INTESTINAL IMMUNE SYSTEM-MODULATING ACTIVITY THROUGH PEYER'S PATCH OF FLAVONOID GLYCOSIDE PURIFIED FROM CITRUS UNSHIU PEEL

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Abstract

ABSTRACT

After methanol extract (CUP-2) with intestinal immune system-modulating activity through Peyer's patch was prepared from Citrus unshiu peel, CUP-2C-2–2 was purified by solvent partitioning, silica gel 60 and Sephadex LH-20 chromatographies (Pharmacia Biotech, Uppsala, Sweden). Ultraviolet-visible spectral, 1H/13C-NMR, and fast atom bombardment mass spectrometry analyses suggested that CUP-2C-2–2 was identified to flavonoid glycoside (5,7,3′,4′-tetrahydroxyflavone linked by glucose) with molecular weight of 725 Da. When the active chloroform layer (CUP-2C) fractionated from CUP-2 was orally administered in mice, the potent activity was observed on the fifth day of 2.0 g/kg body weight/day (1.59-fold of the saline control). Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-6 contents in the culture medium of Peyer's patch cell were also significantly increased (1.80- and 2.20-fold, respectively) compared with the saline control. These results suggested that flavonoid glycoside from C. unshiu peel might stimulate Peyer's patch and produce the multifunctional hematopoietic growth factors such as GM-CSF and IL-6 followed by proliferation of bone marrow cells.

PRACTICAL APPLICATIONS

C. unshiu peel is widely used as the traditional herbal prescription or tea in East Asia. Since the early 1980s, many researchers have been studying the physiologically active substances from citrus fruit peel for the purpose of exploring their more valuable utilization. Current work is focused on low-molecular-weight constituents with intestinal immune system modulating activity through Peyer's patch from citrus peel. It is clearly shown that the purified active substance (CUP-2C-2–2) is characterized as flavonoid glycoside. When the active fraction (CUP-2C) was orally administered in mice, production of hematopoietic growth factors from Peyer's patch cells was stimulated and proliferation of bone marrow cells was induced by these growth factors influxed via systemic circulation. This conclusion supports the rationality of citrus peels as a potential source of biological response modifier for food supplementation or functional foods.

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