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Morphine is an important pain reliever employed in pain management, its extended utilize is hindered by the onset of analgesic tolerance and oxidative stress. Long-term morphine administration causes elevated production of reactive oxygen species (ROS), disrupting mitochondrial function and inducing oxidation. Sirtuin 3 (SIRT3), a mitochondrial protein, is essential in modulating ROS levels by regulating mitochondrial antioxidant enzymes as manganese superoxide dismutase (MnSOD). Our investigation focused on the impact of SIRT3 on hyperalgesia and morphine tolerance in mice, as evaluating the antioxidant effect of the polyphenolic fraction of bergamot (BPF). Mice were administered morphine twice daily for four consecutive days (20 mg/kg). On the fifth day, mice received an acute dose of morphine (3 mg/kg), either alone or in conjunction with BPF or Mn (III)tetrakis (4-benzoic acid) porphyrin (MnTBAP). We evaluated levels of malondialdehyde (MDA), nitration, and the activity of SIRT3, MnSOD, glutamine synthetase (GS), and glutamate 1 transporter (GLT1) in the spinal cord. Our findings demonstrate that administering repeated doses of morphine led to the development of antinociceptive tolerance in mice, accompanied by increased superoxide production, nitration, and inactivation of mitochondrial SIRT3, MnSOD, GS, and GLT1. The combined administration of morphine with either BPF or MnTBAP prevented these effects.

Peri-menopausal discomfort can have a detrimental effect on the physical health of women due to physiological and behavioral changes. Estrogen and progesterone-based hormone therapy can alleviate menopausal symptoms, but estrogen supplementation may have negative health effects. The effectiveness of hormone replacement therapy using natural compounds for peri-menopausal disorders is still uncertain. Evidence from in vivo experiments indicates that Ferula L. extract in ovariectomized rats leads to better sexual behavior. The effect seems to be linked to the phytoestrogenic properties of ferutinin, the primary bioactive compound in the extract. The purpose of this study was to assess the clinical impact of Ferula communis L. extract (titrated at 20% ferutinin, and given at doses of 100 mg/die for 90 days) on the quality of life of 64 menopausal women. The clinical trial was randomized, double-blind, and placebo controlled. Our data showed that Ferula communis L. extract reduced by 67 + 9% all symptoms associated to postmenopausal discomfort and enhanced significantly sexual behavior. In addition, the supplement led to a significant improvement of BMI and oxidative stress decrease in the women who received it, while also keeping platelet aggregation within normal levels. Overall, these results could point to the potential use of supplementation with Ferula communis L. extract to revert or mitigate menopause dysfunction.

Neurodegenerative diseases (NDs) affect millions of people worldwide, and to date, Alzheimer’s and Parkinson’s diseases are the most common NDs. Of the many risk factors for neurodegeneration, the aging process has the most significant impact, to the extent that it is tempting to consider neurodegenerative disease as a manifestation of accelerated aging. However, genetic and environmental factors determine the course of neurodegenerative disease progression. It has been proposed that environmental stimuli influence neuroplasticity. Some clinical studies have shown that healthy lifestyles and the administration of nutraceuticals containing bioactive molecules possessing antioxidant and anti-inflammatory properties have a preventive impact or mitigate symptoms in previously diagnosed patients. Despite ongoing research efforts, the therapies currently used for the treatment of NDs provide only marginal therapeutic benefits; therefore, the focus is now directly on the search for natural products that could be valuable tools in combating these diseases, including the natural compound Andrographis paniculata (Ap) and its main constituent, andrographolide (Andro). Preclinical studies have shown that the aqueous extract of Ap can modulate neuroinflammatory and neurodegenerative responses, reducing inflammatory markers and oxidative stress in various NDs. Therefore, in this review, we will focus on the molecular mechanisms by which Ap and Andro can modulate the processes of neurodegeneration and neuroinflammation, which are significant causes of neuronal death and cognitive decline.

