Canscora lucidissima, a Chinese folk medicine, exerts anti-inflammatory activities by inhibiting the phosphorylation of ERK1/2 in LPS-activated macrophages

Abstract Background Canscora lucidissima (Levl. & Vaniot) Hand.-Mazz. (C. lucidissima), mainly distributed in southern China, has been shown to be effective in the treatment of inflammatory diseases. However, the underlying mechanism of its anti-inflammatory effect is not fully understood. Methods In this study, we investigated the anti-inflammatory mechanism of ethanol extract of C. lucidissima (Cl-EE) in lipopolysaccharide (LPS)-induced inflammatory models. ELISA, real-time PCR, Western blot and luciferase reporter assay were used for the experiments in vitro, and ICR mouse endotoxemia model was used for in vivo test. Results Our data showed that Cl-EE reduced the production of NO by down-regulating the mRNA and protein expression of inducible nitric oxide synthase (iNOS) in LPS-activated RAW 264.7 cells. Meanwhile, it potently decreased other proinflammatory mediators, such as TNF-α, IL-6, MCP-1 and IL-1β at the transcriptional and translational levels. Further study indicated that Cl-EE did not affect NF-κB signaling pathway but significantly suppressed the phosphorylation of ERK1/2, rather than JNK or p38. In a LPS-induced endotoxemia mouse model, a single intraperitoneal injection of Cl-EE (75–300 mg/kg) could lower circulatory TNF-α, IL-6 and MCP-1 levels. Conclusions Collectively, our results indicated that Cl-EE suppressed the phosphorylation level of ERK1/2 thus reducing the transcription and translation of inflammatory genes, thereby exerted anti-inflammatory activity. This study reveals the anti-inflammatory mechanism of C. lucidissima and may provide an effective treatment option for a variety of inflammatory diseases.

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Antinociceptive and Anti-Inflammatory Activities ofCuscuta chinensisSeeds in Mice

The American Journal of Chinese Medicine ◽

10.1142/s0192415x14500153 ◽

2014 ◽

Vol 42 (01) ◽

pp. 223-242 ◽

Cited By ~ 33

Author(s):

Jung-Chun Liao ◽

Wen-Te Chang ◽

Meng-Shiou Lee ◽

Yung-Jia Chiu ◽

Wei-Kai Chao ◽

...

Keyword(s):

Acetic Acid ◽

Inflammatory Diseases ◽

Antinociceptive Effect ◽

Inflammatory Mechanism ◽

Tnf Α ◽

Anti Inflammatory ◽

Highly Correlated ◽

Cuscuta Chinensis ◽

Inflammatory Effect

The seeds of Cuscuta chinensis, Cuscutae Semen, are commonly used as a medicinal material for treating the aching and weakness of the loins and knees, tonifying the defects of the liver and the kidney, and treating the diarrhea due to hypofunction of the kidney and the spleen. Since aching and inflammation are highly correlated with such diseases, the aim of this study is to investigate the possible antinociceptive and anti-inflammatory mechanisms of the seeds of C. chinensis. The antinociceptive effect of the seeds of C. chinensis was evaluated via the acetic acid-induced writhing response and formalin-induced paw licking methods. The anti-inflammatory effect was evaluated via the λ-carrageenan induced mouse paw edema method. The results found that 100 and 500 mg/kg of the methanol extract of the seeds of C. chinensis( CCMeOH) significantly decreased (p < 0.01 and p < 0.001, respectively) the writhing response in the acetic acid assay. Additionally, 20–500 mg/kg of CCMeOHsignificantly decreased licking time at the early (20 and 100 mg/kg, p < 0.001) and late phases (100 mg/kg, p < 0.01; 500 mg/kg, p < 0.001) of the formalin test, respectively. Furthermore, CCMeOH(100 and 500 mg/kg) significantly decreased (p < 0.01 and p < 0.001, respectively) edema paw volume four hours after λ-carrageenan had been injected. The results in the following study also revealed that the anti-inflammatory mechanism of CCMeOHmay be due to declined levels of NO and MDA in the edema paw by increasing the activities of SOD, GPx and GRd in the liver. In addition, CCMeOHalso decreased IL-1β, IL-6, NF-κB, TNF-α, and COX-2 levels. This is the first study to demonstrate the possible mechanisms for the antinociceptive and anti-inflammatory effects of CCMeOHin vivo. Thus, it provides evidence for the treatment of Cuscutae Semen in inflammatory diseases.

