Potential Anti-inflammatory Mechanisms Research Articles

Methanolic leaf extract of Punica granatum attenuates ischemia-reperfusion brain injury in Wistar rats: Potential antioxidant and anti-inflammatory mechanisms.

Objective(s):This study was conducted to evaluate the cerebroprotective effect of methanolic leaf extract of Punica granatum (MePG) in Wistar rats.Materials and Methods:The MePG was initially assessed for in vitro antioxidant activity, and later evaluated on LPS-induced RAW 264.7 cell line assay. Finally, the MePG was evaluated against ischemia-reperfusion (I/R) induced brain injury in Wistar rats.Results:In DPPH, FRAP and ORAC assays, the MePG has exhibited potent antioxidant activity. Further, the MePG has significantly inhibited the generation of nitrite, ROS and TNF-α in LPS-induced RAW 264.7 cell lines. Besides, global ischemia followed by reperfusion caused significant changes in the neurological and behavioral functions in I/R control animals compared to sham control. Additionally, in the I/R control group there was a substantial decrease in the catalase and superoxide dismutase activities; Likewise, reduced glutathione levels reduced and lipid peroxidation levels enhanced significantly. Also, pro-inflammatory cytokines such as TNF-α, IL-6, and ICAM-I were increased and the levels of IL-10 was decreased significantly. Furthermore, the I/R insult caused increase in brain volume and cerebral infarct formation. Similarly, histopathology of the brain tissue revealed hallmarks like necrosis, leukocyte infiltration, cerebral edema and vascular congestion in I/R control. Notably, MePG (200 and 400 mg/kg) pretreatment for 7 days, has attenuated all the I/R-persuaded pathological changes compared to I/R control. In addition, the LC-MS/MS analysis showed presence of acteoside, apigenin, gallic acid, gossypin, pentagalloyl glucose, quercetin, and rutin as major ingredients in the MePG.Conclusion:These findings suggest that the MePG possesses significant cerebroprotective activity.

Regulatory cells in the skin: Pathophysiologic role and potential targets for anti-inflammatory therapies

Inflammation is a fundamental defense mechanism to protect the body from danger, which becomes potentially harmful if it turns chronic. Therapeutic strategies aimed at specifically blocking proinflammatory signals, particularly cytokines, such as IL-4, IL-6, IL-13, IL-17A, or TNF-α, have substantially improved our ability to effectively and safely treat chronic inflammatory diseases. Much less effort has been made to better understand the role of potential anti-inflammatory mechanisms. Here we summarize the current understanding of regulatory cell populations in the context of chronic inflammation, namely macrophages, Langerhans cells, myeloid-derived suppressor cells, and regulatory T and B lymphocytes. Emphasis is given to the skin because many different immune-related diseases occur in the skin. Development, phenotype, function, and evidence for their role in animal models of inflammation, as well as in the corresponding human diseases, are described. Finally, the feasibility of using regulatory cells as targets for potentially disease-modifying therapeutic strategies is discussed.

Anti-inflammatory effects of Zhishi and Zhiqiao revealed by network pharmacology integrated with molecular mechanism and metabolomics studies

