Carrageenan Injection Research Articles

The Anti-Inflammatory and Antioxidant Effects of Sodium Propionate.

The major end-products of dietary fiber fermentation by gut microbiota are the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate, which have been shown to modulate host metabolism via effects on metabolic pathways at different tissue sites. Several studies showed the inhibitory effects of sodium propionate (SP) on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. We carried out an in vitro model of inflammation on the J774-A1 cell line, by stimulation with lipopolysaccharide (LPS) and H2O2, followed by the pre-treatment with SP at 0.1, 1 mM and 10 mM. To evaluate the effect on acute inflammation and superoxide anion-induced pain, we performed a model of carrageenan (CAR)-induced rat paw inflammation and intraplantar injection of KO2 where rats received SP orally (10, 30, and 100 mg/kg). SP decreased in concentration-dependent-manner the expression of cicloxigenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) following LPS stimulation. SP was able to enhance anti-oxidant enzyme production such as manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1) following H2O2 stimulation. In in vivo models, SP (30 and 100 mg/kg) reduced paw inflammation and tissue damage after CAR and KO2 injection. Our results demonstrated the anti-inflammatory and anti-oxidant properties of SP; therefore, we propose that SP may be an effective strategy for the treatment of inflammatory diseases.

Analgesic, anti-inflammatory and antipyretic activities of ethanolic extract of stem bark of Anogeissus latifolia Roxb

BackgroundStem bark of Anogeissus latifolia Roxb (family: Combretaceae) is used traditionally and ethnomedicinally to alleviate pain, inflammation and fever conditions. The current study investigates the analgesic, anti-inflammatory and antipyretic activities of ethanolic extract of stem bark of Anogeissus latifolia Roxb.MethodThe HPLC studies were carried out to standardize the stem bark ethanolic extract of Anogeissus latifolia (ALEE) using ellagic acid as a marker. ALEE was screened for analgesic (formalin-induced pain and acetic acid induced writhing) and anti-inflammatory (formalin and carrageenan-induced paw oedema) activities in Wistar rats. Before 1 h of acetic acid or formalin or carrageenan injection, rats were orally fed with ALEE (100, 200 and 400 mg/kg), Aspirin (100 mg/kg) or Indomethacin (10 mg/kg). Antipyretic effect was studied in brewer’s yeast-induced pyrexia model in rats using Paracetamol (100 mg/kg) as a standard drug.ResultsHPLC analysis of ALEE revealed the presence of ellagic acid. ALEE treatment (200 and 400 mg/kg) significantly inhibited pain response in both models. ALEE treatments prevented the raise of paw volume in both in-vivo models with percent inhibition of 44.40 and 46.21, respectively at 5 h. ALEE also showed a significant reduction of yeast-induced pyrexia till 4 h of treatment.ConclusionALEE exhibited analgesic, anti-inflammatory and antipyretic property in experimental models and validates traditional use of ALEE in pain, inflammation and fever.

Diallyl Disulfide Suppresses Inflammatory and Oxidative Machineries following Carrageenan Injection-Induced Paw Edema in Mice.

Diallyl disulfide (DADS) is the major organosulfur constituent in garlic, with a variety of pharmacological activities including antioxidant and anti-inflammatory. Here, we examined the potential antiedematous impact of DADS- versus carrageenan-mediated paw edema in mice. Carrageenan injection potentiated an inflammatory reaction as presented by the elevated serological C-reactive protein (CRP) levels and transcription of tumor necrosis factor-alpha (TNF-α, Tnfα), interleukin-1 beta (IL-1β, Il1b), interleukin-2 (IL-2, Il2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2, Ptgs2), prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1, Ccl1), nuclear factor kappa B (NF-κB), and myeloperoxidase (MPO) activity, while interleukin-10 (IL-10) was declined in the injured paw tissue. Additionally, carrageenan elevated lipid peroxidation in terms of malondialdehyde (MDA) and decreased glutathione content (GSH). Remarkably, DADS was found to inhibit the inflammatory signaling, suppressed the developed oxidative damage, and protected the histopathological alterations in the inflamed paw tissue in response to carrageenan injection. Our findings suggest that DADS could be used as an alternative therapy used to alleviate the pathophysiological changes associated with the genesis of paw edema through its potent anti-inflammatory and antioxidant impacts.

