Role In Anti-inflammatory Effects Research Articles

The composition of linoleic acid and conjugated linoleic acid has potent synergistic effects on the growth and death of RAW264.7 macrophages: The role in anti-inflammatory effects

Linoleic acid (LA) is an omega-6 polyunsaturated fatty acid. Conjugated linoleic acid (CLA) is a family of LA isomers that includes both a trans fatty acid and a cis fatty acid. Both fatty acids play a nutritional role in maintaining health. Inflammation is critical in the pathogenesis of many diseases, including cancer. This study found that the combination of LA and CLA (LA/CLA), each of which had no effect, had a strong anti-synergistic effect on inflammatory macrophage RAW264.7 cells in vitro. Cells were cultured in a DMEM containing fetal bovine serum with or without either LA, CLA, or a combination of LA/CLA. The composition of LA and CLA at a comparatively lower concentration synergistically suppressed cell growth, resulting in a reduction in cell number. The underlying mechanism of this effect was based on reduced levels of Ras, PI3K, Akt, MAPK, and mTOR and elevated levels of p21, p53, and Rb, which are associated with cell growth. In addition, the combination of LA and CLA at a lower concentration stimulated potential cell death associated with increased caspase-3 and cleaved caspase-3 levels. Notably, this composition synergistically suppressed the production of TNF-α, IL-6, and PGE2, which are a major mediator of inflammation, with lipopolysaccharide stimulation in RAW264.7 cells This effect was associated with decreased levels of COX-1, COX-2, and NF-κB p65. This study may provide a useful tool for treating inflammatory conditions with the composition of LA and CLA.

Predicting the anti-inflammatory mechanism of Radix Astragali using network pharmacology and molecular docking.

According to current research, the primary active ingredients of Radix Astragali (RA), such as saponins, flavonoids, and polysaccharides, play an important role in anti-inflammatory effects. However, the exact molecular mechanism underlying the action was not elucidated to date. Our research attempted to determine the active components in RA and to investigate the interaction between the active components and targets involved in the anti-inflammation activity by network pharmacology and molecular docking. The active components and targets of RA were screened out by TCMSP. Thereafter, through the "anti-inflammation effect" and "inflammation" as the keywords, disease targets were obtained from the GeneCards database. The PPI network was constructed with Cytoscape 3.8.0 software to screen core targets. The GO function and KEGG analysis were enriched and analyzed through the Metascape platform, obtaining the 3-dimensional view of the core targets from the PDB database, and then, performing molecular docking in AutoDock Vina, a heatmap was constructed using the binding free energies in GraphPad Prism 8. The Discovery Studio software was used for docking analysis, and eventually, the docking results were visualized. We also explored the targets and signaling pathways of Astragaloside IV acting on anti-inflammatory effects via constructing compound-disease-target-pathway network. 18 active components and 45 targets of RA were screened out. The main anti-inflammatory active components of RA were quercetin, Astragaloside IV, kaempferol, 7-O-methylisomucronulatol, and formononetin, and the strongly interacting core proteins were TNF, IL6, IL1B, TLR4, CXCL8, CCL2, IL10, VEGFA, and MMP9. The signal pathways mainly involved include Lipid and atherosclerosis, IL-17 signaling pathway, Chagas disease, leishmaniasis, and TNF signaling pathway. Moreover, molecular docking showed that the 2 most active compounds, Astragaloside IV and kaempferol, could efficiently bind with the targets TNF, TLR4, and IL10. Astragaloside IV may play a part in anti-inflammatory effects through pathways such as HIF-1 signaling pathway, Inflammatory bowel disease and Hepatitis B ect. RA exhibits the characteristic of multicomponent and multitarget synergistic effects in exerting anti-inflammatory effects and the effective component of RA is Astragaloside IV, targeting TNF, TLR4, and IL10.

The potential of the herbal plants of tourism (Curcuma Longa Linn) as a traditional medicine in preventing infections and Section caesarian wound healing

Objective:. This literature review aims to determine herbal medicines in healing and preventing infection in Sectio Caesarea wounds. Method : a literature Review method that synthesizes literature studies by identifying, analyzing, and evaluating data from previous studies. Result: There were 27 indexed and reputable journals, including 17 international journals and nine national journals. The results of the analysis showed the presence of turmeric content that plays an active role in wound healing, namely alkaloids, saponins, tannins, and essential oils as anti-inflammatory, antibacterial, and antiproliferative. Conclusion : The content of metabolites that play an important role in the wound healing process are flavonoids, saponins, and essential oils because these metabolites play a role in anti-inflammatory effects on wounds.