Diabetes is a complex chronic disease, and among the affected patients, cardiovascular disease (CVD)is the most common cause of death. Consequently, the evidence for the cardiovascular benefit of glycaemic control may reduce long-term CVD rates. Over the years, multiple pharmacological approaches aimed at controlling blood glucose levels were unable to significantly reduce diabetes-related cardiovascular events. In this view, a therapeutic strategy combining SGLT2 inhibitors and plant extracts might represent a promising solution. Indeed, countering the main cardiometabolic risk factor using plant extracts could potentiate the cardioprotective action of SGLT2 inhibitors. This review highlights the main molecular mechanisms underlying these beneficial effects that could contribute to the better management of diabetic patients.

Background: Bergamot polyphenolic fraction (PF) extract exerts a beneficial against liver steatosis. However, the fundamental processes underlying this beneficial effect of bergamot PF remain elusive. In this work, we examined the effect of bergamot PF extract on 2D and 3D hepatocyte cultures. Material and Methods: We evaluated the effect of bergamot PF in 2D and 3D cultures from rat, human hepatoma cells, and human primary hepatocytes. Results: In 2D cell culture, we demonstrated that incubation with bergamot PF decreases intracellular lipid content and is associated with an increase in expression levels of ß-oxidation genes (Acox1, Pparα, and Ucp2) and lipophagy (Atg7). Moreover, we confirm this effect on 3D spheroids and organoids. Conclusion: Incubation with bergamot PF reduces intracellular lipid neutral fat potentially by increasing intracellular pathways related to beta-oxidation.

Lipid transfer proteins (LTPs) are widely widespread plant food allergens which represents the main cause of food allergy in adults living in the Mediterranean basin. The purpose of this study was to investigate in LTP patients the actual use of prescribed epinephrine auto-injector and appropriateness of its prescription. In addition, we investigated in these patients: (1) occurrence of new food reaction in the following three years after to diagnosis; (2) need and number of access to emergency services; (3) presence of possible predictive factors to further food reactions. One-hundred sixty-five adult patients sensitized to LTPs have been included. During follow-up, we recorded 68 further reactions, most of them (77.9%) characterized by local symptoms; rarely the patients required an emergency-department visits (16.1%) and only one patient (1.7%) used the epinephrine auto-injector. The patients with a previous history of anaphylaxis at baseline turned back to access to emergency services also during the follow-up (p = 0.006). The majority of patients with recorded systemic reactions (p = 0.004) and treated in an emergency room (p = 0.028) did not have any co-factor-enhanced at diagnosis. We noted an association between platanus pollen sensitization and severity of further reactions during the follow-up (p = 0.026). Epinephrine auto-injector were prescribed to 108/165 patients (65.5%) with an over-prescription rate of 25%. The unforeseeable clinical presentation of LTP allergic reactions and the eventual role played by the cofactor make necessary schedule a follow-up to monitor the patients over time and to assess the actual use of epinephrine auto injectors prescribed.

Multiple sclerosis (MS) is a neurological and inflammatory autoimmune disease of the Central Nervous System in which selective activation of T and B lymphocytes prompts a reaction against myelin, inducing demyelination and axonal loss. Although MS is recognized to be an autoimmune pathology, the specific causes are many; thus, to date, it has been considered a disorder resulting from environmental factors in genetically susceptible individuals. Among the environmental factors hypothetically involved in MS, nutrition seems to be well related, although the role of nutritional factors is still unclear. The gut of mammals is home to a bacterial community of about 2000 species known as the “microbiota”, whose composition changes throughout the life of each individual. There are five bacterial phylas that make up the microbiota in healthy adults: Firmicutes (79.4%), Bacteroidetes (16.9%), Actinobacteria (2.5%), Proteobacteria (1%) and Verrucomicrobia (0.1%). The diversity and abundance of microbial populations justifies a condition known as eubiosis. On the contrary, the state of dysbiosis refers to altered diversity and abundance of the microbiota. Many studies carried out in the last few years have demonstrated that there is a relationship between the intestinal microflora and the progression of multiple sclerosis. This correlation was also demonstrated by the discovery that patients with MS, treated with specific prebiotics and probiotics, have greatly increased bacterial diversity in the intestinal microbiota, which might be otherwise reduced or absent. In particular, natural extracts of Aloe vera and bergamot fruits, rich in polyphenols and with a high percentage of polysaccharides (mostly found in indigestible and fermentable fibers), appear to be potential candidates to re-equilibrate the gut microbiota in MS patients. The present review article aims to assess the pathophysiological mechanisms that reveal the role of the microbiota in the development of MS. In addition, the potential for supplementing patients undergoing early stages of MS with Aloe vera as well as bergamot fibers, on top of conventional drug treatments, is discussed.

