Morin is a
flavonoid present in fruits and Chinese herbs. Based on in vitro studies,
morin has been reported to show various beneficial
biological activities. However, there is growing evidence that conjugative metabolism is central to the
biological fate of
flavonoids. Therefore, the
biological effects of
morin could be primarily determined by its conjugated metabolites. In this study, the effects of
morin and its
sulfates/
glucuronides on the production of
nitric oxide (NO) and
cytokines from
lipopolysaccharide (LPS)-activated macrophages were individually investigated and compared. The results indicated that the 50% NO production was inhibited from LPS-activated RAW 264.7 cells by 1.25 mM
morin and 1.25 microM
morin sulfates/
glucuronides. Meanwhile, the 50% inhibition concentration (IC50) values of
morin and
morin sulfates/
glucuronides in activated peritoneal macrophages were 1.5 mM
morin and 1.5 microM
morin sulfates/
glucuronides, respectively. In addition, 30% of the
tumor necrosis factor-alpha (
TNF-alpha) and 35% of the
interleukin (IL)-12 productions from activated macrophages were inhibited by 2-2.5 mM
morin and 2-2.5 microM
morin sulfates/
glucuronides, respectively. Furthermore, phagocyte activities in the peripheral blood of those for mice dosed with
morin for two months were about 65-70% of controls. Lower NO production and reduced macrophage phagocytic activities corresponded to LPS-resistant state. These findings indicated that
morin may exhibit anti-inflammatory activity and reduced the incidence of experimental
septic shock through decreasing the functions of macrophages and may regulate immune response through modulating the
cytokine profiles. Therefore,
morin could be a promising therapeutic candidate for inflammatory disease due to the strong activity of its metabolites.