Kyungheechunggan-Tang-01, a New Herbal Medication, Suppresses LPS-Induced Inflammatory Responses through JAK/STAT Signaling Pathway in RAW 264.7 Macrophages

Medicinal plants have been used as alternative therapeutic tools to alleviate inflammatory diseases. The objective of this study was to evaluate anti-inflammatory properties of Kyungheechunggan-tang- (KCT-) 01, KCT-02, and Injinchunggan-tang (IJCGT) as newly developed decoctions containing 3–11 herbs in LPS-induced macrophages. KCT-01 showed the most potent inhibitory effects on LPS-induced NO, PGE2, TNF-α, and IL-6 production among those three herbal formulas. In addition, KCT-01 significantly inhibited LPS-induced iNOS and COX-2 at protein levels and expression of iNOS, COX-2, TNF-α, and IL-6 at mRNA levels. Molecular data revealed that KCT-01 attenuated the activation of JAK/STAT signaling cascade without affecting NF-κB or AP-1 activation. In ear inflammation induced by croton oil, KCT-01 significantly reduced edema, MPO activity, expression levels of iNOS and COX-2, and STAT3 phosphorylation in ear tissues. Taken together, our findings suggest that KCT-01 can downregulate the expression of proinflammatory genes by inhibiting JAK/STAT signaling pathway under inflammatory conditions. This study provides useful data for further exploration and application of KCT-01 as a potential anti-inflammatory medicine.

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Glucocorticoids potentiate IL-6-induced SP-B expression in H441 cells by enhancing the JAK-STAT signaling pathway

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00055.2010 ◽

2010 ◽

Vol 299 (4) ◽

pp. L578-L584 ◽

Cited By ~ 17

Author(s):

Andreas Ladenburger ◽

Matthias Seehase ◽

Boris W. Kramer ◽

Wolfgang Thomas ◽

Johannes Wirbelauer ◽

...

Keyword(s):

Gene Expression ◽

Signaling Pathway ◽

Synergistic Effects ◽

Regulation System ◽

Mrna Levels ◽

Α Subunit ◽

Steroid Administration ◽

Stat3 Phosphorylation ◽

Antenatal Steroid ◽

Stat Signaling

The respiratory distress syndrome (RDS) contributes to perinatal morbidity and mortality associated with preterm birth. Surfactant protein B (SP-B) is decreased in RDS. Both maternal antenatal steroid administration and chorioamnionitis reduce the incidence and severity of RDS. An important mediator in chorioamnionitis is IL-6 using the JAK-STAT signaling pathway for signal transduction. We hypothesized that the steroids, betamethasone (BTM) and dexamethasone (DXM), and IL-6 had synergistic effects on SP-B gene expression and STAT3 phosphorylation in H441 cells. DXM and BTM increased SP-B mRNA levels by 16.5 (13.3)-fold and IL-6 alone by 2.3-fold. After 48-h exposure of cells to DXM or BTM, IL-6 caused a significantly greater increase in SP-B mRNA levels (28.1-fold) than IL-6 or glucocorticoids alone. Whereas IL-6 stimulated tyrosine phosphorylation of STAT3 in a time- and dose-dependent way, DXM and BTM had no effect on STAT3 phosphorylation. Both DXM and BTM could potentiate IL-6-induced phosphorylation of STAT3. The synergism of glucocorticoids and IL-6 on SP-B gene expression and the effect of glucocorticoids on IL-6-induced STAT3 phosphorylation could be blocked by a JAK inhibitor. Expression level analysis showed that glucocorticoids increased the expression of the IL-6-binding α-subunit receptor (IL-6R) on mRNA and protein level. Our findings could represent an example of a pulmonary regulation system in which one role of glucocorticoids is to increase the effect of a cytokine by upregulation of its receptor. The described in vitro interaction of IL-6 and glucocorticoids could help explain the clinical observation that prenatal inflammation in preterm babies with antenatal steroid administration can attenuate severity of RDS.