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Analgesic and Anti-Inflammatory Activities of Methanol Extract ofFicus pumilaL. in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/340141 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Chi-Ren Liao ◽

Chun-Pin Kao ◽

Wen-Huang Peng ◽

Yuan-Shiun Chang ◽

Shang-Chih Lai ◽

...

Keyword(s):

Acetic Acid ◽

Methanol Extract ◽

Inflammatory Diseases ◽

Paw Edema ◽

Tissue Destruction ◽

Hplc Fingerprint ◽

Analgesic Effects ◽

Inflammatory Mechanism ◽

Tnf Α ◽

Anti Inflammatory

This study investigated possible analgesic and anti-inflammatory mechanisms of the methanol extract ofFicus pumila(FPMeOH). Analgesic effects were evaluated in two models including acetic acid-induced writhing response and formalin-induced paw licking. The results showedFPMeOHdecreased writhing response in the acetic acid assay and licking time in the formalin test. The anti-inflammatory effect was evaluated by λ-carrageenan-induced mouse paw edema and histopathological analyses.FPMeOHsignificantly decreased the volume of paw edema induced by λ-carrageenan. Histopathologically,FPMeOHabated the level of tissue destruction and swelling of the edema paws. This study indicated anti-inflammatory mechanism ofFPMeOHmay be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx, and GRd in the liver. Additionally,FPMeOHalso decreased the level of inflammatory mediators such as IL-1β, TNF-α, and COX-2. HPLC fingerprint was established and the contents of three active ingredients, rutin, luteolin, and apigenin, were quantitatively determined. This study provided evidence for the classical treatment ofFicus pumilain inflammatory diseases.

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Nuciferine Inhibits Proinflammatory Cytokines via the PPARs in LPS-Induced RAW264.7 Cells

Molecules ◽

10.3390/molecules23102723 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2723 ◽

Cited By ~ 5

Author(s):

Chao Zhang ◽

Jianjun Deng ◽

Dan Liu ◽

Xingxia Tuo ◽

Yan Yu ◽

...

Keyword(s):

Molecular Mechanism ◽

Raw 264.7 Cells ◽

Luciferase Reporter ◽

Raw 264.7 ◽

Peroxisome Proliferator ◽

Reporter Assay ◽

Peroxisome Proliferator Activated Receptor ◽

Tnf Α ◽

Natural Alkaloid ◽

Anti Inflammatory

Inflammation is important and has been found to be an underlying cause in many acute and chronic human diseases. Nuciferine, a natural alkaloid containing an aromatic ring, is found in the nelumbo nucifera leaves. It has been shown to have potential anti-inflammatory activities, but the molecular mechanism has remained unclear. In this study, we found that nuciferine (10 μM) significantly inhibited the lipopolysaccharide (LPS)-induced inflammatory cytokine IL-6 and TNF-α production in RAW 264.7 cells. In addition, the luciferase reporter assay results of different subtypes of the peroxisome proliferator-activated receptor (PPAR) showed that nuciferine dose-dependently activated all the PPAR activities. Specific inhibitors of PPARα and PPARγ significantly abolished the production of inflammatory cytokines as well as IκBα degradation. However, PPARδ inhibitor did not show this effect. Our results suggested a potential molecular mechanism of the anti-inflammatory effects of nuciferine in LPS-induced inflammation, at least in part, by activating PPARα and PPARγ in RAW 264.7 cells.

