The protective effect of atractylenolide I on systemic inflammation in the mouse model of sepsis created by cecal ligation and puncture

Context: Atractylenolide I (AT-I), an active compound isolated from Atractylodes macrocephala Koidz (Compositae), shows several pharmacological activities.

Objective: Our present study is designed to investigate the protective effect of AT-I on systemic inflammation in the mouse model of sepsis created by cecal ligation and puncture (CLP), and explore the possible mechanism.

Materials and methods: Sepsis mouse model was established by CLP, and the tested dosages of AT-I were 10, 20, and 40?mg/kg (ip). Pro-inflammatory cytokines in serum (TNF-α, IL-1β and IL-6) were determined by the ELISA method; serum lipopolysaccharide (LPS) level was measured by the Limulus Amebocyte Lysate (LAL) test; white blood cells (WBC) were counted by Blood cell analyzer; contents of alanine transaminase (ALT), aspartate transarninase (AST), creatinine (Cre), and blood urea nitrogen (BUN) in serum were determined by automatic biochemistry analyzer. For survival rate tests, CLP mice were observed within 7 days, and body temperature was measured at 0, 4, 8, 12, 24, 48 and 72?h after surgery.

Results: Our results indicated that AT-I significantly increased the survival rate of mice with sepsis (p?<?0.05), whereas the WBCs and levels of LPS, pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), ALT, AST, Cre, and BUN decreased significantly after treatment with AT-I (p?<?0.05).

Conclusion: In conclusion, the AT-I ameliorates sepsis syndrome by reduction of pro-inflammatory cytokines and LPS, and provides an improvement in liver and kidney functions.     

The protective potential of metformin against acetaminophen-induced hepatotoxicity in BALB/C mice

Context: Acetaminophen overdose is regarded to a common cause of acute liver failure. The hepatotoxicity leads to mitochondrial oxidative stress and subsequent necrotic hepatocellular death.

Objective: This study examines the protective effect of metformin on acetaminophen-induced oxidative stress, inflammation and subsequent hepatotoxicity in mice.

Materials and methods: Male BALB/c mice were orally administered to acetaminophen (250?mg/kg/d) for a 7-day period. The mice received metformin (100 and 200?mg/kg/d, p.o.) for 21 days. To evaluate acetaminophen-induced oxidative stress, liver tissue level of malodialdehyde (MDA), end product of membrane lipid peroxidation, and activities of superoxide dismutase (SOD) and glutathione (GSH) were measured. Histological analysis and measurement of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were performed. Moreover, tissue concentrations of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), along with, C-reactive protein (CRP) were assessed.

Results: Acetaminophen caused focal hepatocyte necrosis, inflammation and fatty degeneration, as well as increased tissue levels of AST, ALT, ALP and MDA, and also decreased GSH and SOD activities. Moreover, IL-6, TNF-α and CRP levels were increased following acetaminophen hepatotoxicity. Metformin (200?mg/kg/d) significantly normalized MDA, SOD and GSH levels (p?<?0.001), and exerted a hepatoprotective effect by significant decreasing ALT, AST and ALP concentrations (p?<?0.001). The tissue levels of IL-6, TNF-α and CRP were markedly decreased by 21-day treatment with metformin (200?mg/kg/d) (p?<?0.001).

Discussion: The results suggest metformin protects hepatocytes against acute acetaminophen toxicity. Metformin is indicated to diminish oxidative stress, proinflammatory cytokines, and hepatocyte necrosis.     

Antidepressant-like effects of magnesium lithospermate B in a rat model of chronic unpredictable stress

Abstract

Context: Magnesium lithospermate B (MLB), an active polyphenol acid of Danshen [Radix Salviae miltiorrhizae (Labiatae)], shows neuroprotective and anti-inflammatory effects in vivo and in vitro.

Objective: We hypothesized that MLB might exert antidepressant-like effects by targeting the neuroinflammatory signals.

Materials and methods: Sprague-Dawley rats were subjected to the chronic unpredictable stress (CUS) protocol. Rats in the control group received no CUS during the whole experiment. In the model group, rats were exposed to CUS for 7 weeks. From the beginning of the 5th week, model group rats were randomly grouped and subjected to different treatments. In the experiment, control and model group rats were intraperitoneally (i.p.) injected with saline. MLB was dissolved in saline to give a final concentration, and the rats were injected (i.p.) with 15, 30, or 60?mg/kg MLB once a day for 3 weeks.