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Immunomodulatory role of paliperidone in the poly(I:C) model of schizophrenia

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.541 ◽

2016 ◽

Vol 33 (S1) ◽

pp. s220-s221

Author(s):

K. MacDowell ◽

E. Munarriz-Cuezva ◽

D. Martín-Hernández ◽

A. Sayd ◽

B. García-Bueno ◽

...

Keyword(s):

Antioxidant Enzymes ◽

Inflammatory Responses ◽

Poly I:C ◽

Mrna Levels ◽

Behavioral Test ◽

Inflammatory Pathways ◽

Anti Inflammatory ◽

Cellular Markers ◽

Endogenous Antioxidant

IntroductionAlterations on the innate inflammatory response may underlie the pathophysiology of psychiatric diseases, but the mechanisms implicated remain elusive. Current antipsychotics modulate pro/anti-inflammatory pathways, but the specific mechanisms involved remain elusive. One attractive possibility is the regulation of the intracellular signalling pathways of the innate immune receptors Toll-like 3 (TLR3), which triggers antiviral and inflammatory responses.AimsTo elucidate the regulatory role of paliperidone on maternal immune activation (MIA) induced alterations on TLR3 pathway and on the two emerging endogenous antiinflammatory/antioxidant mechanisms NRF2/antioxidant enzymes pathway and the cytokine milieu regulating M1/M2 polarization in microglia.MethodsPregnant mice were treated with the synthetic Toll-like Receptor 3 (TLR3) agonist Poly(I:C) in gestational day 9 and chronically treated with paliperidone (0,05 mg/kg i.p.) in adult offspring. Animals were sacrificed one day after treatment and behavioral test. Inflammation oxidative stress-related mediators were analysed at mRNA and protein level in prefrontal cortex samples. In addition, behavioral test t-maze was conducted.ResultsPaliperidone prevented TLR3 pathway activation and the subsequent MIA-induced neuroinflammatory response. Also, paliperidone induced an increment in the activity and protein expression of nuclear NRF2, as well as increased mRNA levels of the antioxidant enzymes HO1, SOD and catalase in the MIA model. Otherwise, paliperidone increases the antiinflammatory cytokines levels TGFβ and IL-10 in favour of a M2 microglia profile and increased the levels of the M2 cellular markers ArgI and FOLR2.ConclusionsThe modulation of neuroinflammation and enhancement of endogenous antioxidant/anti-inflammatory pathways by current and new antipsychotics could represent an interesting therapeutic strategy for the future.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Anti-Inflammatory Effect of Auranofin on Palmitic Acid and LPS-Induced Inflammatory Response by Modulating TLR4 and NOX4-Mediated NF-κB Signaling Pathway in RAW264.7 Macrophages

International Journal of Molecular Sciences ◽

10.3390/ijms22115920 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5920

Author(s):

Hyun Hwangbo ◽

Seon Yeong Ji ◽

Min Yeong Kim ◽

So Young Kim ◽

Hyesook Lee ◽

...

Keyword(s):

Palmitic Acid ◽

Signaling Pathway ◽

Chronic Inflammation ◽

Inhibitory Effect ◽

Simultaneous Treatment ◽

Monocyte Chemoattractant Protein 1 ◽

Protein Levels ◽

Raw264.7 Macrophages ◽

Anti Inflammatory ◽

Factor Α

Chronic inflammation, which is promoted by the production and secretion of inflammatory mediators and cytokines in activated macrophages, is responsible for the development of many diseases. Auranofin is a Food and Drug Administration-approved gold-based compound for the treatment of rheumatoid arthritis, and evidence suggests that auranofin could be a potential therapeutic agent for inflammation. In this study, to demonstrate the inhibitory effect of auranofin on chronic inflammation, a saturated fatty acid, palmitic acid (PA), and a low concentration of lipopolysaccharide (LPS) were used to activate RAW264.7 macrophages. The results show that PA amplified LPS signals to produce nitric oxide (NO) and various cytokines. However, auranofin significantly inhibited the levels of NO, monocyte chemoattractant protein-1, and pro-inflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor-α, and IL-6, which had been increased by co-treatment with PA and LPS. Moreover, the expression of inducible NO synthase, IL-1β, and IL-6 mRNA and protein levels increased by PA and LPS were reduced by auranofin. In particular, the upregulation of NADPH oxidase (NOX) 4 and the translocation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) induced by PA and LPS were suppressed by auranofin. The binding between the toll-like receptor (TLR) 4 and auranofin was also predicted, and the release of NO and cytokines was reduced more by simultaneous treatment with auranofin and TLR4 inhibitor than by auranofin alone. In conclusion, all these findings suggested that auranofin had anti-inflammatory effects in PA and LPS-induced macrophages by interacting with TLR4 and downregulating the NOX4-mediated NF-κB signaling pathway.

