IDWE treated, compared with model rats. Furthermore, IDWE-treated group also exhibited a down-regulated protein expression of NF-κB p65 and Bax, up-regulated Bcl-2 protein expression.ConclusionsIDWE could effectively alleviate the course of liver cirrhosis in rat model, which may be a potent hepatoprotective agent in clinical therapy in the future.

Prunella vulgaris L. attenuates experimental autoimmune thyroiditis by inducing indoleamine 2,3-dioxygenase 1 expression and regulatory T cell expansion

BackgroundPrunella vulgaris L. (P. vulgaris) has traditionally been used to treat swelling and inflammation of the thyroid gland. This study aimed to evaluate the effects of P. vulgaris on experimental autoimmune thyroiditis (EAT) and explore the roles of indoleamine 2,3-dioxygenase 1 (IDO1) and regulatory T cells (Tregs) in these P. vulgaris-mediated effects. MethodsThe main bioactive compounds in P. vulgaris were analysed by high-performance liquid chromatography. An EAT model was established by immunization of Lewis rats with thyroglobulin via subcutaneous injection. Thyroid volume was assessed by ultrasound, and lymphatic infiltration in the thyroid was evaluated by haematoxylin and eosin staining. The serum levels of thyroglobulin antibody (TgAb) and cytokines were measured by indirect enzyme-linked immunosorbent assay. The percentage of CD4+CD25+Foxp3+ Tregs was detected by flow cytometry. The mRNA and protein levels of IDO1 were measured by qRT-PCR and Western blotting, respectively. The levels of tryptophan (Trp) and kynurenine (Kyn) in serum and faecal samples were assessed with a fluorometric kit and spectrophotometry. ResultsThe main bioactive compound in P. vulgaris was rosmarinic acid. The TgAb level and thyroid volume in EAT rats were significantly decreased after administration of P. vulgaris (P < 0.01). The inflammation score in EAT rats that were administered P. vulgaris was significantly lower than that in the EAT controls (P < 0.01). In addition, P. vulgaris promoted the expansion of splenic Tregs and increased the production of IL-10 and TGF-β (P < 0.01) in EAT rats. Moreover, P. vulgaris induced IDO1 mRNA and protein expression in the spleen and intestine in P. vulgaris-treated EAT rats (P < 0.01). Finally, Trp levels were reduced and Kyn levels and the Kyn/Trp ratio were increased in the serum of P. vulgaris-treated EAT rats. ConclusionWe were the first to demonstrate the role of IDO1-induced Treg expansion in P. vulgaris-mediated attenuation of EAT. Our study provides insight into the immunopathogenesis of autoimmune thyroiditis and shows the potential therapeutic value of P. vulgaris.

Blackcurrant (Ribes nigrum) Extract Prevents Dyslipidemia and Hepatic Steatosis in Ovariectomized Rats.

Estrogen is involved in lipid metabolism. Menopausal women with low estrogen secretion usually gain weight and develop steatosis associated with abnormal lipid metabolism. A previous study showed that blackcurrant (Ribes nigrum L.) extract (BCE) had phytoestrogen activity. In this study, we examined whether BCE improved lipid metabolism abnormalities and reduced liver steatosis in ovariectomized rats, as a menopausal animal model. Twelve-week-old ovariectomized (OVX) rats were fed a regular diet (Ctrl) or a 3% BCE supplemented diet while sham rats were fed a regular diet for three months. Body weight, visceral fat weight, levels of serum triglycerides, total cholesterol, and LDL cholesterol decreased in the BCE-treated OVX and sham rats, but not in OVX Ctrl rats. The results of hematoxylin and eosin staining revealed that BCE decreased the diameters of adipocytes and the nonalcoholic fatty liver disease activity score. Furthermore, quantitative RT-PCR indicated a decreased expression of hepatitis-related genes, such as tumor necrosis factor-α, IL-6, and IL-1β in OVX rats after BCE treatment. This is the first study that reported improvement of lipid metabolism abnormalities in OVX rats by BCE administration. These results suggest that the intake of BCE alleviated dyslipidemia and prevented nonalcoholic steatohepatitis during menopause in this animal model.