BackgroundThe inflammatory response has a complex pathogenesis; thus, it is a critical contributor to the development and complication of many diseases. Zhishi and Zhiqiao are famous Citrus herbal medicines that are rich in bioactive phenolic constituents with multiple anti-inflammatory activities. PurposeEstablishment of a multi-component-target-pathway network strategy to investigate the usage of Zhishi and Zhiqiao on inflammatory diseases can provide a reference for mechanisms of traditional Chinese medicine (TCM). Study DesignA multi-component-target-pathway network strategy was constructed to elucidate the various antiinflammatory effects of Zhishi and Zhiqiao by integrating multi-constituent determination, network pharmacology, molecular mechanisms in cells and integrated metabolomics in animals. MethodsBased on the quantitatively determined global and characteristic chemical profiles of Zhishi and Zhiqiao, the component-target-pathway network was predicted by network pharmacology coupled with text mining and docking. The potential antiinflammatory mechanism of the various components in Zhishi and Zhiqiao were verified using LPS-induced inflammatory responses in RAW 264.7 cells. The different metabolic regulating effects of Zhishi and Zhiqiao against an LPS-induced inflammation model were investigated using a plasma metabolomics strategy. ResultsThe molecular mechanism of Zhishi mainly suppressed the MAPK signaling pathway, whereas Zhiqiao emphasized the PPAR-AKT signaling pathways simultaneously to block the inflammatory process. Meanwhile, Zhishi and Zhiqiao both exhibited an anti-inflammatory effect by inhibiting the NF-κB signaling pathway to reduce the production of inflammatory mediators. In the metabolomics study, Zhishi and Zhiqiao exhibited variant corrections of the disordered metabolic pathways through amino acid metabolism, glycometabolism and lipid metabolism. ConclusionAll of these results indicate that Zhishi and Zhiqiao, in a diversified mixture, exert their anti-inflammatory effect through variant pathways. These findings can assist in developing the use of Zhishi and Zhiqiao for inflammatory diseases.

The gastroprotective effect of N-acetylcysteine and genistein in indomethacin-induced gastric injury in rats.

The protective effect of N-acetylcysteine (NAC) and genistein (GEN) on an experimental model of indomethacin (IND)-induced gastric injury was investigated. A total of 50 male rats were divided into 5 groups: (1) control, (2) IND, (3) NAC pretreated, (4) GEN pretreated, and (5) NAC+GEN pretreated. Rats in groups 3-5 were orally administered NAC (500 mg/kg), GEN (10 mg/kg), or both, respectively, once daily for 7 days before the induction of gastric injury by IND (50 mg/kg). The stomach was removed for biochemical analysis and histopathological examination. Pretreatment with NAC, GEN, or both significantly improved ulcer indices and increased nitric oxide level and superoxide dismutase activity. They also significantly decreased malondialdehyde, tumour necrosis factor α levels, and myeloperoxidase activity, and downregulated matrix metalloproteinase 9 (MMP-9) gene expression compared to the IND group. NAC alone ameliorated IND-induced apoptosis, whereas GEN only significantly increased prostaglandin E2 level. Further, coadministration of both resulted in a significantly better gastroprotective effect versus solo administration. Coadministration of NAC and GEN has an additive gastroprotective effect in IND-induced gastric injury, which may be through interaction of their potential cytoprotective, antioxidant, anti-inflammatory, and antiapoptotic mechanisms together with regulation of MMP-9 expression.

13 - Potential anti-inflammatory mechanism of action of mesenchymal stromal cells in osteoarthritis patients results in overall improvement in pain and symptoms

13 - Potential anti-inflammatory mechanism of action of mesenchymal stromal cells in osteoarthritis patients results in overall improvement in pain and symptoms

Cereal Fiber Ameliorates High-Fat/Cholesterol-Diet-Induced Atherosclerosis by Modulating the NLRP3 Inflammasome Pathway in ApoE-/- Mice.

Cereal fiber is associated with decreasing the risk of cardiovascular diseases. However, whether cereal fiber modulates inflammatory response and improves atherosclerosis remains unclear. This study evaluated the anti-atherosclerotic effect of cereal fibers from oat or wheat bran and explored the potential anti-inflammatory mechanisms. Male ApoE-/- mice were given a high-fat/cholesterol (HFC) diet or a HFC diet supplemented with 0.8% oat fiber or wheat bran fiber. After 18 weeks of the feeding period, serum lipids and inflammatory cytokines were measured. The relative protein levels of the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway and nuclear factor κB (NF-κB) were determined by the western blot method in aorta tissues. Pathologically, oat fiber and wheat fiber significantly reduced atherosclerotic plaques by 43.3 and 27.1%, respectively. Biochemically, cereal fiber markedly decreased the protein levels of myeloid differentiation factor 88 (MyD88) and toll-like receptor 4 (TLR4) in aortic tissues. The expression of NF-κB was similarly inhibited by both cereal fibers. In comparison to wheat bran fiber, oat fiber had greater effects in reducing the plague size and inhibiting TLR4/MyD88/NF-κB pathways. Such differences might come from modulation of the NLRP3 inflammasome pathway because the expressions of the cleavage of caspase-1 and interleukin (IL)-1β were inhibited only by oat fiber. The present study demonstrates that cereal fibers can attenuate inflammatory response and atherosclerosis in ApoE-/- mice. Such effects are pronounced with oat fiber and likely mediated by specific inhibition of oat fiber on the NLRP3 inflammasome pathway.

