Anti-Inflammatory Activity of Citric Acid-Treated Wheat Germ Extract in Lipopolysaccharide-Stimulated Macrophages

Jeong, Hojin; Choi, Yongseok; Lee, Jae-Kang; Lee, Beomjoon; Kim, Wooki; Kang, Hee

doi:10.3390/nu9070730

Cited by 37 publications

(29 citation statements)

References 35 publications

(46 reference statements)

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“…NF-κB regulates the activation and differentiation of T cells and inflammasomes ( Chi et al, 2015 ; Gan et al, 2016 ). NF-κB p65 is a pivotal transcription factor of M1 macrophages and induces a great amount of inflammatory genes, including TNF-α, IL-1β, IL-6, IL-10, IL-12 and cyclooxygenase-2 ( Jeoung et al, 2013 ; Jeong et al, 2017 ). Inactivation of the NF-κB, Stat3 is related to the potential pro-apoptotic signaling pathways ( Xiang et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Root Extract of Polygonum cuspidatum Siebold & Zucc. Ameliorates DSS-Induced Ulcerative Colitis by Affecting NF-kappaB Signaling Pathway in a Mouse Model via Synergistic Effects of Polydatin, Resveratrol, and Emodin

Liu

Sui

et al. 2018

Front. Pharmacol.

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Background: Polygonum cuspidatum Siebold & Zucc. (PCS) has antibacterial properties and may prevent Ulcerative colitis (UC) but related molecular mechanism remains unknown. NF-κB signaling pathway is associated with inflammatory responses and its inactivation may be critical for effective therapy of UC.Methods: UC mouse (C57BL/6J) model was established by using dextran sulfate sodium (DSS). The extract of PCS (PCSE) was prepared by using ethanol and its main ingredients were measured by HPLC. Thirty-two UC mice were evenly assigned into DG (received vehicle control), LG (0.1 g/kg PCSE daily), MG (0.2 g/kg PCSE daily) and HG (0.4 g/kg PCSE daily) groups. Meanwhile, 8 healthy mice were assigned as a control group (CG). Serum pharmacokinetics of PCS was measured by using HPLC. After 8-day treatment, weight, colon length and disease activity index (DAI) were measured. Inflammatory cytokines and oxidant biomarkers were measured by ELISA kits. The levels of cytokines, and key molecules in NF-κB pathway, were measured by using Western Blot. The effects of main ingredients of PCSE on cytokines and NF-κB signaling pathway were explored by using intestinal cells of a mouse UC model. The normality criterion was evaluated using the Saphiro–Wilk test. The quantitative variables were compared using the paired Student’s-t test.Results: The main ingredients of PCSE were polydatin, resveratrol and emodin. Polydatin may be transformed into resveratrol in the intestine of the mice. PCSE prevented DSS-caused weight loss and colon length reduction, and improved histopathology of UC mice (P < 0.05). PCSE treatment increased the serum levels of IL-10 and reduced the levels of IL-1 beta, IL-6 and TNF-α (P < 0.05). PCSE increased the activities of SOD, CAT, GPX and reduced the level of MDA, BCL-2, beta-arrestin, NF-κB p65 and the activity of MPO (P < 0.05). The combination of polydatin, resveratrol or emodin, and or PCSE exhibited higher inhibitory activities for cytokines and NF-κB signaling related molecules than any one of the three ingredients with same concentration treatment.Conclusion: Oral administration of PCSE suppressed NF-κB signaling pathway and exerts its anti-colitis effects via synergistic effects of polydatin, resveratrol or emodin.

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Section: Introductionmentioning

confidence: 99%

Root Extract of Polygonum cuspidatum Siebold & Zucc. Ameliorates DSS-Induced Ulcerative Colitis by Affecting NF-kappaB Signaling Pathway in a Mouse Model via Synergistic Effects of Polydatin, Resveratrol, and Emodin

Liu

Sui

et al. 2018

Front. Pharmacol.

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“…In LPS-treated mice, increased TNF-α in mice brain tissue and iNOS expression in the cytoplasm of hepatocytes were decreased after treatment of citric acid [34]. In a recent study, wheat germ extract with citric acid was reported to inhibit secretion of the pro-inflammatory cytokines, TNF-α, IL-6, and IL-12 and the synthesis of COX-2, as well as phosphorylation of NF-κB p65 and p38 kinase in LPS-activated macrophages [35]. In addition, calcium citrate showed antioxidant enzyme activities, and inhibited NO production by suppression of the expression of pro-inflammatory mediators (NF-κB, iNOS, and COX-2) and cytokines (TNF-α, IL-1β, and IL-6) in LPS-stimulated RAW 264.7 macrophages [36].…”