Results: MLB administration significantly reduced: (1) the immobility time in the forced swimming test (19?s, p?<?0.05); (2) the immobility time in the tail suspension test (76.3?s, p?<?0.05); (3) the corticosterone (CORT) concentrations in the serum (21.7?nmol/L, p?>?0.05); (4) the pro-inflammatory cytokine levels in the serum – TNF-α (92.1?pg/ml, p?<?0.05), IL-1β (86.9?pg/ml, p?<?0.05), and IL-6 (93.8?pg/ml, p?<?0.05); (5) pro-inflammatory cytokine levels in tissue – TNF-α (3.2?pg/mg protein, p?<?0.05), IL-1β (1.5?pg/mg protein, p?>?0.05), and IL-6 (6.3?pg/mg protein, p?<?0.05); and (6) phospho-NF-κB (1.6, p?<?0.05) and phospho-IκB-α (0.4, p?<?0.05) expression in tissue.

Discussion and conclusion: The results suggested that MLB might exert therapeutic actions on depression-like behavior and the HPA axis hyperactivity in CUS rats, and the mechanisms underlying the antidepressant-like effects of MLB might be mediated by regulation of the expression of NF-κB and IκB-α in rats.     

Anti-arthritic activity of ethanol extract of Fagopyrum cymosum with adjuvant-induced arthritis in rats

Abstract

Context: Fagopyrum cymosum (Trey.) Meisn (Polygonaceae) (EFC) has long been used as a folk medicine to treat various ailments of the lung, dysentery and rheumatism in China.

Objective: The present study evaluated the anti-arthritic effect of 95% ethanol extract of EFC (extract of Fagopyrum cymosum).

Materials and methods: The anti-arthritic activity was investigated by adjuvant arthritic (AA) rat model induced by Freund’s complete adjuvant (FCA). The AA rats were randomly separated into different groups and then treated with EFC (40, 80 and 160?mg/kg) from day 7 to day 28 after immunization. Arthritis was evaluated by hind paw swelling, polyarthritis index, body weight and index of immune organs. In addition, the severity of arthritis in the knee joints was evaluated by histopathological and hemorheological examination. The levels of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-α) in the serum were assessed by ELISA.

Results: The high dose level of EFC (160?mg/kg) significantly suppressed the swelling of hind paw of AA rats (p?<?0.01) and inhibited their body weight loss (p?<?0.01). Based on histopathological examination, all EFC groups showed great amelioration compared with the model group. EFC (80 and 160?mg/kg) also decreased the plasma viscosity in different shear rates (p?<?0.01). Moreover, EFC significantly reduced the production of IL-1 and TNF-α in the serum of AA (p?<?0.01).

Discussion and conclusion: This study provides a scientific basis for the claims that F. cymosum is effective in preventing and suppressing the development and progression of experimental arthritis, with reductions in inflammatory response.     

Anti-inflammatory effects of curcumin are associated with down regulating microRNA-155 in LPS-treated macrophages and mice

Context: The natural polyphenolic compound curcumin has been proved to modulate innate immune responses and possess anti-inflammatory properties. Nevertheless, the mechanism remains poorly understood, particularly regarding curcumin-regulated miRNAs under inflammatory response.

Objective: This study investigates the role of miRNA-155 in the effects of curcumin on inflammatory response in cell and a mouse model.

Materials and methods: The anti-inflammatory activity of curcumin (5, 10 and 15?μM, 2?h) in lipopolysaccharide (LPS, 200?ng/mL)-induced cells were measured by quantitative PCR. The animals were treated orally by 20?mg/kg curcumin for 3?days before an LPS intraperitoneal injection (10?mg/kg, 16?h). MicroRNA (miRNA) expression and the underlying molecular mechanisms were assessed using transfection technique and western blotting.

Results and discussion: Curcumin efficiently inhibited LPS-induced cytokines (TNF-α, IL-6) and microRNA-155 (miR-155) expression (p?50 21.8 and 22.3?μM at 48?h, respectively). Moreover, the levels of cytokines were suppressed by curcumin in miR-155 mimics transfected cells (p?p?p?Conclusions: Curcumin’s ability to suppress LPS-induced inflammatory response may be due to the inhibition of miR-155.     

