Protocatechuic Acid Counteracts Oxidative Stress And Inflammation In Carrageenan- Induced Paw Edema in Mice

PCA (protocatechuic acid), a phenolic compound found in teas, fruits and vegetables, is widely recognized with its antioxidant and anti-inflammatory activities. Here we verified the protective role of PCA on carrageenan-induced paw edema in mice. PCA (25 mg/kg and 50 mg/kg) administration was applied for five consecutive days prior to the carrageenan injection. Diclofenac sodium (20 mg/kg) was used as a reference drug. PCA pretreatment notably decreased the volume of the developed edema and alleviated the histopathological alterations induced by carrageenan. Additionally, PCA administration enhanced the cellular antioxidant capacity as demonstrated by the increased levels of catalase, superoxide dismutase and reduced glutathione, in addition to the decreased malondialdehyde level in the edematous tissue. Interestingly, PCA administration was able to suppress the developed inflammatory response upon carrageenan injection as indicated by the decreased levels and expression of pro-inflammatory cytokines and mediators including tumor necrosis factor alpha, interlukin-1 beta, interlukin-6, inducible nitric oxide synthase, nitric oxide, cyclooxygenase-II, prostaglandin E2, monocyte chemoattractant protein-1, myeloperoxidase and nuclear factor kappa B. These results collectively confirm the protective effect of PCA against carrageenan-induced paw edema owing to its antioxidant and anti-inflammatory characteristics.

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.

Anti-Inflammatory Activity of Rhaphidophora pinnata (L.F) Schott Leaf Extract

BACKGROUND: Cancer growth is influenced by many factors and in general it is an interaction between gene factors and environmental factors, especially the microenvironment that exists around cancer. The inflammatory response plays a decisive role in various stages of cancer growth. AIM: The aim of this study was to determine the anti-inflammatory activity of ethanol extract of Rhaphidophora pinnata leaves. METHODS: R. pinnata leaf extract was obtained by percolation method using 96% ethanol as the solvent at room temperature. Anti-inflammatory activity was determined based on the paw edema method. Thirty male albino mice were treated orally with sodium carboxyl cellulose suspension (as negative control group), R. pinnata leaf extract (35, 70, 140, and 280 mg/kgBW), and diclofenac (as positive control group), 60 min before 0.2 mL 1% carrageenan injection. The paw thickness was measured using plethysmometer before injecting the carrageenan and after 1, 2, 3, 4, 5, and 6 h. RESULTS: The subplantar injection of carrageenan caused a time-dependent paw edema in the mice. Oral administration of R. pinnata leaf extract inhibited paw swelling at 1, 2, 3 4, 5, and 6 h after carrageenan injection. R. pinnata leaf extracts doses of 35, 70, 140, and 280 mg/kgBW gave a percentage inhibition of 56.56%, 56.18%, 62.77%, and 49.30%, respectively. The effective dose of R. pinnata leaf extract as an anti-inflammatory was 140 mg/kgBW. CONCLUSION: Ethanol extract of R. pinnata leaf has anti-inflammatory activity in male albino mice.

Cashew (Anacardium occidentale L.) Nuts Counteract Oxidative Stress and Inflammation in an Acute Experimental Model of Carrageenan-Induced Paw Edema

Background: Anacardium occidentale L. is a medicinal plant with powerful anti-oxidative and anti-inflammatory properties. Acute inflammatory events cause tissue alterations, decrease of anti-oxidative endogenous enzymes such as superoxide dismutase, catalase and glutathione, neutrophils infiltration, increase in the activities of myeloperoxidase, malondialdehyde, and pro-inflammatory release. Methods: Paw edema was induced by subplantar injection of carrageenan into the right hind paw in rats, but 30 min before a group of animals were orally treated with 100 mg/kg of cashew nuts to evaluate the anti-inflammatory and anti-oxidative response. Results: In the present work, we found that (1) cashew nuts reduced the development of carrageenan-induced paw edema limiting the formation of edema and pain; (2) cashew nuts ameliorated the diminutions of the anti-oxidative enzymes caused by carrageenan injection; (3) cashew nuts decreased myeloperoxidase malondialdehyde activity induced by carrageenan; and (4) cashew nuts acted by blocking pro-inflammatory cytokines response and nitrate/nitrite formation stimulated by carrageenan injection. Conclusions: The mechanisms of anti-inflammatory and analgesic effects exerted by cashew nuts were relevant to oxygen free radical scavenging, anti-lipid peroxidation, and inhibition of the formation of inflammatory cytokines.

