Mannose Treatment: A Promising Novel Strategy to Suppress Inflammation

Zhang, Wei; Cheng, Hao; Gui, Yuanyuan; Zhan, Qipeng; Li, Si; Qiao, Wenliang; Tong, Aiping

doi:10.3389/fimmu.2021.756920

Cited by 39 publications

(31 citation statements)

References 56 publications

(84 reference statements)

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“…This study determined the mRNA and protein expression levels of IL-1β, IL-6, IL-10, IL-17, TNF-α, G-CSF, and GM-CSF in gingival tissues after D-mannose treatment in periodontitis rats, which showed that D-mannose alleviated gingival in ammation in periodontitis rats in vivo and in vitro. Our ndings added evidence to the opinion that Dmannose treatment is a promising novel strategy to suppress in ammation [17]. Researches prove that there are many immune cells involved in the periodontitis process, producing the in ammatory factors.…”

Section: Discussionsupporting

confidence: 56%

D-mannose alleviates chronic periodontitis in rats by regulating the functions of neutrophils

Li,

Chen,

Zhu

et al. 2024

Preprint

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Background Periodontitis is a chronic inflammatory disease without effective treatment. Nowadays, the critical role of neutrophils in periodontitis is getting better and better understood. The study aimed to explore the protective effects of D-mannose on chronic periodontitis and determine whether its underlying mechanisms is related to neutrophils. Methods To explore the protective effects of D-mannose on chronic periodontitis, the rat model of lipopolysaccharide (LPS)-induced periodontitis was established, followed by D-mannose treatment by oral gavage. To evaluate the protective effects of D-mannose against periodontal bone loss, methylene blue staining, hematoxylin and eosin (H&E) staining, and micro-CT scanning were utilized. Then, immunofluorescence (IF), Western Blot, and RT-PCR were applied to assess the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and IL-17), anti-inflammatory cytokine (IL-10), tumor necrosis factor-alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), ten-eleven translocation 2 (TET2), and key glycolytic enzymes (HK1, HK2, PFKFB3), and to examine D-mannose's impact on the recruitment and activation of neutrophils in the gingiva. Additionally, neutrophils isolated from the peripheral blood of healthy rats were treated with LPS and D-mannose, and changes in the expression levels of myeloperoxidase (MPO), IL-1β, IL-6, IL-17, IL-10, and TET2 were observed via IF. Results In vivo, D-mannose inhibited LPS-induced alveolar bone resorption in rats and suppressed the expression levels of IL-1β, IL-6, IL-17, TNF-α, G-CSF, GM-CSF, TET2, HK1, HK2, and PFKFB3, upregulated the expression level of IL-10, and inhibited the recruitment and activation of neutrophils in LPS-treated rat gingival tissues. In vitro, D-mannose was found to inhibit the activation of neutrophils stimulated by LPS, downregulate the expression of IL-1β, IL-6, IL-17, and TET2, and upregulate the expression of IL-10. Conclusions D-mannose can alleviate chronic periodontitis in rats by regulating the functions of neutrophils, potentially associated with the expression of TET2 and glycolysis, providing new insights into the potential application of D-mannose to chronic periodontitis.

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Section: Discussionsupporting

confidence: 56%

D-mannose alleviates chronic periodontitis in rats by regulating the functions of neutrophils

Li,

Chen,

Zhu

et al. 2024

Preprint

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“…Previous studies have indicated that mannose has anti-inflammatory effects on various diseases, such as asthma, colitis and osteoarthritis [ 35 ]. These findings suggest that the administration of mannose could be a potential treatment approach for multiple diseases simultaneously.…”

Section: Discussionmentioning

confidence: 99%

“…Investigating both aspects mentioned above will further expand the clinical applications of mannose. Although many studies have employed mannose concentrations lower than 40 mmol/L, our CCK-8 experiments revealed that NP cells have a maximum tolerance to mannose at a concentration of 40 mmol/L [ 19 , 35 ]. Therefore, a more precise exploration of the dosing of orally administered mannose is crucial for its clinical application.…”