The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for the involvement of opioid system and cytokines

Abstract

Context: Pain corresponds to the most frequent reason for visits to physicians, and its control by conventional drugs is accompanied by several side effects, making treatment difficult. For this reason, new chemical entities derived from natural products still hold great promise for the future of drug discovery to pain treatment.

Objective: The objective of this study was to evaluate the antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic monoterpene, and its possible mechanisms of action.

Materials and methods: Mice treated acutely with PC (25, 50, or 100?mg/kg, i.p.) were screened for carrageenan-induced hyperalgesia and the inflammatory components of its cascade (30–180?min), carrageenan-induced pleurisy (4?h), and tail-flick test (1–8?h). Also, we observed the PC effect on the generation of nitric oxide by macrophages and the activation of neurons in the periaqueductal gray (PAG) by immunofluorescence.

Results: PC reduced (p?<?0.001) the hyperalgesia induced by carrageenan, TNF-α, dopamine, and PGE₂. PC decrease total leukocyte migration (100?mg/kg: p?<?0.01), neutrophils (50 and 100?mg/kg: p?<?0.05 and 0.001), and TNF-α (25, 50, and 100?mg/kg: p?<?0.01, 0.05, and 0.001, respectively), besides reducing NO production (p?<?0.05) in vitro. PC produced antinociceptive effect in tail-flick test (p?<?0.05), which was antagonized by naloxone, naltrindole, nor-BNI, and CTOP, and increased (p?<?0.001) the number of c-Fos-immunoreactive neurons in PAG.

Discussion and conclusion: These results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.     

Hepatoprotective effect of withanolide-rich fraction in acetaminophen-intoxicated rat: decisive role of TNF-α, IL-1β, COX-II and iNOS

Context: Overdose of acetaminophen (APAP) is common in humans and is often associated with hepatic damage. Withania somnifera (L.) Dunal (Solanaceae) shows multiple pharmacological activities including antioxidant and anti-inflammatory potential.

Objective: To evaluate the possible mechanism of hepatoprotective activity of withanolide-rich fraction (WRF) isolated from a methanolic extract of Withania somnifera roots.

Materials and methods: Hepatotoxicity was induced by oral administration of APAP (750?mg/kg, p.o.) for 14 d. The control group received the vehicle. APAP-treated animals were given either silymarin (25?mg/kg) or graded doses of WRF (50, 100 and 200mg/kg) 2?h prior to APAP administration. Animals were killed on 15th day and blood and liver tissue samples were collected for the further analysis.

Results: In WRF-treated group, there was significant and dose-dependent (p?<?0.01 and p?<?0.001) decrease in serum bilirubin, ALP, AST and ALT levels with significant and dose-dependent (p?<?0.01 and p?<?0.001) increase in hepatic SOD, GSH and total antioxidant capacity. The level of MDA and NO decreased significantly (p?<?0.01) by WRF treatment. Up-regulated mRNA expression of TNF-α, IL-1β, COX-II and iNOS was significantly down-regulated (p?<?0.001) by WRF. Histological alternations induced by APAP in liver were restored to near normality by WRF pretreatment.

Conclusion: WRF may exert its hepatoprotective action by alleviating inflammatory and oxido-nitrosative stress via inhibition of TNF-α, IL-1β, COX-II and iNOS.     

Ameliorative effects of physcion 8-O-β-glucopyranoside isolated from Polygonum cuspidatum on learning and memory in dementia rats induced by Aβ1–40

Abstract

Context: Polygonum cuspidatum Sieb. Et Zucc. (Polygonaceae) has been traditionally used in folk medicine to treat various diseases.

Objective: This study investigates the ameliorative effects of physcion 8-O-β-glucopyranoside (PSG) isolated from P. cuspidatum on learning and memory in dementia rats induced by Aβ_1–40.

Materials and methods: Dementia rats were prepared by intracerebroventricular injection of Aβ_1–40. PSG (5, 10, 20, and 40?mg/kg/d, for 5?d) was administered orally. Ameliorative activity of PSG in dementia rats was evaluated by the Morris water maze (MWM) test, and its mechanisms were explored by evaluating AchE activity, levels of DA, NE, and 5-HT in hippocampus, and drebrin protein expressions in hippocampus.