Potential anti-inflammatory mechanism of action of mesenchymal stromal cells in osteoarthritis patients results in overall improvement in pain and symptoms

Potential anti-inflammatory mechanism of action of mesenchymal stromal cells in osteoarthritis patients results in overall improvement in pain and symptoms

Diosgenin Protects Rats from Myocardial Inflammatory Injury Induced by Ischemia-Reperfusion

BackgroundDiosgenin, a phytosteroid sapogenin, has anti-inflammatory properties shown to reduce myocardial ischemia-reperfusion injury (MIRI). However, the specific mechanism by which this is achieved is not clear. This study investigated the protective effects of diosgenin on myocardial ischemia/reperfusion (I/R) and the potential anti-inflammatory mechanisms.Material/MethodsHealthy adult male SD rats, body weight (b.w.) 250–280 g, were used to model ischemia-reperfusion injury (IRI) and were administered diosgenin (50 mg/kg and 100 mg/kg b.w.) intragastrically for 4 consecutive weeks before surgery. The left anterior descending artery (LAD) was ligated to induce myocardial ischemia for 30 min and reperfusion for 30 min, 60 min, and 120 min while relevant indicators were detected.ResultsBoth 50 mg and 100 mg diosgenin oral administration increased left ventricular developed pressure (LVDP) and maximum changing rate of ventricular pressure (±dp/dtmax), decreased left ventricular end-diastolic pressure (LVEDP), and myocardial enzyme markers. TTC staining suggested that diosgenin reduced myocardial infarct size in the rat model. Pathological results showed that myocardial ischemia and inflammation were alleviated by diosgenin. In addition, the increased expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) in serum, and myeloperoxidase (MPO) in myocardium were significantly suppressed by diosgenin administration. Diosgenin further inhibited the phosphorylation of transcription factor NF-κB and modulated the expression of downstream inflammatory cytokines by regulating the activation of p38-MAPK and JNK pathways.ConclusionsResults demonstrate diosgenin plays an anti-inflammatory role in the protection of MIRI through regulation of p38-MAPK and JNK pathways and phosphorylation of NF-κB.

Coccomyxa Gloeobotrydiformis Polysaccharide Inhibits Lipopolysaccharide-Induced Inflammation in RAW 264.7 Macrophages

Background/Aims: Inflammation plays a vital role in the etiology and pathogenesis of chronic noncommunicable diseases (NCDs), which are the leading health issues throughout the world. Our previous studies verified the satisfactory therapeutic effects of Coccomyxa gloeobotrydiformis (CGD) polysaccharide on several NCDs. In this study, we aimed to investigate the anti-inflammatory effects of CGD polysaccharide, and the corresponding molecular mechanisms, on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. Methods: A viability assay and a lactate dehydrogenase (LDH) assay were used to measure the cytotoxic effects of CGD polysaccharide on LPS-stimulated RAW264.7 cells. To investigate the potential anti-inflammatory mechanisms of CGD polysaccharide in LPS-stimulated RAW264.7 cells, nitric oxide (NO) production was determined using a NO assay and the expression of inflammatory mediators (PGE₂, iNOS and COX-2), inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10) and inflammation-related signaling pathways (the MAPK/NF-κB, PI3K/AKT/JNK, JAK/STAT and Nrf2/HO-1pathways) were observed by western blotting. The translocation of NF-κB p65 was also observed using an immunofluorescent assay. Results: CGD polysaccharide significantly inhibited LPS-induced NO production and PGE₂ expression by reducing the expression of iNOS and COX-2. It also suppressed the expression of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β, and up-regulated the expression of the anti-inflammatory cytokine IL-10. Further experiments demonstrated that CGD polysaccharide could inhibit inflammatory signaling pathways (the MAPK/NF-κB, PI3K/AKT/JNK and JAK/STAT pathways). At the same time, it enhanced the anti-inflammatory pathway Nrf2/HO-1. In addition, CGD polysaccharide did not display any cytotoxic effects, even at a high concentration. Conclusion: Taken together, the results suggest that CGD polysaccharide significantly inhibits LPS-induced inflammation in RAW264.7 cells. This effect lies in its regulatory effects on the signaling pathways MAPK/ NF-κB, PI3K/AKT/JNK, JAK/STAT and Nrf2/HO-1.Our findings reveal that CGD polysaccharide has the potential to be used as a relatively safe and effective drug as part of the treatment of NCDs.