Dimethyl Itaconate Attenuates CFA-Induced Inflammatory Pain via the NLRP3/ IL-1β Signaling Pathway.

Itaconate plays a prominent role in anti-inflammatory effects and has gradually been ushered as a promising drug candidate for treating inflammatory diseases. However, its significance and underlying mechanism for inflammatory pain remain unexplored. In the current study, we investigated the effects and mechanisms of Dimethyl Itaconate (DI, a derivative of itaconate) on Complete Freund’s adjuvant (CFA)-induced inflammatory pain in a rodent model. Here, we demonstrated that DI significantly reduced mechanical allodynia and thermal hyperalgesia. The DI-attenuated neuroinflammation was evident with the amelioration of infiltrative macrophages in peripheral sites of the hind paw and the dorsal root ganglion. Concurrently, DI hindered the central microglia activation in the spinal cord. Mechanistically, DI inhibited the expression of pro-inflammatory factors interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α) and upregulated anti-inflammatory factor IL-10. The analgesic mechanism of DI was related to the downregulation of the nod-like receptor protein 3 (NLRP3) inflammasome complex and IL-1β secretion. This study suggested possible novel evidence for prospective itaconate utilization in the management of inflammatory pain.

Efficacy and safety of low-level light therapy by delicate pulsed light combined with low-dose oral isotretinoin for the treatment of acne vulgaris: a randomized split-face study.

Acne vulgaris (AV) is a common dermatosis that causes psychological problems. Isotretinoin is the first-line treatment for moderate-to-severe AV, but its onset of effect is delayed. Although light-based therapy is widely used in the treatment of AV, there is a lack of reports on delicate pulsed light (DPL) which has a narrow therapeutic spectrum (500-600 nm). Low-level light therapy (LLLT) has shown an emerging role in anti-inflammatory effects and skin repair. This study investigates the efficacy and safety of low-dose oral isotretinoin combined with LLLT using DPL in patients with moderate-to-severe AV. Thirty-six patients with moderate-to-severe AV were enrolled and received low-dose oral isotretinoin (10-20 mg/day). The two sides of the face were randomly assigned to receive DPL (6-9 J/cm2) or not at an interval of 2 weeks for 4 treatment sessions (weeks 0, 2, 4, 6). Photos, GAGS score, counts of papules, pustules, comedones, TEWL, melanin and erythema index, side effects, efficacy, and satisfactory score were recorded at each visit and at 4 weeks after the final treatment (week 10). Thirty-three patients completed the study. DPL and oral isotretinoin combined therapy exhibited significantly improved GAGS score as well as the number of the lesions from week 2 and maintained until week 10. At the end of the observation, the improvement of GAGS was 70.88% on the DPL and isotretinoin combined side versus 62.12% on the side with isotretinoin monotherapy (p = 0.0009). The improvement for papule number was 61.58% on the DPL combined side versus 43.33% on the control side (p < 0.0001), for comedone was 63.15% versus 43.30% (p = 0.0008). TEWL and indexes of melanin and erythema also had better outcomes with DPL combined therapy at week 10. All the side effects were temporary and tolerable; no adverse effects were observed. Oral low-dose isotretinoin combined with LLLT by DPL offers a combination with reduced side effects and better outcomes within a limited treatment duration, which advances the onset of effect of isotretinoin monotherapy and improves lesion clearance.

