scholarly journals Anti-inflammatory effects of Morus alba Linne bark on the activation of toll-like receptors and imiquimod-induced ear edema in mice

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Umeyama ◽  
Besse Hardianti ◽  
Shiori Kasahara ◽  
Dya Fita Dibwe ◽  
Suresh Awale ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Morus Alba ◽  
Raw264.7 Cells ◽  
Luciferase Reporter ◽  
Γδt Cells ◽  
Ear Edema ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory

Abstract Background Morus alba L. bark has been widely used in traditional medicine for treating several inflammatory diseases, such as hypertension, diabetes mellitus and coughing; however, the molecular mechanisms underlying its anti-inflammatory effects are not well understood. Methods We examined the effects of an extract of Morus alba L. bark (MabE) on Toll-like receptor (TLR) ligand-induced activation of RAW264.7 macrophages using a luciferase reporter assay and immunoassays. For the in vivo experiment, we used an imiquimod-induced ear edema model to examine the anti-inflammatory effects of MabE. Results MabE inhibited the TLR ligand-induced activation of NF-κB in RAW264.7 cells without affecting their viability. Consistent with the inhibition of NF-κB activation, MabE also inhibited the production of IL-6 and IL-1β from TLR ligand-treated RAW264.7 cells. In vivo MabE treatment inhibited the ear swelling of IMQ-treated mice, in addition to the mRNA expression of IL-17A, IL-1β and COX-2. The increases in splenic γδT cells in IMQ-treated mice and the production of IL-17A from splenocytes were significantly inhibited by MabE treatment. Conclusion Our study suggests that the anti-inflammatory effects of MabE on the activation of the macrophage cell line RAW246.7 by TLRs and IMQ-induced ear edema are through the inhibition of NF-κB activation and IL-17A-producing γδT cells, respectively.

scholarly journals Anti-Inflammatory Activity of Quercetogetin Isolated from Citrus Unshiu Peel Involves Suppression of NF-κB and MAPK Signaling Pathways in LPS-induced RAW264.7 Macrophages

2018 ◽  
Author(s):  
Eun Suk Son ◽  
Jeong-Wooung Park ◽  
Hye Ran Park ◽  
Woorijarang Han ◽  
Dae Eun Yun ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Raw264.7 Cells ◽  
Raw 264.7 Cells ◽  
Citrus Peel ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Citrus peel has been used in Asian traditional medicine for the treatment of cough, asthma, and bronchial disorders. However, the anti-inflammatory effect of quercetogetin (QUE), a polymethoxylated flavone isolated from the peel of citrus unshui is poorly understood. We investigated the anti-inflammatory effect and the molecular mechanisms of QUE in lipopolysaccharide (LPS)-induced RAW264.7 cells. QUE inhibited the production of NO and prostaglandin E2 by suppressing the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. QUE suppressed the production of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. QUE also inhibited the translocation of the nuclear factor kappa B subunit, p65, into the nucleus by interrupting the phosphorylation of IκB-α in LPS-induced RAW 264.7 cells. Based on the finding that QUE significantly decreased p-ERK protein expression in LPS-induced RAW264.7 cells, we confirmed that suppression of the inflammatory process by QUE was mediated through the MAPK pathway. This is the first report on the strong anti-inflammatory effects of QUE, which is a compound that can potentially be used as a therapeutic agent for inflammatory diseases.

scholarly journals Impressic Acid Attenuates the Lipopolysaccharide-Induced Inflammatory Response by Activating the AMPK/GSK3β/Nrf2 Axis in RAW264.7 Macrophages

