Effects of CDP-Choline and Choline on COX Pathway in LPS-Induced Inflammatory Response in Rats

Bariş, Elif; Simsek, Oguzhan; Efe, Hande; Öncü, Şeyma; Gelal, Ayşe; Hamurtekin, Emre; Tosun, Metiner; Özbal, Seda; Yüce, Zeynep; ARICI, Mustafa

doi:10.3923/ijp.2021.84.96

Cited by 6 publications

(8 citation statements)

References 39 publications

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“…Moreover, the inhibition of TLR4 may be beneficial for the regulation of ketone body levels and the decrease in 3HB levels. Choline has been reported to treat LPS-induced inflammation in rats by reducing PTGS2 levels ( Baris et al, 2021 ). And long-term choline deficiency diet can lead to increased hepatic PTGS2 levels ( Motino et al, 2016 ; He et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated network analysis and metabolomics reveal the molecular mechanism of Yinchen Sini decoction in CCl4-induced acute liver injury

Zheng,

Shi,

Meng

et al. 2023

Front. Pharmacol.

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Objective: Yinchen Sini decoction (YCSND), a traditional Chinese medicine (TCM) formula, plays a crucial role in the treatment of liver disease. However, the bioactive constituents and pharmacological mechanisms of action remain unclear. The present study aimed to reveal the molecular mechanism of YCSND in the treatment of acute liver injury (ALI) using integrated network analysis and metabolomics.Methods: Ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) was utilized to identify metabolites in YCSND, and high-performance liquid chromatography (HPLC) was applied to evaluate the quality of four botanical drugs in YCSND. Cell damage and ALI models in mice were established using CCl4. 1H-NMR metabolomics approach, along with histopathological observation using hematoxylin and eosin (H&E), biochemical measurements, and reverse transcription quantitative real-time PCR (RT-qPCR), was applied to evaluate the effect of YCSND on CCl4- induced ALI. Network analysis was conducted to predict the potential targets of YCSND in ALI.Result: Our results showed that 89 metabolites in YCSND were identified using UHPLC-QE-MS. YCSND protected against ALI by reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) contents and increasing those of superoxide dismutase (SOD), and glutathione (GSH) both in vivo and in vitro. The 1H-NMRmetabolic pattern revealed that YCSND reversed CCl4-induced metabolic abnormalities in the liver. Additionally, the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis identified five pathways related to liver injury, including the PI3K-AKT, MAPK, HIF-1, apoptosis, and TNF signaling pathways. Moreover, RT-qPCR showed YCSND regulated the inflammatory response (Tlr4, Il6, Tnfα, Nfκb1, Ptgs2, and Mmp9) and apoptosis (Bcl2, Caspase3, Bax, and Mapk3), and inhibited PI3K-AKT signaling pathway (Pi3k and Akt1). Combined network analysis and metabolomics showed a link between the key targets (Tlr4, Ptgs2, and Mmp9) and vital metabolites (choline, xanthine, lactate, and 3-hydroxybutyric acid) of YCSND in ALI.Conclusion: Overall, the results contribute to the understanding of the therapeutic effects of YCSND on ALI, and indicate that the integrated network analysis and metabolomics could be a powerful strategy to reveal the pharmacological effects of TCM.

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Section: Discussionmentioning

confidence: 99%

Integrated network analysis and metabolomics reveal the molecular mechanism of Yinchen Sini decoction in CCl4-induced acute liver injury

Zheng,

Shi,

Meng

et al. 2023

Front. Pharmacol.

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“…Saline, choline, and CDP-choline injections were repeated at the 6th hour. The CDP-choline dose was determined as equieffective choline dose as reported earlier (25,27). Rats were sacrifi ced by decapitation at the 24th hour under mild ether anesthesia at the end of the experimental protocol and kidneys were removed and cryopreserved immediately for further analyses.…”

Section: Methodsmentioning

confidence: 99%

“…Total choline levels in kidney tissue were analyzed via a spectrophotometric total choline/acetylcholine kit (Biovision, K615, USA) according to the manufacturer instructions (25).…”

Section: Measurement Of Total Choline Levelsmentioning

confidence: 99%

“…We previously showed that choline and CDP-choline administration downregulate LPS-induced Cyclooxygenase (COX)-2 pathway along with prostaglandin production while producing positive effects on sepsis severity and survival of animals with endotoxemia (25). COX pathway and prostaglandin production contribute to oxidative damage in animals with various disorders including infl ammation (5,26).…”

Section: Introductionmentioning

confidence: 99%

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Choline and citicoline ameliorate oxidative stress in acute kidney injury in rats