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The role of celecoxib as a potential inhibitor in the treatment of inflammatory diseases - a review

Current Medicinal Chemistry ◽

10.2174/0929867328666210910125229 ◽

2021 ◽

Vol 28 ◽

Author(s):

Josiane Viana Cruz ◽

Joaquín María Campos Rosa ◽

Njogu Mark Kimani ◽

Silvana Giuliatti ◽

Cleydson Breno Rodrigues dos Santos

Keyword(s):

Side Effects ◽

Inflammatory Diseases ◽

Structural Basis ◽

Potential Inhibitor ◽

Cyclooxygenase 1 ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors

: This article presents a simplified view of celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) has, predominantly, two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role that is related to homeostatic effects in renal and platelets, while the latter is mainly responsible for induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and without side effects. To this end, of the generation of non-steroidal anti-inflammatory drugs from “coxibs”, celecoxib is the only potent selective COX-2 inhibitor that is still commercially available. Thus, the compound celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for COX-2 enzyme. In this review, we provide highlights where such inhibition should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs) which act as COX-2 inhibitors with lesser side effects on the human body.

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Constitutive activation of STAT-3 and downregulation of SOCS-3 expression induced by adrenalectomy

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.281.6.r2048 ◽

2001 ◽

Vol 281 (6) ◽

pp. R2048-R2058 ◽

Cited By ~ 24

Author(s):

Abram M. Madiehe ◽

Ling Lin ◽

Christy White ◽

H. Doug Braymer ◽

George A. Bray ◽

...

Keyword(s):

Dna Binding ◽

Signaling Pathway ◽

Leptin Receptor ◽

Binding Activity ◽

Janus Kinase ◽

Adrenal Steroids ◽

Western Blots ◽

Protein Levels ◽

Dna Binding Activity ◽

Stat Signaling

Removal of adrenal steroids by adrenalectomy (ADX) slows or reverses the development of many forms of obesity in rodents, including those that are leptin or leptin receptor deficient. Obesity is associated with hyperleptinemia and leptin resistance. We hypothesized that glucocorticoids impair leptin receptor signaling and that removal thereof would activate the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathway. The inhibitory effect of leptin (2.5 μg icv) on food intake was enhanced in ADX rats. A combination of ribonuclease protection assays, RT-PCR, Western blots, and mobility shift assays was used to evaluate the leptin signaling pathway in whole hypothalami from sham-operated, ADX and corticosterone-replaced ADX (ADX-R) Sprague-Dawley rats that were treated acutely with either saline vehicle or leptin intracerebroventricularly. ADX increased the expression of leptin receptor mRNA, increased STAT-3 mRNA and protein levels, induced constitutive STAT-3 phosphorylation and DNA binding activity, and also reduced suppressor of cytokine signaling-3 (SOCS-3) mRNA and protein levels. ADX and leptin treatment increased STAT-3 phosphorylation, but with no concomitant increase in DNA binding activity. Leptin and ADX decreased NPY mRNA expression, but their combination did not further decrease NPY mRNA. Corticosterone supplementation of ADX rats partially reversed many of these effects. In conclusion, ADX through activation of STAT-3 and inhibition of SOCS-3 activates the JAK-STAT signaling pathway. These effects most probably explain the ability to prevent the development of obesity by removal of adrenal steroids.