Results: Our results indicated that PSG (5, 10, 20, and 40?mg/kg/d) significantly inhibited the prolonged latency in dementia rats (p?<?0.05), and inhibitory rates were 16.5, 22.7, 33.0, and 44.8% after 5?d of learning, indicating that PSG improves learning and memory of dementia rats. Furthermore, PSG significantly decreased AchE activity (10, 20, and 40?mg/kg/d; p?<?0.05), increased 5-HT (20 and 40?mg/kg/d, p?<?0.05), NE (10, 20, and 40?mg/kg/d; p?<?0.05), and DA levels (5, 10, 20, and 40?mg/kg; p?<?0.05) in the hippocampus. Additionally, PSG obviously decreased the Aβ contents in hippocampus (10, 20, and 40?mg/kg/d; p?<?0.05), and up-regulated drebrin protein expressions (5, 10, 20, and 40?mg/kg/d; p?<?0.05).

Conclusions: PSG can significantly enhance learning and memory in Aβ_1–40-induced dementia rats, and the mechanisms may be related to increase levels of Ach, 5-HT, NE, and DA, decrease Aβ contents, and up-regulation of drebrin proteins in hippocampus.     

Hesperidin,a flavanoglycone attenuates experimental diabetic neuropathy via modulation of cellular and biochemical marker to improve nerve functions

Aim: Diabetic neuropathy (DN) is one of the most common long-term complications of diabetes mellitus and clinically can be characterized by an elevated nociceptive response with electrophysiological conduction abnormalities. The present investigation was designed to evaluate the neuroprotective effect of hesperidin against STZ induced diabetic neuropathic pain in laboratory rats.

Materials and methods: DN was induced in Sprague–Dawley rats (150–200?g) by intraperitoneal administration of streptozotocin (STZ) (55?mg/kg, p.o.). Rats were divided into various groups, namely, STZ control (vehicle), hesperidin (25, 50, and 100?mg/kg, p.o.), insulin (10?IU/kg, s.c.), and combination of hesperidin (100?mg/kg, p.o.) with insulin (10?IU/kg, s.c.) for 4 weeks. Various behavioral (allodynia and hyperalgesia), biochemical parameters [oxido-nitosative stress, Na–K–ATPase, aldose reductase (AR)], and molecular changes (TNF-α and IL-1β) along with hemodynamic changes were determined.

Results: Rats treated with hesperidin (50 and 100?mg/kg, p.o., 4 weeks) significantly reduced (p?p?p?Conclusion: In combination with insulin, hesperidin not only attenuated the diabetic condition but also reversed neuropathic pain via control over hyperglycemia as well as hyperlipidemia to down-regulate generation of free radical, release of pro-inflammatory cytokines as well as elevation in membrane bound enzyme.     

Cryptoporus volvatus polysaccharides attenuate LPS-induced expression of pro-inflammatory factors via the TLR2 signaling pathway in human alveolar epithelial cells

Context: Cryptoporus volvatus (Peck) Hubb grows wild in China, and its fruiting bodies have been used traditionally to treat asthma and bronchitis.

Objectives: This study evaluates the anti-inflammatory effect of Cryptoporus polysaccharides (CP) extracted from fruiting bodies of C. volvatus on lipopolysaccharide (LPS)-induced pro-inflammatory factors and the signaling pathways involved in human alveolar epithelial cells.

Materials and methods: To evaluate the effects of CP on LPS-induced pro-inflammatory factors, A549 cells were pre-incubated with CP 1, 10, and 100?μg/ml for 1?h and then stimulated with LPS 10?μg/ml for 24?h. The expression of pro-inflammatory factors monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), Toll-like receptor 2 (TLR2), and phosphorylation of ERK1/2, p38, and NF-κB p65 were measured by q-PCR, ELISA, and western blotting.

