Quercetin and its derivative Q2 modulate chromatin dynamics in adipogenesis and Q2 prevents obesity and metabolic disorders in rats

Nettore, Immacolata Cristina; Rocca, Carmine; Mancino, Giuseppina; Albano, Luigi; Amelio, Daniela; Grande, Fedora; Puoci, Francesco; Pasqua, Teresa; Desiderio, Silvio; Mazza, Rosa; Terracciano, Daniela; Colao, Annamaria; Béguinot, Francesco; Russo, Gian Luigi; Dentice, Monica; Macchia, Paolo Emidio; Sinicropi, Maria Stefania; Angelone, Tommaso; Ungaro, Paola

doi:10.1016/j.jnutbio.2019.03.019

Cited by 46 publications

(30 citation statements)

References 75 publications

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“…The expression of CB2-Rs in the central nervous system is increased in neurodegenerative pathologies, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and in some tumours like gliomas [14]. In addition to the involvement in physiological functions, CB2-Rs are implied in numerous pathological processes, so they can represent an interesting target in order to obtain agonist molecules for the treatment of many pathological conditions, including neuropathic pain, inflammation, neuroinflammatory and neurodegenerative pathologies (Parkinson's disease, Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis), spinal and brain injuries, stroke, ischemia, anxiety disorder, depression, colitis, fibrosis and liver ischemia, atherosclerosis, osteoporosis, osteoarthritis, diabetes, obesity, and some types of cancer [9,[12][13][14][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

et al. 2019

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β-Caryophyllene (BCP), a natural bicyclic sesquiterpene, is a selective phytocannabinoid agonist of type 2 receptors (CB2-R). It isn’t psychogenic due to the absence of an affinity to cannabinoid receptor type 1 (CB1). Among the various biological activities, BCP exerts anti-inflammatory action via inhibiting the main inflammatory mediators, such as inducible nitric oxide synthase (iNOS), Interleukin 1 beta (IL-1β), Interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF-α), nuclear factor kapp a-light-chain-enhancer of activated B cells (NF-κB), cyclooxygenase 1 (COX-1), cyclooxygenase 2 (COX-2). Peroxisome proliferator-activated receptors alpha (PPAR-α) effects are also mediated by the activation of PPAR-α and PPAR-γ receptors. In detail, many studies, in vitro and in vivo, suggest that the treatment with β-caryophyllene improves the phenotype of animals used to model various inflammatory pathologies, such as nervous system diseases (Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, stroke), atherosclerosis, and tumours (colon, breast, pancreas, lymphoma, melanoma and glioma cancer). Furthermore, pre-clinical data have highlighted that BCP is potentially useful in Streptococcus infections, osteoporosis, steatohepatitis, and exerts anticonvulsant, analgesic, myorelaxing, sedative, and antidepressive effects. BCP is non-toxic in rodents, with a Lethal dose, 50% (LD50) greater than 5000 mg/kg. Nevertheless, it inhibits various cytochrome P450 isoforms (above all, CYP3A4), which metabolise xenobiotics, leading to adverse effects, due to drug levels over therapeutic window. All the reported data have highlighted that both pharmacological and toxicological aspects need to be further investigated with clinical trials.

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Section: Introductionmentioning

confidence: 99%

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

et al. 2019

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“…To date, a special attention for both prophylactic and therapeutic interventions in T2D is directed to diet nutrients, able to regulate the metabolism and in uence the consumer's health 47 . Quercetin is a nutraceutical compound with anti-in ammatory and antioxidant effects both in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Quercetin is a nutraceutical compound with anti-in ammatory and antioxidant effects both in vivo and in vitro. Possible mechanisms of actions include inhibition of COX-2, NF-kB and MAPK pathways, post-translational modi cations and elimination of senescent cells [47][48][49] . Here, we have shown that quercetin ameliorates the local low-grade in ammation by reducing the expression of TNF-α and the release of a number of in ammatory cytokines in MSCs isolated from IGT and T2D morbid obese subjects.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous Adipose Tissue Cell-derived Cytokines Are Early Markers of Impaired Glucose Tolerance in Severe Obesity

D’Esposito¹,

Ambrosio²,

Liguoro³

et al. 2021

Preprint

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Background Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose tolerance is not clear. Methods 92 severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an Oral Glucose Tolerance Test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or Type 2 Diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and Mesenchymal Stem Cells (MSCs) were isolated, characterized and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines and growth factors were assessed by multiplex ELISA. Results Serum levels of IL-9, IL-13 and MIP-1β were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were 3-fold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1β and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein, were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT–derived MSCs to quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines. Conclusion In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and may be, at least in part, attenuated by quercetin.

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“…Among these derivatives, Q2 and Q5 have better bioavailability and stability than other derivatives. It was found that Q2 has a better anti-obesity effect and remission on metabolic disorders with respect to Que ( Nettore et al, 2019 ). The evaluation of the bioavailability of Q5 has reached 19% at the end of the experiment compared to Que (11%) in vitro .…”

Section: Protective Effects Against Calcium Overloadmentioning

confidence: 99%

Protective Mechanisms of Quercetin Against Myocardial Ischemia Reperfusion Injury

Zhang

Wang

2020

Front. Physiol.

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Quercetin has attracted more attention in recent years due to its protective role against ischemia/reperfusion injury. Quercetin can alleviate oxidative stress injury through the inhibition of NADPH oxidase and xanthine oxidase, blockage of the Fenton reaction, and scavenging of reactive oxygen species. Quercetin can also exert anti-inflammatory and anti-apoptotic effects by reducing the response to inflammatory factors and inhibiting cell apoptosis. Moreover, it can induce vasodilation effects through the inhibition of endothelin-1 receptors, the enhancement of NO stimulation and the activation of the large-conductance calcium-activated potassium channels. Finally, Quercetin can also antagonize the calcium overload. These multifaceted activities of Quercetin make it a potential therapeutic alternative for the treatment of ischemia/reperfusion injury.

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Quercetin and its derivative Q2 modulate chromatin dynamics in adipogenesis and Q2 prevents obesity and metabolic disorders in rats

Cited by 46 publications

References 75 publications

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

Subcutaneous Adipose Tissue Cell-derived Cytokines Are Early Markers of Impaired Glucose Tolerance in Severe Obesity

Protective Mechanisms of Quercetin Against Myocardial Ischemia Reperfusion Injury

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