Combination chemoprevention with grape antioxidants

Abstract

Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resveratrol, quercetin, kaempferol, catechin, epicatechin, and anthocyanins (cyanidin and malvidin) constitute more than 70% of the grape polyphenols. Therefore, these have been relatively well-studied for their chemopreventive effects against a variety of cancers. While a wealth of information is available individually on cancer chemopreventive/anti-proliferative effects of resveratrol and quercetin, limited information is available regarding the other major constituents of grape. Studies have also suggested that multiple grape antioxidants, when used in combination, alone or with other agents/drugs show synergistic or additive anti-proliferative response. Based on strong rationale emanating from published studies, it seems probable that a combination of multiple grape-ingredients alone or together with other agents could impart ‘additive synergism’ against cancer.

Smart Combinations of Bioactive Compounds in Fruits and Vegetables May Guide New Strategies for Personalized Prevention of Chronic Diseases

“…Over the last decade, it has become clear that phytochemicals are capable of modulating enzymes and signaling kinases resulting in effects on multiple genes and signaling cascades, which form the base for the underlying molecular mechanisms of disease prevention. This is achieved by interaction of the phytochemicals with specific molecular targets, thereby triggering different signal transduction processes at various levels (Table ) …”

“…The main underlying hypothesis is that disease preventive actions that result from the combined effect of different compounds affecting multiple mechanisms of action is more effective as compared to the effects induced by an individual compound activating only one single molecular mechanism. In the following years, many studies have been published on additive and synergistic effects of combinations of phytochemicals . Most of the literature is based on in vivo and in vitro studies focusing on the effects of resveratrol in combination with other phytochemicals.…”

“…Main results include restauration of disturbed energy metabolism and inflammatory responses, and reduced tumorigenesis . A more recent overview by the same group, presents the results from studies on combination effects of grape phytochemicals and show that multiple ingredients of grapes are likely to provide synergistic chemopreventive effects, both in vivo and in vitro, and particularly at the level of radical scavenging, modulation of gene, and protein expression in relevant genes for disease prevention, inhibition of cell proliferation and increased apoptosis, and a reduction of tumor growth and frequency …”

“…This is achieved by interaction of the phytochemicals with specific molecular targets, thereby triggering different signal transduction processes at various levels (Table 2). [23,[31][32][33][37][38][39][40][41][42][43][44]…”

Influence of processing and storage of integral grape juice (Vitis labrusca L.) on its physical and chemical characteristics, cytotoxicity, and mutagenicity in vitro

“…Then, integral grape juice is rich in flavonols, anthocyanins, phenolic acids, hydroxycinnamic and hydroxybenzoic acids, resveratrol, glucose, fructose, amino acids, polypeptides, proteins, tartaric acid, malic acid, citric acid, vitamins such as thiamine, riboflavin, niacin, ascorbic acid, and inositol, and mineral elements such as potassium, sodium, calcium, magnesium, phosphorus, iron, manganese, copper, zinc, lithium, and rubidium (Melo et al, 2016;Nassiri-Asl and Hosseinzadeh, 2016;Singh et al, 2016).…”