2021 ◽  
Vol 22 (2) ◽  
pp. 762
Author(s):  
Gi Ho Lee ◽  
Ji Yeon Kim ◽  
Sun Woo Jin ◽  
Thi Hoa Pham ◽  
Jin Song Park ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Raw264.7 Cells ◽  
Raw264.7 Macrophages ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Inflammatory diseases are caused by excessive inflammation from pro-inflammatory mediators and cytokines produced by macrophages. The Nrf2 signaling pathway protects against inflammatory diseases by inhibiting excessive inflammation via the regulation of antioxidant enzymes, including HO-1 and NQO1. We investigated the anti-inflammatory effect of impressic acid (IPA) isolated from Acanthopanax koreanum on the lipopolysaccharide (LPS)-induced inflammation and the underlying molecular mechanisms in RAW264.7 cells. IPA attenuated the LPS-induced production of pro-inflammatory cytokines and reactive oxygen species, and the activation of the NF-κB signaling pathway. IPA also increased the protein levels of Nrf2, HO-1, and NQO1 by phosphorylating CaMKKβ, AMPK, and GSK3β. Furthermore, ML385, an Nrf2 inhibitor, reversed the inhibitory effect of IPA on LPS-induced production of pro-inflammatory cytokines in RAW264.7 cells. Therefore, IPA exerts an anti-inflammatory effect via the AMPK/GSK3β/Nrf2 signaling pathway in macrophages. Taken together, the findings suggest that IPA has preventive potential for inflammation-related diseases.

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

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.

scholarly journals Dual Effect of Soloxolone Methyl on LPS-Induced Inflammation In Vitro and In Vivo

2020 ◽  
Vol 21 (21) ◽  
pp. 7876
Author(s):  
Andrey V. Markov ◽  
Aleksandra V. Sen’kova ◽  
Valeriya O. Babich ◽  
Kirill V. Odarenko ◽  
Vadim A. Talyshev ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Nuclear Factor Κb ◽  
Raw264.7 Cells ◽  
Migration Activity ◽  
Akt Phosphorylation ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
And Migration

Plant-extracted triterpenoids belong to a class of bioactive compounds with pleotropic functions, including antioxidant, anti-cancer, and anti-inflammatory effects. In this work, we investigated the anti-inflammatory and anti-oxidative activities of a semisynthetic derivative of 18βH-glycyrrhetinic acid (18βH-GA), soloxolone methyl (methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate, or SM) in vitro on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and in vivo in models of acute inflammation: LPS-induced endotoxemia and carrageenan-induced peritonitis. SM used at non-cytotoxic concentrations was found to attenuate the production of reactive oxygen species and nitric oxide (II) and increase the level of reduced glutathione production by LPS-stimulated RAW264.7 cells. Moreover, SM strongly suppressed the phagocytic and migration activity of activated macrophages. These effects were found to be associated with the stimulation of heme oxigenase-1 (HO-1) expression, as well as with the inhibition of nuclear factor-κB (NF-κB) and Akt phosphorylation. Surprisingly, it was found that SM significantly enhanced LPS-induced expression of the pro-inflammatory cytokines interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW264.7 cells via activation of the c-Jun/Toll-like receptor 4 (TLR4) signaling axis. In vivo pre-exposure treatment with SM effectively inhibited the development of carrageenan-induced acute inflammation in the peritoneal cavity, but it did not improve LPS-induced inflammation in the endotoxemia model.

scholarly journals 4-Hydroxy-7-Methoxycoumarin Inhibits Inflammation in LPS-activated RAW264.7 Macrophages by Suppressing NF-κB and MAPK Activation

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4424
Author(s):  
Jin Kyu Kang ◽  
Chang-Gu Hyun
Keyword(s):  
Nitric Oxide ◽  
Nuclear Factor Kappa B ◽  
Inflammatory Diseases ◽  
Raw264.7 Cells ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Alternative Medicines ◽  
Raw264.7 Macrophages ◽  
Extracellular Signal ◽  
Anti Inflammatory