Results: CP decreased LPS-induced mRNA expression of MCP-1, TNF-α, and IL-1β (IC₅₀?=?83.3, 85.2, and 91.6?μg/ml, respectively) and their correspondent protein expression (IC₅₀?=?88.6, 76.4, and 81.6?μg/ml, respectively). Investigation of potential mechanisms indicated that CP 100?μg/ml reduced LPS-induced expression of TLR2 mRNA (66.9%, p?<?0.01) and protein (63.2%, p?<?0.01) that was a result of the decreased pro-inflammatory factors. LPS induction increased the expression of TLR2 and the phosphorylation of p38 and ERK1/2, NF-kB p65 concomitantly. CP 100?μg/ml inhibited the LPS-induced phosphorylation of the signaling proteins (p?<?0.05).

Conclusions: This suggests that CP pretreatment down-regulates LPS-mediated inflammation in lung epithelial cells. This study further confirmed that CP is a potential anti-inflammatory drug for the treatment of airway inflammatory diseases.     

Effect of curcumin in mice model of vincristine-induced neuropathy

Abstract

Context: Curcumin exhibits a wide spectrum of biological activities which include neuroprotective, antinociceptive, anti-inflammatory, and antioxidant activity.

Objective: The present study evaluates the effect of curcumin in vincristine-induced neuropathy in a mice model.

Materials and methods: Vincristine sulfate (0.1?mg/kg, i.p. for 10 consecutive days) was administered to mice to induce neuropathy. Pain behavior was assessed at different days, i.e., 0, 7, 10, and 14?d. Sciatic nerve total calcium, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), nitric oxide (NO), and lipid peroxidation (LPO) were also estimated after the 14th day of study. Pregabalin (10?mg/kg, p.o.) and curcumin (15, 30, and 60?mg/kg, p.o.) were administered for 14 consecutive days.

Results: Curcumin at 60?mg/kg significantly attenuated the vincristine-induced neuropathic pain manifestations in terms of thermal hyperalgesia (p?<?0.001) and allodynia (p?<?0.001); mechanical hyperalgesia (p?<?0.001); functional loss (p?<?0.001); and in the delayed phase of formalin test (p?<?0.001). Curcumin at 30 and 60?mg/kg exhibited significant changes (p?<?0.001) in antioxidant levels and in total calcium levels in vincristine-injected mice.

Conclusion: Curcumin at 30 and 60?mg/kg dose levels significantly attenuated vincristine-induced neuropathy which may be due to its multiple actions including antinociceptive, calcium inhibitory, and antioxidant effect.     

Tumour necrosis factor-alpha levels in aqueous humour and serum from patients with uveitis: the involvement of HLA-B27

SUMMARY

Objective: To study the local and systemic levels of the tumour necrosis factor-α in patients with active uveitis and to determine the implication of TNF-α in rheumatological uveitis and to observe if this relationship is more significant in the B27 positive patients.

Patients and methods: Patients were selected on the basis of a diagnosis of uveitis of any aetiology. Data from 23 patients were stratified into two categories according to the presence or absence of systemic rheumatic disease. The first group comprised nine patients with rheumatic disease; the second group contained 14 patients without rheumatic disease. The patients were also sub-classified into those who were HLA-B27 positive (14 patients) and those who were not. TNF-α levels in serum and aqueous humour from a group of 16 patients with uncomplicated cataracts were analysed as a control group.

Results: In the control group (n?=?16) the serum TNF-α concentration was 13.1?±?2.9pg/ml and the aqueous humour concentration of TNF-α was 0.56?±?1.53?pg/ml. In uveitis patients (n?=?23) the serum TNF-α concentration was 35.35?±?26.77?pg/ml and the aqueous humour concentration of TNF-α was 15.1?±?1.70?pg/ml (p?<?0.01). In HLA-B27 positive patients (n?=?9) the serum TNF-α concentration was 45.56?±?34.17?pg/ml and the aqueous humour concentration of TNF-α was 15.89?±?0.93?pg/ml. In HLA-B27 negative patients (n?=?14) the serum TNF-α concentration was 28.79?±?19.38?pg/ml and aqueous humour concentration of TNF-α was 14.57?±?1.91?pg/ml (p?<?0.01).

Conclusions: The concentration of TNF-α in aqueous humour in patients who are HLA-B27 positive is significantly greater than in those who are B27 negative. No significant differences in the concentrations of TNF-α in serum or aqueous humour in patients with or without rheumatic diseases were detected. TNF-α is a cytokine that may participate actively in the pathogenesis of clinical uveitis.     