Beneficial Effects of Inflammatory Cytokine-Targeting Aptamers in an Animal Model of Chronic Prostatitis

Non-bacterial prostatitis is an inflammatory disease that is difficult to treat. Oligonucleotide aptamers are well known for their stability and flexibility in conjugating various inflammatory molecules. In this study, we investigated the effects of inflammatory cytokine-targeting aptamers (ICTA), putative neutralizers of TNF-alpha and IL-1 beta activation, on local carrageenan-induced prostate inflammation, allodynia, and hyperalgesia in rats. In vitro evaluation confirmed the binding capability of ICTA. Intraprostatic injection of carrageenan or control vehicle was performed in six-week-old rats, and ICTA (150 µg) or vehicle was administered in the prostate along with carrageenan injection. The von Frey filament test was performed to determine mechanical allodynia, and prostate inflammation was examined seven days after drug administration. Local carrageenan administration resulted in a reduction of the tactile threshold. The levels of mononuclear cell infiltration, pro-inflammatory cytokine interleukin-1 beta (b), caspase-1 (casp-1), and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing proteins 1 and 3 (NALP1 and NALP3) in the prostate of rats were increased seven days after carrageenan injection. Treatment with ICTA significantly attenuated the carrageenan-induced hyperalgesia and reduced the elevated levels of proteins including TNF-a and IL-1b in the rats. Apoptosis markers, B-cell lymphoma 2-associated X protein (Bax) and caspase-3, were elevated in ICTA-treated Chronic pelvic pain syndrome (CPPS) rats. These results suggest that ICTA provides protection against local carrageenan-induced enhanced pain sensitivity, and that the neutralization of proinflammatory cytokines may result in inflammatory cell apoptosis.

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.

Activated spinal astrocytes contribute to the later phase of carrageenan-induced prostatitis pain

Background Prostatodynia is the main symptom of chronic prostatitis and the main reason that patients go to the hospital for treatment. Although a variety of factors, including inflammatory immune response, nervous system sensitization, and psychological factors, have been shown to play important roles in the induction and development of chronic pain in prostatitis, the underlying cause of chronic prostatodynia maintenance in prostatitis patients remains unclear. Methods A mouse model of chronic prostatitis induced by carrageenan injection was used. The von Frey test was used to measure pain behavior. The microglial and astrocyte activations were immunohistochemically demonstrated with antibodies against Iba1 and GFAP. The expression of cytokine or signaling pathway was detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting. Results In this study, we provide several lines of evidence to demonstrate that activated spinal astrocytes contribute to the later phase (5 weeks after carrageenan injection) of carrageenan-induced prostatitis pain. First, activation of spinal astrocytes but not microglia was found in the spinal cord dorsal horn at 5 weeks. Second, intrathecal injection of the astroglial toxin L-2-Aminoadipate acid (L-AA) but not microglial inhibitor minocycline reduced mechanical allodynia at 5 weeks. Third, chronic prostatitis induced a profound and persistent upregulation of connexin-43 hemichannels in spinal astrocytes, and spinal injection of the connexin-43 inhibitor carbenoxolone (CBX) effectively reduced pain symptoms. Fourth, increased expression and release of chemokine C-X-C motif ligand 1 (CXCL1) in the spinal dorsal horn and intrathecal injection of a CXCL1 neutralizing antibody or the CXCR2 (a major receptor of CXCL1) antagonist SB225002 significantly reduced mechanical allodynia at 5 weeks. Conclusions In this study, we found that a novel mechanism of activated spinal astrocytes plays a crucial role in maintaining chronic prostatitis-induced persistent pain via connexin-43-regulated CXCL1 production and secretion.

Pain-Relieving Effect of 4.4 MHz of Pulsed Radiofrequency on Acute Knee Arthritis in Rats

Objective Drug injections and surgery are popular treatments for knee joint osteoarthritis. However, these treatments are invasive, and new noninvasive treatments with similar or better efficacy are needed. Here, we evaluated the application of 4.4 MHz of pulsed radiofrequency (PRF) as a new treatment. Methods Acute arthritis was induced by injection of carrageenan into the intra-articular space of the knee in male rats. At 4.5 hours after arthritis induction, PRF with the treatment protocol of three seconds on and off was applied to the affected knee joint for 20 minutes. The changes in pain behavior were evaluated by comparing the peak weight load values of both hind paws at pretreatment and four, six, seven, eight, and 24 hours after treatment. And we also used Western blotting and immunohistochemistry to measure the inflammatory changes in the synovial membrane of the inflamed knee. Results We found that the 20-minute application of PRF with the treatment protocol significantly recovered the weight load reduction at six-, seven-, and eight-hour time points after carrageenan injection. COX-2 and IL-1β levels were significantly reduced in the inflamed rats after PRF application at six and eight hours post–carrageenan injection. Immunohistochemistry showed that PRF significantly reduced inflammatory cell infiltration at six hours post–carrageenan injection. Conclusions . Our results indicate that noninvasive PRF application inhibited pain-related behavior and decreased inflammatory cytokine expression in the inflamed knee joints of rats. Accordingly, PRF application can serve as a potential therapeutic treatment to relieve pain associated with peripheral joint/tissue damage or inflammation.