scholarly journals Evidence for Anti-Inflammatory Activity of Isoliquiritigenin, 18β Glycyrrhetinic Acid, Ursolic Acid, and the Traditional Chinese Medicine Plants Glycyrrhiza glabra and Eriobotrya japonica, at the Molecular Level

Medicines ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. 55 ◽  
Author(s):  
Jun-Xian Zhou ◽  
Michael Wink
Keyword(s):  
Ursolic Acid ◽  
Glycyrrhetinic Acid ◽  
Glycyrrhiza Glabra ◽  
Eriobotrya Japonica ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Background: We investigated the effect of root extracts from the traditional Chinese medicine (TCM) plants Glycyrrhiza glabra L., Paeonia lactiflora Pall., and the leaf extract of Eriobotrya japonica (Thunb.) Lindl., and their six major secondary metabolites, glycyrrhizic acid, 18β glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, paeoniflorin, and ursolic acid, on lipopolysaccharide (LPS)-induced NF-κB expression and NF-κB-regulated pro-inflammatory factors in murine macrophage RAW 264.7 cells. Methods: The cytotoxicity of the substances was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. RAW 264.7 cells were treated with LPS (1 μg/mL) or LPS plus single substances; the gene expression levels of NF-κB subunits (RelA, RelB, c-Rel, NF-κB1, and NF-κB2), and of ICAM-1, TNF-α, iNOS, and COX-2 were measured employing real-time PCR; nitric oxide (NO) production by the cells was quantified with the Griess assay; nuclear translocation of NF-κB was visualized by immunofluorescence microscopy with NF-κB (p65) staining. Results: All the substances showed moderate cytotoxicity against RAW 264.7 cells except paeoniflorin with an IC50 above 1000 μM. Glycyrrhiza glabra extract and Eriobotrya japonica extract, as well as 18β glycyrrhetinic acid and isoliquiritigenin at low concentrations, inhibited NO production in a dose-dependent manner. LPS upregulated gene expressions of NF-κB subunits and of ICAM-1, TNF-α, iNOS, and COX-2 within 8 h, which could be decreased by 18β glycyrrhetinic acid, isoliquiritigenin and ursolic acid similarly to the anti-inflammatory drug dexamethasone. NF-κB translocation from cytoplasm to nucleus was observed after LPS stimulation for 2 h and was attenuated by extracts of Glycyrrhiza glabra and Eriobotrya japonica, as well as by 18β glycyrrhetinic acid, isoliquiritigenin, and ursolic acid. Conclusions: 18β glycyrrhetinic acid, isoliquiritigenin, and ursolic acid inhibited the gene expressions of ICAM-1, TNF-α, COX-2, and iNOS, partly through inhibiting NF-κB expression and attenuating NF-κB nuclear translocation. These substances showed anti-inflammatory activity. Further studies are needed to elucidate the exact mechanisms and to assess their usefulness in therapy.

scholarly journals Auraptene, a Monoterpene Coumarin, Inhibits LTA-Induced Inflammatory Mediators via Modulating NF-κB/MAPKs Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Chih-Hsuan Hsia ◽  
Thanasekaran Jayakumar ◽  
Wan-Jung Lu ◽  
Joen-Rong Sheu ◽  
Chih-Wei Hsia ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Nuclear Translocation ◽  
Polyacrylamide Gel Electrophoresis ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Objective. Oxidative stress-mediated inflammatory events involve in the progress of several diseases such as asthma, cancers, and multiple sclerosis. Auraptene (AU), a natural prenyloxycoumarin, possesses numerous pharmacological activities. Here, the anti-inflammatory effects of AU were investigated in lipoteichoic acid- (LTA-) induced macrophage cells (RAW 264.7). Methods. The expression of cyclooxygenase (COX-2), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS) and the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38 MAPK, c-Jun N-terminal kinase (JNK), heme oxygenase (HO-1), p65, and IκBα were all identified by western blotting assay. The level of nitric oxide (NO) was measured by spectrometer analysis. The nuclear translocation of p65 nuclear factor kappa B (NF-κB) was assessed by the confocal microscopic staining method. Native polyacrylamide gel electrophoresis was performed to perceive the activity of antioxidant enzyme catalase (CAT). Results. AU expressively reduced NO production and COX-2, TNF-α, IL-1 β, and iNOS expression in LTA-stimulated cells. AU at higher concentration (10 µM) inhibited ERK and JNK, but not p38 phosphorylation induced by LTA. Moreover, AU blocked IκB and p65 phosphorylation, and p65 nuclear translocation. However, AU pretreatment was not effective on antioxidant HO-1 expression, CAT activity, and reduced glutathione (GSH, a nonenzymatic antioxidant), in LTA-induced RAW 264.7 cells. Conclusion. The findings of this study advocate that AU shows anti-inflammatory effects via reducing NF-κB/MAPKs signaling pathways.