Phenolic compounds of Solanum xanthocarpum play an important role in anti-inflammatory effects

• 51 phenolic compounds including seven new compounds have been separated. • 40 known compounds were isolated from Solanum xanthocarpum for the first time. • The inhibitory activities of the NO release of LPS-induced RAW 264.7 cells were performed. • The possible mechanism of NO inhibition was investigated using molecular docking. • The bioinformatic analysis further revealed the potential anti-inflammatory targets. Solanum xanthocarpum is used for the treatment of rheumatic arthritis, toothache, sore throats, carbuncle, furuncle, and other inflammatory diseases in traditional Chinese medicine and Ayurvedic medical system, with the phenolic compounds being one of its principal components. In this study, 51 phenolic compounds including seven new compounds 1 , 2 , 9 , 13 , 17, 22 , and 40 were isolated from the fruits of Solanum xanthocarpum . 40 known compounds 3 – 8, 10 – 12, 14 – 16, 18 – 21, 23 – 25, 28 – 32, 35 – 39, 41 – 51 were firstly isolated from Solanum xanthocarpum . Their structures were determined by comprehensive spectroscopic analyses, X-ray crystallography, NMR calculations, chemical methods, and comparisons of spectroscopic data. The results of anti-inflammatory assays indicated that most isolated compounds ( 3 – 7 , 11 – 30 , 32 – 37 , 39 , 40 , 42 , 43 , 45 , and 48 – 51 ) possessed significant inhibitory activities of the NO release of LPS-induced RAW 264.7 cells, with IC 50 values ranging from 10.46 to 47.59 μM. Further analysis by molecular docking implied that most bioactive compounds could interact with the amino acid residues of iNOS proteins, supporting the anti-inflammatory activity of the compounds. Especially, compounds 17 – 20 , 26 – 27 , 32 , and 34 showed strong affinities with iNOS proteins. The bioinformatic analysis further revealed the potential anti-inflammatory targets of the phenolic compounds isolated from the fruits of Solanum xanthocarpum .

Antioxidant, Anti-Inflammatory and Antithrombotic Effects of Ginsenoside Compound K Enriched Extract Derived from Ginseng Sprouts

Partially purified ginsenoside extract (PGE) and compound K enriched extract (CKE) were prepared from ginseng sprouts, and their antioxidant, anti-inflammatory and antithrombotic effects were investigated. Compared to the 6-year-old ginseng roots, ginseng sprouts were found to have a higher content of phenolic compounds, saponin and protopanaxadiol-type ginsenoside by about 56%, 36% and 43%, respectively. PGE was prepared using a macroporous adsorption resin, and compound K(CK) was converted and enriched from the PGE by enzymatic hydrolysis with a conversion rate of 75%. PGE showed higher effects than CKE on radical scavenging activity in antioxidant assays. On the other hand, CKE reduced nitric oxide levels more effectively than PGE in RAW 264.7 cells. CKE also reduced pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β and IL-6 than PGE. Tail bleeding time and volume were investigated after administration of CKE at 70–150 mg/kg/day to mice. CKE administered group showed a significant increase or increased tendency in bleeding time than the control group. Bleeding volume in the CKE group increased than the control group, but not as much as in the aspirin group. In conclusion, ginseng sprouts could be an efficient source of ginsenoside, and CKE converted from the ginsenosides showed antioxidant, anti-inflammatory and antithrombotic effects. However, it was estimated that the CKE might play an essential role in anti-inflammatory effects rather than antioxidant effects.

Chondroprotective effects of purple corn anthocyanins on advanced glycation end products induction through suppression of NF-\u03baB and MAPK signaling

Formation of advanced glycation end products (AGEs), which are associated with diabetes mellitus, contributes to prominent features of osteoarthritis, i.e., inflammation-mediated destruction of articular cartilage. Among the phytochemicals which play a role in anti-inflammatory effects, anthocyanins have also been demonstrated to have anti-diabetic properties. Purple corn is a source of three major anthocyanins: cyanidin-3-O-glucoside, pelargonidin-3-O-glucoside and peonidin-3-O-glucoside. Purple corn anthocyanins have been demonstrated to be involved in the reduction of diabetes-associated inflammation, suggesting that they may have a beneficial effect on diabetes-mediated inflammation of cartilage. This investigation of the chondroprotective effects of purple corn extract on cartilage degradation found a reduction in glycosaminoglycans released from AGEs induced cartilage explants, corresponding with diminishing of uronic acid loss of the cartilage matrix. Investigation of the molecular mechanisms in human articular chondrocytes showed the anti-inflammatory effect of purple corn anthocyanins and the metabolite, protocatechuic acid (PCA) on AGEs induced human articular chondrocytes via inactivation of the NFκb and MAPK signaling pathways. This finding suggests that purple corn anthocyanins and PCA may help ameliorate AGEs mediated inflammation and diabetes-mediated cartilage degradation.

