Novel Mechanisms of Herbal Therapies for Inhibiting HMGB1 Secretion or Action

Wu, Andrew H.; He, Lili; Long, Wei; Zhou, Qiuping; Zhu, Shu; Wang, Ping; Fan, Saijun; Wang, Haichao

doi:10.1155/2015/456305

Cited by 28 publications

(35 citation statements)

References 133 publications

(154 reference statements)

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“…However, it may be modified by acetylation and translocate into the cytoplasm and then released from activated cells [34]. Thus, deacetylation of HMGB1 by SIRT1 prevents its translocation from nucleus to cytoplasm and subsequent release [35].…”

Section: Resultsmentioning

confidence: 99%

Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis

Hong

Zheng

Zhang

et al. 2018

Free Radical Biology and Medicine

112

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Aims: Sepsis-caused multiple organ failure remains the major cause of morbidity and mortality in intensive care units. Nicotinamide riboside (NR) is a precursor of nicotinamide adenine dinucleotide (NAD+), which is important in regulating oxidative stress. This study investigated whether administration of NR prevented oxidative stress and organ injury in sepsis. Methods: Mouse sepsis models were induced by injection of lipopolysaccharides (LPS) or feces-injection-inperitoneum. NR was given before sepsis onset. Cultured macrophages and endothelial cells were incubated with various agents. Results: Administration of NR elevated the NAD+ levels, and elicited a reduction of oxidative stress, in-flammation and caspase-3 activity in lung and heart tissues, which correlated with attenuation of pulmonary microvascular permeability and myocardial dysfunction, leading to less mortality in sepsis models. These protective effects of NR were associated with decreased levels of plasma high mobility group box-1 (HMGB1) in septic mice. Consistently, pre-treatment of macrophages with NR increased NAD+ content and reduced HMGB1 release upon LPS stimulation. NR also prevented reactive oxygen species (ROS) production and apoptosis in endothelial cells induced by a conditioned-medium collected from LPS-treated macrophages. Furthermore, inhibition of SIRT1 by EX527 offset the negative effects of NR on HMGB1 release in macrophages, and ROS and apoptosis in endothelial cells. Conclusions: Administration of NR prevents lung and heart injury, and improves the survival in sepsis, likely by inhibiting HMGB1 release and oxidative stress via the NAD+/SIRT1 signaling. Given NR has been used as a health supplement, it may be a useful agent to prevent organ injury in sepsis.

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Section: Resultsmentioning

confidence: 99%

Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis

Hong

Zheng

Zhang

et al. 2018

Free Radical Biology and Medicine

112

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“…17 Preclinical animal studies of inflammatory diseases such as sepsis revealed that both GLY and CBX inhibit expression, extracellular secretion and cytokine activity of HMGB1 and other proinflammatory cytokines. 16,38 However, the underlying mechanisms of GLY or CBX regulation of the extracellular cytokine activity of HMGB1 in inflammatory diseases remained poorly understood. Recent studies, however, using an endotoxemic mouse model and LPS-treated RAW 264.7 cells shed some light on this issue, showing that GLY treatment induced heme oxygenase 1 expression via a p38MAPK/Nrf2 pathway, inhibiting HMGB1 extracellular secretion and hence its extracellular cytokine activity.…”

Section: Discussionmentioning

confidence: 99%

“…16–18 Glycyrrhizin is a glycoconjugated triterpene extracted from licorice root ( Glycyrrhiza glabra ). It possesses numerous pharmacologic effects 19 and has been shown effective in animal models of sepsis, 20 colitis, 21 lung, 22 and brain 23 injury.…”

mentioning

confidence: 99%

Glycyrrhizin Reduces HMGB1 and Bacterial Load in Pseudomonas aeruginosa Keratitis

