Berberine suppresses proinflammatory responses through AMPK activation in macrophages

2009 ◽  
Vol 296 (4) ◽  
pp. E955-E964 ◽  
Author(s):  
Hyun Woo Jeong ◽  
Kuan Chi Hsu ◽  
Joo-Won Lee ◽  
Mira Ham ◽  
Jin Young Huh ◽  
...  
Keyword(s):  
Peritoneal Macrophages ◽  
Dominant Negative ◽  
Raw 264.7 Cells ◽  
Ampk Activation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Compound C ◽  
Proinflammatory Responses ◽  
Cox 2 ◽  
Amp Activated Protein Kinase ◽  
Oxide Synthase

Berberine (BBR) has been shown to improve several metabolic disorders, such as obesity, type 2 diabetes, and dyslipidemia, by stimulating AMP-activated protein kinase (AMPK). However, the effects of BBR on proinflammatory responses in macrophages are poorly understood. Here we show that BBR represses proinflammatory responses through AMPK activation in macrophages. In adipose tissue of obese db/db mice, BBR treatment significantly downregulated the expression of proinflammatory genes such as TNF-α, IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Consistently, BBR inhibited LPS-induced expression of proinflammatory genes including IL-1β, IL-6, iNOS, MCP-1, COX-2, and matrix metalloprotease-9 in peritoneal macrophages and RAW 264.7 cells. Upon various proinflammatory signals including LPS, free fatty acids, and hydrogen peroxide, BBR suppressed the phosphorylation of MAPKs, such as p38, ERK, and JNK, and the level of reactive oxygen species in macrophages. Moreover, these inhibitory effects of BBR on proinflammatory responses were abolished by AMPK inhibition via either compound C, an AMPK inhibitor, or dominant-negative AMPK, implying that BBR would downregulate proinflammatory responses in macrophages via AMPK stimulation.

scholarly journals Novel Mechanisms Modulating Palmitate-Induced Inflammatory Factors in Hypertrophied 3T3-L1 Adipocytes by AMPK

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Naru Morita ◽  
Toshio Hosaka ◽  
Atsuko Kitahara ◽  
Toshitaka Murashima ◽  
Hirohisa Onuma ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Mek Inhibitor ◽  
Inflammatory Factors ◽  
Ampk Activation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Compound C ◽  
Extracellular Signal ◽  
Underlying Mechanisms ◽  
Amp Activated Protein Kinase

Objective. A growing body of evidence indicates that AMP-activated protein kinase (AMPK) contributes to not only energy metabolic homeostasis but also the inhibition of inflammatory responses. However, the underlying mechanisms remain unclear. To elucidate the role of AMPK, in this study, we observed the effects of AMPK activation on monocyte chemoattractant protein-1 (MCP-1) release in mature 3T3-L1 adipocytes. Methods. We observed signal transduction pathways regulating MCP-1, which increased in obese adipocytes, in an in vitro model of hypertrophied 3T3-L1 adipocytes preloaded with palmitate. Results. Palmitate-preloaded cells exhibited significant increase in MCP-1 release and triglyceride (TG) deposition. Increased MCP-1 release and TG deposition were significantly decreased by an AMPK activator. In addition, the AMPK activator not only markedly diminished MCP-1 secretion but also augmented phosphorylation of nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase (ERK) 1/2. In contrast, MCP-1 release suppression was abolished by the AMPK inhibitor compound C and the MEK inhibitor U0126. Conclusions. MCP-1 release from hypertrophied adipocytes is suppressed by AMPK activation through the NF-κB and ERK pathways. These findings provide evidence that AMPK plays a crucial role in ameliorating obesity-induced inflammation.

scholarly journals Inositol-Requiring Enzyme 1-Dependent Activation of AMPK Promotes Brucella abortus Intracellular Growth

2016 ◽  
Vol 198 (6) ◽  
pp. 986-993 ◽  
Author(s):  
Ning Liu ◽  
Yingying Li ◽  
Chunyan Dong ◽  
Xiaohan Xu ◽  
Pan Wei ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Underlying Mechanism ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Ros Production ◽  
Ampk Activation ◽  
Intracellular Growth ◽  
Serine Threonine Kinase ◽  
Content Type ◽  
Amp Activated Protein Kinase