Epothilone B prevents lipopolysaccharide-induced inflammatory osteolysis through suppressing osteoclastogenesis via STAT3 signaling pathway.

Inflammatory osteolysis is a common osteolytic specificity that occurs during infectious orthopaedic surgery and is characterized by an imbalance in bone homeostasis due to excessive osteoclast bone resorption activity. Epothilone B (Epo B) induced α-tubulin polymerization and enhanced microtubule stability, which also played an essential role in anti-inflammatory effect on the regulation of many diseases. However, its effects on skeletal system have rarely been investigated. Our study demonstrated that Epo B inhibited osteoclastogenesis in vitro and prevented inflammatory osteolysis in vivo. Further analysis showed that Epo B also markedly induced mature osteoclasts apoptosis during osteoclastogenesis. Mechanistically, Epo B directly suppressed osteoclastogenesis by the inhibitory regulation of the phosphorylation and activation of PI3K/Akt/STAT3 signaling directly, and the suppressive regulation of the CD9/gp130/STAT3 signaling pathway indirectly. The negative regulatory effect on STAT3 signaling further restrained the translocation of NF-κB p65 and NFATc1 from the cytosol to the nuclei during RANKL stimulation. Additionally, the expression of osteoclast specific genes was also significantly attenuated during osteoclast fusion and differentiation. Taken together, these findings illustrated that Epo B protected against LPS-induced bone destruction through inhibiting osteoclastogenesis via regulating the STAT3 dependent signaling pathway.

Modulation of gut microbiota in rats fed whole egg diets by processing duck egg to preserved egg

Pidan, as the preserved duck egg, is a traditional alkaline-pickled food in China. Previous studies have suggested preserved egg white has an anti-inflammatory effect, though the mechanism of action was unclear. In this work, the difference of peptides distribution in the digestive products was identified from those of duck egg. The effects of preserved egg diet on the modulation of gut microbiota as well as the alteration in fecal metabolites were further investigated. Minor variations of gut microbiota in phylum level were observed between preserved and fresh duck egg diet groups, even though, preserved egg diet intake attributed to increases in the relative abundance of Prevotella and Phascolarctobacterium (p < 0.05), while Ruminococcaceae and Allobaculum were quantitatively decreased (p < 0.05). In terms of metabolites, the contents of acetic acid (p < 0.01) and propionic acid (p < 0.05) were significantly increased in the preserved egg diet group. It was speculated that the preserved egg diet might alter the proportion of short-chain fatty acids (SCFAs) in the gut of rats by modulating specific intestinal bacteria, and subsequently play an active role in anti-inflammatory effects. Compared to the fresh egg group, the bacterial produced SCFAs of preserved egg group were increased in abundance (p < 0.05), which may have potential anti-obesity and anti-inflammatory effects. The results provide a novel insight into the relationship between preserved egg intake, gut microbiota and potential positive effects on host health.

UPLC-MS identification and anticomplement activity of the metabolites of Sophora tonkinensis flavonoids treated with human intestinal bacteria

Anticomplement activity played an important role in anti-inflammatory effects of traditional Chinese herbs. The total flavonoids of Sophora tonkinensis (TFST) were inactive on the complement system but showed obvious anticomplement activity after incubated with human intestinal bacteria in vitro. In order to discover the metabolic activation of TFST by intestinal flora, the constituents of TFST and its metabolites were identified by UPLC-ESI-LTQ/MS. Their anticomplement activities were evaluated through the classical and alternative pathway. As a result, eighteen flavonoids were identified, including seven flavonoid glycosides, five aglycones and six isoprenylated flavonoids. All the glycosides (daidzein-4′-glucoside-rhamnoside, sophorabioside, rutin, isoquercitrin, quercitrin, ononin, trifolirhizin) were metabolized into their corresponding aglycones in different extent by human intestinal bacteria, resulting in the contents of the five aglycones were highly increased in 24 h. However, no changes have occurred on the six isoprenylated flavonoids. Interestingly, three aglycones (quercetin, formononetin and maackiain) had significantly more potent anticomplement activities than their prototype glycosides. The results indicated that the enhancement of TFST anticomplement activity was attributed to the active aglycones, especially formononetin and quercetin, produced by human intestinal bacteria. These aglycones are likely to be among the potential active components of S. tonkinensis for its inhibiting inflammation effects.