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Potential role of a series of lysine-/leucine-rich antimicrobial peptide in inhibiting lipopolysaccharide-induced inflammation

Biochemical Journal ◽

10.1042/bcj20180483 ◽

2018 ◽

Vol 475 (22) ◽

pp. 3687-3706 ◽

Cited By ~ 3

Author(s):

Weibing Dong ◽

Xin Zhu ◽

Xuan Zhou ◽

Ying Yang ◽

Xin Yan ◽

...

Keyword(s):

Cell Membrane ◽

Signaling Pathway ◽

Inflammatory Responses ◽

Antimicrobial Activities ◽

Host Cells ◽

Inflammatory Factors ◽

Human Macrophage ◽

U937 Cells ◽

Wide Range ◽

Anti Inflammatory

Antimicrobial peptides have broad-spectrum killing activities against bacteria, enveloped viruses, fungi and several parasites via cell membrane permeation and exhibit primarily immunomodulatory and anti-infective functions in their interactions with host cells. However, the mechanism underlying their anti-inflammatory activity remains to be elucidated. L-K6, an analog of temporin-1CEb isolated from the skin secretion of Rana chensinensis, has demonstrated a wide range of antimicrobial activities against gram-negative and gram-positive bacteria. In this study, the potent anti-inflammatory mechanism of L-K6 and its analogs in lipopolysaccharide (LPS)-stimulated human macrophage U937 cells were evaluated. We found that L-K6 suppressed the expression of inflammatory factors by two downstream signaling components in the MyD88-dependent pathway, including the mitogen-activated protein kinases (MAPKs) and the NF (nuclear factor)-κB signaling pathway, but its analog L-K5, which had the same amino acid sequence as L-K6 but no Lys residue at the –COOH terminal, only inhibited the phosphorylation of I-κB and NF-κB. Importantly, L-K6 and L-K5 were actively taken up by U937 cells through an independent cell membrane disruption mechanism and were eventually localized to the perinuclear region. The L-K6 uptake process was mediated by endocytosis, but L-K5 was specifically taken up by U937 cells via TLR4 endocytosis. Our results demonstrated that L-K6 can neutralize LPS and diassociate LPS micelles to inhibit LPS from triggering the proinflammatory signaling pathway, and by partially inhibiting inflammatory responses by the intracellular target. However, L-K5 may mainly inhibit proinflammatory responses by intracellular reporters to modulate the NF-κB signaling pathway.

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p38/AP-1 Pathway in Lipopolysaccharide-Induced Inflammatory Responses Is Negatively Modulated by Electrical Stimulation

Mediators of Inflammation ◽

10.1155/2013/183042 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Deok Jeong ◽

Jaehwi Lee ◽

Young-Su Yi ◽

Yanyan Yang ◽

Kyoung Won Kim ◽

...

Keyword(s):

Electrical Stimulation ◽

Inflammatory Response ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Physiological Role ◽

Peritoneal Macrophages ◽

Cellular Level ◽

Transcriptional Level ◽

Weak Current ◽

Anti Inflammatory

Electrical stimulation with a weak current has been demonstrated to modulate various cellular and physiological responses, including the differentiation of mesenchymal stem cells and acute or chronic physical pain. Thus, a variety of investigations regarding the physiological role of nano- or microlevel currents at the cellular level are actively proceeding in the field of alternative medicine. In this study, we focused on the anti-inflammatory activity of aluminum-copper patches (ACPs) under macrophage-mediated inflammatory conditions. ACPs generated nanolevel currents ranging from 30 to 55 nA in solution conditions. Interestingly, the nanocurrent-generating aluminum-copper patches (NGACPs) were able to suppress both lipopolysaccharide-(LPS-) and pam3CSK-induced inflammatory responses such as NO and PGE2production in both RAW264.7 cells and peritoneal macrophages at the transcriptional level. Through immunoblotting and immunoprecipitation analyses, we found that p38/AP-1 could be the major inhibitory pathway in the NGACP-mediated anti-inflammatory response. Indeed, inhibition of p38 by SB203580 showed similar inhibitory activity of the production of TNF-αand PGE2and the expression of TNF-αand COX-2 mRNA. These results suggest that ACP-induced nanocurrents alter signal transduction pathways that are involved in the inflammatory response and could therefore be utilized in the treatment of various inflammatory diseases such as arthritis and colitis.

