Massimiliano Gasparrini

The effects of bioactive compounds from plant foods on mitochondrial function: A focus on apoptotic mechanisms

Mitochondria are essential organelles for cellular integrity and functionality maintenance and their imparement is implicated in the development of a wide range of diseases, including metabolic, cardiovascular, degenerative and hyperproliferative pathologies. The identification of different compounds able to interact with mitochondria for therapeutic purposes is currently becoming of primary importance. Indeed, it is well known that foods, particularly those of vegetable origin, present several constituents with beneficial effects on health. This review summarizes and updates the most recent findings concerning the mechanisms through which different dietary compounds from plant foods affect mitochondria functionality in healthy and pathological in vitro and in vivo models, paying particular attention to the pathways involved in mitochondrial biogenesis and apoptosis.

The Healthy Effects of Strawberry Polyphenols: Which Strategy behind Antioxidant Capacity?

Current evidence indicates that the consumption of strawberries, a natural source of a wide range of nutritive and bioactive compounds, is associated with the prevention and improvement of chronic-degenerative diseases. Studies involving cells and animals provide evidence on the anti-inflammatory, anticarcinogenic and antiproliferative activity of the strawberry. Epidemiological and clinical studies demonstrate that its acute consumption increases plasma antioxidant capacity, improves circulating inflammatory markers and ameliorates postprandial glycemic response. At the same time, a protracted intake reduces chronic inflammation and improves plasma lipid profile, supporting cardiovascular health, especially in individuals with increased risk for metabolic syndrome. To explain these beneficial effects, much attention has been paid in the past to the antioxidant properties of strawberry polyphenols. However, recent research has shown that their biological and functional activities are related not only to the antioxidant capacity but also to the modulation of many cellular pathways involved in metabolism, survival, proliferation, and antioxidant defenses. The aim of this review is to update and discuss the molecular and cellular mechanisms proposed in recent studies to elucidate the healthy effects of strawberry polyphenols against the most common chronic diseases, such as cancer, cardiovascular diseases, metabolic syndrome, and inflammation.

Polyphenol-rich strawberry extract protects human dermal fibroblasts against hydrogen peroxide oxidative damage and improves mitochondrial functionality.

Strawberry bioactive compounds are widely known to be powerful antioxidants. In this study, the antioxidant and anti-aging activities of a polyphenol-rich strawberry extract were evaluated using human dermal fibroblasts exposed to H2O2. Firstly, the phenol and flavonoid contents of strawberry extract were studied, as well as the antioxidant capacity. HPLC-DAD analysis was performed to determine the vitamin C and β-carotene concentration, while HPLC-DAD/ESI-MS analysis was used for anthocyanin identification. Strawberry extract presented a high antioxidant capacity, and a relevant concentration of vitamins and phenolics. Pelargonidin- and cyanidin-glycosides were the most representative anthocyanin components of the fruits. Fibroblasts incubated with strawberry extract and stressed with H2O2 showed an increase in cell viability, a smaller intracellular amount of ROS, and a reduction of membrane lipid peroxidation and DNA damage. Strawberry extract was also able to improve mitochondrial functionality, increasing the basal respiration of mitochondria and to promote a regenerative capacity of cells after exposure to pro-oxidant stimuli. These findings confirm that strawberries possess antioxidant properties and provide new insights into the beneficial role of strawberry bioactive compounds on protecting skin from oxidative stress and aging.

The Composition and Biological Activity of Honey: A Focus on Manuka Honey

Honey has been used as a food and medical product since the earliest times. It has been used in many cultures for its medicinal properties, as a remedy for burns, cataracts, ulcers and wound healing, because it exerts a soothing effect when initially applied to open wounds. Depending on its origin, honey can be classified in different categories among which, monofloral honey seems to be the most promising and interesting as a natural remedy. Manuka honey, a monofloral honey derived from the manuka tree (Leptospermum scoparium), has greatly attracted the attention of researchers for its biological properties, especially its antimicrobial and antioxidant capacities. Our manuscript reviews the chemical composition and the variety of beneficial nutritional and health effects of manuka honey. Firstly, the chemical composition of manuka honey is described, with special attention given to its polyphenolic composition and other bioactive compounds, such as glyoxal and methylglyoxal. Then, the effect of manuka honey in wound treatment is described, as well as its antioxidant activity and other important biological effects.