Comparison of the effect between electroacupuncture and NSAIDs on pain memory based on cAMP/PKA/CREB pathway in anterior cingulate gyrus

To observe the direct intervention effects of electroacupuncture (EA) and non-steroid anti-inflammatory drugs (NSAIDs) on pain memory, and to explore their effects on cAMP/PKA/cAMP pathway in anterior cingulate gyrus (ACC). Fifty clean healthy male SD rats were randomly divided into a control group, a model group, an indomethacin group, an EA group and a sham EA group, 10 rats in each group. Except the control group, the pain memory model was established in the remaining four groups by twice injection of carrageenan at foot; 0.1 mL of 2%λ-carrageenan was subcutaneously injected at the left foot of rats; 14 days later, when the pain threshold of rats of each group returned to the basic level, the second injection was performed with the same procedure. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36) for 30 min; the rats in the indomethacin group was treated with indomethacin intragastric administration with the dose of 3 mg/kg; the rats in the sham EA group was treated with EA without electricity at the point 0.3 mm forward "Zusanli" (ST 36) with the depth of 2 mm for 30 min; the rats in the control group was not given any invention. All the above interventions were performed 5 h, 1 d, 2 d and 3 d after the second injection of 2% λ-carrageenan. The left-side paw withdrawal thresholds (PWT) were observed before the first injection, 4 h, 3 d, 5 d after the first injection, before the second injection and 4 h, 1 d, 2 d, 3 d after the second injection. Three days after the second injection, the number of positive cells of cAMP, p-PKA, p-CREB and the number of positive cells of protein co-expression in the right ACC brain area were detected by immunofluorescence, and the relative protein expression of p-PKA and p-CREB were detected by Western blot. Compared with the control group, the PWTs in the model group decreased significantly 4 h, 3 d and 5 d after the first injection and 1 d, 2 d and 3 d after the second injection (P<0.05); compared with the control group, the positive expression of cAMP, p-PKA and p-CREB in the right ACC brain area in the model group increased significantly (P<0.05), and the number of positive cells of the co-expression of cAMP/p-PKA and p-PKA/p-CREB also increased significantly (P<0.05). Compared with the model group, indomethacin group and sham EA group, the PWTs in the EA group were increased significantly 1 d, 2 d and 3 d after the second injection (P<0.05); compared with the model group, indomethacin group and sham EA group, the positive expression of p-PKA and p-CREB in the right ACC brain area in the EA group decreased significantly (P<0.05), and the number of positive cells of co-expression of cAMP/p-PKA and p-PKA/p-CREB was decreased significantly (P<0.05). Compared with the model group and sham EA group, the positive expression of cAMP in the right ACC brain area was decreased in the EA group (P<0.05). EA have a direct intervention effect on pain memory, which have significant advantage over NSAIDs in the treatment of chronic pain. The advantage effect of EA on pain memory may be related to the inhibition of cAMP/PKA/CREB pathway in ACC area.

The apoptosis clearance signal phosphatidylserine inhibits leukocyte migration and promotes inflammation resolution in vivo

Previous studies have shown that phagocytosis of apoptotic cells can tune the macrophage phenotype and trigger the resolution of inflammation. This mechanism is largely dependent on the recognition of phosphatidylserine (PS) residues on the outer membrane of dying cells. Therefore, we sought to assess the effects of PS-containing liposomes (mimics of apoptotic cells) on the leukocyte migration profile during the inflammatory process in vivo.Inflammation was induced by carrageenan injection into air pouches created on the dorsal region of mice, as this model enables convenient access to the exudates for further investigation. Mice were treated with PBS, PS-containing or phosphatidylcholine (PC)-containing liposomes (10, 30 or 100 mg/kg intraperitoneally [i.p.]). Starting 8 h after carrageenan injection, the level of leukocyte infiltration was monitored over three days. The PS-containing, but not PC-containing, liposomes reduced the polymorphonuclear (PMN) and mononuclear (MN) leukocyte influx into the inflamed pouches in a dose-dependent fashion. Most notably, these effects could also be adoptively transferred; that is, they were also found in mice injected with a liposome-free peritoneal lavage obtained from the mice that had received the intraperitoneal PS-liposome treatment. The effect of treatment with the PS-induced soluble mediators (PS-ISMs) was found to be dependent on the presence of peritoneal macrophages and was susceptible to heat, trypsin degradation, and cycloheximide treatment. The PS-containing liposomes promoted the reduction of PMN leukocyte influx by triggering the release of anti-inflammatory autacoids with a proteinaceous nature that were produced de novo after PS exposure.