Red nucleus IL-6 mediates the maintenance of neuropathic pain by inducing the productions of TNF-α and IL-1β through the JAK2/STAT3 and ERK signaling pathways.

We previously reported that interleukin (IL)-6 in the red nucleus (RN) is involved in the maintenance of neuropathic pain induced by spared nerve injury (SNI), and exerts a facilitatory effect via Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and extracellular signal-regulated kinase (ERK) signal transduction pathways. The present study aimed at investigating the roles of tumor necrosis factor-α (TNF-α) and IL-1β in RN IL-6-mediated maintenance of neuropathic pain and related signal transduction pathways. Being similar to the elevation of RN IL-6 three weeks after SNI, increased protein levels of both TNF-α and IL-1β were also observed in the contralateral RN three weeks after the nerve injury. The upregulations of TNF-α and IL-1β were closely correlative with IL-6 and suppressed by intrarubral injection of a neutralizing antibody against IL-6. Administration of either the JAK2 antagonist AG490 or the ERK antagonist PD98059 to the RN of rats with SNI remarkably increased the paw withdrawal threshold (PWT) and inhibited the up-regulations of local TNF-α and IL-1β. Further experiments indicated that intrarubral injection of exogenous IL-6 in naive rats apparently lowered the PWT of the contralateral hindpaw and boosted the local expressions of TNF-α and IL-1β. Pretreatment with AG490 could block IL-6-induced tactile hypersensitivity and suppress the up-regulations of both TNF-α and IL-1β. However, injection of PD98059 in advance only inhibited the upregulation of IL-1β, but not TNF-α. These findings indicate that RN IL-6 mediates the maintenance of neuropathic pain by inducing the productions of TNF-α and IL-1β. IL-6 induces the expression of TNF-α through the JAK2/STAT3 pathway, and the production of IL-1β through the JAK2/STAT3 and ERK pathways.

Mechanism of salidroside relieving the acute hypoxia-induced myocardial injury through the PI3K/Akt pathway.

ObjectiveThe objective was to investigate the anti-inflammatory effects of salidroside through the PI3K/Akt signaling pathway and its protective effects on acute hypoxia-induced myocardial injury in rats.MethodsA total of 24 healthy Sprague-Dawley male rats were selected as the experimental subjects. All rats were divided into 4 groups by using the random number table method, with 6 rats in each group. The groups included the normal control group, the salidroside group, the hypobaric hypoxia group, and the hypobaric hypoxia + salidroside group. Rats in the salidroside group were fed in the original animal laboratory and were intragastrically administered with salidroside every morning at a dosage of 35 mg/kg. Rats in the normal control group were intragastrically administered with an equal dosage of saline. Rats in the hypobaric hypoxia + salidroside group were intragastrically administered with salidroside every morning at a dosage of 35 mg/kg, who were fed in the hypoxic experiment module for animals. The altitude was increased to 4000 m, and the rats were kept in the module for 24 h. Rats in the hypobaric hypoxia group were intragastrically administered with an equal dosage of saline in the same environment, and the altitude was increased to 4000 m after administration. Parameters of blood gas analysis, histopathological changes in cardiac tissues, cardiac indexes, and inflammatory factors IL-6 and TNF-α levels of rats in groups were compared.Results1. The cardiac indexes of rats in groups were compared. The differences between the hypobaric hypoxia group and the hypobaric hypoxia + salidroside group were statistically significant (P < 0.05). 2. The results of blood gas analysis of rats in groups were compared. The differences between the hypobaric hypoxia group and the hypobaric hypoxia + salidroside group were significantly different (P < 0.05). 3. In the hypobaric hypoxia group, the myocardial cells of rats were arranged disorderly and shaped differently, with cases such as edema, degeneration, necrosis, nucleus pyknosis, and massive infiltration of inflammatory cells. In the hypobaric hypoxia + salidroside group, the above-mentioned pathological changes in myocardial cells were relieved. 4. Compared with the hypobaric hypoxia group, in the hypobaric hypoxia + salidroside group, the concentrations of IL-6 and TNF-α in rats decreased apparently, and the differences were statistically significant (P < 0.05).ConclusionSalidroside had the repairing and protective effects on the hypobaric hypoxia-induced myocardial injuries in rats. The application of salidroside could reduce the inflammatory responses of rats with hypobaric hypoxia-induced myocardial injuries through PI3K/Akt signaling pathway, thereby protecting the myocardial cells.

