Narrow Results

Electroacupuncture (EA) is used to relieve various kinds of pain. However, the mechanistic basis of electroacupuncture analgesia (EAA) in inflammatory pain remains unclear. In the present study, we investigated whether endogenous peripheral corticotropin-releasing factor (CRF) or interleukin-1β (IL-1) participated in EAA during hyperalgesia elicited by carrageenan-induced inflammation. Carrageenan was subcutaneously administered by intraplantar (i.pl.) injection of the left hind paw to induce inflammation. Nociceptive thresholds were measured using the paw pressure threshold (PPT) (Randall Sellito Test). Rats received 3 Hz EA in the left anterior tibial muscles for 1 hour after carrageenan injection. The selective CRF antagonist, α-helical CRF, or the recombinant IL-1 receptor antagonist, IL-1ra, was administered by i.pl. injection of the inflamed paw or by intravenous (i.v.) injection 1 hour before EA. PPT decreased significantly 3 hours after carrageenan injection. This decrease persisted at least 24 hours after carrageenan injection. EA resulted in significant increases of PPT, moreover, PPT elevations lasted 24 hours after carrageenan injection. By contrast, PPT elevations produced by EA were dose-dependently antagonized by local i.pl. injection of α-helical CRF or IL-1ra. This PPT elevation was not influenced by i.v. injection of α-helical CRF or IL-1ra. These findings suggest that peripheral CRF or IL-1 participate in EAA during hyperalgesia. The release of CRF or IL-1 elicited by EA may trigger the release of opioid peptides within inflamed tissue which may activate peripheral opioid receptors and inhibit the pain.

Bee venom (BV) has been used to relieve pain and reduce inflammation in traditional Oriental medicine, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). We previously reported that the BV injection into a traditional acupuncture point (Zusanli) reduced arthritis-associated edema and nociceptive responses in Freund's adjuvant-induced arthritis in rats (Kwon et al., 2001). This study was designed to evaluate the anti-inflammatory and anti-cytokine effect of BV on a murine type-II collagen-induced arthritis (CIA) model. Male mice were immunized by spontaneous injection of 100 μg of an emulsion of bovine type-II collagen and complete Freund's adjuvant (CFA), with a booster injection after 2 weeks. In the experimental group, 0.1 ml BV was injected at acupuncture point (Zusanli) near both knees twice a week for a total of 5 times. In the control group, normal saline was injected at the same frequencies. These injections began 5 weeks after the first collagen injection. Starting the 3rd week after the first collagen injection, we examined limb swelling and severity of arthritis twice a week. At 8 weeks, mice were sacrificed and synovial tissue was examined with the light microscope and serum cytokines (IL-1β and TNF-α) were measured by ELISA.

The incidence of arthritis, the mean arthritis index and the number of arthritic limbs were significantly lower in the treatment compared to the control group (63% versus 75%, 3.4% versus 8.5%, 23% versus 75%, respectively). Among the serum proinflammatory cytokines, the production of TNF-α in the BV group was suppressed compared to the control group (59+/-4.5 versus 99.5+/-6.5, p<0.05), but IL-1β was not suppressed. The examination of the histopathology of the joints of murine CIA showed decreased inflammation signs and less lymphocyte infiltration after BV acupuncture therapy. Acupuncture therapy with BV suppressed the development of arthritis and caused inhibition of the immune responses in type-II collagen-induced arthritis.

The effects of extract of Paederia scandens (LOUR.) MERRILL (Rubiaceae) (EPS), a Chinese traditional herbal medicine, on inflammatory and immune responses and their mechanisms in MSU crystals-induced (GA) rats were studied. GA rats were established. Ankle joint volume of rats was measured by volume meter; the level of TNF-α and IL-1β was determined by radioimmunoassay. mRNA expressions of TNF-α and IL-1β in synovial tissue of GA rats were analyzed by RT-PCR, and the expression of NF-κB was detected by immunohistochemistry. The administration of EPS (2.25, 4.5 g/kg, ig 9 days) inhibited the inflammatory response in GA rats. The mRNA expressions of TNF-α and IL-1β were also significantly suppressed in synovial tissue. In addition, EPS (2.25, 4.5 g/kg, ig 9 days) inhibited the expression of TNF-α and IL-1β and the biological activity of NF-κB. These results suggested that EPS possesses antiinflammatory effects by modulating pro-inflammatory mediators' production in synovial tissue and inactivating NF-κB pathway transmembrane signal transduction which plays a crucial role in the pathogenesis of this disease.

Lavender essential oil (LEO) is one the most favorite and widely used essential oils in aromatherapy. Many studies have demonstrated its functions in calming, assisting sleep, reducing pain and muscular spasms and its antiseptic function. To date, however, the mechanism of LEO on inflammation response is not well understood. In this study, we examined the effect of LEO on 5 μg/ml lipopolysaccharide (LPS) induced inflammation reaction in human monocyte THP-1 cells. We found treatment of 0.1% LEO significantly increased cell viability and inhibited the IL-1β and superoxide anion generation in LPS-stimulated THP-1 cells. Treatment with LEO down-regulated both LPS-induced protein levels of phospho-NF-κB and membrane Toll-llike receptor 4. To determine whether the chaperone protein was involved in the reaction, we determined the levels of Heat Shock Protein 70 (HSP70). Our results showed that LEO increased HSP70 expression in LPS-stimulated THP-1 cells, suggesting that the LEO inhibited LPS-induced inflammatory effect might be associated with the expression of HSP70.

