Citrulline cooperatively exerts an anti‑inflammatory effect on synovial cells with glucosamine and N‑acetylglucosamine

Yamagishi, Yoshie; Someya, Akimasa; Nagaoka, Isao

doi:10.3892/br.2020.1304

Cited by 7 publications

(6 citation statements)

References 20 publications

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“…Diet with high methionine has been shown to attenuate arthritic severity in rats ( 26 ). Both citrulline and arginine have anti-inflammatory properties and arginine is in phase 2 trial in treatment of RA ( 27 , 28 ). Reduced levels of both arginine and citrulline suggest alterations in microbial diversity with compensatory microbial changes.…”

Section: Discussionmentioning

confidence: 99%

Eggerthella lenta augments preclinical autoantibody production and metabolic shift mimicking senescence in arthritis

Balakrishnan,

Luckey,

Wright

et al. 2023

Sci. Adv.

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Although the etiology of rheumatoid arthritis (RA) is unknown, a strong genetic predisposition and the presence of preclinical antibodies before the onset of symptoms is documented. An expansion of Eggerthella lenta is associated with severe disease in RA. Here, using a humanized mouse model of collagen-induced arthritis, we determined the impact of E. lenta abundance on RA severity. Naïve mice gavaged with E. lenta produce preclinical rheumatoid factor and, when induced for arthritis, develop severe disease. The augmented antibody response was much higher in female mice, and among patients with RA, women had higher average load of E. lenta . Expansion of E. lenta increased CXCL5 and CD4 T cells, and both interleukin-17– and interferon-γ–producing B cells. Further, E. lenta gavage caused gut dysbiosis and decline in amino acids and nicotinamide adenine dinucleotide with an increase in microbe-dependent bile acids and succinyl carnitine causing systemic senescent-like inflammation.

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Section: Discussionmentioning

confidence: 99%

Eggerthella lenta augments preclinical autoantibody production and metabolic shift mimicking senescence in arthritis

Balakrishnan,

Luckey,

Wright

et al. 2023

Sci. Adv.

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“…However, the serum levels of this inflammatory biomarker were significantly reduced in the l -CIT group. Some in-vitro and in-vivo studies indicated that the l -CIT supplementation reduces serum inflammatory cytokines such as IL-6 [ 51 – 53 ]. Furthermore, a clinical study has supported the IL-6 lowering effect of CIT (10 g/day) for ten days [ 54 ]; while, Breuillard et al [ 55 ] reported a positive relationship between IL-6 productions and CIT concentration associated to a decrease in tumor necrosis factor-alpha (TNF-α) production in the peritoneal macrophages in obese diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

“…l -CIT supplementation had no significant effect on serum MCP-1and TLR-4 levels, whereas the serum TLR-4 levels were significantly reduced in the l -CIT group compared to the baseline.To the best of our knowledge, we could not find a randomized controlled trial assessing meta-inflammatory biomarkers in T2D patients. However, the effects of the l -CIT or watermelon component, as a source of l -CIT, on TLR-4 and MCP-1 were studied in some animal studies [ 24 , 36 , 51 , 56 ]. For example, Jegatheesan et al [ 24 ] reported that the administration of 1 g/kg/d l -CIT in nonalcoholic fatty liver disease (NAFLD) rats reduced TLR4 gene expression.…”

Section: Discussionmentioning

confidence: 99%

The effects of citrulline supplementation on meta-inflammation and insulin sensitivity in type 2 diabetes: a randomized, double-blind, placebo-controlled trial