EFFECTS OF TELMISARTAN ON PLASMA INTERLEUKIN-6 AND C-REACTIVE PROTEIN LEVELS IN MONOSODIUM GLUTAMATE-INDUCED OBESITY IN WISTAR ALBINO RATS

Objectives: The objectives of this study were to evaluate the effects of telmisartan on plasma interleukin (IL)-6 and C-reactive protein (CRP) levels in monosodium glutamate (MSG)-induced obesity in Wistar albino rats.&#x0D; Methods: MSG at the dose of 500 mg/kg body weight is dissolved in distilled water and administered for 22 days. On the 9th day, telmisartan 7.5 mg/kg body weight is administered. After completion of experiment, body weight and biochemical parameters such as plasma IL-6 and CRP levels are measured using enzyme-linked immunosorbent assay.&#x0D; Results: Telmisartan significantly decreased plasma IL-6 and CRP levels in MSG-treated obese rats.&#x0D; Conclusion: Telmisartan, probably through its peroxisome proliferator-activated receptor-γ agonistic activity, produces significant anti-obesity effects in rats and may help in treating obese patients with metabolic syndrome.

Protective effect of astragalus injection against myocardial injury in septic young rats via inhibition of JAK/STAT signal pathway and regulation of inflammation

Purpose: To investigate the protective effect of astragalus injection against myocardial injury in septic young rats, and the underlying mechanism of action.&#x0D; Methods: Seventy-two healthy Sprague Dawley (SD) rats were randomly selected and used to establish a young rat model of sepsis. The young rats were randomly divided into 3 groups: sham, model and astragalus injection groups. Each group had 24 young rats. Serum cardiac troponin I (cTnI), IL-10, IL-6, JAK2 and STAT3 were measured after op.&#x0D; Results: Compared with sham group, serum cTnI level in the model group was significantly higher, while serum cTnI level of the drug group was significantly lower than that of the model group (p &lt; 0.05). Compared with model group, the level of IL-10 in the myocardial tissue of the drug group was significantly elevated, while IL-6 level was lower (p &lt; 0.05). Relative to sham rats, myocardial JAK2 and STAT3 protein levels in model rats were high. However, myocardial JAK2 and STAT3 proteins in the drug-treated rats were significantly downregulated, relative to model rats (p &lt; 0.05).&#x0D; Conclusion: Astragalus injection upregulates IL-10 and IL-6 in rats by inhibiting the activation of JAK/STAT signal pathway, and via maintenance of pro-inflammation/anti-inflammation balance. Thus, astragalus exerts protective effect against myocardial injury in sepsis, and can potentially be developed for use as such in clinical practice.&#x0D; Keywords: Astragalus injection, JAK/STAT signal pathway, Pro-inflammatory/anti-inflammatory imbalance, Sepsis, Myocardial injury

Protective Effect of Iridoid Glycosides of the Leaves of Syringa oblata Lindl. on Dextran Sulfate Sodium-Induced Ulcerative Colitis by Inhibition of the TLR2/4/MyD88/NF-κB Signaling Pathway.