Cancer is one of the most widespread diseases globally and one of the leading causes of death. Known cancer treatments are chemotherapy, surgery, radiation therapy, targeted hormonal therapy, or a combination of these methods. Antitumor drugs, with different mechanisms, interfere with cancer growth by destroying cancer cells. However, anticancer drugs are dangerous, as they significantly affect both cancer cells and healthy cells. In addition, there may be the onset of systemic side effects perceived and mutagenicity, teratogenicity, and further carcinogenicity. Many polyphenolic extracts, taken on top of common anti-tumor drugs, can participate in the anti-proliferative effect of drugs and significantly reduce the side effects developed. This review aims to discuss the current scientific knowledge of the protective effects of polyphenols of the genera Vaccinium, Citrus, Olea, and Cynara on the side effects induced by four known chemotherapy, Cisplatin, Doxorubicin, Tamoxifen, and Paclitaxel. In particular, the summarized data will help to understand whether polyphenols can be used as adjuvants in cancer therapy, although further clinical trials will provide crucial information.

Doxorubicin (Doxo) is a widely used antineoplastic drug which often induces cardiomyopathy, leading to congestive heart failure through the intramyocardial production of reactive oxygen species (ROS). Icariin (Ica) is a flavonoid isolated from Epimedii Herba (Berberidaceae). Some reports on the pharmacological activity of Ica explained its antioxidant and cardioprotective effects. The aim of our study was to assess the protective activities of Ica against Doxo-detrimental effects on rat heart-tissue derived embryonic cardiac myoblasts (H9c2 cells) and to identify, at least in part, the molecular mechanisms involved. Our results showed that pretreatment of H9c2 cells with 1 μM and 5 μM of Ica, prior to Doxo exposure, resulted in an improvement in cell viability, a reduction in ROS generation, the prevention of mitochondrial dysfunction and mPTP opening. Furthermore, for the first time, we identified one feasible molecular mechanism through which Ica could exerts its cardioprotective effects. Indeed, our data showed a significant reduction in Caveolin-1(Cav-1) expression levels and a specific inhibitory effect on phosphodiesterase 5 (PDE5a) activity, improving mitochondrial function compared to Doxo-treated cells. Besides, Ica significantly prevented apoptotic cell death and downregulated the main pro-autophagic marker Beclin-1 and LC3 lipidation rate, restoring physiological levels of activation of the protective autophagic process. These results suggest that Ica might have beneficial cardioprotective effects in attenuating cardiotoxicity in patients requiring anthracycline chemotherapy through the inhibition of oxidative stress and, in particular, through the modulation of Cav-1 expression levels and the involvement of PDE5a activity, thereby leading to cardiac cell survival.

Cancer is one of the leading causes of death globally, associated with multifactorial pathophysiological components. In particular, genetic mutations, infection or inflammation, unhealthy eating habits, exposition to radiation, work stress, and/or intake of toxins have been found to contribute to the development and progression of cancer disease states. Early detection of cancer and proper treatment have been found to enhance the chances of survival and healing, but the side effects of anticancer drugs still produce detrimental responses that counteract the benefits of treatment in terms of hospitalization and survival. Recently, several natural bioactive compounds were found to possess anticancer properties, capable of killing transformed or cancerous cells without being toxic to their normal counterparts. This effect occurs when natural products are associated with conventional treatments, thereby suggesting that nutraceutical supplementation may contribute to successful anticancer therapy. This review aims to discuss the current literature on four natural bioactive extracts mostly characterized by a specific polyphenolic profile. In particular, several activities have been reported to contribute to nutraceutical support in anticancer treatment: (1) inhibition of cell proliferation, (2) antioxidant activity, and (3) anti-inflammatory activity. On the other hand, owing to their attenuation of the toxic effect of current anticancer therapies, natural antioxidants may contribute to improving the compliance of patients undergoing anticancer treatment. Thus, nutraceutical supplementation, along with current anticancer drug treatment, may be considered for better responses and compliance in patients with cancer. It should be noted, however, that when data from studies with bioactive plant preparations are discussed, it is appropriate to ensure that experiments have been conducted in accordance with accepted pharmacological research practices so as not to disclose information that is only partially correct.