Antrodia cinnamomea Oligosaccharides Suppress Lipopolysaccharide-Induced Inflammation through Promoting O-GlcNAcylation and Repressing p38/Akt Phosphorylation.

Antrodia cinnamomea (AC), an edible fungus growing in Taiwan, has various health benefits. This study was designed to examine the potential inhibitory effects of AC oligosaccharides on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. By trifluoroacetic acid degradation, two oligosaccharide products were prepared from AC polysaccharides at 90 °C (ACHO) or 25 °C (ACCO), which showed different oligosaccharide identities. Compared to ACCO, ACHO displayed better inhibitory effects on LPS-induced mRNA expression of pro-inflammatory cytokines including IL-6, IL-8, IL-1β, TNF-α and MCP-1 in macrophage cells. Further, ACHO significantly suppressed the inflammation in lung tissues of LPS-injected C57BL/6 mice. The potential anti-inflammatory molecular mechanism may be associated with the promotion of protein O-GlcNAcylation, which further skewed toward the marked suppression of p38 and Akt phosphorylation. Our results suggest that the suppressive effect of AC oligosaccharides on inflammation may be an effective approach for the prevention of inflammation-related diseases.

Crocus sativus L. aqueous extract reduces atherogenesis, increases atherosclerotic plaque stability and improves glucose control in diabetic atherosclerotic animals

Background and aimsWe aimed to evaluate a possible atheroprotective effect of saffron aqueous extract (SFE), and its potential anti-inflammatory mechanisms, in apoE knockout (ApoE−/−) mice. MethodsFifty male, ApoE−/− mice, fed a high-fat diet (HFD) for 12 weeks, were randomized into 5 groups: (1) baseline group, euthanatized, without intervention, (2) three saffron groups, receiving HFD and 30,60,90 mg/kg/day of SFE, respectively, for four weeks, per os through gavage, after reconstitution in water for injection (WFI), (3) control group (COG), receiving daily HFD and the same volume of WFI (four weeks). After blood sampling and euthanasia, aortic roots were excised and analyzed for gene expression and/or percentage of aortic stenosis, relative content of macrophages, smooth muscle cells (SMCs), connective tissue, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases-2,-3,-9 (MMP-2,-3,-9) and their inhibitor (TIMP-2) and IL-6. SFE doses were determined by a pilot serum pharmacokinetic study in C57BL/6J wild-type mice. ResultsSFE did not affect body weight and total cholesterol levels (p > 0.05), while high SFE dose significantly ameliorated glucose and triglycerides profiles compared to other groups (p < 0.05). SFE considerably decreased aortic stenosis in a dose-dependent manner (p < 0.05). Furthermore, increasing SFE doses proportionally reduced macrophages content and increased within plaques content of collagen, elastin, and SMCs, promoting more stable plaque phenotype compared to COG (p < 0.05). Those effects seemed to be associated with a considerable reduction (>30%) in IL-6, TNF-α, MCP-1, MMP-2,-3,-9 (p < 0.05) and MMP-2/TIMP-2 ratio. ConclusionsSFE exerted dose-dependent anti-atherosclerotic and plaque-stabilizing effects in Apo-E−/− mice, probably mediated by a favorable modification of inflammatory mechanisms, which requires further investigation.