Iridoid glycoside (IG) is the major active fraction extracted from the leaves of Syringa oblata Lindl. In view of its antimicrobial and antidiarrheal potential, it could be beneficial for the treatment of ulcerative colitis (UC). In the present study, IG (20, 40, and 80 mg/kg) was administered orally for 14 days to dextran sulfate sodium- (DSS-) induced colitis rats. The anti-inflammatory effects of IG on DSS-induced UC were evaluated by comparing observations in DSS-induced colitis and drug-treated groups using disease activity index (DAI), macroscopic score, histological analysis, and apoptosis assay. To elucidate the antioxidant mechanisms of IG on NOX-dependent ROS production, the activities of 8-OHdG, NOX1, and NOX2 in DSS-induced colitis were determined. The levels of proinflammatory cytokines such as IL-2, IL-4, IL-5, IL-12p40, and IL-13 were detected. The inflammation-associated protein and mRNA expressions of TLR-2, TLR-4, MyD88, and NF-κBp65 were assessed by immunohistochemistry and real-time quantitative PCR, respectively. The results suggested that IG treatment significantly reduced DAI, macroscopic score, and histological damage compared to untreated animals (p < 0.01), whereas administration of IG remarkably attenuated the upregulation of 8-OHdG, NOX1, and NOX2 and the expression of proinflammatory cytokines such as IL-2, IL-4, IL-5, IL-12p40, and IL-13 in DSS-treated rats in a concentration-dependent manner. In addition, IG treatment could dose dependently suppress the protein and mRNA levels of TLR-2, TLR-4, MyD88, and NF-κBp65. The dose of IG that produced the most significant protective effect was 80 mg/kg. The above results demonstrate that IG exerts its inhibitory effect on cell apoptosis, oxidative stress, and proinflammatory cytokines in DSS-induced colitis through modulation of the TLR2/4/MyD88/NF-κB signaling pathway.

Effect of moxibustion on body weight and peripheral and cerebral cortical IL-6 and IL-10 levels in fatigue rats

To observe the effect of moxibustion at "Zusanli"(ST36) on peripheral and central IL-6, IL-10 and IL-10/IL-6 changes in fatigue rats, so as to explore its mechanisms underlying relief of fatigue. Twenty-one male SD rats were randomly divided into normal control, model and moxibustion groups with 7 rats in each group. The fatigue model was induced by exhausted weight-loaded swimming, once daily for 21 days. Moxibustion was applied to bilateral ST36 once every other day, for successive 11 times. The overall state and the body weight were observed. The levels of IL-6 and IL-10 in the serum, gastrocnemius and frontal cortex tissues were detected by enzyme-linked immunosorbent assay (ELISA). Compared with the normal group, the body weight was significantly reduced on the 7th, 14th, and 21st day in the model group (P<0.05), and considerably increased on the 14th and 21st day in the moxibustion group relevant to the model group (P<0.05). After modeling, the levels of IL-6 in the serum, gastrocnemius and frontal cortex were significantly increased (P<0.05, P<0.01), while those of IL-10 was obviously decreased (P<0.05, P<0.01) in the model group relevant to the normal group, and ratio of IL-10/IL-6 was obviously decreased in the serum and frontal cortex of the model group relevant to the normal group (P<0.01). After the moxibustion intervention, the levels of IL-10 in the serum and frontal cortex were significantly increased (P<0.05), and ratio of IL-10/IL-6 in the serum and frontal cortex was significantly increased (P<0.01), while the IL-6 contents in the gastrocnemius and frontal cortex were notably decreased in the moxibustion group relevant to the model group (P<0.05). Moxibustion can inhibit weight-loaded swimming induced decrease of body weight in fatigue rats, which may be associated with its effects in balancing the levels of peripheral and central pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10.

Bioactive fractions from Securidaca inappendiculata alleviated collagen-induced arthritis in rats by regulating metabolism-related signaling.

