Dipotassium glycyrrhizate via HMGB1 or AMPK signaling suppresses oxidative stress during intestinal inflammation

Vitali, Roberta; Palone, Francesca; Pierdomenico, Maria; Negroni, Anna; Cucchiara, Salvatore; Aloi, Marina; Oliva, Salvatore; Stronati, Laura

doi:10.1016/j.bcp.2015.07.039

Cited by 33 publications

(22 citation statements)

References 44 publications

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“…It is well known that UC is characterized by the production of a wide range of inflammatory cytokines [41]. Oxidative stress and inflammation are always associated with each other, and the use of antioxidants can be protective against inflammatory diseases [43]. To determine the effects of the maggot extracts on DSS-induced colitis, mRNA levels of the proinflammatory cytokines and Nrf2 in the colons were measured using quantitative real-time PCR.…”

Section: Resultsmentioning

confidence: 99%

Maggot Extracts Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis via the Activation of Nrf2

Wang

Luo

et al. 2019

Oxidative Medicine and Cellular Longevity

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Ulcerative colitis (UC) is a common chronic remitting disease driven through altered immune responses with production of inflammatory cytokines. Oxidant/antioxidant balance is also suggested to be an important factor for the recurrence and progression of UC. Maggots are known as a traditional Chinese medicine also known as “wu gu chong.” NF-E2-related factor-2 (Nrf2) transcription factor regulates the oxidative stress response and also represses inflammation. The aim of this study was to investigate the effects of maggot extracts on the amelioration of inflammation and oxidative stress in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and evaluate if the maggot extracts could repress inflammation and oxidative stress using RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In the present study, we found that the maggot extracts significantly prevented the loss of body weight and shortening of colon length in UC induced by DSS. Furthermore, DSS-induced expression of proinflammatory cytokines at both mRNA and protein levels in the colon was also attenuated by the maggot extracts. In addition, the maggot extracts could significantly suppress the expression of interleukin- (IL-) 1β, IL-6, TNF-α, NFκB p65, p-IκB, p22-phox, and gp91-phox in LPS-stimulated RAW 264.7 cells and colonic tissues. The maggot extracts increased the level of Nrf2 and prevented the degradation of Nrf2 through downregulating the expression of Keap1, which resulted in augmented levels of HO-1, SOD, and GSH-Px and reduced levels of MPO and MDA. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of the maggot extracts in mice with colitis and RAW 264.7 cells. Taken together, our data for the first time confirmed that the maggot extracts ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf2/HO-1 pathway. This study sheds light on the possible development of an effective therapeutic strategy for inflammatory bowel diseases.

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Section: Resultsmentioning

confidence: 99%

Maggot Extracts Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis via the Activation of Nrf2

Wang

Luo

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…AMPK activation inhibits COX‐2 expression in LPS‐treated RAW264.7 cells . To investigate whether AMPK is involved in the inhibition of COX‐2, 5‐LOX, and CYP4A by Sal, we measured the phosphorylation of AMPK in MSU crystal‐treated RAW264.7 macrophages.…”

Section: Resultsmentioning

confidence: 99%

Frontline Science: Reprogramming COX-2, 5-LOX, and CYP4A-mediated arachidonic acid metabolism in macrophages by salidroside alleviates gouty arthritis