Actinidia callosa var. ephippioides (ACE) has been widely used to treat anti-pyretic, antinociceptive, anti-inflammation, abdominal pain and fever in Taiwan. This study aims to determine the mechanism of anti-inflammatory activities of ethyl acetate fraction of ACE (EA-ACE) using a model of λ-carrageenan (Carr)-induced paw edema in mouse model. In HPLC analysis, chemical characterization of EA-ACE was established. In order to investigate the anti-inflammatory mechanism of EA-ACE, we have detected the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the paw edema. Serum NO, tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were evaluated. Chemical characterization from HPLC indicated that EA-ACE contains betulinic acid, ursolic acid and oleanolic acid. In the anti-inflammatory test, EA-ACE decreased the paw edema after Carr administration, increased the activities of CAT, SOD, and GPx and decreased the MDA level in the edema paw at the 5th hr after Carr injection. EA-ACE affects the serum NO, TNF-α, and IL-1β levels at the 5th hr after Carr injection. EA-ACE decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions by Western blotting. Actinidia callosa var. ephippioides have the potential to provide a therapeutic approach to inflammation-associated disorders.

Traditionally, Phyllanthus acidus (Phyllanthaceae) has been used for the treatment of rheumatism, bronchitis, asthma, respiratory disorders, and hepatitis. Recently, we showed that a methanol extract of Phyllanthaceae (Pa-ME) has a potent anti-inflammatory activity in RAW264.7 cells and strongly ameliorates HCl/EtOH-induced gastric ulcers in mice by targeting the Src/Syk of NF-κB. In the present study, we explored the molecular mechanism of Pa-ME on the AP-1 activation pathway and evaluated its potential hepatoprotective effects. To do this, we employed lipopolysaccharide (LPS)-stimulated RAW264.7 cells and U937 cells and an LPS/D-galactosamine (D-GaIN)-induced acute hepatitis mouse model. We utilized a multitude of assays, including immunoblotting analysis, reporter gene assays, and mRNA expression analysis, to determine the effect of Pa-ME on the AP-1 pathway. Pa-ME strikingly suppressed the production of LPS-induced pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). Furthermore, Pa-ME also strongly inhibited activator protein-1 (AP-1) activation and mitogen-activated protein kinase (MAPK) phosphorylation in LPS-stimulated RAW264.7 macrophages cells and the U937 monocyte like human cell line. Moreover, pre-treatment with Pa-ME exhibited strong hepatoprotective and curative effects in an LPS/D-Gal-induced mouse hepatitis model as evidenced by a decrease in elevated serum AST and ALT levels and the amelioration of histological damage. Taken together, our data suggest that Pa-ME might play a crucial ethnopharmacological role as a hepatoprotective herbal remedy by suppressing MAPK signaling and the activity of the downstream transcription factor AP-1.

Canine transmissible venereal tumor (CTVT) is a tumor which can be transmitted naturally through mucosa contact between dogs. When CTVT cells are experimentally inoculated on dogs, they will grow rapidly (Progressive/P phase) and then regress (Regressive/R phase) spontaneously. Therefore, it is a good model to investigate the interactions between tumor cells and host immune system. Previous studies have shown that CTVT cells cannot grow in the dogs restored from CTVT inoculation. To investigate the possible mechanism, this study characterized the CTVT-specific immune response of the peripheral blood mononuclear cells (PBMCs) which isolated from the blood of "naïve" or "CTVT-restored" dogs. The phenotypes (CD3, CD4, CD8, or CD21) of PBMCs were examined by flowcytometry. In response to CTVT stimulation, proliferation, IFN-γ secretion, and cytotoxicity of PBMCs were analyzed. Expression level of proinflammatory cytokines (TNF-α, IL-1β, IL-6, TGF-β), Th1 (IL-2, IFN-γ), and Th2 cytokines (IL-4, IL-10) and cytotoxic proteins (Granzyme B, Perforin) in PBMCs was also evaluated by real-time RT-PCR. The results indicated that there is no significant difference between two groups on lymphocyte phenotypes. Proliferation, IFN-γ secretion, and cytotoxicity of PBMCs between two groups showed no significant difference, except naïve PBMCs present higher proliferation after Con-A stimulation. Production of IL-1β and IL-6 in naïve PBMCs was higher than that in CTVT-restored PBMCs (p < 0.05). The production difference of IL-1β and IL-6 between two groups might be the reason why CTVT cannot be reinoculated on CTVT-restored dog. However, further investigations are necessary to explore the exact role of these cytokines in CTVT growth.