ABSTRACTAMP-activated protein kinase (AMPK) is a serine/threonine kinase that is well conserved during evolution. AMPK activation inhibits production of reactive oxygen species (ROS) in cells via suppression of NADPH oxidase. However, the role of AMPK during the process ofBrucellainfection remains unknown. Our data demonstrate thatB. abortusinfection induces AMPK activation in HeLa cells in a time-dependent manner. The known AMPK kinases LKB1, CAMKKβ, and TAK1 are not required for the activation of AMPK byB. abortusinfection. Instead, this activation is dependent on the RNase activity of inositol-requiring enzyme 1 (IRE1). Moreover, we also found thatB. abortusinfection-induced IRE1-dependent activation of AMPK promotesB. abortusintracellular growth with peritoneal macrophages via suppression of NADPH-derived ROS production.IMPORTANCEPrevious studies showed thatB. abortusinfection does not promote any oxidative burst regulated by NADPH oxidase. However, the underlying mechanism remains elusive. We report for the first time that AMPK activation caused byB. abortusinfection plays important role in NADPH oxidase-derived ROS production.

scholarly journals Inhibitory Effect of 1,5-Dimethyl Citrate from Sea Buckthorn (Hippophae rhamnoides) on Lipopolysaccharide-Induced Inflammatory Response in RAW 264.7 Mouse Macrophages

Foods ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 269 ◽  
Author(s):  
Su Cheol Baek ◽  
Dahae Lee ◽  
Mun Seok Jo ◽  
Kwang Ho Lee ◽  
Yong Hoon Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Sea Buckthorn ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Mouse Macrophages ◽  
Cox 2 ◽  
Oxide Synthase

Hippophae rhamnoides L. (Elaeagnaceae; commonly known as “sea buckthorn” and “vitamin tree”), is a spiny deciduous shrub whose fruit is used in foods and traditional medicines. The H. rhamnoides fruit (berry) is rich in vitamin C, with a level exceeding that found in lemons and oranges. H. rhamnoides berries are usually washed and pressed to create pomace and juice. Today, the powder of the aqueous extract of H. rhamnoides berries are sold as a functional food in many countries. As part of our ongoing effort to identify bioactive constituents from natural resources, we aimed to isolate and identify those from the fruits of H. rhamnoides. Phytochemical analysis of the extract of H. rhamnoides fruits led to the isolation and identification of six compounds, namely, a citric acid derivative (1), a phenolic (2), flavonoids (3 and 4), and megastigmane compounds (5 and 6). Treatment with compounds 1–6 did not have any impact on the cell viability of RAW 264.7 mouse macrophages. However, pretreatment with these compounds suppressed lipopolysaccharide (LPS)-induced NO production in RAW 264.7 mouse macrophages in a concentration-dependent manner. Among the isolated compounds, compound 1 was identified as the most active, with an IC50 of 39.76 ± 0.16 μM. This value was comparable to that of the NG-methyl-L-arginine acetate salt, a nitric oxide synthase inhibitor with an IC50 of 28.48 ± 0.05 μM. Western blot analysis demonstrated that compound 1 inhibited the LPS-induced expression of IKKα/β (IκB kinase alpha/beta), I-κBα (inhibitor of kappa B alpha), nuclear factor kappa-B (NF-κB) p65, iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) in RAW 264.7 cells. Furthermore, LPS-stimulated cytokine production was detected using a sandwich enzyme-linked immunosorbent assay. Compound 1 decreased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) production in LPS-stimulated RAW 264.7 cells. In summary, the mechanism of action of 1 included the suppression of LPS-induced NO production in RAW 264.7 cells by inhibiting IKKα/β, I-κBα, NF-κB p65, iNOS, and COX-2, and the activities of IL-6 and TNF-α.

scholarly journals The Immunomodulatory Activities of Picria Fel-Terrae Lour Herbs towards RAW 264.7 Cells

2019 ◽  
Vol 7 (1) ◽  
pp. 24-28
Author(s):  
Novycha AuliaFendri ◽  
Rosidah ◽  
Yuandani ◽  
Sri Suryani ◽  
Denny Satria
Keyword(s):  
Ethyl Acetate ◽  
Inflammatory Biomarkers ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Chromatography Method ◽  
Tnf Α ◽  
Gene Level ◽  
Pcr Method ◽  
Cox 2 ◽  
Oxide Synthase