High density lipoprotein promoting proliferation and migration of type II alveolar epithelial cells during inflammation state

BackgroundTo investigate the effect and mechanism of high density lipoprotein (HDL) on type II alveolar epithelial cells during inflammation state.MethodsThe original generation of type II alveolar epithelial cells were separated in rats and treated with PBS/LPS/HDL/HDL + LPS. To observe the proliferation and migration of type II alveolar epithelial cells with bromodeoxyuridine(BrdU) assay, transwell assay and wound healing experiments. In addition, western blot detected the expression of TP-binding cassette transporter A1 (ABCA1), cystic fibrosis transmembrane conductance regulator (CFTR) and the phosphorylation of AKT/extracellular signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK). Enzyme-linked immunosorbent assay (ELISA) tested the secretion of tumor necrosis factor a(TNF-a)/interleukin 1a(IL-1a)/IL-6.ResultsHDL promoted the proliferation (↑17%, p < 0.001 HDL+ LPS vs. LPS) and migration (wounding healing: ↑93%, p < 0.001 HDL+ LPS vs. LPS; transwell migration: ↑154%, p < 0.001 HDL+ LPS vs. LPS) of type II alveolar epithelial cells. Furthermore, HDL increased the phosphorylation of MAPK, but not AKT/ERK. And HDL decreased the secretion of TNF-a (↓46%, p < 0.01 HDL+ LPS vs. LPS) and IL-1a (↓45%, p < 0.001 HDL+ LPS vs. LPS), but not IL-6. In addition, HDL up-regulated the expression of ABCAI (↑99%, p < 0.001 HDL vs. CON) and down-regulated the expression of CFTR (↓25%, p < 0.05 HDL vs. CON) in type II alveolar epithelial cells.ConclusionsHDL increases the phosphorylation of MAPK, which promotes the proliferation and migration of type II alveolar epithelial cells. And it decreased the secretion of TNF-a/IL-1a and the expression of CFTR. All these suggest that HDL plays an important role in anti-inflammatory effect in inflammation state of lung.

Serotonins of safflower seeds play a key role in anti-inflammatory effect in lipopolysaccharide-stimulated RAW 264.7 macrophages

Safflower (Carthamus tinctorius) seeds are well- known traditional oriental medicines that have long been used for the remedies of blood stasis and bone formation in east Asia. In this study, ethyl acetate (EtOAc) was used for extraction of the main chemical compounds from C. tinctorius seeds. Four major compounds were identified, acacetin, cosmosiin, N-feruloyl serotonin and N-(p-coumaroyl) serotonin. Each compound was evaluated for its inhibitory activity against the inflammatory process of macrophages. All compounds significantly inhibited production of lipopolysaccharide (LPS)- stimulated nitric oxide (NO) and pro-inflammatory cytokines. The protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were dramatically decreased by serotonins in a dose-dependent manner in LPS-stimulated RAW 264.7 macrophages. These results suggest that serotonin derivatives from safflower seeds may reduce inflammation- related diseases.

IL-10 plays a pivotal role in anti-inflammatory effects of resveratrol in activated microglia cells.

The development of agents that can modulate microglial activation has been suggested as one potential strategy for the treatment or prevention of neurodegenerative diseases. Among these agents, resveratrol, with its anti-inflammatory action, has been described to have neuroprotective effects. In this paper we demonstrate that in LPS-stimulated microglia resveratrol pretreatment reduced, in a dose-dependent manner, pro-inflammatory cytokines IL-1β, TNF-α and IL-6 mRNA expression and increased the release of anti-inflammatory interleukin (IL)-10. Moreover, resveratrol pretreatment up-regulated the phosphorylated forms of JAK1 and STAT3, as well as suppressor of cytokine signaling (SOCS)3 protein expression in LPS activated cells, demonstrating that the JAK-STAT signaling pathway is involved in the anti-inflammatory effect exerted by resveratrol. By supplementing the cultures with an IL-10 neutralizing antibody (IL-10NA) we obtained the opposite effect. Taken together, these data allow us to conclude that the LPS-induced pro-inflammatory response in microglial cells can be markedly reduced by resveratrol, through IL-10 dependent up-regulation of SOCS3, requiring the JAK-STAT signaling pathway.