Phenolic compounds, biological activities and trace elements of Capparis ovata var. canescens

Introduction: Capparis species (Capparaceae), also called caper, grow naturally in various regions of the world. Caper is a plant with medicinal and aromatic properties. Flower buds, root bark, and fruits of the plant are used in folk medicine due to their analgesic, wound healing, cell regeneration, tonic, and diuretic effects. Objective: The aim of this research was to evaluate in vitro (anti-urease, antioxidant, anticholinesterase) and in vivo (anti-inflammatory) biological activities of caper (C. ovata var. canescens). In addition, we aimed to identify its major phenolic compounds using high performance liquid chromatography with a photodiode array detector (HPLC-DAD) and confirmate them using quadrupole time-of-flight liquid chromatography with tandem mass spectrometry (Q-TOF-LC/MS). Also, we quantified the concentrations of several trace and major elements in plant samples using inductively coupled plasma-mass spectrometry (ICP-MS). Methods: The antioxidant, anti-urease and anticholinesterase activities of different plant extracts were evaluated using DPPH, FRAP, ABTS/TEAC, Indophenol and Ellman tests. The identification of phenolic compounds and trace element contents was performed using HPLC and Q-TOF-LC/MS and ICP-MS. Results: Soxhlet methanol extract exhibited the strongest anti-urease, antioxidant (ABTS/TEAC) and anticholinesterase activity. Soxhlet and maceration methanol extracts demonstrated significant anti-inflammatory effect in the altered edema size after the second hour of carrageenan injection. The active phenolic compounds in Soxhlet methanol extract were identified as rutin, quercetin-hexoside-hexoside, quercetin-3-O-hexoside and kaempferol-3-O-rutinoside. In addition, the average concentrations of vanadium, chromium, manganese, cobalt, copper, nickel, arsenic, selenium, zinc and lead were within the permissible limits defined by WHO for medicinal plants. However, it was found that the concentrations of cadmium and iron were higher than the maximum permissible limits. Conclusion: Our results suggest that although caper has a strong biological activity, it should be consumed carefully due to the excess amount of cadmium and iron elements it contains.

PPARβ/δ Agonism Upregulates Forkhead Box A2 to Reduce Inflammation in C2C12 Myoblasts and in Skeletal Muscle.

Daily activities expose muscles to innumerable impacts, causing accumulated tissue damage and inflammation that impairs muscle recovery and function, yet the mechanism modulating the inflammatory response in muscles remains unclear. Our study suggests that Forkhead box A2 (FoxA2), a pioneer transcription factor, has a predominant role in the inflammatory response during skeletal muscle injury. FoxA2 expression in skeletal muscle is upregulated by fatty acids and peroxisome proliferator-activated receptors (PPARs) but is refractory to insulin and glucocorticoids. Using PPARβ/δ agonist GW501516 upregulates FoxA2, which in turn, attenuates the production of proinflammatory cytokines and reduces the infiltration of CD45+ immune cells in two mouse models of muscle inflammation, systemic LPS and intramuscular injection of carrageenan, which mimic localized exercise-induced inflammation. This reduced local inflammatory response limits tissue damage and restores muscle tetanic contraction. In line with these results, a deficiency in either PPARβ/δ or FoxA2 diminishes the action of the PPARβ/δ agonist GW501516 to suppress an aggravated inflammatory response. Our study suggests that FoxA2 in skeletal muscle helps maintain homeostasis, acting as a gatekeeper to maintain key inflammation parameters at the desired level upon injury. Therefore, it is conceivable that certain myositis disorders or other forms of painful musculoskeletal diseases may benefit from approaches that increase FoxA2 activity in skeletal muscle.