AIM: To investigate immunomodulatory activities of Picria fel-terrae Lour herbs extract against inflammatory biomarkers by conducting cell culture experiments. MATERIAL AND METHODS: The herbs of Picria fel-terrae Lour were dried and extracted with n-hexane, ethyl acetate, 96% ethanol, followed by evaporation and freeze-drying. Phytochemicals screening were analysed with thin layer chromatography method. Cell viability was assessed with MTT assay. The genes of Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-6, interleukin (IL)-1β and inducible Nitric Oxide Synthase (iNOS), Cyclooxygenase (COX-2) in lipopolysaccharide (LPS)-induced macrophages were analysed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method. RESULTS: Phytochemicals screening showed the presence of steroids in n-hexane extract (ENPFH) and flavonoids, glycosides, saponins, tannins in ethyl acetate (EEAPFH) and ethanol (EEPFH) extracts. The Viability of RAW 264.7 cell toward ENPFH, EEAPFH, and EEPFH (1-200 μgmL-1) showed no toxicity effects. At the gene level, ENPFH; EEAPFH; EEPFH decreased the gene expression of TNF-α, IL-6, IL-1β, iNOS, and COX-2 which induced with LPS (1 μgmL-1). CONCLUSIONS: Our results suggest that extracts of Picria fel-terrae Lour Herbs possesses immunomodulatory activities by inhibiting selected inflammatory biomarkers at the gene levels in LPS-induced macrophages.

scholarly journals A Central Role for Neuronal Adenosine 5′-Monophosphate-Activated Protein Kinase in Cancer-Induced Anorexia

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5220-5229 ◽  
Author(s):  
Eduardo R. Ropelle ◽  
José R. Pauli ◽  
Karina G. Zecchin ◽  
Mirian Ueno ◽  
Cláudio T. de Souza ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Food Intake ◽  
Life Span ◽  
Energy Homeostasis ◽  
Ampk Activation ◽  
Chronic Infusion ◽  
The Central Nervous System ◽  
Amp Activated Protein Kinase ◽  
Oxide Synthase ◽  
Cancer Anorexia

The pathogenesis of cancer anorexia is multifactorial and associated with disturbances of the central physiological mechanisms controlling food intake. However, the neurochemical mechanisms responsible for cancer-induced anorexia are unclear. Here we show that chronic infusion of 5-amino-4imidazolecarboxamide-riboside into the third cerebral ventricle and a chronic peripheral injection of 2 deoxy-d-glucose promotes hypothalamic AMP-activated protein kinase (AMPK) activation, increases food intake, and prolongs the survival of anorexic tumor-bearing (TB) rats. In parallel, the pharmacological activation of hypothalamic AMPK in TB animals markedly reduced the hypothalamic production of inducible nitric oxide synthase, IL-1β, and TNF-α and modulated the expression of proopiomelanocortin, a hypothalamic neuropeptide that is involved in the control of energy homeostasis. Furthermore, the daily oral and intracerebroventricular treatment with biguanide antidiabetic drug metformin also induced AMPK phosphorylation in the central nervous system and increased food intake and life span in anorexic TB rats. Collectively, the findings of this study suggest that hypothalamic AMPK activation reverses cancer anorexia by inhibiting the production of proinflammatory molecules and controlling the neuropeptide expression in the hypothalamus, reflecting in a prolonged life span in TB rats. Thus, our data indicate that hypothalamic AMPK activation presents an attractive opportunity for the treatment of cancer-induced anorexia.

Anti-inflammatory effect of chitosan oligosaccharides in RAW 264.7 cells

2010 ◽  
Vol 5 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Eun-Jin Yang ◽  
Jong-Gwan Kim ◽  
Ji-Young Kim ◽  
Seong Kim ◽  
Nam Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Protein Expression ◽  
Inducible Nitric Oxide Synthase ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Chitosan Oligosaccharides ◽  
Cox 2 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

