Santa Cirmi

Flavonoid Fraction of Bergamot Juice Reduces LPS-Induced Inflammatory Response through SIRT1-Mediated NF-κB Inhibition in THP-1 Monocytes

Plant polyphenols exert anti-inflammatory activity through both anti-oxidant effects and modulation of pivotal pro-inflammatory genes. Recently, Citrus bergamia has been studied as a natural source of bioactive molecules with antioxidant activity, but few studies have focused on molecular mechanisms underlying their potential beneficial effects. Several findings have suggested that polyphenols could influence cellular function by acting as activators of SIRT1, a nuclear histone deacetylase, involved in the inhibition of NF-κB signaling. On the basis of these observations we studied the anti-inflammatory effects produced by the flavonoid fraction of the bergamot juice (BJe) in a model of LPS-stimulated THP-1 cell line, focusing on SIRT1-mediated NF-κB inhibition. We demonstrated that BJe inhibited both gene expression and secretion of LPS-induced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) by a mechanism involving the inhibition of NF-κB activation. In addition, we showed that BJe treatment reversed the LPS-enhanced acetylation of p65 in THP-1 cells. Interestingly, increasing concentrations of Sirtinol were able to suppress the inhibitory effect of BJe via p65 acetylation, underscoring that NF-κB–mediated inflammatory cytokine production may be directly linked to SIRT1 activity. These results suggest that BJe may be useful for the development of alternative pharmacological strategies aimed at reducing the inflammatory process.

Bergamot juice extract inhibits proliferation by inducing apoptosis in human colon cancer cells.

Colorectal cancer (CRC) is a leading cause of cancer mortality in the industrialized world, second to lung cancer. A lot of evidences highlight that a diet rich in fruits and vegetables may reduce the risk of some types of cancer including CRC. In this study we demonstrate that Citrus bergamia juice extracts (BJe) reduces CRC cell growth by multiple mechanisms. Low BJe concentrations inhibit MAPKs pathway and alter apoptosis-related proteins, that in turn induce cell cycle arrest and apoptosis in HT-29 cells. Instead, high concentrations of BJe induce oxidative stress causing DNA damage. Our study highlights the role of BJe as modulator of cell apoptosis in CRC cells and strengthens our previous hypothesis that the flavonoid fraction of bergamot juice may play a role as anti-cancer drug.

NF-κB mediates the antiproliferative and proapoptotic effects of bergamot juice in HepG2 cells

AIMS Among cancers, hepatocellular carcinoma is one of the commonest worldwide, and its incidence is increasing around the world. A lot of evidence underlines that natural substances usually consumed in the diet can have an important role in the prevention of cancer. In this study we investigated the molecular mechanisms underlying the antiproliferative activity of Citrus bergamia (bergamot) juice (BJ) in human hepatocellular carcinoma HepG2 cells. MAIN METHODS HepG2 cells were exposed to BJ and then cell proliferation, cell cycle progression, apoptosis and NF-κB nuclear translocation were evaluated. KEY FINDINGS Here we present results demonstrating that BJ reduced the growth rate of human hepatocellular carcinoma HepG2 cells in a time- and concentration-dependent manner, by a mechanism involving the activation of apoptotic machinery via both intrinsic and extrinsic pathways. Moreover, BJ increased expression of P53 and P21 proteins that may be responsible for the HepG2 cell cycle arrest in G2 phase. In addition, BJ reduced NF-κB nuclear translocation. SIGNIFICANCE Our data demonstrate the ability of BJ in reducing the growth of HepG2 cells, revealing its mechanism of action and suggesting a promising role as anticancer drugs.

Effects of bergamot essential oil and its extractive fractions on SH-SY5Y human neuroblastoma cell growth.

The goals were to investigate the mechanisms underlying the antiproliferative effects of bergamot essential oil (BEO) and to identify the compounds mainly responsible for its SH‐SY5Y cells growth rate inhibition.

Flavonoid Fraction of Orange and Bergamot Juices Protect Human Lung Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Stress

It has been reported that oxidant/antioxidant imbalance triggers cell damage that in turn causes a number of lung diseases. Flavonoids are known for their health benefits, and Citrus fruits juices are one of the main food sources of these secondary plant metabolites. The present study was designed to evaluate the effect of the flavonoid fraction of bergamot and orange juices, on H2O2-induced oxidative stress in human lung epithelial A549 cells. First we tested the antioxidant properties of both extracts in cell-free experimental models and then we assayed their capability to prevent the cytotoxic effects induced by H2O2. Our results demonstrated that both Citrus juice extracts reduce the generation of reactive oxygen species and membrane lipid peroxidation, improve mitochondrial functionality, and prevent DNA-oxidative damage in A549 cells incubated with H2O2. Our data indicate that the mix of flavonoids present in both bergamot and orange juices may be of use in preventing oxidative cell injury and pave the way for further research into a novel healthy approach to avoid lung disorders.

Neurodegenerative Diseases: Might Citrus Flavonoids Play a Protective Role?