Low-intensity ultrasound attenuates paw edema formation and decreases vascular permeability induced by carrageenan injection in rats

BackgroundTherapeutic potential of low-intensity ultrasound (LIUS) has become evident in various musculoskeletal diseases. We have previously shown that LIUS has an inhibitory effect on local edema in various diseases including the arthritis and brain injury. In this study, we examined whether LIUS can attenuate paw edema formation vis-à-vis vascular permeability and inflammation in rats induced by carrageenan. LIUS with a frequency of 1 MHz and the intensities of 50, 100, or 200 mW/cm2 were exposed on rat paws for 10 min immediately after carrageenan injection.ResultsCarrageenan injection induced paw edema which was peaked at 6 h and gradually decreased nearly to the initial baseline value after 72 h. LIUS showed a significant reduction of paw edema formation at 2 and 6 h at all intensities tested. The highest reduction was observed at the intensity of 50 mW/cm2. Histological analyses confirmed that LIUS clearly decreased the carrageenan-induced swelling of interstitial space under the paw skin and infiltration of polymorphonuclear leukocytes. Moreover, Evans Blue extravasation analyses exhibited a significant decreases of vascular permeability by LIUS. Finally, immunohistochemical staining showed that expression of pro-inflammatory proteins, namely, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) induced by carrageenan injection was reduced back to the normal level after LIUS stimulation.ConclusionsThese results provide a new supporting evidence for LIUS as a therapeutic alternative for the treatment of edema in inflammatory diseases such as cellulitis.

Acute Mono-Arthritis Activates the Neurohypophysial System and Hypothalamo-Pituitary Adrenal Axis in Rats.

Various types of acute/chronic nociceptive stimuli cause neuroendocrine responses such as activation of the hypothalamo-neurohypophysial [oxytocin (OXT) and arginine vasopressin (AVP)] system and hypothalamo-pituitary adrenal (HPA) axis. Chronic multiple-arthritis activates the OXT/AVP system, but the effects of acute mono-arthritis on the OXT/AVP system in the same animals has not been simultaneously evaluated. Further, AVP, not corticotropin-releasing hormone (CRH), predominantly activates the HPA axis in chronic multiple-arthritis, but the participation of AVP in HPA axis activation in acute mono-arthritis remains unknown. Therefore, we aimed to simultaneously evaluate the effects of acute mono-arthritis on the activity of the OXT/AVP system and the HPA axis. In the present study, we used an acute mono-arthritic model induced by intra-articular injection of carrageenan in a single knee joint of adult male Wistar rats. Acute mono-arthritis was confirmed by a significant increase in knee diameter in the carrageenan-injected knee and a significant decrease in the mechanical nociceptive threshold in the ipsilateral hind paw. Immunohistochemical analysis revealed that the number of Fos-immunoreactive (ir) cells in the ipsilateral lamina I–II of the dorsal horn was significantly increased, and the percentage of OXT-ir and AVP-ir neurons expressing Fos-ir in both sides of the supraoptic (SON) and paraventricular nuclei (PVN) was increased in acute mono-arthritic rats. in situ hybridization histochemistry revealed that levels of OXT mRNA and AVP hnRNA in the SON and PVN, CRH mRNA in the PVN, and proopiomelanocortin mRNA in the anterior pituitary were also significantly increased in acute mono-arthritic rats. Further, plasma OXT, AVP, and corticosterone levels were significantly increased in acute mono-arthritic rats. These results suggest that acute mono-arthritis activates ipsilateral nociceptive afferent pathways at the spinal level and causes simultaneous and integrative activation of the OXT/AVP system. In addition, the HPA axis is activated by both AVP and CRH in acute mono-arthritis with a distinct pattern compared to that in chronic multiple-arthritis.

Antiarthritic and Antihyperalgesic Properties of Ethanolic Extract from Gomphrena celosioides Mart. (Amaranthaceae) Aerial Parts.