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.

Fermentation Improves Anti-Inflammatory Effect of Sipjeondaebotang on LPS-Stimulated RAW 264.7 Cells

2012 ◽  
Vol 40 (04) ◽  
pp. 813-831 ◽  
Author(s):  
You-Chang Oh ◽  
Won-Kyung Cho ◽  
Yun Hee Jeong ◽  
Ga Young Im ◽  
Min Cheol Yang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Mediators ◽  
High Performance ◽  
Biological Effects ◽  
Inhibitory Effect ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory

Sipjeondaebotang (SJ) has been used as a traditional drug in east-Asian countries. In this study, to provide insight into the biological effects of SJ and SJ fermented by Lactobacillus, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in macrophages. The investigation was focused on whether SJ and fermented SJ could inhibit the production of pro-inflammatory mediators such as prostaglandin (PG) E2 and nitric oxide (NO) as well as the expressions of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB in LPS-stimulated RAW 264.7 cells. We found that SJ modestly inhibited LPS-induced PGE2, NO and TNF-α production as well as the expressions of COX-2 and iNOS. Interestingly, fermentation significantly increased its inhibitory effect on the expression of all pro-inflammatory mediators. Furthermore, fermented SJ exhibited increased inhibition of p38 MAPK and c-Jun NH2-terminal kinase (JNK) MAPK phosphorylation as well as NF-κB p65 translocation by reduced IκBα degradation compared with either untreated controls or unfermented SJ. High performance liquid chromatography (HPLC) analysis showed fermentation by Lactobacillus increases liquiritigenin and cinnamyl alcohol contained in SJ, which are known for their anti-inflammatory activities. Finally, SJ fermented by Lactobacillus exerted potent anti-inflammatory activity by inhibiting MAPK and NF-κB signaling in RAW 264.7 cells.

scholarly journals Anti-inflammatory activity of pectic enzyme-treated pectin on lipopolysaccharide-induced RAW 264.7 cells

2019 ◽  
Vol 1 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Cian-Song Huang ◽  
Qiao-Lin Li ◽  
Diana Lo ◽  
Yuh-Tai Wang ◽  
Ming-Chang Wu
Keyword(s):  
Western Blot ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Pectic Enzyme ◽  
Western Blot Method ◽  
Tnf Α ◽  
Cox 2 ◽  
Necrosis Factor ◽  
Normal Macrophage

The purpose of this study was to investigate the ability and pathway of the pectic enzyme-treated (PET) pectin to inhibit the inflammation of macrophage RAW 264.7 induced by lipopolysaccharide. Results showed that PET-pectin produced from 1% substrate and 48 h reaction time had the highest antioxidative activity, thus these parameters were used to produce PET-pectin used in this study. PET-pectin showed no cell cytotoxicity to normal macrophage RAW 264.7 and reduce the nitrite secretion from LPS-induced RAW 264.7 by 20%. Finally, the expression of cytokines, including NO synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and tumor necrosis factor (TNF-α) were analyzed by western blot. In the western blot method, it was found that iNOS, COX-2, NF-κB, TNF-α and other proteins that activated NO production had a downtrend. It was found that PET-pectin possess promising activity to mitigate the inflammatory response.

scholarly journals Effects of Sibseonsan as an Anti-Inflammatory, Anti-Wrinkle, and Skin Whitening Treatment

2020 ◽  
Vol 37 (2) ◽  
pp. 88-93
Author(s):  
Na Young Jo
Keyword(s):  
Treatment Group ◽  
Cell Line ◽  
Radical Scavenging ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α ◽  
Anti Inflammatory