Abbaszadeh

Azizi

Mobasseri

et al. 2021

Diabetol Metab Syndr

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Background This study aimed to examine the effects of l-citrulline (l-CIT) on low-grade inflammation (meta-inflammation) and insulin sensitivity in type 2 diabetes (T2D) patients since it has exhibited hypoglycemic and anti-inflammatory effects in most animal studies. Methods In this double-blind, placebo-controlled randomized clinical trial, 54 patients with T2D referred to specialized clinics of Tabriz University of Medical Sciences were assigned to l-CIT group (receiving orally one 3 g sachet of l-CIT daily before breakfast) or placebo group (receiving orally one 3 g sachet of microcrystalline cellulose daily before breakfast) for eight weeks. Serum levels of fasting blood glucose, hemoglobin A1c (HbA1c), CIT, monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), and toll-like receptor 4 (TLR-4) were determined. The quantitative insulin sensitivity check index (QUICKI) and homeostatic model assessment of β-cell function (HOMA-B) index were estimated at the baseline and post-intervention. Results No significant difference was observed between the studied parameters at the baseline. l-CIT supplementation significantly reduced not only serum concentrations of fasting blood glucose but also HbA1c, serum IL-6 and TLR-4 levels in the l-CIT group (p < 0.05). Additionally, at the end of the study serum levels of CIT increased significantly in l-CIT group compared to the baseline and placebo group. Fasting blood glucose concentrations and HbA1c significantly decreased after the intervention compared to the placebo. There was no significant difference in serum IL-6, TLR-4, MCP-1 levels, as well as QUICKI and HOMA-B index between the two groups, even after adjusting for baseline variables and confounders. Conclusions Our findings revealed that, although l-CIT supplementation significantly reduced fasting blood glucose concentrations, HbA1c and increased serum levels of CIT. It seems it could not significantly improve insulin sensitivity and meta-inflammation biomarkers. Additional studies with longer duration and different doses of l-CIT are required. Trial registration The protocol of this clinical trial is registered at the Iranian Registry of Clinical Trials (registration no: IRCT20100209003320N16 at www.irct.ir)

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“…We have been investigating the anti-inflammatory effects of various functional food materials, such as glucosamine, citrulline, methionine, and chondroitin sulfate, on IL-6 and IL-8 production by IL-1β-stimulated synovial cells (22,23), and revealed that these materials inhibit cytokine production by suppressing signaling molecules, including nuclear factor (NF)-κB, extracellular signal regulated kinases (ERK)1/2, and p38 mitogen-activated protein kinase (MAPK). However, the anti-inflammatory effects of isoflavones (daidzein, genistein, and glycitein) on inflammatory cytokine production by IL-1β-stimulated synovial cells have not yet been examined.…”

Section: Introductionmentioning

confidence: 99%

Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells

2021

Self Cite

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The present study investigated the effects of isoflavone derivatives (daidzein, genistein and glycitein) on the production of inflammatory cytokines (IL-6 and IL-8) by IL-1β-stimulated synovial cells. Synovial MH7A cells were stimulated with IL-1β in the absence or presence of isoflavone derivatives, and IL-6 and IL-8 production was measured by ELISA. The results of the present study indicated that daidzein significantly inhibited the production of IL-6, but not IL-8. Conversely, neither genistein nor glycitein exerted any inhibitory effects on the production of IL-6 or IL-8 by IL-1β-stimulated synovial cells. To elucidate the molecular mechanisms underlying the daidzein-mediated inhibition of IL-6 production, the present study examined the effects of daidzein on the phosphorylation (activation) of NF-κB p65, ERK1/2 and p38 MAPK. Daidzein significantly inhibited the phosphorylation of NF-κB p65 and ERK1/2, but not p38 MAPK in IL-1β-stimulated MH7A cells. The present study revealed that among the isoflavone derivatives examined (daidzein, genistein and glycitein), daidzein inhibited the production of IL-6, but not IL-8, by IL-1β-stimulated synovial MH7A cells via the suppression of NF-κB p65 and ERK1/2 activation. Collectively, these results suggested that daidzein may have potential as a therapeutic agent for the treatment of arthritic disorders through its anti-inflammatory effects via the inhibition of IL-6 production.

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Citrulline cooperatively exerts an anti‑inflammatory effect on synovial cells with glucosamine and N‑acetylglucosamine

Cited by 7 publications

References 20 publications

Eggerthella lenta augments preclinical autoantibody production and metabolic shift mimicking senescence in arthritis

Eggerthella lenta augments preclinical autoantibody production and metabolic shift mimicking senescence in arthritis

The effects of citrulline supplementation on meta-inflammation and insulin sensitivity in type 2 diabetes: a randomized, double-blind, placebo-controlled trial

Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells

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