Gomphrena celosioides Mart. (Amaranthaceae) is used in folk medicine as a natural analgesic, and in Brazil, the species of genus Gomphrena is used for rheumatism. However, scientific evidence which supports its popular use as an analgesic is scarce. This study assessed the antiarthritic and antihyperalgesic activities of the ethanolic extract obtained from G. celosioides aerial parts on Swiss or C57BL/6 mice. The antiarthritic and antihyperalgesic potential of Gomphrena celosioides was evaluated using paw edema, mechanical hyperalgesia, cold allodynia, carrageenan-induced pleurisy, articular inflammation zymosan-induced, Freund's complete adjuvant-induced inflammation zymosan-induced peritonitis, and carrageenan-induced adhesion and rolling experiment models. All doses of G. celosioides (300, 700, and 1000 mg/kg) significantly reduced edema formation in all the intervals evaluated, whereas the mechanical hyperalgesia was reduced 3 hours after the carrageenan injection. The cold hyperalgesia was significantly decreased 3 (700 mg/kg) and 4 hours (700 and 1000 mg/kg) after the carrageenan injection. Ethanolic extract of G. celosioides at 1000 mg/kg reduced the total leukocyte number, without interfering in the protein extravasation in carrageenan-induced pleurisy model. Ethanolic extract of G. celosioides (300 mg/kg) was also able to reduce significantly the leukocyte migration in zymosan-induced articular edema, while a reduction of the adhesion and migration and leukocyte rolling was induced by the ethanolic extract of G. celosioides (300 mg/kg) in zymosan-induced peritonitis. In Freund's complete adjuvant-induced inflammation model, an edema formation and mechanical hyperalgesia reduction were induced by the ethanolic extract of G. celosioides on day 22, whereas the cold allodynia was reduced on day 6 of treatment with the extract. These results show that ethanolic extract of G. celosioides has antihyperalgesic and antiarthritic potential in different acute and persistent models, explaining, at least in part, the ethnopharmacological relevance of this plant as a natural analgesic agent.

Analgesic and antiinflammatory activities of the capilliposide derived from Lysimachia capillipes Hemsl., a traditional Chinese medicinal herb

Pain and inflammation are associated with the pathophysiology of different clinical conditions. The Lysimachia capillipes Hemsl. capilliposide (LCc) is the main bioactive component of this Chinese medicinal herb, which is widely used as a remedy for the treatment of colds and arthritis. This study investigated the analgesic and antiinflammatory activities of LCc in an animal model. LCc had no significant influence on the spleen, lung, liver and stomach coefficients in mice. Pharmacological studies showed that LCc at all doses (40, 60 and 90 mg/kg) increased the latency period of paw licking induced by thermal stimulation, and at the dose of 40 mg/kg it significantly suppressed abdominal writhing episodes of mice induced by intraperitoneal (i.p.) injection of acetic acid. LCc also had antiinflammatory effect on inflammation models. Doses of 60 and 90 mg/kg suppressed paw edema induced by subcutaneous (s.c.) injection of carrageenan. Mechanistic studies revealed that the antiinflammatory effect of LCc was associated with inhibition of the production of malondialdehyde (MDA), prostaglandin E2 (PGE2), tumor necrosis factor (TNF-?), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in paw tissue of carrageenan-injected mice. These results show that LCc has analgesic and antiinflammatory effects in mice.

Anti-inflammatory and anti-angiogenesis effect of bee pollen methanolic extract using air pouch model of inflammation.

Background and purpose:Research on new drugs with a natural source and low side effects is a priority in pharmacology studies. The present study was conducted to investigate the anti-inflammatory and anti-angiogenesis effects of bee pollen extract in the air pouch model of inflammation.Experimental approach:To achieve this goal, male rats were moderately anesthetized and then 20 and 10 mL of sterile air were subcutaneously injected into the intrascapular area of the back of the rat on first and third days, respectively. On day 6, inflammation was induced by intrapouch injection of carrageenan. Normal saline in the control group and bee pollen methanolic extract (50, 100, and 200 mg/pouch) were administered at day 6, simultaneously with carrageenan, and then for 2 consecutive days only normal saline and the extracts were injected. Following sacrificing the rats the pouch was opened and the exudate volume, leukocyte accumulation, granulation tissue weight, vascular endothelial growth factor (VEGF), interleukin 1beta, and tumor necrosis factor alpha (TNF-α) concentrations were determined 3 days after induction of inflammation. In order to investigate the angiogenesis, the granulation tissue was removed, homogenized in the Drabkin’s reagent, and then centrifuged. The supernatant was filtered and the hemoglobin concentration was determined using a spectrophotometer.Results:Bee pollen extract significantly decreased the exudate volume, leukocyte accumulation, granulation tissue weight, angiogenesis, VEGF, and TNF-α concentration.Conclusion and implications:The findings of the current study revealed that bee pollen methanolic extract has an anti-inflammatory and anti-angiogenesis effect, which could be attributed to the inhibition of VEGF and TNF-α production in the inflammatory exudates.