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Diterpenoid Compounds Isolated from Chloranthus oldhamii Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK/NF-κB Pathway

Molecules ◽

10.3390/molecules26216540 ◽

2021 ◽

Vol 26 (21) ◽

pp. 6540

Author(s):

Lin-Chieh Chiu ◽

Jir-You Wang ◽

Chao-Hsiung Lin ◽

Chung-Hua Hsu ◽

Lie-Chwen Lin ◽

...

Keyword(s):

Folk Medicine ◽

Inhibitory Effect ◽

Mapk Signaling ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Inflammatory Mechanism ◽

Tnf Α ◽

Anti Inflammatory ◽

Mapk Signaling Pathways ◽

Major Target

Chloranthus oldhamii Solms (CO) is a folk medicine for treating infection and arthritis pain but its pharmacological activity and bioactive compounds remain mostly uncharacterized. In this study, the anti-inflammatory compounds of C. oldhamii were identified using an LPS-stimulated, NF-κB-responsive RAW 264.7 macrophage reporter line. Three diterpenoid compounds, 3α-hydroxy-ent-abieta-8,11,13-triene (CO-9), 3α, 7β-dihydroxy-ent-abieta-8,11,13-triene (CO-10), and decandrin B (CO-15) were found to inhibit NF-κB activity at nontoxic concentrations. Moreover, CO-9 and CO-10 suppressed the expression of IL-6 and TNF-α in LPS-stimulated RAW 264.7 cells. The inhibitory effect of CO-9 on TNF-α and IL-6 expression was further demonstrated using LPS-treated bone marrow-derived macrophages. Furthermore, CO-9, CO-10, and CO-15 suppressed LPS-triggered COX-2 expression and downstream PGE2 production in RAW 264.7 cells. CO-9 and CO-10 also reduced LPS-triggered iNOS expression and nitrogen oxide production in RAW 264.7 cells. The anti-inflammatory mechanism of the most effective compound, CO-9, was further investigated. CO-9 attenuated LPS-induced NF-κB activation by reducing the phosphorylation of IKKα/β (Ser176/180), IκBα (Ser32), and p65 (Ser534). Conversely, CO-9 did not affect the LPS-induced activation of MAPK signaling pathways. In summary, this study revealed new anti-inflammatory diterpenoid compounds from C. oldhamii and demonstrated that the IKK-mediated NK-κB pathway is the major target of these compounds.

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Aktivitas Antiinflamasi Crude Extract Fukoidan dari Sargassum crassifolium pada Sel RAW 264.7 yang Diinduksi LPS

Jurnal Kefarmasian Indonesia ◽

10.22435/jki.v9i2.1547 ◽

2019 ◽

pp. 97-105

Author(s):

Pangartika Hikariastri ◽

Hendig Winarno ◽

Kusmardi Kusmardi ◽

Dian Ratih Laksmitawati ◽

Syamsudin Abdillah

Keyword(s):

Crude Extract ◽

Macrophage Activation ◽

Basic Mechanism ◽

Inflammatory Activity ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Proinflammatory Mediators ◽

Promising Target ◽

Tnf Α ◽

Anti Inflammatory

Inflammation is known as the basic mechanism underlying various chronic diseases. Macrophage activation by inflammatory stimulus induces the release of inflammatory mediators, thus the mediators becoming a promising target of anti-inflammatory drug development. Previous studies indicated that fucoidan has anti-inflammatory activity by inhibiting the release of proinflammatory mediators. The aim of this study is determining anti-inflammatory activity of fucoidan crude extract form Sargassum crassifolium Garut waters by observing its effect on proinflammatory cytokines TNF-α, IL-1β, dan IL-6. Fucoidan is a polysaccharide substance which has various characteristics, depending on the source and the extraction method which is influencing its bioactivity. Sargassum crassifolium collected from Garut-West Java is extracted using diluted HCl 0,1 M and precipitated with ethanol to obtain fucoidan crude extract. The crude extract is tested on LPS-induced RAW 264.7 cells to evaluate its effect on TNF-α, IL-1β, and IL-6 level using ELISA method. The result showed that fucoidan crude extract decreased the level of TNF-α by the dose of 25 and 50 μg/ml, and decreased the level of IL-1β and IL-6 by the dose of 25 μg/ml. The dose of 50 μg/ml failed to inhibit IL-1β and IL-6 production. This study showed that fucoidan crude extract derived from S. crassifolium has anti-inflammatory activity to RAW 264.7 cells by the dose of 25 μg/ml.