MiRNA-146a and Intervertebral Disc Homeostasis: In Vitro, Ex Vivo Studies

Introduction Expressions of miR-146a in chondrocytes were shown controversial effect according to different studies. This study is designed to demonstrate for the first time that MiRNA-146a is involved in intervertebral disc homeostasis, and its role in anti-inflammatory effect via both in vitro and ex vivo tests. Materials and Methods NP cells isolated from bovine tails in monolayer were transfected with synthetic miR-146a, and IL-1 was administered in parallel to provoke a catabolic response, using PCR and WB to confirm its effects. Then, histologic analysis using an ex vivo organ culture model of miR-146a KO mouse was used. Results In bovine disc NP cells in vitro experiment, PCR results showed the presence of IL-1 significantly increase the expression of all the cytokines when compared with the control group. Transfection of miR-146a antagonized IL-1 mediated increase of degrading enzymes and the inflammatory related cytokines. WB results also confirmed the miR-146a effects. Ex vivo mice whole disc organ culture model showed when challenged by IL-1, the 146KO NPs showed more serious decrease of GAG and degeneration, compared with WT NPs. And the numbers of MMP-13 and Adamts5 positive cells were significantly increased in the NPs of 146-a KO mouse than the WT. Conclusion The overexpression of miR-146a of bovine NP cells showed strong anti-inflammatory effects, and we thought that miR-146a might also be involved in the process of IVD degeneration, which is closely related with inflammatory factors. The relative importance of miR-146a as compared with other miRNA or proinflammatory factors in the process of IVD degeneration, however, needs further investigations. Disclosure of Interest None declared

The Neoflavonoid Latifolin Isolated from MeOH Extract ofDalbergia odoriferaAttenuates Inflammatory Responses by Inhibiting NF-κB ActivationviaNrf2-Mediated Heme Oxygenase-1 Expression

In Korea and China, the heartwood of Dalbergia odorifera T. Chen is an important traditional medicine used to treat blood disorders, ischemia, swelling, and epigastric pain. In this study, we investigated the inhibitory effects of latifolin, a major neoflavonoid component isolated from the MeOH extract of D. odorifera, on the inflammatory reaction of thioglycollate-elicited peritoneal macrophages exposed to lipopolysaccharide, with a particular focus on heme oxygenase-1 (HO-1) expression and nuclear factor-κB (NF-κB) signaling. Latifolin significantly inhibited the protein and mRNA expression of inducible nitric oxide synthase and COX-2, reduced NO, prostaglandins E2, tumor necrosis factor-α, and interleukin-1β production in primary murine peritoneal macrophages exposed to lipopolysaccharide. Latifolin also suppressed inhibitor κB-α levels, NF-κB nuclear translocation, and NF-κB DNA-binding activity. Furthermore, latifolin upregulated HO-1 expression via nuclear transcription factor-E2-related factor 2 (Nrf2) nuclear translocation. In addition, using inhibitor tin protoporphyrin IX (SnPP), an inhibitor of HO-1, it was verified that the inhibitory effects of latifolin on the proinflammatory mediators and NF-κB DNA-binding activity were associated with the HO-1 expression. These results suggested that the latifolin-mediated up-regulation of HO-1 expression played a critical role in anti-inflammatory effects in macrophages. This study therefore identified potent therapeutic effects of latifolin, which warrants further investigation as a potential treatment for inflammatory diseases.

Oridonin suppresses transplant rejection by depleting T cells from the periphery

Oridonin is a natural compound purified from Rabdosia rubescens that has remarkable anti-inflammatory and antitumor activities. Although oridonin has been used in traditional Chinese medicine for many years to treat inflammatory diseases, the underlying mechanisms of these activities are not well understood. In this paper, we explored whether oridonin could be used in transplantation and the mechanisms of its immunosuppression. Oridonin efficacy in transplantation is manifested by prolonged graft survival and decreased graft infiltration. Oridonin induces T cell apoptosis in a concentration- and time-dependent manner. In vivo, oridonin depleted large numbers of T cells from the spleen and peripheral blood. Decreased T cell numbers resulted from apoptosis, which was accompanied by increased phagocyte numbers in the periphery. Reduction in the number of thymocytes was observed in mice treated for 8days, and CD4+CD8+ cells were more sensitive to apoptosis induced by oridonin. Additionally, successive treatment with oridonin for 16days resulted in a considerable reduction in the total number of spleen cells and spleen volume. Thus, T cell depletion may play an essential role in prolonged graft survival and immunosuppression induced by oridonin.