Section: Discussionmentioning

confidence: 99%

D-mannose alleviates intervertebral disc degeneration through glutamine metabolism

Dong,

Jiao,

Wang

et al. 2024

Military Med Res

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Background Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus (NP) cells plays a central role. Presently, the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes. D-mannose (referred to as mannose) has demonstrated anti-catabolic properties in various diseases. Nevertheless, its therapeutic potential in IVDD has yet to be explored. Methods The study began with optimizing the mannose concentration for restoring NP cells. Transcriptomic analyses were employed to identify the mediators influenced by mannose, with the thioredoxin-interacting protein (Txnip) gene showing the most significant differences. Subsequently, small interfering RNA (siRNA) technology was used to demonstrate that Txnip is the key gene through which mannose exerts its effects. Techniques such as colocalization analysis, molecular docking, and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP. To elucidate the mechanism of action of mannose, metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose. Next, various methods, including integrated omics data and the Gene Expression Omnibus (GEO) database, were used to validate the one-way pathway through which TXNIP regulates glutamine. Finally, the therapeutic effect of mannose on IVDD was validated, elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats. Results In both in vivo and in vitro experiments, it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism. From a mechanistic standpoint, it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein (MondoA), resulting in the upregulation of TXNIP. This upregulation, in turn, inhibits glutamine metabolism, ultimately accomplishing its anti-catabolic effects by suppressing the mitogen-activated protein kinase (MAPK) pathway. More importantly, in vivo experiments have further demonstrated that compared with intradiscal injections, oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes. Conclusions In summary, through integrated multiomics analysis, including both in vivo and in vitro experiments, this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis. These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD. Compared to existing clinically invasive or pain-relieving therapies for IVDD, the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.

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“…Since it has been well summarized in the recent past that mannose is a novel suppressor of inflammation (Zhang et al, 2021), we only emphasize the point that mannose treatment could be a safe and promising strategy to suppress and to treat autoimmunity and asthma. More than that, mannose could also suppress woundinginduced inflammation in skin (Jokela et al, 2013).…”

Section: The Anti-inflammatory Effects Of Mannosementioning

confidence: 99%

“…During the last few years, mannose has been shown to have many physiological benefits and applications, such as suppressing inflammation (Zhang et al, 2021), and suppressing tumor growth and metastasis (Gonzalez et al, 2018). Besides suppressing Type 1 diabetes, asthma and macrophage-mediated inflammation (Zhang et al, 2017;Torretta et al, 2020), a most recent study has shown that mannose can suppress experimental autoimmune encephalomyelitis (EAE) by inducing treg cells, suggesting that Mannose may be a potential adjuvant therapy for multiple sclerosis (MS) (Hwang et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Mannose: A Sweet Option in the Treatment of Cancer and Inflammation

et al. 2022

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As a natural sugar, mannose is a type of hexose that is abundant in many different types of fruits. Since mannose is rarely used for glycolysis in mammals, studies on the role of mannose have not attracted much attention. Glycosylation of specific proteins was thought to be the major function of mannose. Surprisingly, during the past few years, mannose was found to be effective in promoting immune tolerance and suppressing inflammatory diseases related to autoimmunity and allergy. Moreover importantly, mannose was also found to be efficient in suppressing tumors by suppressing glycolysis and enhancing chemotherapeutic agents. In this review, we summarize the recent studies of mannose on antitumor properties and anti-inflammatory characteristics. We emphasize that mannose could play a beneficial role in the treatment of a variety of diseases, including cancers and inflammatory diseases, and could be a novel therapeutic strategy that deserves continued evaluation.

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Mannose Treatment: A Promising Novel Strategy to Suppress Inflammation

Cited by 39 publications

References 56 publications

D-mannose alleviates chronic periodontitis in rats by regulating the functions of neutrophils

D-mannose alleviates chronic periodontitis in rats by regulating the functions of neutrophils

D-mannose alleviates intervertebral disc degeneration through glutamine metabolism

Mannose: A Sweet Option in the Treatment of Cancer and Inflammation

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