Ekanayaka

McClellan

Barrett

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeHigh mobility group box 1 (HMGB1) contributes to poor disease outcome in Pseudomonas aeruginosa keratitis. This study tests the prophylactic effect of treatment with HMGB1 inhibitors, glycyrrhizin (GLY) and its derivative, carbenoxolone (CBX), for Pseudomonas keratitis.MethodsWe treated C57BL/6 (B6) mice subconjunctivally with GLY or CBX, infected with a noncytotoxic clinical isolate (KEI 1025) or a cytotoxic strain (ATCC 19660) of P. aeruginosa, and injected intraperitoneally with either agent. Clinical score, photography with a slit lamp, real-time RT-PCR, ELISA, myeloperoxidase (MPO) assay, bacterial plate count, histopathology, and absorbance assays were used to assess treatment efficacy and bacteriostatic activity.ResultsAfter KEI 1025 infection, GLY treatment reduced HMGB1 (mRNA and protein levels) and improved disease outcome with significant reduction in mRNA levels of IL-1β, TLR4, CXCL2, and IL-12; protein expression (IL-1β, CXCL2); neutrophil infiltrate; and bacterial load. Treatment with GLY enhanced antimicrobial proteins, including CRAMP and mBD2, but not mBD3. Glycyrrhizin also reduced clinical scores and improved disease outcome in corneas infected with strain 19660. However, neither HMGB1 mRNA or protein levels were reduced, but rather, CXCL2 expression (mRNA and protein), neutrophil infiltrate, and bacterial load were reduced statistically. Treatment with GLY initiated 6 hours after infection reduced plate count; GLY also was bacteriostatic for KEI 1025 and ATCC 19660.ConclusionsGlycyrrhizin reduces HMGB1 and is protective against P. aeruginosa–induced keratitis with a clinical isolate that is noncytotoxic. It was similar, but less effective when used after infection with a cytotoxic strain, which did not reduce HMGB1.

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“…Several molecular mechanisms by which herbal components effectively block HMGB1 release are postulated [18]. Glycyrrhizin inhibits LPS-triggered HMGB1 release through binding to HMGB1 in order to induce conformational changes that prevent DNA binding [18, 19].…”

Section: Introductionmentioning

confidence: 99%

A Dalbergia odorifera extract improves the survival of endotoxemia model mice by inhibiting HMGB1 release

Choi

Park

Hwang

et al. 2017

BMC Complement Altern Med

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Background Dalbergia odorifera T. Chen (Leguminosae) is an indigenous medicinal herb that is widely used as a popular remedy in northern and eastern Asia. However, the cellular mechanisms underlying the biological activity of D. odorifera are not fully elucidated.MethodsAnti-inflammatory effect of D. odorifera extract (DOE) was determined through intraperitoneal injection in a mouse model of endotoxemia induced by lipopolysaccharide (LPS). RAW 264.7 cells, a murine macrophage, were also treated with LPS to generate a cellular model of inflammation, and investigated the anti-inflammatory activity and underlying mechanisms of DOE and its constituent isoliquiritigenin.ResultsDOE dose-dependently inhibited LPS-induced release of high mobility group box 1 (HMGB1), a late proinflammatory cytokine, and decreased cytosolic translocation of HMGB1 in RAW264.7 cells. This inhibitory effect of DOE on HMGB1 release was observed in cells treated with DOE before or after LPS treatment, suggesting that DOE is effective for both treatment and prevention. In addition, DOE significantly inhibited LPS-induced formation of nitric oxide (NO) and expression of inducible NO synthase (iNOS) in a dose-dependent manner. These effects of DOE were accompanied by suppression of HMGB1 release triggered by LPS, suggesting a possible mechanism by which DOE modulates HMGB1 release through NO signaling.Isoriquiritigenin, a constituent of DOE, also attenuated LPS-triggered NO formation and HMGB1 release in RAW264.7 cells, indicating that isoriquiritigenin is an indexing molecule for the anti-inflammatory properties of DOE. Furthermore, c-Jun N-terminal kinase, but not extracellular signal-regulated kinase and p38, mediated DOE-dependent inhibition of HMGB1 release and NO/iNOS induction in RAW 264.7 cells exposed to LPS. Notably, administration of DOE ameliorated survival rates in a mouse model of endotoxemia induced by LPS, where decreased level of circulating HMGB1 was observed.ConclusionThese results suggest that DOE confers resistance to LPS-triggered inflammation through NO-mediated inhibitory effects on HMGB1 release.

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Novel Mechanisms of Herbal Therapies for Inhibiting HMGB1 Secretion or Action

Cited by 28 publications

References 133 publications

Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis

Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis

Glycyrrhizin Reduces HMGB1 and Bacterial Load in Pseudomonas aeruginosa Keratitis

A Dalbergia odorifera extract improves the survival of endotoxemia model mice by inhibiting HMGB1 release

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