Bariş¹,

Simsek²,

Arıcı³

et al. 2022

BLL

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OBJECTIVES: The purpose of this study is to investigate the effects of cholinergic anti-infl ammatory pathway (CAP)-activating drugs, choline and citicoline (Cytidinediphosphate-choline, CDP-choline), on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) parameters and the contribution of NADPH Oxidase4 (NOX4) p22phox. BACKGROUND: Endotoxemia induces a systemic infl ammatory response characterized by the production of pro-infl ammatory mediators and reactive oxygen species (ROS), which eventually develops acute kidney injury (AKI). NADPH Oxidase4 (NOX4) p22phox pathway contributes to the development of endotoxemiainduced AKI. Infl ammatory response can be controlled by CAP. METHODS: Expressions levels of KIM-1, TNF-α, NOX4, p22phox and NFκB in the kidney tissues of rats were analyzed via RT-PCR in experimental groups; 1. Control, 2. LPS (10 mg/kg) + saline, 3. LPS + CDPcholine (375 mg/kg) and 4. LPS + choline (90 mg/kg). Choline and ROS levels in kidney tissues were also measured by a spectrofl uorometric assay. RESULTS: LPS-induced elevations of ROS levels were decreased by CDP-choline or choline administration (p < 0.001). LPS-elevated KIM-1, TNFα, NOX4, p22 phox, and NFκB expressions were signifi cantly decreased by choline or CDP-choline treatments (p < 0.001). CONCLUSION: Decreased ROS production in kidney tissues in treatment groups suggests that choline or CDP-choline may have therapeutic potential in endotoxemia-associated AKI via downregulating NOX4 and p22phox expressions (Tab. 1, Fig. 5, Ref. 45).

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“…In addition, LPS was shown to stimulate PGD2 production through the activation of the nuclear factor-kappa B (NF-κB) signaling pathway involved in the regulation of allergic and inflammatory responses ( Ricciotti and FitzGerald, 2011 ; Joo and Sadikot, 2012 ). The release and circulation of PGs and pro-inflammatory cytokines generate an inflammatory response, leading to an increase in capillary permeability, hemodynamic changes, extensive endothelial cell damage, septic shock, sepsis, and multiple organ failure ( Bernik et al, 2002 ; Baris et al, 2021a ; Bigagli et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Nicotinic acetylcholine receptor-mediated effects of varenicline on LPS-elevated prostaglandin and cyclooxygenase levels in RAW 264.7 macrophages

Baris,

Arici,

Tosun

2024

Front. Mol. Biosci.

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Introduction: The purpose of this study is to delineate anti-inflammatory and antioxidant potential of varenicline, a cigarette smoking cessation aid, on decreasing lipopolysaccharide (LPS)-elevated proinflammatory cytokines in RAW 264.7 murine macrophage cultures which we showed earlier to occur via cholinergic anti-inflammatory pathway (CAP) activation. To this end, we investigated the possible suppressive capacity of varenicline on LPS-regulated cyclooxygenase (COX-1 and COX-2) via α7 nicotinic acetylcholine receptor (α7nAChR) activation using the same in vitro model.Materials and Methods: In order to test anti-inflammatory effectiveness of varenicline, the levels of COX isoforms and products (PGE2, 6-keto PGF1α, a stable analog of PGI2, and TXA2) altered after LPS administration were determined by Enzyme Linked Immunosorbent Assay (ELISA). The antioxidant effects of varenicline were assessed by measuring reductions in reactive oxygen species (ROS) using a fluorometric intracellular ROS assay kit. We further investigated the contribution of nAChR subtypes by using non-selective and/or selective α7nAChR antagonists. The results were compared with that of conventional anti-inflammatory medications, such as ibuprofen, celecoxib and dexamethasone.Results: Varenicline significantly reduced LPS-induced COX-1, COX-2 and prostaglandin levels and ROS to an extent similar to that observed with anti-inflammatory agents used.Discussion: Significant downregulation in LPS-induced COX isoforms and associated decreases in PGE2, 6-keto PGF1α, and TXA2 levels along with reduction in ROS may be partly mediated via varenicline-activated α7nAChRs.

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Effects of CDP-Choline and Choline on COX Pathway in LPS-Induced Inflammatory Response in Rats

Cited by 6 publications

References 39 publications

Integrated network analysis and metabolomics reveal the molecular mechanism of Yinchen Sini decoction in CCl4-induced acute liver injury

Integrated network analysis and metabolomics reveal the molecular mechanism of Yinchen Sini decoction in CCl4-induced acute liver injury

Choline and citicoline ameliorate oxidative stress in acute kidney injury in rats

Nicotinic acetylcholine receptor-mediated effects of varenicline on LPS-elevated prostaglandin and cyclooxygenase levels in RAW 264.7 macrophages

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