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Abstract P207: Role of (Pro)Renin Receptor in the Pathogenesis of Colon Cancer

Hypertension ◽

10.1161/hyp.66.suppl_1.p207 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Akira Nishiyama ◽

Juan Wang ◽

Shinichi Yachida ◽

Genevieve Nguyen ◽

Takuo Hirose ◽

...

Keyword(s):

Colon Cancer ◽

Signaling Pathway ◽

Western Blotting ◽

Cell Number ◽

Ductal Adenocarcinoma ◽

Mrna Levels ◽

Protein Levels ◽

Colon Cancer Cell Lines ◽

Cancer Tissues

(Pro)renin receptor ((P)RR) is a component of the Wnt receptor complex (Science, 2010). We have recently demonstrated that (P)RR plays an important role in the tumorigenesis of pancreatic ductal adenocarcinoma via the activation of Wnt/β-catenin signaling pathway (Shibayama et al. Sci Rep. 2015). Since the patients with colon cancer often show aberrantly activated Wnt/β-catenin-dependent signaling pathway by the mutations of its components, we investigated the possible role of (P)RR and Wnt/β-catenin signaling pathway in carcinogenesis of colon cancer. Real-time PCR was used for measuring mRNA levels of (P)RR. Protein levels of (P)RR was determined by Western blotting and immunohistochemistry. Activated β-catenin levels were determined by Western blotting. Cell proliferative ability was evaluated by counting the cell number in cultured colon cancer cell lines, HCT116 and DLD-1 cells. As compared to normal colon tissues (n=6), mRNA and protein levels of (P)RR were increased by 2.6- and 2.2-fold, respectively, in colon cancer tissues (n=9), which were associated with increased activated β-catenin levels (by 2.8-fold, P<0.05). However, plasma soluble (P)RR levels were not changed in patients with colon cancer (n=9). (P)RR and activated β-catenin levels were also increased in HCT116 (by 2.2- and 2.7-fold, n=5, respectively) and DLD-1 cells (by 1.9- and 2.8-fold, n=5, respectively). In these cells, inhibiting (P)RR with an siRNA attenuated the activity of β-catenin and reduced the proliferative abilities (n=5, P<0.05, respectively). These data suggest that (P)RR contributes to the tumorigenesis of colon cancer through the activation of Wnt/β-catenin signaling pathway.

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Archidendron lucidum Exerts Anti-Inflammatory Effects by Targeting PDK1 in the NF-κB Pathway

The American Journal of Chinese Medicine ◽

10.1142/s0192415x20500226 ◽

2020 ◽

Vol 48 (02) ◽

pp. 429-444

Author(s):

Minkyeong Jo ◽

Young-Su Yi ◽

Jae Youl Cho

Keyword(s):