The regulatory effect of oxymatrine on the TLR4/MyD88/NF-κB signaling pathway in lipopolysaccharide-induced MS1 cells

BackgroundOxymatrine (OM), a major quinolizidine alkaloid extracted from the roots of Sophora flavescens, has been proved to regulate a variety of signaling pathways to produce a wide range of pharmacological effects. ObjectivesThe regulatory effects of OM on the TLR4/MyD88/NF-κB signaling pathway under the stimulation of lipopolysaccharide (LPS) in MS1 cells were explored to illuminate the potential anti-inflammatory mechanism of OM for pancreatitis treatment. MethodsThe signaling molecules related to the TLR4/MyD88/NF-κB pathway in MS1 cells were detected by Western blotting under different conditions, including OM pretreatment and LPS stimulation. The mRNA expression levels of TLR4, MyD88, NF-κB p65 and IκBα were detected by real-time PCR. The NF-κB p65 nuclear translocation in MS1 cells was measured by immunofluorescence, and the pro-inflammatory cytokine of IL-1β was detected by ELISA. ResultsIncreased levels of TLR4, MyD88 and NF-κB p65, induced by LPS stimulation, were significantly inhibited by OM pretreatment in MS1 cells. The decreased protein, but not mRNA, level of IκBα induced by LPS stimulation was increased by OM pretreatment. Meanwhile, LPS induced NF-κB p65 protein translocation to the nucleus as well as LPS increased expression of IL-1β were also inhibited by OM pretreatment. ConclusionInhibitory effects of OM on molecules related to the TLR4/MyD88/NF-κB signaling pathway in pancreatic microvascular endothelial cells can alleviate inflammatory responses.

Downregulation of P-selectin glycoprotein ligand-1 as a potential anti-inflammatory mechanism.

Downregulation of P-selectin glycoprotein ligand-1 as a potential anti-inflammatory mechanism.

Pentamidine blocks hepatotoxic injury in mice.

VLX103 effectively decreases toxin-induced liver injury in mice and may be an effective therapy for this and other forms of human liver disease. (Hepatology 2017;66:922-935).

RAW 264.7 대식세포에서 유산균으로 발효한 다시마와 톳의 항염증 효과

This study was conducted to investigate alterations of seaweed composition upon Lactobacillus rhamnosus GG (LGG) fermentation as well as potential anti-inflammatory effects and mechanism (s) of water extracts and fermented water extracts of Laminaria japonica (LJ) and Hizikia fusiforme (HF) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Total polyphenol, total sugar, and reducing sugar contents were measured in LJ and HF water extracts before and after fermentation by LGG. Alterations of inflammatory cytokine levels in cell culture media were measured by ELISA, and levels of phosphorylation of c-jun NH2-terminalkinase (JNK) and extra cellular signal regulated kinase (ERK) were examined by Western blot analysis. LGG fermentation of LJ and HF altered total polyphenol and sugar contents in water extracts of LJ and HF. LPS-induced production of pro-inflammatory cytokines such as IL-6 and TNF-α was significantly reduced by HF-f compared to control in RAW264.7 cells. Consistent with reduction of anti-inflammatory cytokine, interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels by HF-f, HF-f also significantly reduced phosphorylation of ERK and JNK in LPS-stimulated RAW264.7 cells. In addition, LJ-f and HF also significantly reduced phosphorylation of JNK and ERK induced by LPS in RAW264.7 cells. Overall, our result suggests that HF-f among the four tested seaweed extracts is the most potent antiinflammatory agent, and its mechanism of action is partially mediated by reduction of JNK and ERK phosphorylation as well as IL-6 and TNF-α production in LPS-stimulated RAW264.7 cells.

Fish oil supplementation attenuates neuroinflammation and alleviates depressive-like behavior in rats submitted to repeated lipopolysaccharide.

