Dietary Geraniol by Oral or Enema Administration Strongly Reduces Dysbiosis and Systemic Inflammation in Dextran Sulfate Sodium-Treated Mice

Fazio, Luigia De; Spisni, Enzo; Cavazza, Elena; Strillacci, Antonio; Candela, Marco; Centanni, Manuela; Ricci, Chiara; Rizzello, Fernando; Campieri, Massimo; Valerii, Maria Chiara

doi:10.3389/fphar.2016.00038

Cited by 37 publications

(45 citation statements)

References 35 publications

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“…ALI, which is mainly characterized by pulmonary inflammation and apoptosis, is a common clinical disease in humans [ 8 ], and the mortality rate remains high at approximately 30–50% [ 27 ]. GOH, a special type of acyclic monoterpene alcohol, has been widely used to treat many diseases related to inflammation, including dextran sulfate sodium (DSS)-induced colitis in mice [ 28 ]. Moreover, GOH has been shown to inhibit cell apoptosis in traumatic spinal cord injury (SCI) [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Geraniol alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis

et al. 2017

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Geraniol (GOH), a special type of acyclic monoterpene alcohol, has been widely used to treat many diseases associated with inflammation and apoptosis. Acute lung injury (ALI) is a common clinical disease in humans characterized by pulmonary inflammation and apoptosis. In the present study, we investigated the protective effects of GOH in a mouse model of ALI induced by the intranasal administration of lipopolysaccharide (LPS) and elucidated the underlying molecular mechanisms in RAW 264.7 cells. In vivo, GOH treatment markedly ameliorated pathological injury and pulmonary cell apoptosis and reduced the wet/dry (W/D) weight ratio of lungs, myeloperoxidase (MPO) activity and the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). In vitro, the levels of pro-inflammatory cytokines, iNOS and COX-2 were significantly increased in LPS-stimulated RAW 264.7 cells, an effect that was decreased by GOH treatment. Moreover, GOH treatment dramatically reduced the expression of Toll-like receptor 4 (TLR4) and then prevented the nuclear factor-κB (NF-κB) activation. GOH treatment also promoted anti-apoptotic Bcl-2 expression and inhibited pro-apoptotic Bax and Caspase-3 expression. Furthermore, knockdown of TLR4 expression exerted a similar effect and inhibited the phosphorylation of p65, as well as the Bax and Caspase-3 expression. Taken together, these results suggest that GOH treatment alleviates LPS-induced ALI via inhibiting pulmonary inflammation and apoptosis, a finding that might be associated with the inhibition of TLR4-mediated NF-κB and Bcl-2/Bax signalling pathways.

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Section: Discussionmentioning

confidence: 99%

Geraniol alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis

et al. 2017

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“…It is known to exert a wide spectrum of pharmacological activities, namely antimicrobial ( Thapa et al, 2012 ), anti-inflammatory ( Chen and Viljoen, 2010 ), antioxidant ( Khan et al, 2013 ) and neuroprotective ( Rekha et al, 2013 ) effects. For example, oral administration of geraniol as an antimicrobial agent effectively prevented colitis-associated dysbiosis and decreased the systemic inflammatory profile of colitic mice ( De Fazio et al, 2016 ). Moreover, oral administration of geraniol supported the ability of dopaminergic neurons to survive free radical injury by inducing the production of antioxidant enzymes and reducing the expression of apoptotic markers ( Rekha et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes

et al. 2018

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Geraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intestinal cells, and its pharmacokinetics and bioavailability after intravenous and oral administration to rats. In addition, we systematically investigated the potential hepatotoxic effects of high doses of geraniol on hepatic phase I, phase II and antioxidant enzymatic activities and undertook a hematochemical analysis on mice. Permeation studies performed via HPLC evidenced geraniol permeability coefficients across an in vitro model of the human intestinal wall for apical to basolateral and basolateral to apical transport of 13.10 ± 2.3 × 10-3 and 2.1 ± 0.1⋅× 10-3 cm/min, respectively. After intravenous administration of geraniol to rats (50 mg/kg), its concentration in whole blood (detected via HPLC) decreased following an apparent pseudo-first order kinetics with a half-life of 12.5 ± 1.5 min. The absolute bioavailability values of oral formulations (50 mg/kg) of emulsified geraniol or fiber-adsorbed geraniol were 92 and 16%, respectively. Following emulsified oral administration, geraniol amounts in the cerebrospinal fluid of rats ranged between 0.72 ± 0.08 μg/mL and 2.6 ± 0.2 μg/mL within 60 min. Mice treated with 120 mg/kg of geraniol for 4 weeks showed increased anti-oxidative defenses with no signs of liver toxicity. CYP450 enzyme activities appeared only slightly affected by the high dosage of geraniol.

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“…Most reports suggested 5–7 days of DSS treatment as a good starting point to construct an IBD mouse model. 16, 18 Mice treated with DSS for 7 days, however, lost greater than 20% of their body weight and were considered moribund. Therefore in this study, we treated the mice with DSS for 5 days to establish IBD with a moderate severity and then challenged with C. difficile spore to develop the IBD and CDI comorbidity model.…”

Section: Discussionmentioning

confidence: 99%

“…The disease activity index (DAI) was calculated by well-established and validated scores as described in Table 1. 16, 18 On day 8, some mice were sacrificed by CO 2 inhalation and then the colon was excised and fixed in formalin solution for histopathological assessment or prepared for cytokine/chemokine analysis.…”

Section: Methodsmentioning

confidence: 99%

Mice with Inflammatory Bowel Disease are Susceptible toClostridium difficileInfection With Severe Disease Outcomes

Zhou

Hamza

Fleur

et al. 2018

Inflammatory Bowel Diseases

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Background Over the past several decades, there has been a significant increase in the incidence of Clostridium difficile infection (CDI) in patients suffering from inflammatory bowel disease (IBD). However, a wild-type animal model is not available to study these comorbid diseases. Methods We evaluated the susceptibility to CDI of mice with dextran sulfate sodium salt (DSS)-induced colitis (IBD mice) with or without antibiotic exposure; we examined the histopathology and cytokine response in the concomitant diseases after the model was created. Results No CDI occurs in healthy control mice, wherease the incidence of CDI in IBD mice is 40%; however, in IBD mice that received antibiotics, the incidence of CDI is 100% and the disease is accompanied by high levels of toxins in the mouse feces and sera. Compared to IBD and CDI alone, those IBD mice infected with C. difficile have more severe symptoms, toxemia, histopathological damage, and higher mortality. Moreover, several proinflammatory cytokines and chemokines are significantly elevated in the colon tissues from IBD mice infected with C. difficile. Conclusions We, for the first time, demonstrate in an animal model that mice with dextran sulfate sodium induced-inflammatory bowel disease are significantly more susceptible to C. difficile infection, and that the bacterial infection led to more severe disease and death. These findings are consistent with clinical observations, thus, the animal model will permit us to study the pathogenesis of these concurrent diseases and to develop therapeutic strategies against the comorbidity of IBD and CDI.

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Dietary Geraniol by Oral or Enema Administration Strongly Reduces Dysbiosis and Systemic Inflammation in Dextran Sulfate Sodium-Treated Mice

Cited by 37 publications

References 35 publications

Geraniol alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis

Geraniol alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis

Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes

Mice with Inflammatory Bowel Disease are Susceptible toClostridium difficileInfection With Severe Disease Outcomes

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