Signaling Pathway ◽

Hplc Analysis ◽

Inflammatory Diseases ◽

Interleukin 1 ◽

Inflammatory Activity ◽

Raw264.7 Cells ◽

Luciferase Reporter ◽

No Production ◽

Pharmacological Activities ◽

Anti Inflammatory

Pharmacological activities of some Leguminosae family members were reported. Pharmacological activities of Archidendron lucidum, a Leguminosae family member have never been explored. Therefore, this study investigated anti-inflammatory effects of an Archidendron lucidum methanol extract (Al-ME). In this study, anti-inflammatory effects of Al-ME were investigated in LPS-stimulated RAW264.7 cells and HCl/EtOH-induced gastritis mice by MTT assay, nitric oxide (NO) production assay, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase reporter assay, and Western blotting. High-performance liquid chromatography (HPLC) analysis identified ethnopharmacological compounds in Al-ME. Al-ME inhibited NO production without cytotoxicity in peritoneal macrophages and RAW264.7 cells stimulated with LPS or Pam3CSK4. Al-ME downregulated mRNA expression of inflammatory genes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2)) and pro-inflammatory cytokines (tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), and IL-6). Al-ME exerted anti-inflammatory activity in LPS-stimulated RAW264.7 cells by inhibiting nuclear factor-kappa B (NF-[Formula: see text]B) signaling pathway. HPLC analysis identified quercetin, luteolin, and kaempferol as major anti-inflammatory components in Al-ME. Al-ME ameliorated HCl/EtOH-induced gastritis symptoms in mice by suppressing iNOS and IL-6 mRNA expressions and I[Formula: see text]B[Formula: see text] phosphorylation. Therefore, these results suggest that Al-ME exhibited anti-inflammatory activity by targeting NF-[Formula: see text]B signaling pathway, implying that Al-ME could be potent anti-inflammatory medications to prevent and treat inflammatory diseases.

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Novel Anti-inflammatory Effects of Canagliflozin Involving Hexokinase II in Lipopolysaccharide-Stimulated Human Coronary Artery Endothelial Cells

Cardiovascular Drugs and Therapy ◽

10.1007/s10557-020-07083-w ◽

2020 ◽

Author(s):

Laween Uthman ◽

Marius Kuschma ◽

Gregor Römer ◽

Marleen Boomsma ◽

Jens Kessler ◽

...

Keyword(s):

Endothelial Cells ◽

Coronary Artery ◽

Inflammatory Responses ◽

Vascular Inflammation ◽

Glycolytic Enzyme ◽

Human Coronary Artery ◽

Hexokinase Ii ◽

Protein Levels ◽

Inflammatory Mechanism ◽

Anti Inflammatory

Abstract Purpose Vascular inflammation and disturbed metabolism are observed in heart failure and type 2 diabetes mellitus. Glycolytic enzyme hexokinase II (HKII) is upregulated by inflammation. We hypothesized that SGLT2 inhibitors Canagliflozin (Cana), Empagliflozin (Empa) or Dapagliflozin (Dapa) reduces inflammation via HKII in endothelial cells, and that HKII-dependent inflammation is determined by ERK1/2, NF-κB. and/or AMPK activity in lipopolysaccharide (LPS)-stimulated human coronary artery endothelial cells (HCAECs). Methods HCAECs were pre-incubated with 3 μM or 10 μM Cana, 1 μM, 3 μM or 10 μM Empa or 0.5 μM, 3 μM or 10 μM Dapa (16 h) and subjected to 3 h LPS (1 μg/mL). HKII was silenced via siRNA transfection. Interleukin-6 (IL-6) release was measured by ELISA. Protein levels of HK I and II, ERK1/2, AMPK and NF-κB were detected using infra-red western blot. Results LPS increased IL-6 release and ERK1/2 phosphorylation; Cana prevented these pro-inflammatory responses (IL-6: pg/ml, control 46 ± 2, LPS 280 ± 154 p < 0.01 vs. control, LPS + Cana 96 ± 40, p < 0.05 vs. LPS). Cana reduced HKII expression (HKII/GAPDH, control 0.91 ± 0.16, Cana 0.71 ± 0.13 p < 0.05 vs. control, LPS 1.02 ± 0.25, LPS + Cana 0.82 ± 0.24 p < 0.05 vs. LPS). Empa and Dapa were without effect on IL-6 release and HKII expression in the model used. Knockdown of HKII by 37% resulted caused partial loss of Cana-mediated IL-6 reduction (pg/ml, control 35 ± 5, LPS 188 ± 115 p < 0.05 vs. control, LPS + Cana 124 ± 75) and ERK1/2 activation by LPS. In LPS-stimulated HCAECs, Cana, but not Empa or Dapa, activated AMPK. AMPK activator A769662 reduced IL-6 release. Conclusion Cana conveys anti-inflammatory actions in LPS-treated HCAECs through 1) reductions in HKII and ERK1/2 phosphorylation and 2) AMPK activation. These data suggest a novel anti-inflammatory mechanism of Cana through HKII.

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