Depression is frequently associated with inflammation, whereas omega-3 polyunsaturated fatty acids (PUFAs) primarily found in fish oil possess anti-inflammatory properties. Although converging studies suggest an antidepressant effect of PUFAs, there is limited evidence directly linking the neuro-immune modulating features of PUFAs to the antidepressant actions. Therefore, we assessed the effects of fish oil (FO) supplementation on behavioral changes, inflammatory cytokine expression and oxidative reactions in frontal cortex and hippocampus of rats following repeated peripheral immune challenge by lipopolysaccharide (LPS) for 2weeks (500μg/kg every other day). Repeated LPS administration induced the rats to a depressive-like state and increased mRNA expression of pro-inflammatory cytokines, including 1L-1β, 1L-6 and TNF-α, in frontal cortex and hippocampus. FO supplementation attenuated the LPS-induced abnormal behavior and brain inflammatory response. Concurrent with the antidepressant action, FO also reduced LPS-induced oxidative reactions and neural apoptosis in the rat brain, as evidenced by decreased malondialdehyde (MDA) production, increased catalase activities and inhibited pro-apoptotic protein Bax mRNA expression. In addition, FO inhibited activation of NF-κB and iNOS induced by LPS. Interestingly, we found FO suppressed the activation of the inflammasome NLRP3 and ionotropic purinergic receptor P2X7R evoked by LPS, suggesting a potential anti-inflammatory mechanism for PUFAs. Besides, FO also restored the LPS-induced neurochemical disturbance, especially the balance between serotonin and kynurenine branches of tryptophan metabolism, which is tightly associated with depression. These findings provide novel insights into the antidepressant action of PUFAs and further strengthen the link between inflammation and depression.

The investigation of anti-inflammatory activity of Yi Guanjian decoction by serum metabonomics approach

Yi Guanjian (YGJ), one of the Chinese herbal medicines most commonly used in western countries, reported to possess significant anti-inflammatary effects that inhibit the process of inflammation. However, the mechanisms underlying its anti-inflammation effects remain largely unresolved. This study was aimed to investigate the anti-inflammatory activity of YGJ and to explore its potential anti-inflammatory mechanisms by serum metabonomics approach. An xylene-induced mouse right-ear-edema model was used as an inflammatory response in vivo model. Ear edema, prostaglandin E2 (PGE2) and Tumor-Necrosis-Factor-alpha (TNF-α) were detected. Then, serum metabolic profiling was analyzed and pathway analysis performed on the biomarkers reversed after YGJ administration and further integration of metabolic networks. The results showed that YGJ alleviated ear edema and decreased serum PGE2 and TNF-α levels. Fourteen biomarkers were screened, and the levels were all reversed to different degrees after YGJ administration. These biomarkers were mainly related to linoleic acid metabolism, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism and citrate cycle (TCA cycle). In metabolic networks, glycine and pyruvate were node molecules. This indicated that YGJ could significantly inhibit inflammatory response triggered by acute local stimulation and exerted anti-inflammatory activity mainly by regulating node molecules.

Protective Effects of Genistein and Puerarin against Chronic Alcohol-Induced Liver Injury in Mice via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms.

This study aimed to investigate the protective effect of genistein or puerarin on chronic alcohol-induced liver injury in vivo and to explore the underlying mechanisms of hepatoprotective effects. Mice were administered genistein or puerarin (0.3 mmol kg(-1) body weight) and gastrically infused with 50% alcohol once per day for 5 weeks. Levels of serum transaminases, serum and hepatic lipids, hepatic antioxidant capacities, inflammation, apoptosis, and histopathological sections were analyzed. Results showed that genistein and puerarin exhibited similar effects in ameliorating alcohol-induced liver injury. However, genistein is more effective than puerarin in decreasing levels of malondialdehyde (1.05 ± 0.0947 vs 1.28 ± 0.213 nmol/mg pro, p < 0.05), tumor necrosis factor α (3.12 ± 0.498 vs 3.82 ± 0.277 pg/mg pro, p < 0.05), interleukin-6 (1.46 ± 0.223 vs 1.88 ± 0.309 pg/mg pro, p < 0.05), whereas puerarin is more effective than genistein in ameliorating serum activities or levels of alanine transaminase (35.8 ± 3.95 vs 42.6 ± 6.56 U/L, p < 0.05) and low-density lipoprotein cholesterol (1.12 ± 0.160 vs 1.55 ± 0.150 mmol/L, p < 0.05). In conclusion, both genistein and puerarin effectively alleviate hepatic damage induced by chronic alcohol administration through potential antioxidant, anti-inflammatory, or anti-apoptotic mechanisms.