Kalopanaxsaponin A Exerts Anti-Inflammatory Effects in Lipopolysaccharide-Stimulated Microglia via Inhibition of JNK and NF-κB/AP-1 Pathways

Microglial activation plays an important role in the development and progression of various neurological disorders such as cerebral ischemia, multiple sclerosis, and Alzheimer’s disease. Thus, controlling microglial activation can serve as a promising therapeutic strategy for such brain diseases. In the present study, we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-inflammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-κB and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-inflammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinflammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-inflammatory effects of kalopanaxsaponin A in LPS-stimulated microglia.

Reduction of intercellular adhesion molecule 1 may play a role in anti-inflammatory effect of hyaluronic acid in a rat model of severe non-bacterial cystitis

To evaluate the impact of intercellular adhesion molecule 1 (ICAM-1) in hyaluronic acid (HA) therapy in rats model of severe non-bacterial cystitis. Cystitis models in Sprague-Dawley female rats were produced by combination of intraperitoneal cyclophosphamide (CYP) with intravesical protamine/lipopolysaccharide (PS/LPS). HA or heparin (0.5 ml) was introduced intravesically to rats' bladders followed PS/LPS. Bladder tissue was prepared for histology including mast cell presence and measurement of ICAM-1, tumor necrosis factor (TNF)-α, and interleukin 6 (IL-6). Cystitis model using intraperitoneal CYP and intravesical SP/LPS showed serious inflammation, higher mast cell count with elevated ICAM-1, TNF-α, and IL-6 levels. After intravesical heparin or HA treatment, incidence of grades 3-4 bladder inflammation and tissue ICAM-1 level were only significantly lower in HA group (P = 0.017, P = 0.021, respectively), but not in heparin group (P = 0.12, P = 0.798, respectively). Remarkably lower level of TNF-α (P = 0.003) and ICAM-1 (P = 0.006) was detected in HA-treated rats compared with heparin-treated rats. Inflammation grade and ICAM-1 level had strong correlation (P < 0.001). IL-6 level after HA or heparin instillation had no difference. Intravesical administration of HA decreased the severity of bladder inflammation, mast cell presence, and levels of ICAM-1 and TNF-α in a rat model of severe non-bacterial cystitis; its effect was more obvious than that of heparin. Reduction of ICAM-1 may play a role in the anti-inflammatory effect of HA.

Fluticasone propionate increases CD4 +CD25 + T regulatory cell suppression of allergen-stimulated CD4 +CD25 − T cells by an IL-10–dependent mechanism

Background Corticosteroids are the most effective anti-inflammatory therapy for allergic diseases, and these drugs inhibit T H2 T-cell activation. We previously reported that CD4 +CD25 + T cells from atopic donors suppressed allergen-stimulated T cells less than those from nonatopic donors. Objective We sought to determine the effect of fluticasone propionate (FP) on allergen-stimulated CD4 +CD25 − T cells and on the suppressive ability of CD4 +CD25 + T cells. Methods CD4 +CD25 + and CD4 +CD25 − T cells were separated from peripheral blood of atopic and nonatopic volunteers and cultured alone or mixed in the presence of allergen. Effects of FP were assessed by means of addition to cultures or preincubation with CD4 +CD25 + T cells. Results FP inhibited allergen-stimulated proliferation of CD4 +CD25 − T cells in a dose-dependent manner. Preincubation of CD4 +CD25 + T cells in FP increased subsequent suppressive activity of these cells in allergen-stimulated cultures with CD4 +CD25 − T cells. This effect was seen when cells were obtained from both nonatopic and atopic donors but was less for cells obtained from atopic individuals. Prior exposure of CD4 +CD25 + T cells to FP also increased subsequent IL-10 production by these cells when stimulated with allergen, and addition of anti-IL-10 antibody reversed the steroid-induced enhancement of suppression in mixed cultures. Conclusion Increased suppression by CD4 +CD25 + T cells might play a role in anti-inflammatory effects of corticosteroids in asthma and allergic diseases.