Parietal Block Using Bupivacaine in the Rat: An Anatomical, Behavioral and Histological Study.

PurposeAnimal models of regional anaesthesia are useful for studying the effects of blocks and improve their efficacy. The aim of our experiments was to validate a multi-site paravertebral block in the rat.Material and methodsDissection and indigo carmine dye injection were performed in five rats (3 rats were dissected and 2 were dye injected). In other groups (n=7rats/group), after inflammation inductive carrageenan injection in the abdominal wall, bupivacaine or saline was injected laterally to the spinal column at the T5, T10, L1, L4 and S1 level. The efficacy of the block on mechanical nociception was measured using von Frey hairs. In addition, we measured c-Fos immunoreactive nuclei in the cord.ResultsThe multi-site injection showed a perinervous distribution of the injected solution without intra-thoracic, intra-abdominal or epidural diffusion. Bilateral block with a relatively small volume of bupivacaine (0.5 mL) significantly increased the threshold to mechanical pain as compared to control (p=0.007) and significantly decreased the number of c-Fos immunoreactive nuclei in the posterior horn of the spinal cord (p<0.0001).ConclusionThis study shows that a parietal abdominal wall block is easy to perform in the rat. This block allows investigators to explore the mechanisms of action of abdominal parietal wall blocks.

Synergistic Effects of Metformin and Cocoa Flavanol on Inflammatory and Oxidant Markers Induced by Carrageenan: Pathophysiological Approach

Background and Aim: The present study aims to evaluate the effects of metformin, cocoa flavanol and their combination as anti-inflammatory and antioxidant drugs. Methods: Forty adult male albino mice are divided into five groups: Control, Carrageenan (Cg), Cg Metformin (Met), Cg Cocoa and Cg Met Cocoa groups. Cg is used to induce the inflammation through injection of it in the paw of the hind leg and into the trunk of mice. Also, Met is applied intraperitoneally at the same time of Cg injection while Cocoa is received orally seven days before carrageenan injection. Biochemical estimation of inflammatory mediators (COX-2, PGE2, TNF-α, CRP) and selected oxidative stress markers (MDA, SOD, GSH) was performed. Results: This study elucidated the marvellous leverage of the metformin, cocoa flavanol and their combination as anti-inflammatory and antioxidant drugs, where metformin and Cocoa decreased all inflammatory mediators (COX-2, PGE2, TNF-α, CRP) with high significant (P<0.01) in comparing with Cg group. In addition, the level of MDA is decreased significantly (P<0.01), while the levels of SOD and GSH are increased significantly (P<0.01) in comparing with Cg group. Interestingly, their combination restored normal levels of the inflammatory mediators and the oxidative stress markers. Conclusion: I concluded that Met and cocoa are powerful anti-inflammatory substances and can ameliorate the oxidative stress that results from inflammation. Additionally, the mixture of them can retrieve the normal levels of all measured parameters.

Anti-Inflammatory Effect of Polyherbal Formulation (PHF) on Carrageenan and Lipopolysaccharide-Induced Acute Inflammation in Rats

Polyherbal formulation (PHF) is composed of Artemisia santolinifolia Turcz, Saussurea salicifolia L. and Hippophae rhamnoides L., which mainly used for inflammatory disorders in traditional Mongolian medicine. The aim of the study was to evaluate the anti-inflammatory effect of PHF in carrageenan and lipopolysaccharide (LPS) induced models of inflammation. The total active constituents of 20% ethanol extract of PHF was determined, using Folin-Ciocalteu reagent and aluminum chloride reagent, respectively. Inflammation models were induced by 1% carrageenan and LPS 7.5 mg/kg in the experimental groups. The levels of serum tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and high mobility group box 1 protein (HMGB-1) were measured in PHF pretreatment groups by enzyme-linked immunosorbent assay (ELISA). The lungs were harvested and evaluated for histopathological assessment on 12 hours after LPS administration. The content of total phenolic was 28.5±0.12 mg/g and flavonoids 12.4±0.42 mg/g. After 60, 120, 180, 240 and 300 min, the data indicate that PHF 75, 150 and 300 mg/kg was significantly effective reducing paw edema volumes induced by carrageenan compared to control (p&lt;0.01). PHF pretreatment significantly reduced levels of serum TNF-α, IL-1β and IL-6 at 300 minutes after carrageenan injection. Moreover, pretreated with PHF 150 mg/kg groups serum levels of TNF-α, IL-1β and HMGB-1 were significantly (p&lt;0.01) reduced compared with the control group after LPS injection. It showed less inflammation and change of pulmonary structure compared with the LPS group at 12 hours after LPS injection. From the results of the study, it was demonstrated that PHF had sufficient potential to treat inflammatory disorders by reducing pro-inflammatory cytokines.

