**5.4. Grapes (***Vitis vinifera***)**

Grapes are one of the most valued conventional fruits worldwide. The grape is considered a source of unique and potentially useful medicinal natural products; they are also used in the manufacturing of various industrial products [75,76](Yadav and others 2009; Vislocky and Fernandez 2010). The main biologically active and well-characterized constituent from the grape is resveratrol, which is known for various medicinal properties in treating human dis‐ eases [75](Yadav and others 2009). Resveratrol was shown to be an irreversible (mechanismbased) inhibitor of CYP3A4 and a non-competitive reversible inhibitor for CYP2E1 in microsomes from rat liver and human liver cells containing cDNA-expressed CYPs [77,78] (Chan and Delucchi 2000; Piver and others 2001). Resveratrol is an electron-rich molecule with two aromatic benzene rings linked by an ethylene bridge. CYP3A-mediated aromatic hydroxylation and epoxidation of resveratrol are possible, resulting in a reactive p-benzo‐ quinone methide metabolite which is capable of binding covalently to CYP3A4, leading to inactivation and potential drug interactions.

quercetin and glycosylated xanthones such as mangiferin [92,93] Quercetin has been shown to possess antioxidant, antimicrobial, antitumor, antihypertensive, antiatherosclerosis, and anti-inflammatory properties [94]. In a series of studies, Rodeiro and others have shown the effects of mango on drug metabolizing enzymes and drug transporters [95, 96] They found that exposure of hepatocytes to mango extract produced a significant reduction (60%) in 7 methoxyresorufin-O-demethylase (MROD; CYP1A2) activity and an increase (50%) in 7 penthoxyresorufin-O-depentylase (PROD; CYP2B1) activity. This group also studied the effect of mangiferin on CYP enzymes and found that mangiferin reduced the activities of five P450s: POD (CYP1A2), midazolam 1'-hydroxylation (M1OH; CYP3A1), diclofenac 4'-hy‐ droxylation (D4OH; CYP2C6), S-mephenytoin 4'-hydroxylation (SM4OH), and chlorzoxa‐ zone 6-hydroxyaltion (C6OH; CYP2E1). Recently, mango and mango-derived polyphenols have been shown to potentially affect the activity of the multidrug transporter P-gp ABCB1 [97]. These findings suggest that mango and its components inhibit the major human P450 enzymes involved in drug metabolism and some transporters. The potential for drug inter‐

Fruit/Vegetable-Drug Interactions: Effects on Drug Metabolizing Enzymes and Drug Transporters

http://dx.doi.org/10.5772/48283

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Guava is an important food crop and medicinal plant in tropical and subtropical countries; it is widely used as food and in folk medicine around the world [98, 99]. A number of me‐ tabolites such as phenolics, flavonoid, carotenoid, terpenoid and triterpene have been found in this fruit. Extracts and metabolites of this plant, particularly those from the leaves and fruit, possess useful pharmacological activities [100]. There is only one report about the ef‐ fect of guava extracts on drug transport: guava extract showed a potent inhibitory effect on P-gp mediated efflux in Caco-2 cells. It was also found to inhibit efflux transport from seros‐ al to mucosal surfaces in the rat ileum [101]. This means that guava could interact with P-gp substrates such as digoxin, fexofenadine, indinavir, vincristine, colchicine, topotecan, and paclitaxel in the small intestine. For this reason, this fruit should be consumed with caution

Berries have been shown to have a positive impact on several chronic conditions including obesity, cancer, and cardiovascular and neurodegenerative diseases [102-104]. Like other fruits, raspberries contain micro- and macronutrients such as vitamins, minerals, and fiber. Their biological properties, however, have been largely attributed to high levels of various phenolic compounds, as well as the interactive synergies among their natural phytochemical components (e.g., ellagic acid, quercetin, gallic acid, anthocyanins, cyanidins, pelargonidins, catechins, kaempferol and salicylic acid). Raspberry or raspberry constituents have antioxi‐ dant and anti-inflammatory properties, and inhibit cancer cell growth [105-107]. Black rasp‐ berries (*Rubus coreanus)* have been called the "king of berries" for their superior health benefits, whereas black mulberry (*Morus nigra)* is most commonly used for its antioxidants properties and for its high bioactive content of phenolics, anthocyanins, and gallic acid. It has been shown that black raspberry and black mulberry are able to inhibit the human

actions with mango fruit should therefore be considered.

**5.8. Guava (***Psidium guajava* **L)**

by patients taking medicines.

**5.9. Raspberry (***Rubus* **spp.)**