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Pro-Resolving Effect of Ginsenosides as an Anti-Inflammatory Mechanism of Panax ginseng

Biomolecules ◽

10.3390/biom10030444 ◽

2020 ◽

Vol 10 (3) ◽

pp. 444 ◽

Cited By ~ 5

Author(s):

Dong-Soon Im

Keyword(s):

Panax Ginseng ◽

Inflammatory Diseases ◽

Indirect Evidence ◽

Action Mechanism ◽

Inflammatory Mechanism ◽

Tnf Α ◽

Main Class ◽

Anti Inflammatory ◽

Inflammation Resolution ◽

Anti Inflammation

Panax ginseng, also known as Korean ginseng, is a famous medicinal plant used for the treatment of many inflammatory diseases. Ginsenosides (ginseng saponins) are the main class of active constituents of ginseng. The anti-inflammatory effects of ginseng extracts were proven with purified ginsenosides, such as ginsenosides Rb1, Rg1, Rg3, and Rh2, as well as compound K. The negative regulation of pro-inflammatory cytokine expressions (TNF-α, IL-1β, and IL-6) and enzyme expressions (iNOS and COX-2) was found as the anti-inflammatory mechanism of ginsenosides in M1-polarized macrophages and microglia. Recently, another action mechanism emerged explaining the anti-inflammatory effect of ginseng. This is a pro-resolution of inflammation derived by M2-polarized macrophages. Direct and indirect evidence supports how several ginsenosides (ginsenoside Rg3, Rb1, and Rg1) induce the M2 polarization of macrophages and microglia, and how these M2-polarized cells contribute to the suppression of inflammation progression and promotion of inflammation resolution. In this review, the new action mechanism of ginseng anti-inflammation is summarized.

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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

Applied Sciences ◽

10.3390/app11136055 ◽

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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A New Flavonol From Saussurea involucrata With Anti-Inflammatory Activity

Natural Product Communications ◽

10.1177/1934578x211007638 ◽

2021 ◽

Vol 16 (5) ◽

pp. 1934578X2110076

Author(s):

Sheng Pan ◽

Zi-Guan Zhu

Keyword(s):

Nitric Oxide ◽

Aerial Part ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Spectroscopic Methods ◽

Soluble Extract ◽

Saussurea Involucrata ◽

Tnf Α ◽

Anti Inflammatory

A new flavonol named 6-(2'',3''-epoxy-3''-methylbutyl)-resokaempferol (1), together with five known compounds (2-6) were isolated from the EtOAc-soluble extract of the aerial part of Saussurea involucrata. Their structures were elucidated on the basis of spectroscopic methods. All compounds were evaluated for their anti-inflammatory effects by measuring the production of nitric oxide (NO) and TNF-α in vitro. Among them, compound 1 showed potential inhibitory activity on the production of NO and TNF-α in LPS-induced RAW 264.7 cells with IC50 values of 48.0 ± 1.5 and 41.4 ± 1.7 µM, respectively.

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Fisetin inhibits lipopolysaccharide-induced inflammatory response by activating β-catenin, leading to a decrease in endotoxic shock

Scientific Reports ◽

10.1038/s41598-021-87257-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ilandarage Menu Neelaka Molagoda ◽

Jayasingha Arachchige Chathuranga C Jayasingha ◽

Yung Hyun Choi ◽

Rajapaksha Gedara Prasad Tharanga Jayasooriya ◽

Chang-Hee Kang ◽

...

