br Prospect It is apparent

Prospect It is apparent that the elucidation and establishment of the direct interaction of food nanoparticles with the lymphatic is a formidable undertaking. It requires concerted multidisciplinary approaches of biochemistry, immunology, physiology, histology, food science, colloid science, nanotechnology, etc. The efforts, however, will be worthwhile. Long existing puzzles will be solved, such as why most phytochemicals can take effects with little or no bioavailability [24]. A new supermolecular approach will be established to understand food health function, which is a model closer to the real food complex system than the single topotecan approach currently employed.
Introduction Citrus peel is rich in flavonoids including methylated derivatives such as polymethoxyflavones (PMFs). Flavonoids are typically found throughout the whole fruit whereas PMFs are found exclusively in the peels of Citrus genus, particularly in the peels of sweet oranges (Citrus sinensis) and mandarin oranges (Citrus reticulate). PMFs have been shown to exhibit a broad spectrum of biological activity including cancer prevention, inhibition of inflammation, and anti-tumor properties [1–4]. It has been suggested that the consumption of citrus fruits may prevent the development of certain human cancers. It is also commonly recognized that cancer induction can be prevented by certain food phytochemicals, and flavonoids in Citrus fruits and juices have been recognized as prominent cancer preventing agents [5,6]. Gold lotion (GL), made from the peels of 6 citrus fruits available in Japan, namely, navel oranges, citrus hassaku, citrus limon, citrus natsudaidai, citrus miyauchi and satsuma, was initially developed as a cosmetic product to protect skin from UV irradiation. Consumers later reported anecdotal evidence that GL possessed anti-cancer property based on topical application of GL to treat melanoma, and oral ingestion for prostate, lung and liver cancers. After two years (1984–1986) of safety evaluation, GL was found to be non-toxic by the Huntingdon Research Center in UK (Reports from Miyauchi Citrus Research Center). Subsequent chemical analysis of GL has revealed the abundant existence of flavonoids and PMFs, which stimulated us to further investigate its anti-inflammation and anti-cancer activity systematically in animal models. Previous research has shown that inflammation is causally linked to carcinogenesis and acts as a driving force in premalignant and malignant transformation of cells [7]. In the past two decades, mouse skin models have been developed to elucidate the mechanism of inflammation as it relates to tumor promotion and progression [8]. In skin, the epidermis is the main target for various initiators and promoters. In the mouse skin model of acute inflammation, TPA has been used as a potent tumor promoter. In addition to tumor promotion, TPA also causes responses in mouse skin such as arachidonic acid cascade and epidermal ornithine decarboxylase (ODC) induction [9,10]. Moreover, TPA also induces epidermal cell proliferation, recruits inflammatory cells, increases production of reactive oxygen species (ROS) leading to oxidative DNA damage, and reduces DNA repairing capability. More importantly, topical application of TPA to mice leads to edema and papilloma formation by enhancing the expression of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) [11]. Studies show that COX-2 and iNOS are important enzymes that mediate a majority of known inflammatory processes. Additionally, up-regulation of COX-2 and/or iNOS has been associated with the pathophysiology of certain types of human cancers as well as inflammatory disorders [12]. The mouse skin model has been used for decades as a reliable and conventional model for studying the mechanisms of carcinogenesis and modulation of sequential steps involved in the process [13]. Skin tumors can be induced by the sequential application of a sub-threshold dose of a carcinogen (initiation stage) followed by repetitive treatment with a non-carcinogenic promoter [14]. Topical application of TPA, the classical tumor promoter to mouse skin, has been shown to generate a number of biochemical alterations, changes in cellular functions, and histological changes leading to skin tumor promotion [15]. The changes that have exhibited the highest correlation with skin tumor-promoting activity of TPA include skin edema, epidermal hyperplasia, inflammation, proliferation and oxidative stress [16]. The skin changes have been defined as biomarkers of skin tumor promotion, and could be used to evaluate the potency of chemo-preventive agents against tumorigenesis [17,18].