Anti-endotoxin effects of terpenoids fraction from Hygrophila auriculata in lipopolysaccharide-induced septic shock in rats

Context: Hygrophila auriculata (K. Schum) Heine (Acanthaceae) has been traditionally used for the treatment of various ailments such as inflammation, rheumatism, jaundice and malaria.

Objective: The present study aims to separate terpenoid fraction (TF) from alcohol (70%) extract of the whole plant of Hygrophila auriculata and assess its anti-inflammatory activity.

Materials and methods: HPTLC analysis of TF was performed for the estimation of lupeol. Edema was induced in Wistar albino rats by subplanter injection of 0.1?ml of 1% (w/v) carrageenan into the right hind paw after 1?h of TF administration (100 and 200?mg/kg oral). Septic shock was induced by intraperitoneal administration of LPS (100?μg/kg) in rats and interleukins (IL-1β and IL-6), tumor necrosis factor (TNF-α), superoxide dismutase (SOD), lipid peroxidation (LPO), and nitric oxide (NO) were measured in serum. AutoDock 4.2 was used for molecular docking.

Results: Administration of TF significantly (p?<?0.005) restored the serum levels of cytokines, LPO (7.77?±?0.034 versus 4.59?±?0.059?nmole of TBARS), NO (9.72?±?0.18 versus 4.15?±?0.23?µmol nitrite/mg of wet tissue), and SOD (4.89?±?0.036 versus 7.83?±?0.033?Unit/mg protein) compared with the LPS-challenged rats. Analysis of in silico results revealed that TNF-α is the most appropriate target in eliciting anti-inflammatory activity.

Conclusion: The present findings suggest that TF of Hygrophila auriculata possesses great promise as an anti-inflammatory agent which may be due to its antioxidant effect. Molecular docking results could be exploited for lead optimization and development of suitable treatment of inflammatory disorders.     

Effects and mechanisms of pirfenidone,prednisone and acetylcysteine on pulmonary fibrosis in rat idiopathic pulmonary fibrosis models

Context: Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown.

Objective: This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF.

Materials and methods: Rat IPF model was established by endotracheal injection of 5?mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats. Pirfenidone (P, 100?mg/kg once daily), prednisone (H, 5?mg/kg once daily) and acetylcysteine (N, 4?mg/kg 3 times per day) were used to treat the rat model by intragastric administration for 45 consecutive days, respectively. The normal rats without IPF were used as the controls. After 15, 30 and 45 days of drug treatment, lung histopathology was assessed. The expression of Cav-1 was determined using real-time quantitative PCR and Western blot; the expression of tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was determined by enzyme-linked immunosorbent assay.

Results: After 15, 30 and 45 days of drug treatment, comparison of the three drug-treated groups with the model group showed significantly lower (p?p?p?r?=??0.506, p?r?=?-0.676, p?r?=??0.590, p?r?=??0.530, p?r?=??0.553, p?Discussion and conclusion: Pirfenidone, prednisone and acetylcysteine can inhibit airsacculitis and pulmonary fibrosis in rat IPF models, which may be related with enhanced caveolin-1, reduced TNF-α, TGF-β1, PDGF.     

Tumor necrosis factor-α induced protein 6 attenuates acute lung injury following paraquat exposure

Context: Paraquat exposure commonly occurs in the developing countries and the mortality rate is high. However, there is currently no consensus on the efficacy of treatment for paraquat exposure.

Objective: The study was aimed to explore the effects of tumor necrosis factor-α (TNF-α) induced protein 6 (TSG-6) on acute lung injury (ALI) following paraquat exposure in rats.

Materials and methods: Male Sprague–Dawley (SD) rats were randomly divided into the sham group (n?=?8), the paraquat group (n?=?8), and the paraquat TSG-6-treated group (n?=?8). Rats were administered with 50?mg/kg of paraquat intraperitoneally. At 1?h after exposure, rats were treated with 30?μg of recombinant human TSG-6 (rhTSG-6) intraperitoneally. After 6?h of exposure, ALI scores were evaluated by histology and the expression of pro-inflammatory cytokines in lung was assayed using real-time RT-PCR.

Results: ALI scores were significantly lower in the paraquat TSG-6-treated group, compared with the paraquat group (p?<?0.05). The expression of interleukin (IL)-1β, IL-6, and TNF-α mRNA was significantly lower in the paraquat TSG-6-treated group, compared with the paraquat group (p?<?0.01, respectively).