Background: Restrictions due to the COVID-19 pandemic limited patients’ access to hospital care. The aims of this study were to assess dietary nutritional status, quality of life (QoL), and adherence to dietary therapy before and after 30-day personalized diet therapy through telenutrition tools in patients with systemic nickel allergic syndrome (SNAS). Methods: Each SNAS patient underwent the following allergological procedures: (a) face-to-face visit (nutritional visit and QoL evaluation) with prescription of one out of five personalized and balanced dietary plans different for calorie intake, (b) video call visit for dietary evaluation and assessment of adherence to diet after 15 days, and (c) video call visit for dietary and QoL evaluation and assessment of adherence to diet therapy after 30 days (end of study). Results: We enrolled 20 SNAS patients. After 15 and 30 days, we found a statistically significant improvement in anthropometric findings after diet therapy, a significant adherence rate to low-nickel diet (60% and 80%, respectively), and an improvement in QoL with an increase in almost all psychometric indices. Conclusions: Our study demonstrates that telenutrition can be a valid tool to monitor nutritional status and adherence to balanced low-Ni diet positively affecting QoL in SNAS patients during the COVID-19 pandemic.

Cardiovascular disease is the leading cause of death and disability in the Western world. In order to safeguard the structure and the functionality of the myocardium, it is extremely important to adequately support the cardiomyocytes. Two cellular organelles of cardiomyocytes are essential for cell survival and to ensure proper functioning of the myocardium: mitochondria and the sarcoplasmic reticulum. Mitochondria are responsible for the energy metabolism of the myocardium, and regulate the processes that can lead to cell death. The sarcoplasmic reticulum preserves the physiological concentration of the calcium ion, and triggers processes to protect the structural and functional integrity of the proteins. The alterations of these organelles can damage myocardial functioning. A proper nutritional balance regarding the intake of macronutrients and micronutrients leads to a significant improvement in the symptoms and consequences of heart disease. In particular, the Mediterranean diet, characterized by a high consumption of plant-based foods, small quantities of red meat, and high quantities of olive oil, reduces and improves the pathological condition of patients with heart failure. In addition, nutritional support and nutraceutical supplementation in patients who develop heart failure can contribute to the protection of the failing myocardium. Since polyphenols have numerous beneficial properties, including anti-inflammatory and antioxidant properties, this review gathers what is known about the beneficial effects of polyphenol-rich bergamot fruit on the cardiovascular system. In particular, the role of bergamot polyphenols in mitochondrial and sarcoplasmic dysfunctions in diabetic cardiomyopathy is reported.

Doxorubicin is an anthracycline that is commonly used as a chemotherapy drug due to its cytotoxic effects. The clinical use of doxorubicin is limited due to its known cardiotoxic effects. Treatment with anthracyclines causes heart failure in 15–17% of patients, resulting in mitochondrial dysfunction, the accumulation of reactive oxygen species, intracellular calcium dysregulation, the deterioration of the cardiomyocyte structure, and apoptotic cell death. Polyphenols have a wide range of beneficial properties, and particular importance is given to Bergamot Polyphenolic Fraction; Oleuropein, one of the main polyphenolic compounds of olive oil; and Cynara cardunculus extract. These natural compounds have particular beneficial characteristics, owing to their high polyphenol contents. Among these, their antioxidant and antoproliferative properties are the most important. The aim of this paper was to investigate the effects of these three plant derivatives using an in vitro model of cardiotoxicity induced by the treatment of rat embryonic cardiomyoblasts (H9c2) with doxorubicin. The biological mechanisms involved and the crosstalk existing between the mitochondria and the endoplasmic reticulum were examined. Bergamot Polyphenolic Fraction, Oleuropein, and Cynara cardunculus extract were able to decrease the damage induced by exposure to doxorubicin. In particular, these natural compounds were found to reduce cell mortality and oxidative damage, increase the lipid content, and decrease the concentration of calcium ions that escaped from the endoplasmic reticulum. In addition, the direct involvement of this cellular organelle was demonstrated by silencing the ATF6 arm of the Unfolded Protein Response, which was activated after treatment with doxorubicin.