Background: The purpose of this study was to investigate whether Sibseonsan (SSS) is an effective anti-inflammatory, anti-wrinkling, and whitening agent.Methods: To determine whether SSS had an anti-inflammatory effect, a murine macrophage cell line was used (RAW 264.7) and production of DPPH, NO, TNF-α, and PGE2 were measured. To ascertain potential anti-wrinkle effects of SSS in these cells, collagenase and elastase production were measured. To verify whether SSS had a whitening effect, tyrosinase activity and DOPA staining were performed using a melanoma cell line (B16/F10).Results: There was no significant reduction in survival of SSS-treated RAW 264.7 cells, up to 400 μg/mL. Free radical scavenging (23.96 ± 1.85%) was observed in RAW 264.7 cells treated with SSS at a concentration of 400 μg/mL. The SSS treatment group (400 μg/mL) significantly inhibited NO production compared with the LPS stimulated treatment group. The SSS treatment of macrophage cells appeared to reduce production of TNF-α in a concentration dependent manner. There was a significant reduction in the concentration of PGE<sub>2</sub> by about 25% in the SSS treatment (400 μg/mL) group (<i>p</i> = 0.05). Compared with the control, the production of collagenase and elastase in B16/F10 cells treated with SSS (400 μg/mL) was greater by 26.37% and 45.71%, respectively. The SSS treatment (400 μg/mL) group showed a significant reduction by about 17% in tyrosinase production in B16/F10 cells. The SSS treatment group showed little change in DOPA staining.<br>Conclusion: SSS extract may be useful for the treatment and prevention of inflammatory diseases and may have anti-wrinkle and whitening effects. These results may support the use of SSS in clinical practice.

scholarly journals Demonstrating the relationship between the phytochemical profile of different teas with relative antioxidant and anti-inflammatory capacities

2017 ◽  
Vol 7 (6) ◽  
pp. 375 ◽  
Author(s):  
Xiu-Min Chen ◽  
David D Kitts ◽  
Zhili Ma
Keyword(s):  
Camellia Sinensis ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Gm Csf ◽  
Rooibos Tea ◽  
Ifn Γ ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Stimulating Factor

Background: Indigenous or traditional aqueous plant extracts are commonly used by as much as 80% of the world’s population for primary health needs. Teas including Camellia sinensis teas and herbal teas were characterized for phytochemical content and the potential to offer specific bioactivities that could benefit human health by mitigating oxidative stress and inflammation. Context and purpose of this study: In present study, we compared the phytochemical profiles, antioxidant and anti-inflammatory activities of four Camellia sinensis (white, green, oolong, and black) teas and two herbal (Rooibos and Yerba mate) teas that are produce and consumed by different population worldwide. We also studied the impact of Rooibos tea on the production of inflammatory mediators, including nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and different cytokines in Raw 264.7 cells, both with or without interferon γ (IFN-γ) and lipopolysaccharide (LPS) stimulation.Results: White tea had the highest total phenolic content (TPC) and antioxidant activity among these six teas examined, whereas, Rooibos tea has the lowest TPC, antioxidant and anti-inflammatory activities. Yerba mate tea had the greatest potential to inhibit NO production in IFN-γ and LPS-induced Raw 264.7 cells. The anti-inflammatory activity of teas was found to be correlated with antioxidant activity and phytochemical composition. Among the six teas examined, only Rooibos tea was found to induce NO in unstimulated Raw 264.7 cells. Under basal conditions, Rooibos tea induced interleukin (IL)-1α (IL-1α), IL-1β, IL-6, IL-10, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor- alpha (TNF-α), iNOS and COX-2 production. However, Rooibos tea also showed a dose-dependent inhibition of IL-6, IL-10, iNOS and COX-2 expression in stimulated Raw 264.7 cells. Although high concentration Rooibos tea was affective to inhibit induced IL-1α, G-CSF and GM-CSF, low concentration Rooibos tea also can up-regulate the expression of these cytokines. No inhibitory effects of all teas examined were found on mitigation of IL-1β and TNF-α.Conclusions: Rooibos tea can show dual functions on inflammation, by either promoting an inflammatory response to cytokines induction or, alternatively inhibit inflammation on exposure to cytokine treatment, such as tissue injury or a pathogen infection. Rooibos tea also has marked value in mitigating disease states such as hypertension and cardiovascular diseases where induction of NO production is important.Keywords: Camellia sinensis, Rooibos tea, herbal tea, inflammation, cytokine, antioxidant

scholarly journals Lanostane Triterpenoids from the Fruiting Bodies of Fomes officinalis and Their Anti-Inflammatory Activities