Securidaca inappendiculata is a xanthone rich medicinal plant that has been used in the treatment of inflammation and autoimmune diseases like rheumatoid arthritis (RA) for centuries; however, the material base and mechanism of action responsible for its anti-arthritis effect still remains elusive. The objective of this study is to evaluate the therapeutic effects of xanthone-enriched extract of the plant against collagen-induced arthritis (CIA) in rats and explore the underlying mechanisms. The xanthone-deprived fraction (XDF) and xanthone-rich fraction (XRF) were obtained by using a resin adsorption coupled with acid-base treatment method, and their chemical composition difference was characterized by UPLC-MS/MS analysis. Effects of the two on CIA were analyzed using radiographic, histological, and immunohistochemical analyses. The results indicated that XRF alleviated joint structures destructions with the higher efficacy than XDF, and decreased levels of TNF-α, IL-6, and anti-cyclic citrullinated peptide antibody in CIA rats significantly. Furthermore, XRF inhibited nicotinamide phosphoribosyl transferase (NAMPT) mediated fat biosynthesis and utilization indicated by clinical evidences and metabonomics analysis, which thereby disrupted energy-metabolism feedback. In addition, Toll-like Receptor 4 and High Mobility Group Protein 1 expressions were downregulated in XRF-treated CIA rats. Collective evidences suggest NAMPT could be an ideal target for RA treatments and reveal a novel antirheumatic mechanism of S. inappendiculata by regulating NAMPT controlled fat metabolism.

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

Our previous studies have shown that abdominal paracentesis drainage (APD) is a safe and effective strategy for patients with severe acute pancreatitis (SAP). However, the underlying mechanisms behind APD treatment remain poorly understood. Given that apoptosis is a critical pathological response of SAP, we here aim to investigate the effect of APD on cell apoptosis in pancreatic tissues during SAP and to explore its potential molecular mechanism. SAP was induced by 5% sodium-taurocholate retrograde while APD group was inserted a drainage tube into the right lower abdomen of rats immediately after SAP induction. Histopathological staining, serum amylase, endotoxin and inflammatory mediators were measured. Cell apoptosis, apoptosis-related proteins and signaling pathway were also evaluated. Our results demonstrated that APD treatment significantly attenuated pancreatic damage and decreased the serum levels of amylase, endotoxin, TNF-α, IL-1 and IL-6 in rats with SAP. Notably, APD treatment enhanced cell apoptosis and reduced necrosis in pancreatic tissues, as evidenced by Tunnel staining, the increased pro-apoptosis proteins (Cleaved-caspase-3 and bax) and decreased anti-apoptosis protein (Bcl-2). Moreover, the effect of APD on cell apoptosis was further confirmed by the regulatory pathway of PI3K/AKT and NF-kB signaling pathway. These results suggest that APD attenuates the severity of SAP by enhancing cell apoptosis via suppressing PI3K/AKT signaling pathway. Our findings provide new insights for understanding the effectiveness of APD in patients with SAP.

Tanshinone IIA Alleviates CCL2-Induced Leaning memory and Cognition Impairment in Rats: A Potential Therapeutic Approach for HIV-Associated Neurocognitive Disorder.

Chemokine CC motif ligand 2 (CCL2) is one of the most recognized proinflammatory chemokines, and the expression of CCL2 in the cerebrospinal fluid of patients infected with HIV-1 is significantly higher than that of healthy people. As such, it is seen as an important cause of HIV-associated neurocognitive disorder (HAND). Our previous investigation has confirmed the pathological role of CCL2 in mediating brain damage leading to cognitive dysfunction. Currently, however, research on therapeutic drugs for the central nervous system targeting CCL2 is very limited. Our present study used brain stereotactic technology to induce cognitive impairment in rats by injecting CCL2 (5 ng) into the bilateral hippocampus. To investigate the protective effect and mechanism of Tanshinone IIA (25, 50, 75 mg/kg/d) on CCL2-induced learning memory and cognitive impairment in rats, we performed the Morris water maze (MWM) and novel object recognition tests (NORT) on the rats. The results showed that Tanshinone IIA significantly alleviated CCL2-induced learning memory and cognitive dysfunction. Further studies on the hippocampal tissue of the rats revealed that Tanshinone IIA treatment significantly increased the activity of SOD and GSH-Px while the level of MDA decreased compared to the model group. Additionally, the relative expression of apoptosis-associated genes caspase-3, caspase-8, and caspase-9 and inflammation-associated genes IL-1β and IL-6 in Tanshinone IIA-treated rats was lower than that in model rats. Finally, we confirmed hippocampal neuron loss and apoptosis by Nissl staining and TdT-mediated dUTP Nick end labeling (TUNEL). Taken together, these data imply that Tanshinone IIA can ameliorate CCL2-induced learning memory and cognitive impairment by impacting oxidative stress, inflammation, and apoptosis. Tanshinone IIA may be a potential therapeutic agent for the treatment of HAND.