Antipyretic, anti-inflammatory and analgesic activities of Periplaneta americana extract and underlying mechanisms

Periplaneta americana is a common traditional Chinese medicinal material which has been used to treat arthritis, fever, aches, pains, and inflammation of the extremities for several hundred years. However, little scientific data exists in literature to support its use. The purpose of this study was to evaluate the antipyretic, anti-inflammatory and analgesic activities of Periplaneta americana extract (PAE) and explore its underlying mechanism. The antipyretic, anti-inflammatory and analgesic activities were evaluated by LPS-induced fever, carrageenan-induced paw edema, abdominal writhing, hot plate and formalin tests, respectively. The mechanism of action was explored by antioxidant activity analysis, inflammatory cytokines expression and febrile mediator measurement, and pathway activation analysis. The results from UHPLC-HRMS indicated that the extract was found to contain dopamine, coumarin, dipeptide, vitamin, organic acid, amino acid and its metabolites, and other organic compounds. PAE showed in a dose-dependent manner antioxidant activity and reduced the protein production and mRNA expression of NO, IL-1β, IL-6, and TNF-α in RAW 264.7 cells in vitro. Moreover, PAE significantly and dose-dependently inhibited the writhing responses and licking time in formalin tests, increased response latency in the hot plate test, reduced carrageenan-induced paw edema and inflammation in mice, decreased LPS-induced rT increase in rats. Furthermore, PAE treatment markedly inhibited the increase in the levels of NO, IL-6, IL-1β, TNF-α, PGE2 and cAMP in plasma of fevered rat, greatly suppressed the activation of inflammatory response pathway and the change of MDA and GSH concentration, MPO and SOD activity as well as FRAP capacity in paw induced by carrageenan injection. In conclusion, the findings suggested that PAE produced potential antinociceptive, anti-inflammatory and antipyretic effects by reducing production of endogenous inflammatory mediators and blocking the MAPK/NF-κB signaling pathway which support the claim for its traditional use in the treatment of various diseases.

Synthesis, pharmacological evaluation and molecular docking of novel R-/S-2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid as dual anti-inflammatory anti-platelet aggregation agents.

R-/S-2-(2-hydroxypropanamido) benzoic acid (R-/S-HPABA), marine-derived anti-inflammatory antiplatelet drugs, were initially synthesised in our group. However, preliminary research showed that R-/S-HPABA were eliminated rapidly because of extensive hydroxylation metabolism of phenyl ring in vivo. In order to reduce significant hydroxylation metabolism to improve pharmacological activity and bioavailability, trifluoromethyl group was incorporated into R-/S-HPABA to synthesise R-/S-2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid (R-/S-HFBA), respectively. The purposes of this study were to report the synthesis of R-/S-HFBA and compare the anti-inflammatory antiplatelet effect and pharmacokinetic properties of R-/S-HFBA with those of R-/S-HPABA. Carrageenan-induced rat paw edema assay was used for the evaluation of the anti-inflammatory activity. R-/S-HFBA showed better results in inhibiting edema and were able to prolong the anti-inflammatory effect after carrageenan injection. The antiplatelet aggregation activity of R-/S-HFBA and R-/S-HPABA was studied on arachidonic acid-induced platelet aggregation of rabbit platelet-rich plasma. The aggregation inhibition rate of R-/S-HFBA was significantly (p < 0.05) higher than that of R-/S-HPABA, respectively. Molecular docking study revealed that R-/S-HFBA possess more potent binding affinity with COX-1/COX-2 than R-/S-HPABA, respectively, and that the presence of trifluoromethyl group leads to increase in activity of R-/S-HFBA. R-/S-HFBA also afford more favorable pharmacokinetic properties than R-/S-HPABA, respectively, such as higher Cmax, larger AUC0-∞, and longer t1/2, which, as expected, are more metabolically stable.