Section: Compound 1 Downregulated Il-6 and Tnf-α Production In Lps-stmentioning

confidence: 98%

“…The active compound, 1,5-dimethyl citrate (1), was a simple derivative of citric acid present in many plants and fruits [34][35][36][37]. An anti-inflammatory effect of citric acid derivatives has been reported in previous studies [34][35][36][37]. In LPS-treated mice, increased TNF-α in mice brain tissue and iNOS expression in the cytoplasm of hepatocytes were decreased after treatment of citric acid [34].…”

Section: Compound 1 Downregulated Il-6 and Tnf-α Production In Lps-stmentioning

confidence: 99%

“…To the best of our knowledge, this study is the first to evaluate the anti-inflammatory activity of citric acid derivative isolated from sea buckthorn on LPS-induced inflammatory response in RAW 264.7 mouse macrophages. The active compound, 1,5-dimethyl citrate (1), was a simple derivative of citric acid present in many plants and fruits [34][35][36][37]. An anti-inflammatory effect of citric acid derivatives has been reported in previous studies [34][35][36][37].…”

Section: Compound 1 Downregulated Il-6 and Tnf-α Production In Lps-stmentioning

confidence: 99%

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Inhibitory Effect of 1,5-Dimethyl Citrate from Sea Buckthorn (Hippophae rhamnoides) on Lipopolysaccharide-Induced Inflammatory Response in RAW 264.7 Mouse Macrophages

Baek

Lee

et al. 2020

Foods

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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.

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“…Benzoquinones have been reported to play important roles in bioenergetic transport, oxidative phosphorylation, electron transport processes, and the inhibition of adipogenesis [1][2][3][4]. 2,6-Dimethoxy-1,4-benzoquinone (DMBQ) is a natural phytochemical present in fermented wheat germ [5], and has been reported to exhibit various biological properties including anti-inflammatory, antitumor, and antibacterial activities [6][7][8]. Recent research has shown that wheat germ extract elicits anti-adipogenic and antioxidant effects in 3T3-L1 adipocytes [9].…”

Section: Introductionmentioning

confidence: 99%

2,6-Dimethoxy-1,4-benzoquinone Inhibits 3T3-L1 Adipocyte Differentiation via Regulation of AMPK and mTORC1

et al. 2018

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2,6-Dimethoxy-1,4-benzoquinone is a natural phytochemical present in fermented wheat germ. It has been reported to exhibit anti-inflammatory, antitumor, and antibacterial activities. However, the anti-adipogenic effects of 2,6-dimethoxy-1,4-benzoquinone and the mechanisms responsible have not previously been elucidated. Such findings may have ramifications for the treatment of obesity. 2,6-Dimethoxy-1,4-benzoquinone (5 and 7.5 µM) significantly reduced the expression of various adipogenic transcription factors, including peroxisome proliferator-activated receptor- and CCAAT/enhancer binding protein as well as adipocyte protein 2 and fatty acid synthase. 2,6-Dimethoxy-1,4-benzoquinone upregulated AMP-dependent protein kinase phosphorylation and inhibited the mature form of sterol regulatory element-binding protein 1c. Notably, 2,6-dimethoxy-1,4-benzoquinone attenuated mammalian target of rapamycin complex 1 activity in 3T3-L1 and mouse embryonic fibroblast cells. These findings highlight a potential role for 2,6-dimethoxy-1,4-benzoquinone in the suppression of adipogenesis. Further studies to determine the anti-obesity effects of 2,6-dimethoxy-1,4-benzoquinone in animal models appear warranted.

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Anti-Inflammatory Activity of Citric Acid-Treated Wheat Germ Extract in Lipopolysaccharide-Stimulated Macrophages

Cited by 37 publications

References 35 publications

Root Extract of Polygonum cuspidatum Siebold & Zucc. Ameliorates DSS-Induced Ulcerative Colitis by Affecting NF-kappaB Signaling Pathway in a Mouse Model via Synergistic Effects of Polydatin, Resveratrol, and Emodin

Root Extract of Polygonum cuspidatum Siebold & Zucc. Ameliorates DSS-Induced Ulcerative Colitis by Affecting NF-kappaB Signaling Pathway in a Mouse Model via Synergistic Effects of Polydatin, Resveratrol, and Emodin

Inhibitory Effect of 1,5-Dimethyl Citrate from Sea Buckthorn (Hippophae rhamnoides) on Lipopolysaccharide-Induced Inflammatory Response in RAW 264.7 Mouse Macrophages

2,6-Dimethoxy-1,4-benzoquinone Inhibits 3T3-L1 Adipocyte Differentiation via Regulation of AMPK and mTORC1

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