Promegranate Peel as Prophylactic Agent of Rheumatoid Arthritis : Study on MMP-9, IL-6, TNF- α, and Arthritic Score of Rheumatoid-arthritic Rats

Rheumatoid arthritis (RA) is a joint disease, chronically cause permanent joint impairment leading to inability of daily life activities. Early diagnosis and preven-tive managements of RA are recommended to overcome the disease. The current drugs provide benefits for RA patients, unfortunately could not be used for long period and as prevention agents, due to the adverse effects. Even though clinical and laboratory studies of pomegranate for osteoarthritis and RA had been done, the effects of the pomegranate peel on MMP-9, TNF-α, and IL-6 of RA are still unrevealed. TNF-α promotes inflammation process in RA and collaborates with osteoclasts to trigger osteoporosis. IL-6 shows negative effect on osteoblasts dif-ferentiation and MMP-9 stimulates cartilage degradation and inflammation mediat-ed by synovial fibroblast. This study measured TNF-α, IL-6, MMP-9, and arthri-tis score (AS) of RA rats treated with ethanolic extract of pomegranate peel (EPP) to evaluate its potency as a RA prevention agent. Male Lewis rats (three groups, five each), 200 g, received 80 mg, 160 mg, and 320 mg of EPP/rat respectively, in alternate day, within 60 days. On the 30th day, the rats were subcutaneously in-jected with 0,1 ml mycobacterium-complete Freund’s adjuvant (1 mg/mL) on plan-tar of the right hind paws to induce RA. Serum IL-6 and TNF-α were determined by ELISA. Immunohistochemistry processed-synovial MMP-9 slices of ankle joints were evaluated by light microscope (400× magnification). Arthritis score of Smit was used to determined AS. Data were analyzed by Kruskall Wallis, Mann Whitney U, and Pearson correlation test. p 0.05). In conclusion, the results indicate the EPP may potential to be devel-oped as preventive agent of rheumatoid arthritis.

Investigation of toll-like receptor (TLR) 4 inhibitor TAK-242 as a new potential anti-rheumatoid arthritis drug

BackgroundProper blocking of toll-like receptor (TLR) activation during disease progression has been reported to have inhibitory effect on the pathogenesis of rheumatoid arthritis (RA). We tested whether the TLR4 inhibitor TAK-242 had potential as a remedy for rheumatoid arthritis.MethodsThe therapeutic effect of TAK-242 was tested in vitro using the human rheumatoid fibroblast-like synoviocyte (FLS) line MH7A or primary human FLS and in an adjuvant-induced arthritis (AIA) rat model.ResultsTAK-242 dose dependently inhibited the increased expression of IL-6, IL-8, MMP-1, and VEGF in LPS-stimulated MH7A cells. It also inhibited the expression of IL-6 and IL-8 in poly(I:C), TLR3 activator-stimulated primary FLS, but not in IL-1β-stimulated primary FLS. These findings suggest that TAK-242 blocks a specific signaling pathway to some degree. Further, TAK-242 slightly inhibited mobilization of NF-κB into nuclei. In the AIA rat model, TAK-242 significantly reversed the body weight and paw thickness of AIA rats to the normal state at a dose of 5 mg/kg, but not at 3 mg/kg, and reduced the increased serum level of IL-6 and VEGF in AIA rats. It also significantly ameliorated inflammatory symptoms of joint tissues at day 21 of treatment, according to histology and RT-PCR.ConclusionsBased on the drug repositioning concept, TAK-242, which is used for the treatment of TLR4-mediated inflammatory diseases, shows potential for cost-effective development as a remedy for rheumatoid arthritis or to control the progression of RA.