Anti-inflammatory effects of avocado peels against inflammation induced by carrageenan in mice

The aim of this research is to investigate the anti-inflammatory activity of avocado peel against carrageenan-induced inflammation in mice. The group of mice that was used as a negative control group to test the anti-inflammatory activity of infusion and decoction (group I) were given aquadest, while the group for testing the activity of extract (group II) was given CMC-Na. The positive control group (group III) was given potassium diclofenac. Groups IV-VI were given avocado peel infusion with the following doses 667.5; 1335; and 2670 mg/kgBW respectively. Groups VII-IX were given avocado peel decoction with the same doses as the previous groups. Groups X-XII were given 830; 1670; and 3330 mg/kgBW of avocado peel extract respectively. The paw edema were measured using a digital caliper for 6 hours afterwards after carrageenan injection. There were a significant (p&lt;0.05) reduction in paw edema at all doses of infusion, decoction, and extract of avocado peel. Based on the research, it can be concluded that the avocado peels have anti-inflammatory activities.

Clindamycin inhibits nociceptive response by reducing tumor necrosis factor-α and CXCL-1 production and activating opioidergic mechanisms.

Clindamycin, a bacteriostatic semisynthetic lincosamide, is useful in the management of infections caused by aerobic and anaerobic Gram-positive cocci, including bacteremic pneumonia, streptococcal toxic shock syndrome and sepsis. It has been recently demonstrated that clindamycin inhibits in vitro and in vivo inflammatory cytokine production. In the present study, we investigated the effects of clindamycin in acute and chronic models of pain and inflammation in mice and the underlying mechanisms. Intraperitoneal (i.p.) administration of clindamycin (400mg/kg) increased the animal's latency to exhibit the nociceptive behavior induced by noxious heat (hot plate model). Intrathecal injection of clindamycin (2, 10 and 50µg) also increased the animals' latency to exhibit the nociceptive behavior. Tactile hypersensitivity and paw edema induced by intraplantar (i.pl.) injection of carrageenan were attenuated by previous administration of clindamycin (200 and 400mg/kg, i.p.). Clindamycin (100, 200 and 400mg/kg, i.p.) also attenuated ongoing tactile hypersensitivity and paw edema induced by i.pl. injection of complete Freund's adjuvant (CFA). The antinociceptive activity of clindamycin (400mg/kg, i.p.) in the hot plate model was attenuated by previous administration of naltrexone (5 and 10mg/kg, i.p.), but not glibenclamide or AM251. CFA-induced production of TNF-α and CXCL-1 was reduced by clindamycin (400mg/kg, i.p.). Concluding, clindamycin exhibits activities in acute and chronic models of pain and inflammation. These effects are associated with reduced production of TNF-α and CXCL-1 and activation of opioidergic mechanisms. Altogether, these results indicate that the clindamycin's immunomodulatory effects may contribute to a pharmacological potential beyond its antibiotic property.

Design and synthesis of sulfur cross-linked 1,3,4-oxadiazole-nitro(furan/thiophene)-propenones as dual inhibitors of inflammation and tuberculosis: molecular docking and Hirshfeld surface analysis

A series of 3-[5-nitro(furan/thiophene)-2-yl]-1-aryl-3-(5-aryl-1,3,4-oxadiazol-2-ylthio)prop-2-en-1-one derivatives was synthesized and studied with the aim of developing dual inhibitors of multidrug-resistant tuberculosis and inflammation. The in vivo anti-inflammatory activity results showed excellent inhibition of rat paw edema. The methoxybenzene/nitrofuryl derivative of title compounds showed 83% inhibition of inflammation during 2–6 h after carrageenan injection. All compounds showed anti-tuberculosis activity at MIC of 50 µg/cm3. The molecular docking studies revealed that the oxadiazole and nitrofuran groups played a significant role in the inhibiting site of the enzymes COX1, COX2, 5-LOs, and InhA by forming hydrogen bonding with Tyr 385, Ser 530, Tyr 467, and Tyr 158 amino acid residues, respectively. The novel compounds are active antibacterial agents with potential inhibition on E. coli bacteria. The toxicity results showed good percentage viability of human kidney cell lines with IC50 value greater than 100 µg/cm3 concentration. The Hirshfeld surface analysis and electrostatic potential map of compound showed good intermolecular contacts and hydrogen bonding donor and acceptor potential.