Discussion and conclusion: Administration of rhTSG-6 attenuates ALI following paraquat exposure by suppressing inflammatory response.     

Riboflavin attenuates lipopolysaccharide-induced lung injury in rats

Abstract

Riboflavin (vitamin B2) is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is therefore required by all flavoproteins. Riboflavin also works as an antioxidant by scavenging free radicals. The present study was designed to evaluate the effects of riboflavin against acute lungs injury induced by the administration of a single intranasal dose (20?μg/rat) of lipopolysaccharides (LPS) in experimental rats. Administration of LPS resulted in marked increase in malondialdehyde (MDA) level (p?<?0.01) and MPO activity (p?<?0.001), whereas marked decrease in glutathione (GSH) content (p?<?0.001), glutathione reductase (GR) (p?<?0.001) and glutathione peroxidase (p?<?0.01) activity. These changes were significantly (p?<?0.001) improved by treatment with riboflavin in a dose-dependent manner (30 and 100?mg/kg, respectively). Riboflavin (100?mg/kg, p.o.) showed similar protective effects as dexamethasone (1?mg/kg, p.o.). Administration of LPS showed marked cellular changes including interstitial edema, hemorrhage, infiltration of PMNs, etc., which were reversed by riboflavin administration. Histopathological examinations showed normal morphological structures of lungs tissue in the control group. These biochemical and histopathological examination were appended with iNOS and CAT gene expression. The iNOS mRNA expression was increased significantly (p?<?0.001) and levels of CAT mRNA expression was decreased significantly (p?<?0.001) in the animals exposed to LPS, while treatment with riboflavin significantly (p?<?0.01) improved expression of both gene. In conclusion, the present study clearly demonstrated that riboflavin caused a protective effect against LPS-induced ALI. These results suggest that riboflavin may be used to protect against toxic effect of LPS in lungs.     

Possible involvement of nitric oxide in antidepressant-like effect of silymarin in male mice

Abstract

Context: Silymarin (SM) is extracted from milk thistle Silybum marianum L. [Asteraceae (Compositae)] and known for antioxidative and anti-inflammatory effects.

Objective: The potential antidepressant-like effect of acute SM and possible involvement of nitric oxide (NO) were determined in male mice.

Material and methods: SM was administered orally (5, 10, 20, 50, 100, and 200?mg/kg; p.o.) 60?min before the tests. After assessment of locomotor activity, the immobility time was measured in forced swimming test (FST) and tail suspension test (TST). To assess the possible involvement of NO, a non-specific NO synthase inhibitor, l-NAME (10?mg/kg, i.p.), and a specific iNOS inhibitor, aminoguanidine (AG) (50?mg/kg, i.p.), were administered separately 30?min before SM (20 and 100?mg/kg).

Results: SM at its effective doses 10, 20, 50, and 100?mg/kg decreased the immobility time in a dose-dependent manner (p?<?0.01, p?<?0.05, p?<?0.05, and p?<?0.001, respectively) in FST. SM (10, 20, 50, and 100?mg/kg) also lowered the immobility measure dose dependently in TST (p?<?0.01, p?<?0.05, p?<?0.01, and p?<?0.001, respectively). In addition, 50% of maximum response (ED₅₀) of SM was around 10?mg/kg. The dose 100?mg/kg proved the most effective dose in both the tests. Further, this effect was not related to changes in locomotor activity. Moreover, l-NAME reversed the effect of SM (20 and 100?mg/kg) in FST and SM (100?mg/kg) in TST. However, AG did not influence this impact.

Conclusion: The antidepressant-like effect of SM is probably mediated at least in part through NO and SM may increase NO tune.     

Antidiabetic,antioxidant, and TNF-α lowering properties of extract of the traditionally used plant Ixeris gracilis in alloxan-induced diabetic mice

Abstract

Context: Ixeris gracilis DC. Stebbins (Asteraceae) is a plant considered to be medicinal by local communities of Meghalaya, India.

Objective: To evaluate the antidiabetic potential, antioxidant activity, and effect of the 80% methanolic extract of the leaves of Ixeris gracilis on tumor necrosis factor-α (TNF-α) expression.