Protective effect of EX-527 against high-fat diet-induced diabetic nephropathy in Zucker rats

High-fat diet (HFD)-induced obesity is implicated in diabetic nephropathy (DN). EX-527, a selective Sirtuin 1 (SIRT1) inhibitor, has multiple biological functions; however, its protective effect against DN is yet to be properly understood. This study was aimed to explore the protective effect of EX-527 against DN in HFD-induced diabetic Zucker (ZDF) rats. After 21 weeks of continually feeding HFD to the rats, the apparent characteristics of progressive DN were observed, which included an increase in kidney weight (~160%), hyperglycemia, oxidative stress, and inflammatory cytokines, and subsequent renal cell damage. However, the administration of EX-527 for 10 weeks significantly reduced the blood glucose concentration and kidney weight (~59%). Furthermore, EX-527 significantly reduced the serum concentration of transforming growth factor-β1 (49%), interleukin (IL)-1β (52%), and IL-6 in the HFD-fed rats. Overall, the antioxidant activities significantly increased, and oxidative damage to lipids or DNA was suppressed. Particularly, EX-527 significantly reduced blood urea nitrogen (81%), serum creatinine (71%), microalbumin (43%), and urinary excretion of protein-based biomarkers. Histopathological examination revealed expansion of the extracellular mesangial matrix and suppression of glomerulosclerosis following EX-527 administration. EX-527 downregulated the expression of α-SMA (~64%), TGF-β (25%), vimentin, α-tubulin, fibronectin, and collagen-1 in the kidneys of the HFD-fed rats. Additionally, EX-527 substantially reduced claudin-1 and SIRT1 expression, but increased the expression of SIRT3 in the kidneys of the HFD-fed rats. EX-527 also inhibited the growth factor receptors, including EGFR, PDGFR-β, and STAT3, which are responsible for the anti-fibrotic effect of SIRT-1. Therefore, the administration of EX-527 protects against HFD-induced DN.

Promotion of G1/S Transition and Inhibition of Inflammatory Cytokine Production by Hydroxypyridinone-Coumarin in Osteoarthritis Rats.

BackgroundOsteoarthritis is a joint disorder characterized by articular cartilage degradation leading to joint stiffness and pain. The present study investigated the effect of hydroxypyridinone-coumarin on proliferation of chondrocytes.Material/MethodsChondrocyte proliferation was assessed by MTT assay, and distribution of cells in various phases of the cell cycle was determined using flow cytometry. RT-PCR and Western blot assays were used for assessment of mRNA and protein levels, respectively. Osteoarthritis was induced in the rats by injecting monosodium iodoacetate (5 mg/kg) by the intra-articular route. The rats in the treatment groups were intraperitoneally injected with 5, 10, or 15 mg/kg doses of hydroxypyridinone-coumarin alternately for 1 month.ResultsThe proliferation of chondrocytes was increased significantly (P<0.05) by treatment with hydroxypyridinone-coumarin in a concentration-based manner. The increase in chondrocyte proliferation by hydroxypyridinone-coumarin was maximum at 50 μM. Treatment with hydroxypyridinone-coumarin markedly increased chondrocyte population in S and G2/M phases, with subsequent reduction in G0/G1 phase. The cyclin D1, CDK4, and CDK6 levels in the chondrocytes were increased by treatment with hydroxypyridinone-coumarin. The production of IL-6, TNF-α, and IL-1β in the osteoarthritis rats was markedly suppressed by hydroxypyridinone-coumarin. Treatment of the OA rats with hydroxypyridinone-coumarin markedly reduced the expression of IκB-α and NF-κB p65.ConclusionsThe present study revealed that the proliferative potential of chondrocytes is increased by hydroxypyridinone-coumarin through acceleration of G1/S transition. Moreover, hydroxypyridinone-coumarin treatment reduced inflammatory cytokine production in the osteoarthritis rats. Therefore, hydroxypyridinone-coumarin should be evaluated further for possible use in the treatment of osteoarthritis.