Promising Health Benefits of the Strawberry: A Focus on Clinical Studies

The potential health benefits associated with dietary intake of fruits have attracted increasing interest. Among berries, the strawberry is a rich source of several nutritive and non-nutritive bioactive compounds, which are implicated in various health-promoting and disease preventive effects. A plethora of studies have examined the benefits of strawberry consumption, such as prevention of inflammation disorders and oxidative stress, reduction of obesity related disorders and heart disease risk, and protection against various types of cancer. This review provides an overview of their nutritional and non-nutritional bioactive compounds and which factors affect their content in strawberries. In addition, the bioavailability and metabolism of major strawberry phytochemicals as well as their actions in combating many pathologies, including cancer, metabolic syndrome, cardiovascular disease, obesity, diabetes, neurodegeneration, along with microbial pathogenesis have been reviewed, with a particular attention to human studies.

Chemopreventive and Therapeutic Effects of Edible Berries: A Focus on Colon Cancer Prevention and Treatment.

Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed to their high content of phytochemicals and to their relevant antioxidant properties. In vitro and in vivo studies have demonstrated that berries and their bioactive components exert therapeutic and preventive effects against colon cancer by the suppression of inflammation, oxidative stress, proliferation and angiogenesis, through the modulation of multiple signaling pathways such as NF-κB, Wnt/β-catenin, PI3K/AKT/PKB/mTOR, and ERK/MAPK. Based on the exciting outcomes of preclinical studies, a few berries have advanced to the clinical phase. A limited number of human studies have shown that consumption of berries can prevent colorectal cancer, especially in patients at high risk (familial adenopolyposis or aberrant crypt foci, and inflammatory bowel diseases). In this review, we aim to highlight the findings of berries and their bioactive compounds in colon cancer from in vitro and in vivo studies, both on animals and humans. Thus, this review could be a useful step towards the next phase of berry research in colon cancer.

AMPK as a new attractive therapeutic target for disease prevention: The role of dietary compounds

AMPK is a serine/threonine protein kinase that has the function of maintaining the balance between ATP production and consumption in most eukaryotic cells. It plays a relevant role in regulating cellular metabolism, preserving cellular energy homeostasis, and is involved in many other cellular processes as well as metabolic ones, including cell cycle regulation and endothelial and vascular relaxation. Recently, the effects of naturally occurring compounds able to prevent and treat diseases through AMPK activation have attracted the attention of many researchers. Among such compounds, flavonoids found in natural sources, like quercetin, genistein, epigallocatechins, resveratrol, have been proposed as AMPK activators. This review summarizes and updates the most recent findings concerning the mechanisms through which different dietary compounds, from plant foods, affect the AMPK pathway in healthy and pathological in vitro and in vivo models, paying particular attention to molecular mechanisms involved in diabetes, obesity, metabolic syndrome, cardiovascular disease and cancer.

Strawberry consumption improves aging-associated impairments, mitochondrial biogenesis and functionality through the AMP-activated protein kinase signaling cascade

Dietary polyphenols have been recently proposed as activators of the AMP-activated protein kinase (AMPK) signaling pathway and this fact might explain the relationship between the consumption of polyphenol-rich foods and the slowdown of the progression of aging. In the present work, the effects of strawberry consumption were evaluated on biomarkers of oxidative damage and on aging-associated reductions in mitochondrial function and biogenesis for 8weeks in old rats. Strawberry supplementation increased antioxidant enzyme activities, mitochondrial biomass and functionality, and decreased intracellular ROS levels and biomarkers of protein, lipid and DNA damage (P<0.05). Furthermore, a significant (P<0.05) increase in the expression of the AMPK cascade genes, involved in mitochondrial biogenesis and antioxidant defences, was also detected after strawberry intake. These in vivo results were then verified in vitro on HepG2 cells, confirming the involvement of AMPK in the beneficial effects exerted by strawberry against aging progression.

Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells

We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the “Alba” variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy.

The healthy effects of strawberry bioactive compounds on molecular pathways related to chronic diseases

It is generally accepted that a fruit and vegetable–enriched diet is favorable for human health. The consumption of strawberries, in particular, has been related to the maintenance of well‐being and the prevention of several chronic diseases, owing to the high contents of antioxidants and phytochemicals present in the fruit. Several biological effects have been explained through the total antioxidant capacity exerted by these bioactive compounds, but recently more intricate mechanisms have begun to be examined. In this context, it has been reported that strawberry phenolics are able to exert anti‐inflammatory, anticarcinogenic, antiproliferative, and antiatherosclerotic activities, acting on specific molecular pathways related to antioxidant defenses, metabolism, survival, and proliferation. The overall aim of this work is to discuss and update the cellular and molecular mechanisms recently proposed to clarify the effects of strawberry phenolics on human health, with particular attention to the most common chronic diseases, such as metabolic syndrome, cardiovascular disease, and cancer.