AbstractWe examined the effects of chitosan oligosaccharides (COSs) with different molecular weights (COS-A, 10 kDa < MW < 20 kDa; COS-C, 1 kDa < MW < 3 kDa) on the lipopolysaccharide (LPS)-induced production of prostaglandin E2 and nitric oxide and on the expression of cyclooxygenase-2 and inducible nitric oxide synthase in RAW264.7 macrophages. COS-A (0.4%) and COS-C (0.2%) significantly inhibited PGE2 production in LPS-stimulated macrophages without cytotoxicity. The effect of COS-A and COS-C on COX-2 expression in activated macrophages was also investigated by immunoblotting. The inhibition of PGE2 by COS-A and COS-C can be attributed to the blocking of COX-2 protein expression. COS-A (0.4%) and COS-C (0.2%) also markedly inhibited the LPS-induced NO production of RAW 264.7 cells by 50.2% and 44.1%, respectively. The inhibition of NO by COSs was consistent with decreases in inducible nitric oxide synthase (iNOS) protein expression. To test the inhibitory effects of COS-A and COS-C on other cytokines, we also performed ELISA assays for IL-1β in LPS-stimulated RAW 264.7 macrophage cells, but only a dose-dependent decrease in the IL-1β production exerted by COS-A was observed. In order to test for irritation and the potential sensitization of COS-A and COS-C for use as cosmetic materials, human skin primary irritation tests were performed on 32 volunteers; no adverse reactions of COSs usage were observed. Based on these results, we suggest that COS-A and COS-C be considered possible anti-inflammatory candidates for topical application.

scholarly journals Homocysteine suppresses lipolysis in adipocytes by activating the AMPK pathway

2011 ◽  
Vol 301 (4) ◽  
pp. E703-E712 ◽  
Author(s):  
Zhigang Wang ◽  
Maria Pini ◽  
Tong Yao ◽  
Zhanxiang Zhou ◽  
Changhao Sun ◽  
...  
Keyword(s):  
Independent Risk Factor ◽  
Dependent Manner ◽  
Ampk Activation ◽  
Acetyl Coa Carboxylase ◽  
Glycerol Release ◽  
Compound C ◽  
Artery Disease ◽  
Amp Activated Protein Kinase ◽  
Release Of Glycerol ◽  
Dose Dependent

Hyperhomocysteinemia (HHcy) is an independent risk factor for coronary artery disease. Emerging evidence suggests that HHcy is also associated with adipocyte tissue dysfunction. One of the principal functions of adipose tissue is to provide energy substrate via lipolysis. In the present study, we investigated the effects of homocysteine (Hcy) on lipolysis in adipocytes. We found that Hcy inhibited release of glycerol and fatty acids, two typical indicators of the lipolytic response, in primary adipocytes and fully differentiated 3T3-L1 adipocytes in a dose-dependent manner under both basal and isoproterenol-stimulated conditions. In differentiated 3T3-L1 adipocytes, decreased glycerol and free fatty acid (FFA) release was associated with elevation of intracellular TG content. Further studies showed that Hcy-mediated antilipolytic responses were independent of the cyclic AMP-PKA and MEK-ERK1/2 pathways. However, Hcy increased phosphorylation levels of AMP-activated protein kinase (AMPK) and its downstream enzyme acetyl-CoA carboxylase. Compound C, an AMPK inhibitor, abolished Hcy-induced reduction of glycerol and FFA release under both basal and isoproterenol-stimulated conditions. Furthermore, AMPKα1 siRNA reversed Hcy-inhibited glycerol release. Supplementation of exogenous Hcy in the diet for 2 wk lowered circulating glycerol and FFA levels. Moreover, Hcy supplementation was associated with elevated leptin levels and reduced adiponectin levels in plasma. These results show that Hcy inhibits lipolysis through a pathway that involves AMPK activation.

Activation of AMP-activated protein kinase stimulates proopiomelanocortin gene transcription in AtT20 corticotroph cells

2007 ◽  
Vol 292 (6) ◽  
pp. E1899-E1905 ◽  
Author(s):  
Yasumasa Iwasaki ◽  
Mitsuru Nishiyama ◽  
Takafumi Taguchi ◽  
Machiko Kambayashi ◽  
Masato Asai ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Gene Transcription ◽  
Hpa Axis ◽  
Dominant Negative ◽  
Dependent Manner ◽  
Energy Depletion ◽  
Compound C ◽  
Pomc Gene ◽  
Intracellular Energy ◽  
Amp Activated Protein Kinase