Cardiovascular diseases (CVDs), which include congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, and many other cardiac disorders, cause about 30% of deaths globally; representing one of the main health problems worldwide. Among CVDs, ischemic heart diseases (IHDs) are one of the major causes of morbidity and mortality in the world. The onset of IHDs is essentially due to an unbalance between the metabolic demands of the myocardium and its supply of oxygen and nutrients, coupled with a low regenerative capacity of the heart, which leads to great cardiomyocyte (CM) loss; promoting heart failure (HF) and myocardial infarction (MI). To date, the first strategy recommended to avoid IHDs is prevention in order to reduce the underlying risk factors. In the management of IHDs, traditional therapeutic options are widely used to improve symptoms, attenuate adverse cardiac remodeling, and reduce early mortality rate. However, there are no available treatments that aim to improve cardiac performance by replacing the irreversible damaged cardiomyocytes (CMs). Currently, heart transplantation is the only treatment being carried out for irreversibly damaged CMs. Hence, the discovery of new therapeutic options seems to be necessary. Interestingly, recent experimental evidence suggests that regenerative stem cell medicine could be a useful therapeutic approach to counteract cardiac damage and promote tissue regeneration. To this end, researchers are tasked with answering one main question: how can myocardial regeneration be stimulated? In this regard, natural compounds from plant extracts seem to play a particularly promising role. The present review will summarize the recent advances in our knowledge of stem cell therapy in the management of CVDs; focusing on the main properties and potential mechanisms of natural compounds in stimulating and activating stem cells for myocardial regeneration.

Metabolic syndrome (MetS) represents a set of clinical findings that include visceral adiposity, insulin-resistance, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) levels and hypertension, which is linked to an increased risk of developing type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). The pathogenesis of MetS involves both genetic and acquired factors triggering oxidative stress, cellular dysfunction and systemic inflammation process mainly responsible for the pathophysiological mechanism. In recent years, MetS has gained importance due to the exponential increase in obesity worldwide. However, at present, it remains underdiagnosed and undertreated. The present review will summarize the pathogenesis of MetS and the existing pharmacological therapies currently used and focus attention on the beneficial effects of natural compounds to reduce the risk and progression of MetS. In this regard, emerging evidence suggests a potential protective role of bergamot extracts, in particular bergamot flavonoids, in the management of different features of MetS, due to their pleiotropic anti-oxidative, anti-inflammatory and lipid-lowering effects.

Hyperlipidemia and insulin-resistance are often associated with Non-Alcoholic Fatty Liver Disease (NAFLD) thereby representing a true issue worldwide due to increased risk of developing cardiovascular and systemic disorders. Although clear evidence suggests that circulating fatty acids contribute to pathophysiological mechanisms underlying NAFLD and hyperlipidemia, further studies are required to better identify potential beneficial approaches for counteracting such a disease. Recently, several artichoke extracts have been used for both reducing hyperlipidemia, insulin-resistance and NAFLD, though the mechanism is unclear. Here we used a wild type of Cynara Cardunculus extract (CyC), rich in sesquiterpens and antioxidant active ingredients, in rats fed a High Fat Diet (HFD) compared to a Normal Fat Diet (NFD). In particular, in rats fed HFD for four consecutive weeks, we found a significant increase of serum cholesterol, triglyceride and serum glucose. This effect was accompanied by increased body weight and by histopathological features of liver steatosis. The alterations of metabolic parameters found in HFDs were antagonised dose-dependently by daily oral supplementation of rats with CyC 10 and 20 mg/kg over four weeks, an effect associated to significant improvement of liver steatosis. The effect of CyC (20 mg/kg) was also associated to enhanced expression of both OCTN1 and OCTN2 carnitine-linked transporters. Thus, present data suggest a contribution of carnitine system in the protective effect of CyC in diet-induced hyperlipidemia, insulin-resistance and NAFLD.