Liu

Tang

Liu

et al. 2018

Journal of Leukocyte Biology

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Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and cytochrome P450 (CYP) 4A-mediated arachidonic acid (AA) metabolism play an essential role in human inflammatory disorders. Blocking COX-2 pathway would shunt AA metabolism to the other pathway, thereby decreasing the efficacy and exacerbating adverse effects. Here we demonstrated that reprogramming COX-2, 5-LOX, and CYP4A-mediated AA metabolism in macrophages by salidroside (Sal) ameliorates monosodium urate (MSU) crystal-induced inflammation. Compared with COX-2 inhibitor celecoxib, Sal (80 mg/kg) presented a superior anti-arthritic profile in MSU crystal-treated rats, accompanied with the decreased expression of COX-2, 5-LOX, and CYP4A and production of prostaglandin E2 (PGE 2 ), leukotriene B4 (LTB 4 ), and 20-hydroxyeicosatetraenoic acid in the synovial fluid macrophages. Sal decreased representative M1 marker (iNOS and CD86, etc.) expression and M1 cytokine (TNF-and IL-1 ) production, whereas it increased M2 marker (CD206 and Arg-1) expression and M2 cytokine (TGF-and IL-10) production. The injection of conditioned medium from MSU crystal-treated macrophages into the ankle joint of rats reproduced the gouty inflammation, which was attenuated by Sal. Mechanistically, down-regulation of COX-2, 5-LOX, and CYP4A in the RAW264.7 and NR8383 macrophages by Sal skewed macrophage polarization away from the M1 phenotype, and thereby prevented neutrophil migration and chondrocyte degradation with STAT1 and NF-B inactivation. Conversely, overexpression of COX-2, 5-LOX, CYP4A or STAT1, or exogenous addition of IL-1 or TNF-partially abolished these effects. Together, inhibition of COX-2, 5-LOX, and CYP4A in macrophages by Sal ameliorates MSU crystal-induced inflammation through decreasing TNF-and IL-1 production, and may serve as a novel therapeutic strategy. K E Y W O R D Sarachidonic acid, gouty inflammation, macrophage, metabolism, salidroside INTRODUCTIONGout is the most common inflammatory arthritis in men older than 40 years. 1 Nonsteroidal anti-inflammatory drugs (NSAIDs) are used as Abbreviations: 20-HETE, 20-hydroxyeicosatetraenoic acid; 5-LOX, 5-lipoxygenase; ADAMTS-5, a disintegrin and metalloproteinase with thrombospondin motif 5; Clod, clodronate liposome; COX-2, cyclooxygenase-2; CYP4A, cytochrome P450 4A; LTB 4 , leukotriene B 4 ; MMP-13, Matrix metalloproteinase-13; MSU, monosodium urate; NF-B, nuclear transcription factor kappa B; PGE 2 , prostaglandin E 2 ; Sal, salidroside; STAT1, signal transducers and activators of transcription 1; ZA, zoledronic acid first-line therapy to manage gouty arthritis, whereas the inevitable gastrointestinal or cardiovascular side effects restrict their utilization. 2 Newly developed anti-IL-1 drugs appear to be highly effective, but present limitations such as high cost and hematopoietic disorders. 3 Therefore, there is an urgent need to identify novel agents for gouty arthritis treatment.Gout is triggered by monosodium urate (MSU) crystal deposition in and around joints. Macrophages play a pivotal role in the initiati...

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“…Oxidative stress and inflammation are always associated with each other, and the use of antioxidants can be protective against inflammatory diseases 24 . As a key regulator of detoxification, Nrf2 is responsible for the transcriptional activation of genes encoding antioxidant enzymes.…”

Section: Resultsmentioning

confidence: 99%

Carnosic acid prevents dextran sulfate sodium-induced acute colitis associated with the regulation of the Keap1/Nrf2 pathway

Neng

Xia

Shao

et al. 2017

Sci Rep

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Crohn’s disease and ulcerative colitis are inflammatory bowel diseases (IBDs) with high prevalence in humans. Carnosic acid (CA) has been reported to possess antioxidative properties; however, its role in IBDs has not been determined. In the present study, we found that CA significantly prevented the loss of body weight and shortening of colon length in acute colitis induced by dextran sodium sulfate (DSS). Pronounced infiltration of immune cells and a loss of crypt architecture and goblet cells were ameliorated by CA. CA significantly decreased the activity of MPO and infiltration of F4/80+ macrophages in the colon. DSS-induced pro-inflammatory cytokine mRNA and protein levels in the colon were also attenuated by CA. CA decreased the activation of p65 and c-Jun signalling. CA inhibited DSS-induced NLRP3 inflammasome activation by reducing caspase 1 activity. In addition, CA increased the level of Nrf2 and prevented the degradation of Nrf2 via ubiquitination by blocking the interaction between Cullin3 and Keap1, which resulted in the decrease of Nrf2 target genes. Finally, GSH levels and SOD activity were increased after CA treatment, while MDA and iNOS levels were significantly reduced. Taken together, our data showed that CA may be useful as a potential therapeutic candidate for IBDs.

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Dipotassium glycyrrhizate via HMGB1 or AMPK signaling suppresses oxidative stress during intestinal inflammation

Cited by 33 publications

References 44 publications

Maggot Extracts Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis via the Activation of Nrf2

Maggot Extracts Alleviate Inflammation and Oxidative Stress in Acute Experimental Colitis via the Activation of Nrf2

Frontline Science: Reprogramming COX-2, 5-LOX, and CYP4A-mediated arachidonic acid metabolism in macrophages by salidroside alleviates gouty arthritis

Carnosic acid prevents dextran sulfate sodium-induced acute colitis associated with the regulation of the Keap1/Nrf2 pathway

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