Starvation is known to activate the hypothalamo-pituitary-adrenal (HPA) axis, a representative antistress system in the living organism. In this study, we investigated in vitro whether activation of the AMP-activated protein kinase (AMPK), which is known to occur in intracellular energy depletion, influences the expression of POMC gene that encodes adrenocorticotropin. We first confirmed that each subunit of AMPK was expressed in the AtT20 corticotroph cell line. We then found that AICAR, a cell-permeable AMP analog and an activator of AMPK, potently stimulated the 5′-promoter activity of POMC gene in a dose-dependent manner. The effects were promoter specific because AICAR enhanced the AP1-mediated POMC promoter activities but did not influence other transcription factor-induced transcription. The effect of AICAR on POMC gene transcription was completely eliminated by specific AMPK inhibitor compound C or by dominant negative AMPK, whereas overexpression of constitutively active AMPK mimicked the effect of AICAR. Finally, experiments using specific kinase inhibitors suggested that the PI 3-kinase-mediated signaling pathway is at least partly involved in the effect. Our results suggest that intracellular energy depletion with the resultant activation of AMPK directly stimulates the HPA axis at the pituitary level by increasing the expression of POMC gene.

scholarly journals Role of AMP-activated protein kinase during postovulatory aging of mouse oocytes†

2020 ◽  
Vol 103 (3) ◽  
pp. 534-547
Author(s):  
Guang-Yi Sun ◽  
Shuai Gong ◽  
Qiao-Qiao Kong ◽  
Zhi-Bin Li ◽  
Jia Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Species Difference ◽  
Adenosine Monophosphate ◽  
Cytoplasmic Calcium ◽  
Ampk Activation ◽  
Mouse Oocytes ◽  
Compound C ◽  
Oocyte Aging ◽  
Amp Activated Protein Kinase

Abstract Studies suggested that postovulatory oocyte aging might be prevented by maintaining a high maturation-promoting factor (MPF) activity. Whether AMP-activated protein kinase (AMPK) plays any role in postovulatory oocyte aging is unknown. Furthermore, while activation of AMPK stimulates meiotic resumption in mouse oocytes, it inhibits meiotic resumption in pig and bovine oocytes. Thus, the species difference in AMPK regulation of oocyte MPF activities is worth in-depth studies. This study showed that AMPK activation with metformin or 5-aminoimidazole- 4-carboxamide- 1-beta-d- ribofuranoside and inactivation with compound C significantly increased and decreased, respectively, the activation susceptibility (AS) and other aging parameters in aging mouse oocytes. While AMPK activity increased, MPF activity and cyclic adenosine monophosphate (cAMP) decreased significantly with time post ovulation. In vitro activation and inactivation of AMPK significantly decreased and increased the MPF activity, respectively. MPF upregulation with MG132 or downregulation with roscovitine completely abolished the effects of AMPK activation or inactivation on AS of aging oocytes, respectively. AMPK facilitated oocyte aging with increased reactive oxygen species (ROS) and cytoplasmic calcium. Furthermore, treatment with Ca2+/calmodulin-dependent protein kinase (CaMK) inhibitors significantly decreased AS and AMPK activation. Taken together, the results suggested that AMPK facilitated oocyte aging through inhibiting MPF activities, and postovulatory oocyte aging activated AMPK with decreased cAMP by activating CaMKs via increasing ROS and cytoplasmic calcium.

Anti-Inflammatory Activity ofSchizonepeta tenuifoliathrough the Inhibition of MAPK Phosphorylation in Mouse Peritoneal Macrophages

2008 ◽  
Vol 36 (06) ◽  
pp. 1145-1158 ◽  
Author(s):  
Su-Jin Kim ◽  
Jung-Sun Kim ◽  
In-Young Choi ◽  
Dong-Hyun Kim ◽  
Min-Cheol Kim ◽  
...  
Keyword(s):  
Peritoneal Macrophages ◽  
Mapk Phosphorylation ◽  
Inflammatory Reactions ◽  
Inflammatory Mechanism ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Mouse Peritoneal Macrophages ◽  
Necrosis Factor

Schizonepeta tenuifolia (ST) is a well-known herb to treat the cold and its associated headache. However, the anti-inflammatory mechanism of ST in mouse peritoneal macrophages is not clear. In this study, we demonstrated that ST inhibited lipopolysaccaride (LPS)-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. The maximal inhibition rate of TNF-α and IL-6 production by ST (2 mg/ml) was 48.01 ± 2.8% and 56.45 ± 2.8%, respectively. During the inflammatory process, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were increased in mouse peritoneal macrophages. However, treated with ST decreased the protein level of COX-2 and iNOS, as well as the production of PGE2and NO in LPS-stimulated mouse peritoneal macrophages. In addition, ST inhibited the phosphorylation of MAPK. Taken together, the results of this study suggest an important molecular mechanism by which ST reduces inflammation, which may explain its beneficial effect in the regulation of inflammatory reactions.

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