Materials and methods: Varying doses (250–1000?mg/kg body weight) were administered intraperitoneally to normoglycemic mice and their hypoglycemic properties noted for 24?h; the optimum dose observed was used to evaluate its antihyperglycemic activity and effect on glucose tolerance. In vitro antioxidant activity was analyzed by assessing the DPPH radicals scavenging ability of the extract and the total polyphenols, flavonoid, carbohydrate, and protein contents were determined. Diabetic mice were then subjected to daily intraperitoneal injections of the extract for 12 days after which the antioxidant enzyme activities in the tissues were assayed and serum TNF-α was evaluated by ELISA.

Results: The extract displayed varying hypoglycemic activity. The dose of 250?mg/kg body weight exhibited potent antihyperglycemic activity and improved glucose tolerance. The extract was able to scavenge free radicals (IC₅₀ 57.544?µg/ml) and contained polyphenol (76.269?±?0.204?mg GAE/g dry wt), flavonoid (70.070?±?0.626?mg rutin equivalent/g dry wt), protein (4.368?±?8.916?mg/g dry wt), and carbohydrate (558.189?±?0.002?mg/g dry wt). TNF-α level and overall activity of glutathione peroxidase and superoxide dismutase in the liver, kidney, and brain of extract-treated diabetic mice were improved.

Conclusion: The study supports the inclusion of Ixeris gracilis in the list of plants with antidiabetic potential.     

Effects of Pycnogenol on cisplatin-induced optic nerve injury: an experimental study

Aim: To determine the effects of Pycnogenol on cisplatin-induced optic nerve damage.

Material and method: Totally 18 albino Wistar male rats were assigned into three groups, with six rats in each group as follows: healthy controls (HC group), only cisplatin (2.5?mg/kg) administered group (CIS group) and Pycnogenol (40?mg/kg)?+?cisplatin (2.5?mg/kg) administered group (PYC group). We analyzed the levels of malondialdehyde (MDA) as a marker of lipid peroxidation and oxidative stress, total glutathione (tGSH) as a marker of antioxidant status, nuclear factor-kappa B (NF-κB) and tumor necrosis factor alpha (TNF-α) as inflammatory markers, total oxidative status (TOS) and total antioxidant status (TAS) on eye tissue together with histopathological evaluation of optic nerve in an experimental model.

Results: In CIS group MDA, TOS, TNF-α and NF-κB levels were statistically significantly higher (p?p?p?p?Conclusion: Pycnogenol pretreatment was highly effective in preventing augmentation of cisplatin-induced oxidative stress and inflammation in eye tissue.     

Cognitive effects of vanillic acid against streptozotocin-induced neurodegeneration in mice

Abstract

Context: Vanillic acid (VA), a flavoring agent used in food and drug products, obtained naturally from the plant Angelica sinensis (Oliv.) Diels (Apiaceae), used in the traditional Chinese medicine. It is reported to possess strong antioxidant, anti-inflammatory, and neuroprotective effects. However, the pharmacological effects on oxidative stress-induced neurodegeneration are not well investigated.

Objective: This study investigates the neuroprotective effect of VA on streptozotocin (STZ)-induced neurodegeneration in mice through behavioral and biochemical parameters.

Materials and methods: The behavioral effects were determined using the Y-maze and open-field habituation memory. In biochemical parameters, acetylcholinesterase (AChE), corticosterone, tumor necrosis factor (TNF)-α, and antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase) were measured. Five groups of animals used were of control, negative control, and three separate groups treated with 25, 50, and 100?mg/kg of VA, respectively, for 28?d. Intracerebroventricular (ICV) injections of STZ were performed for all groups except control on 14th and 16th of 28?d of VA treatment.

Results: VA improved spatial learning and memory retention by preventing oxidative stress compared with control animals. VA at 50 and 100?mg/kg dose significantly (p?<?0.001) improved the habituation memory, decreased the AChE, corticosterone, TNF-α, and increased the antioxidants (p?<?0.001). VA (100?mg/kg) exhibited dose-dependent effect in all parameters with p?<?0.001 except antioxidants in which VA showed the significance of p?<?0.01.

Discussion and conclusion: VA exhibited reduction in AChE, TNF-α, and corticosterone with improved antioxidants to contribute neuroprotection and could be an effective therapeutic agent for treating neurodegenerative disorders.