Neurodegenerative diseases (ND) result from the gradual and progressive degeneration of the structure and function of the central nervous system or the peripheral nervous system or both. They are characterized by deterioration of neurons and/or myelin sheath, disruption of sensory information transmission and loss of movement control. There is no effective treatment for ND, and the drugs currently marketed are symptom-oriented, albeit with several side effects. Within the past decades, several natural remedies have gained attention as potential neuroprotective drugs. Moreover, an increasing number of studies have suggested that dietary intake of vegetables and fruits can prevent or delay the onset of ND. These properties are mainly due to the presence of polyphenols, an important group of phytochemicals that are abundantly present in fruits, vegetables, cereals and beverages. The main class of polyphenols is flavonoids, abundant in Citrus fruits. Our review is an overview on the scientific literature concerning the neuroprotective effects of the Citrus flavonoids in the prevention or treatment of ND. This review may be used as scientific basis for the development of nutraceuticals, food supplements or complementary and alternative drugs to maintain and improve the neurophysiological status.

Natural iron chelators: Protective role in A549 cells of flavonoids-rich extracts of Citrus juices in Fe(3+)-induced oxidative stress.

Exogenous iron in particulate matter and imbalanced iron homeostasis cause deleterious effects on health. Natural and synthetic iron chelators may be of therapeutic benefit, therefore we evaluated the protective effect of Citrus flavonoids-rich extracts from bergamot and orange juices in iron overloaded human lung epithelial cells. Cytofluorimetric, biochemical and genotoxic analyses were performed in Fe2(SO4)3 exposed A549, pretreated with each extract whose chemical composition was previously detected. Chelating activity was assessed in cells by a calcein ester. Both extracts reduced the generation of reactive oxygen species and membrane lipid peroxidation, improved mitochondrial functionality, and prevented DNA-oxidative damage in iron-exposed cells. Antioxidant effects were attributed to the chelating property, blocking upstream the redox activity of iron. Flavonoid-rich extracts also induced antioxidant catalase. The bergamot and orange juice extracts had a broad-spectrum protective effect. Their use prevents iron oxidative injury and these natural iron chelators could be used as therapeutic agents.

Citrus bergamia Juice Extract Attenuates β-Amyloid-Induced Pro-Inflammatory Activation of THP-1 Cells Through MAPK and AP-1 Pathways.

Flavonoids have been shown to be effective in protecting against age-related cognitive and motor decline in both in vitro and in vivo models. Recently, a flavonoid-rich extract of Citrus bergamia juice (BJe) has been shown to display anti-oxidant and anti-inflammatory properties against LPS-induced activation of human THP-1 monocytes. In the light of these observations, we wondered whether BJe may be beneficial against neuroinflammatory processes, such as those observed in Alzheimer’s disease. To this aim we used THP-1 monocytes to investigate the mechanisms underlying the beneficial potential of BJe against amyloid-beta1–42 (Aβ1−42) -mediated inflammation. Exposure of THP-1 cells to Aβ1−42 significantly induced the expression and secretion of IL-6 and IL-1β in THP-1 cells and increased the phosphorylation of ERK 1/2 as well as p46 and p54 members of JNK family. Moreover, Aβ1−42 raises AP-1 DNA binding activity in THP-1-treated cells. Interestingly, all these effects were reduced in the presence of BJe. Our data indicate that BJe may effectively counteract the pro-inflammatory activation of monocytes/microglial cells exposed to amyloid fibrils, suggesting a promising role as a natural drug against neuroinflammatory processes.

Anti-Inflammatory Activity of Citrus bergamia Derivatives: Where Do We Stand?

Inflammatory diseases affect a large portion of the worldwide population, and chronic inflammation is a major risk factor for several dangerous pathologies. To limit the side effects of both synthetic and biological anti-inflammatory drugs, the use of herbal medicines, nutraceuticals and food supplements has increased tremendously as alternative and/or complementary medicine to treat several pathologies, including inflammation. During the last decades, the biological properties of Citrus bergamia (bergamot) derivatives have obtained important scientific achievements, and it has been suggested their use in a context of a multitarget pharmacological strategy. Here, we present an overview of the anti-inflammatory properties of bergamot extracts that could represent the scientific basis for develop novel and alternative strategies to improve health status and attenuate inflammatory conditions.

Anti‐infective potential of Citrus bergamia Risso et Poiteau (bergamot) derivatives: a systematic review

Infectious diseases remain among the leading causes of morbidity and mortality worldwide, mainly because of the increase of resistance to chemotherapeutic drugs. Nature is the major source of anti‐infective drugs and could represent a font of medicines that may help overcome antibiotic resistance. Recently, the potential antimicrobial effect of certain plant extracts has attracted attention within the scientific community as alternatives to synthetic drugs. Here, we present a systematic review on the anti‐infective properties of bergamot derivatives that highlight the activity of bergamot essential oil against bacteria, mycetes and larvae, as well as the anti‐Helicobacter pylori effect of bergamot juice and the antimicrobial properties of extracts from bergamot peel. Findings presented herein could be used to develop novel and alternative preventive and therapeutic strategies aimed to overcome antibiotic resistance. Copyright