Keyword(s):

Glycogen Synthase ◽

Endotoxic Shock ◽

Inflammatory Activity ◽

Prostaglandin E ◽

Necrosis Factor Alpha ◽

Zebrafish Larvae ◽

Proinflammatory Mediators ◽

Tnf Α ◽

Anti Inflammatory ◽

Gsk 3Β

AbstractFisetin is a naturally occurring flavonoid that possesses several pharmacological benefits including anti-inflammatory activity. However, its precise anti-inflammatory mechanism is not clear. In the present study, we found that fisetin significantly inhibited the expression of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Additionally, fisetin attenuated LPS-induced mortality and abnormalities in zebrafish larvae and normalized the heart rate. Fisetin decreased the recruitment of macrophages and neutrophils to the LPS-microinjected inflammatory site in zebrafish larvae, concomitant with a significant downregulation of proinflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase-2a (COX-2a), IL-6, and TNF-α. Fisetin inhibited the nuclear localization of nuclear factor-kappa B (NF-κB), which reduced the expression of pro-inflammatory genes. Further, fisetin inactivated glycogen synthase kinase 3β (GSK-3β) via phosphorylation at Ser9, and inhibited the degradation of β-catenin, which consequently promoted the localization of β-catenin into the nucleus. The pharmacological inhibition of β-catenin with FH535 reversed the fisetin-induced anti-inflammatory activity and restored NF-κB activity, which indicated that fisetin-mediated activation of β-catenin results in the inhibition of LPS-induced NF-κB activity. In LPS-microinjected zebrafish larvae, FH535 promoted the migration of macrophages to the yolk sac and decreased resident neutrophil counts in the posterior blood island and induced high expression of iNOS and COX-2a, which was accompanied by the inhibition of fisetin-induced anti-inflammatory activity. Altogether, the current study confirmed that the dietary flavonoid, fisetin, inhibited LPS-induced inflammation and endotoxic shock through crosstalk between GSK-3β/β-catenin and the NF-κB signaling pathways.

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Nepetoidin B from Salvia plebeia R. Br. Inhibits Inflammation by Modulating the NF-κB and Nrf2/HO-1 Signaling Pathways in Macrophage Cells

Antioxidants ◽

10.3390/antiox10081208 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1208

Author(s):

Mina Kim ◽

Ji Yeong Kim ◽

Hee Sun Yang ◽

Jeong-Sook Choe ◽

In Guk Hwang

Keyword(s):

Defense Mechanisms ◽

Inflammatory Diseases ◽

Cell Damage ◽

Treated Group ◽

Raw 264.7 Cells ◽

Resonance Spectroscopy ◽

Raw 264.7 ◽

Related Factor ◽

Anti Inflammatory ◽

Factor Α

Salvia plebeia has been used to treat a variety of inflammatory diseases, as well as colds and bronchitis. Macrophages have antioxidant defense mechanisms to cope with the intracellular reactive oxygen species (ROS) produced as part of the immune response. The nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathway in inflamed macrophages is an appealing target due to its protective effect against ROS-induced cell damage. In this study, nepetoidin B (NeB) was first isolated from S. plebeia and identified by nuclear magnetic resonance spectroscopy. NeB reduced pro-inflammatory mediators (nitric oxide and prostaglandin E2) and cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1β) in LPS-activated RAW 264.7 cells by inhibiting the NF-κB signaling pathway. In the NeB-treated group, catalase and superoxide dismutase levels were significantly higher, and ROS expression decreased. By activating Nrf2 signaling, NeB enhanced HO-1 expression. Furthermore, when the cells were pretreated with tin protoporphyrin (an HO-1 inhibitor), the anti-inflammatory effects of NeB were reduced. Therefore, NeB may activate the Nrf2/ HO-1 pathway. These results reveal the NeB isolated from S. plebeia exerts anti-inflammatory effects by modulating NF-κB signaling and activating the Nrf2/HO-1 pathway in LPS-stimulated RAW 264.7 cells.

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