Metabonomic analysis of biochemical changes in the plasma and urine of carrageenan-induced rats after treatment with Yi-Guan-Jian decoction

The urinary and plasma metabonomics method based on a Agilent-1200 LC system coupled to an Agilent-6410 mass spectrometry (HPLC-MS/MS) had been established to investigate the anti-inflammatory activity of Yi-Guan-Jian (YGJ) decoction and explore its potential anti-inflammatory mechanism. Rat acute inflammation was induced by subcutaneous injection of carrageenan in hind paws. Multivariate statistical approaches, such as principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA) and XCMS online software were used to distinguish normal control group (NG), model group (MG), aspirin-treated group (AG) and Yi-Guan-Jian decoction group (YGJ), aimed at finding out the potential biomarkers. There was a clear separation among the four groups in PCA model. Twenty-five potential biomarkers had been identified using PCA, PLS-DA and XCMS online software. Lastly, we had an enrichment for the related metabolic pathways and screened out the pathways that influence the organism a lot in MetPA, then five mainly metabolism: tryptophan metabolism, lipid metabolism, oxidative stress, glyoxylate and dicarboxylate metabolism, taurine and hypotaurine metabolism were found. In this study, YGJ showed good anti-inflammatory effects and it could suppress the changes of pathologic inflammatory cytokines of carrageenan-induced rat paw edema (CIE). There might be a correlation between these results and the regulation of the disturbed metabolites in urine and plasma. This study demonstrates that metabonomics is a powerful methodology to gain insight into the mechanisms of traditional Chinese medicine (TCM) formula in therapy.

Corynoline Isolated from Corydalis bungeana Turcz. Exhibits Anti-Inflammatory Effects via Modulation of Nfr2 and MAPKs.

Corydalis bungeana Turcz. is an anti-inflammatory medicinal herb used widely in traditional Chinese medicine for upper respiratory tract infections. It is demonstrated that corynoline is its active anti-inflammatory component. The nuclear factor-erythroid-2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and the mitogen-activated protein kinase (MAPK) pathway play important roles in the regulation of inflammation. In this study, we investigated the potential anti-inflammatory mechanism of corynoline through modulation of Nfr2 and MAPKs. Lipopolysaccharide (LPS)-activated RAW264.7 cells were used to explore modulatory role of NO production and the activation of signaling proteins and transcription factors using nitrite assay, Western bloting and qPCR. Treatment with corynoline reduced production of nitric oxide (NO) and the protein and mRNA levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) Treatment also significantly increased the expression of Nrf2, quinone oxidoreductase 1 (NQO1) and hemeoxygenase-1 (HO-1) at the mRNA and protein levels, which demonstrated that corynoline may protect cells from inflammation through the Nrf2/ARE pathway In addition, corynoline suppressed the expression of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), at the mRNA and protein levels. Furthermore, molecular data revealed that corynoline inhibited lipopolysaccharide-stimulated phosphorylation of c-jun NH2-terminal kinase (JNK) and p38. Taken together, these results suggest that corynoline reduces the levels of pro-inflammatory mediators, such as iNOS, COX-2, TNF-α and IL-1β, by suppressing extracellular signal-regulated kinase 1/2 (ERK) and p38 phosphorylation in RAW264.7 cells, which is regulated by the Nrf2/ARE pathway. These findings reveal part of the molecular basis for the anti-inflammatory properties of corynoline.