Coumarins are natural products with promising pharmacological activities owing to their anti-inflammatory, antioxidant, antiviral, anti-diabetic, and antimicrobial effects. Coumarins are present in many plants and microorganisms and have been widely used as complementary and alternative medicines. To date, the pharmacological efficacy of 4-hydroxy-7-methoxycoumarin (4H-7MTC) has not been reported yet. Therefore, in this study, we investigated the anti-inflammatory effects of 4H-7MTC in LPS-stimulated RAW264.7 cells as well as its mechanisms of action. Cells were treated with various concentrations of 4H-7MTC (0.3, 0.6, 0.9, and 1.2 mM) and 40 μM L-N6-(1-iminoethyl)-L-lysine (L-NIL) were used as controls. LPS-stimulated RAW264.7 cells showed that 4H-7MTC significantly reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production without cytotoxic effects. In addition, 4H-7MTC strongly decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Furthermore, 4H-7MTC reduced the production of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. We also found that 4H-7MTC strongly exerted its anti-inflammatory actions by downregulating nuclear factor kappa B (NF-κB) activation by suppressing inhibitor of nuclear factor kappa B alpha (IκBα) degradation in macrophages. Moreover, 4H-7MTC decreased phosphorylation of extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase/stress-activated protein kinase (JNK), but not that of p38 MAPK. These results suggest that 4H-7MTC may be a good candidate for the treatment or prevention of inflammatory diseases such as dermatitis, psoriasis, and arthritis. Ultimately, this is the first report describing the effective anti-inflammatory activity of 4H-7MTC.

scholarly journals LOMIX, a Mixture of Flaxseed Linusorbs, Exerts Anti-Inflammatory Effects through Src and Syk in the NF-κB Pathway

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 859 ◽  
Author(s):  
Zubair Ahmed Ratan ◽  
Deok Jeong ◽  
Nak Yoon Sung ◽  
Youn Young Shim ◽  
Martin J. T. Reaney ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Model Systems ◽  
Kinase Assay ◽  
Luciferase Reporter ◽  
No Production ◽  
Anti Inflammatory

Although flax (Linum usitatissimum L.) has long been used as Ayurvedic medicine, its anti-inflammatory role is still unclear. Therefore, we aimed to investigate the anti-inflammatory role of a linusorb mixture (LOMIX) recovered from flaxseed oil. Effects of LOMIX on inflammation and its mechanism of action were examined using several in vitro assays (i.e., NO production, real-time PCR analysis, luciferase-reporter assay, Western blot analysis, and kinase assay) and in vivo analysis with animal inflammation models as well as acute toxicity test. Results: LOMIX inhibited NO production, cell shape change, and inflammatory gene expression in stimulated RAW264.7 cells through direct targeting of Src and Syk in the NF-κB pathway. In vivo study further showed that LOMIX alleviated symptoms of gastritis, colitis, and hepatitis in murine model systems. In accordance with in vitro results, the in vivo anti-inflammatory effects were mediated by inhibition of Src and Syk. LOMIX was neither cytotoxic nor did it cause acute toxicity in mice. In addition, it was found that LOB3, LOB2, and LOA2 are active components included in LOMIX, as assessed by NO assay. These in vitro and in vivo results suggest that LOMIX exerts an anti-inflammatory effect by inhibiting the inflammatory responses of macrophages and ameliorating symptoms of inflammatory diseases without acute toxicity and is a promising anti-inflammatory medication for inflammatory diseases.

Carpesium macrocephalum Attenuates Lipopolysaccharide-Induced Inflammation in Macrophages by Regulating the NF-κB/IκB-α, Akt, and STAT Signaling Pathways

2013 ◽  
Vol 41 (04) ◽  
pp. 927-943 ◽  
Author(s):  
Sushruta Koppula ◽  
Wan-Jae Kim ◽  
Jun Jiang ◽  
Do-Wan Shim ◽  
Na-Hyun Oh ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
In Vivo Studies ◽  
Raw264.7 Cells ◽  
Traditional Use ◽  
Necrosis Factor Alpha ◽  
Proinflammatory Mediators ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory

Carpesium macrocephalum (CM) Fr. et Sav. (Compositae) has been used in Chinese folk medicine as an analgesic, hemostatic, antipyretic, and to suppress inflammatory conditions. In the present study we aimed to provide scientific evidence for the anti-inflammatory properties of CM extract and evaluate the intrinsic mechanisms involved in both in vitro and in vivo experimental models. In in vitro findings, CM significantly inhibited the LPS-stimulated release of proinflammatory mediators such as nitric oxide, tumor necrosis factor-alpha, prostaglandin E2, and interleukin-6 in RAW264.7 macrophages in a concentration-dependent fashion. The attenuation of inflammatory responses in LPS-activated RAW264.7 cells by CM was closely associated with the suppression of nuclear factor-kappa B (NF-κB) phosphorylation, IκB-α degradation, and phosphorylation of Akt. CM treatment also attenuated the phosphorylation of STAT through TRIF dependent pathways in LPS-activated RAW264.7 cells. In vivo studies revealed that CM extract concentration dependently suppressed the acetic acid-induced vascular permeability in mice. Considering the data obtained regulation of multiple signaling mechanisms involving TRIF and Akt/NF-κB pathways might be responsible for the potent anti-inflammatory action of CM, substantiating its traditional use in inflammatory diseases.

scholarly journals Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 6073
Author(s):  
Laily Rahmawati ◽  
Nur Aziz ◽  
Jieun Oh ◽  
Yo Han Hong ◽  
Byoung Young Woo ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Raw264.7 Cells ◽  
Acute Gastritis ◽  
Anti Inflammatory

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.

Momordica charantia Inhibits Inflammatory Responses in Murine Macrophages via Suppression of TAK1

2018 ◽  
Vol 46 (02) ◽  
pp. 435-452 ◽  
Author(s):  
Woo Seok Yang ◽  
Eunju Yang ◽  
Min-Jeong Kim ◽  
Deok Jeong ◽  
Deok Hyo Yoon ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Momordica Charantia ◽  
Luciferase Reporter ◽  
No Production ◽  
Dependent Manner ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
Dose Dependent

Momordica charantia known as bitter melon is a representative medicinal plant reported to exhibit numerous pharmacological activities such as antibacterial, antidiabetic, anti-inflammatory, anti-oxidant, antitumor, and hypoglycemic actions. Although this plant has high ethnopharmacological value for treating inflammatory diseases, the molecular mechanisms by which it inhibits the inflammatory response are not fully understood. In this study, we aim to identify the anti-inflammatory mechanism of this plant. To this end, we studied the effects of its methanol extract (Mc-ME) on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Specifically, we evaluated nitric oxide (NO) production, mRNA expression of inflammatory genes, luciferase reporter gene activity, and putative molecular targets. Mc-ME blocked NO production in a dose-dependent manner in RAW264.7 cells; importantly, no cytotoxicity was observed. Moreover, the mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were decreased by Mc-ME treatment in a dose-dependent manner. Luciferase assays and nuclear lysate immunoblotting analyses strongly indicated that Mc-ME decreases the levels of p65 [a nuclear factor (NF)-[Formula: see text]B subunit] and c-Fos [an activator protein (AP)-1 subunit]. Whole lysate immunoblotting assays, luciferase assays, and overexpression experiments suggested that transforming growth factor [Formula: see text]-activated kinase 1 (TAK1) is targeted by Mc-ME, thereby suppressing NF-[Formula: see text]B and AP-1 activity via downregulation of extracellular signal-regulated kinases (ERKs) and AKT. These results strongly suggest that Mc-ME exerts its anti-inflammatory activity by reducing the action of TAK1, which also affects the activation of NF-[Formula: see text]B and AP-1.

scholarly journals Procyanidin A1 Alleviates Inflammatory Response induced by LPS through NF-κB, MAPK, and Nrf2/HO-1 Pathways in RAW264.7 cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shan Han ◽  
Hongwei Gao ◽  
Shaoru Chen ◽  
Qinqin Wang ◽  
Xinxing Li ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Raw264.7 Cells ◽  
Tnf Α ◽  
Intracellular Ros ◽  
Anti Inflammatory ◽  
Cellular Thermal Shift Assay

Abstract Inflammation is a complex physiological process that poses a serious threat to people’s health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells administrated with LPS. PCA1 blocked IκB-α degradation, inhibited IKKα/β and IκBα phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro. Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.

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