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4807
Author(s):  
Jianxin Han ◽  
Wei Liu ◽  
Miaomiao Li ◽  
Yanpei Gu ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Spectroscopic Data ◽  
2D Nmr ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Fruiting Bodies ◽  
C 23 ◽  
Inhibitory Activities ◽  
Cox 2 ◽  
Anti Inflammatory

In the current study, further chemical investigation of the fruiting bodies of Fomes officinalis led to isolate seven new 24-methyl-lanostane triterpenoids, named officimalonic acids I−O (1–7). Their structures were elucidated based on the analysis of spectroscopic data (HR-MS, 1D and 2D NMR, UV, IR). Compounds 1−3 possessed an unusual C-23 spirostructure moiety, while compounds 4−7 had 23,26-lactone unit. Anti-inflammatory assay revealed that compounds 3 and 5 exhibited significant inhibitory activities against NO production in LPS-induced RAW 264.7 cells and cyclooxygenase (COX-2).

scholarly journals Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haidy A. Saleh ◽  
Eman Ramdan ◽  
Mohey M. Elmazar ◽  
Hassan M. E. Azzazy ◽  
Anwar Abdelnaser
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Response ◽  
Raw 264.7 Cells ◽  
Inos Mrna ◽  
No Production ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Protective Effects ◽  
Tnf Α ◽  
Ifn Γ

AbstractDoxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

scholarly journals Processed Scutellaria baicalensis Georgi Extract Alleviates LPS-Induced Inflammatory and Oxidative Stress through a Crosstalk between NF-κB and KEAP1/NRF2 Signaling in Macrophage Cells

2021 ◽  
Vol 11 (13) ◽  
pp. 6055
Author(s):  
Akhtar Ali ◽  
En-Hyung Kim ◽  
Jong-Hyun Lee ◽  
Kang-Hyun Leem ◽  
Shin Seong ◽  
...  
Keyword(s):  
Scutellaria Baicalensis ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Scutellaria Baicalensis Georgi ◽  
Anticancer Effects ◽  
Tnf Α ◽  
Clinical Benefits ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory

Prolonged inflammation results in chronic diseases that can be associated with a range of factors. Medicinal plants and herbs provide synergistic benefits based on the interaction of multiple phytochemicals. The dried root of Scutellaria baicalensis Georgi and its compounds possess anti-inflammatory, anti-oxidative, and anticancer effects. Processing is a traditional method to achieve clinical benefits by improving therapeutic efficacy and lowering toxicity. In this study, we investigated the anti-inflammatory and anti-oxidant effect of processed Scutellaria baicalensis Georgi extract (PSGE) against lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Data using Griess assay and ELISA showed that PSGE decreased nitric oxide and prostaglandin E2 (PGE2) levels against LPS. PSGE treatment up-regulated 15-hydroxyprostaglandin dehydrogenase (PGDH), while cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 expression did not change. Interestingly, PGE2 inhibition was regulated by prostaglandin catabolic enzyme 15-PGDH rather than COX-2/mPGES-1, enzymes essential for PGE2 synthesis. Additionally, PSGE-suppressed LPS-induced IL-6 and TNF-α production through NF-κB signaling. NF-κB release from an inactive complex was inhibited by HO-1 which blocked IκBα phosphorylation. The ROS levels lowered by PSGE were measured with the H2DCFDA probe. PSGE activated NRF2 signaling and increased antioxidant Hmox1, Nqo1, and Txn1 gene expression, while reducing KEAP1 expression. In addition, pharmacological inhibition of HO-1 confirmed that the antioxidant enzyme induction by PSGE was responsible for ROS reduction. In conclusion, PSGE demonstrated anti-inflammatory and anti-oxidant effects due to NRF2/HO-1-mediated NF-κB and ROS inhibition.

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