Sadia Afrin

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.

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.

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.

Lipid Accumulation in HepG2 Cells Is Attenuated by Strawberry Extract through AMPK Activation

Regulation of lipid metabolism is essential for treatment and prevention of several chronic diseases such as obesity, diabetes, and cardiovascular diseases, which are responsible for most deaths worldwide. It has been demonstrated that the AMP-activated protein kinase (AMPK) has a direct impact on lipid metabolism by modulating several downstream-signaling components. The main objective of the present work was to evaluate the in vitro effect of a methanolic strawberry extract on AMPK and its possible repercussion on lipid metabolism in human hepatocellular carcinoma cells (HepG2). For such purpose, the lipid profile and the expression of proteins metabolically related to AMPK were determined on cells lysates. The results demonstrated that strawberry methanolic extract decreased total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglycerides levels (up to 0.50-, 0.30-, and 0.40-fold, respectively) while it stimulated the p-AMPK/AMPK expression (up to 3.06-fold), compared to the control. AMPK stimulation led to the phosphorylation and consequent inactivation of acetyl coenzyme A carboxylase (ACC) and inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the major regulators of fatty acids and cholesterol synthesis, respectively. Strawberry treatment also entailed a 4.34-, 2.37-, and 2.47-fold overexpression of LDL receptor, sirtuin 1 (Sirt1), and the peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α), respectively, compared to control. The observed results were counteracted by treatment with compound C, an AMPK pharmacological inhibitor, confirming that multiple effects of strawberries on lipid metabolism are mediated by the activation of this protein.

Strawberry-Tree Honey Induces Growth Inhibition of Human Colon Cancer Cells and Increases ROS Generation: A Comparison with Manuka Honey

Honey is a natural product known to modulate several biological activities including cancer. The aim of the present study was to examine the phytochemical content and the antioxidant activity of Strawberry tree (Arbutus unedo) honey (STH) and its cytotoxic properties against human colon adenocarcinoma (HCT-116) and metastatic (LoVo) cell lines in comparison with Manuka (Leptospermum scoparium) honey (MH). Several unifloral STH and MH were analyzed for their phenolic, flavonoid, amino acid and protein contents, as well as their radical scavenging activities. STH from the Berchidda area showed the highest amount of phenolic, flavonoid, amino acid and protein content, and antioxidant capacity compared to MH. Both STH and MH induced cytotoxicity and cell death in a dose- and time-dependent manner in HCT-116 and LoVo cells, with less toxicity on non-cancer cells. Compared to MH, STH showed more effect at lower concentrations on HCT-116 and LoVo cells. In addition, both honeys increased intracellular reactive oxygen species (ROS) generation. In HCT-116 cells, STH and MH induced similar ROS production but in LoVo cells STH induced a higher percentage of ROS compared to MH. Our results indicate that STH and MH can induce cell growth inhibition and ROS generation in colon adenocarcinoma and metastatic cells, which could be due to the presence of phytochemicals with antioxidant properties. These preliminary results are interesting and suggest a potential chemopreventive action which could be useful for further studies in order to develop chemopreventive agents for colon cancer.

Protective Effect of Strawberry Extract against Inflammatory Stress Induced in Human Dermal Fibroblasts

A protracted pro-inflammatory state is a major contributing factor in the development, progression and complication of the most common chronic pathologies. Fruit and vegetables represent the main sources of dietary antioxidants and their consumption can be considered an efficient tool to counteract inflammatory states. In this context an evaluation of the protective effects of strawberry extracts on inflammatory stress induced by E. coli LPS on human dermal fibroblast cells was performed in terms of viability assays, ROS and nitrite production and biomarkers of oxidative damage of the main biological macromolecules. The results demonstrated that strawberry extracts exerted an anti-inflammatory effect on LPS-treated cells, through an increase in cell viability, and the reduction of ROS and nitrite levels, and lipid, protein and DNA damage. This work showed for the first time the potential health benefits of strawberry extract against inflammatory and oxidative stress in LPS-treated human dermal fibroblast cells.

Strawberry (cv. Romina) Methanolic Extract and Anthocyanin-Enriched Fraction Improve Lipid Profile and Antioxidant Status in HepG2 Cells

Dyslipidemia and oxidation of low density lipoproteins (LDL) are recognized as critical factors in the development of atherosclerosis. Healthy dietary patterns, with abundant fruit and vegetable consumption, may prevent the onset of these risk factors due to the presence of phytochemical compounds. Strawberries are known for their high content of polyphenols; among them, flavonoids are the major constituents, and it is presumed that they are responsible for the biological activity of the fruit. Nevertheless, there are only a few studies that actually evaluate the effects of different fractions isolated from strawberries. In order to assess the effects of two different strawberry extracts (whole methanolic extract/anthocyanin-enriched fraction) on the lipid profile and antioxidant status in human hepatocellular carcinoma (HepG2) cells, the triglycerides and LDL-cholesterol content, lipid peroxidation, intracellular reactive oxygen species (ROS) content and antioxidant enzymes’ activity on cell lysates were determined. Results demonstrated that both strawberry extracts not only improved the lipid metabolism by decreasing triglycerides and LDL-cholesterol contents, but also improved the redox state of HepG2 cells by modulating thiobarbituric acid-reactive substances production, antioxidant enzyme activity and ROS generation. The observed effects were more pronounced for the anthocyanin-enriched fraction.