Yong-Sun Park

Regulation of apoptosis by modified naringenin derivatives in human colorectal carcinoma RKO cells

Flavonoids are micronutrients that are widely detected in foods of plant origin and have been ascribed pharmacological properties. Several biological functions of flavonoids have been thus far identified, whereas there currently exists a lack of evidence to support the relationship between the structure‐activity relationship and apoptosis‐inducing activity. In an attempt to determine the importance of the OH group or substitution of the 5‐ or 7‐carbon in the diphenylpropane skeleton of flavonoids, we selected 14 different flavonoids with different structures, particularly with regard to the 5‐ or 7‐carbon, and found that naringenin treatment caused a slight decrease in the cell viability of the human colorectal carcinoma RKO cells. Next, in order to characterize the effects of specific substitutions of the 7‐carbon of naringenin on apoptosis‐regulatory activities, and in an attempt to develop anti‐proliferative flavonoid derivatives that would be more effective against colon cancer, we originally synthesized several modified naringenin derivatives (MNDs) including 7‐O‐benzyl naringenin (KUF‐1) and 7‐O‐(m‐metoxybenzyl) naringenin (KUF‐2). Treatment with KUF‐1 or KUF‐2 resulted in significant apoptosis‐inducing effects concomitant with losses in mitochondrial membrane potential, caspase activation, intracellular ROS production, and sustained ERK activation. Our data show that KUF‐1 or KUF‐2 regulate the apoptosis of RKO cells via intracellular ROS production coupled with the concomitant activation of the ERK signaling pathway, thereby implying that hydroxylation or substitution at C7 is critical for the apoptosis‐inducing activity of flavonoids. J. Cell. Biochem. 104: 259–273, 2008.

Human glycine α1 receptor inhibition by quercetin is abolished or inversed by α267 mutations in transmembrane domain 2

Quercetin, one of the flavonoids, is a compound of low molecular weight found in fruits and vegetables. Besides its antioxidative effect, quercetin also shows a wide range of diverse neuropharmacological actions. However, the cellular mechanisms of quercetins actions, especially on ligand-gated ion channels and synaptic transmissions, are not well studied. We investigated the effect of quercetin on the human glycine alpha1 receptor channel expressed in Xenopus oocytes using a two-electrode voltage clamp technique. Application of quercetin reversibly inhibited glycine-induced current (I(Gly)). Quercetins inhibition depends on its dose, with an IC(50) of 21.5+/-.2 microM. The inhibition was sensitive to membrane voltages. Site-directed mutations of S267 to S267Y but not S267A, S267F, S267G, S267K, S267L and S267T at transmembrane domain 2 (TM2) nearly abolished quercetin-induced inhibition of I(Gly). In contrast, in site-directed mutant receptors such as S267 to S267I, S267R and S267V, quercetin enhanced I(Gly) compared to the wild-type receptor. The EC(50) was 22.6+/-1.4, 25.5+/-4.2, and 14.5+/-3.1 microM for S267I, S267R and S267V, respectively. These results indicate that quercetin might regulate the human glycine alpha(1) receptor via interaction with amino acid residue alpha267 and that alpha267 plays a key role in determining the regulatory consequences of the human glycine alpha1 receptor by quercetin.

Antibacterial activity of a novel flavonoid, 7-O-butyl naringenin, against methicillin-resistant Staphylococcus aureus (MRSA)

The objective of this study was to evaluate the antibacterial activity of a novel flavonoid, 7-O-butyl naringenin, as well as natural flavonoids (quercetin, naringenin) against methicillin-resistant Staphylococcus aureus (MRSA). 7-O-butyl naringenin showed great anti-MRSA, with a MIC (minimum inhibitory concentration) value of 0.625 mM. The number of cells treated with 25 μM 7-O-butyl naringenin was reduced by 5.2 log CFU/mL compared with the control (DMSO). The result indicated that 7-O-butyl naringenin was more effective than the two natural flavonoids against MRSA, and may have potential as a novel therapeutic agent for MRSA infections.

Antimicrobial Effect of 7-O-Butylnaringenin, a Novel Flavonoid, and Various Natural Flavonoids against Helicobacter pylori Strains

The antimicrobial effect of a novel flavonoid (7-O-butylnaringenin) on Helicobacter pylori 26695, 51, and SS1 strains and its inhibitory effect on the urease activity of the strains were evaluated and compared with those of several natural flavonoids. First, various flavonoids were screened for antimicrobial activities using the paper disc diffusion method. Hesperetin and naringenin showed the strongest antimicrobial effects among the natural flavonoids tested, and thus hesperetin and naringenin were selected for comparison with 7-O-butylnaringenin. The antimicrobial effect of 7-O-butylnaringenin was greater than that of the hesperetin and naringenin. H. pylori 51 was more sensitive to 7-O-butylnaringenin (2 log reduction of colony forming units, p < 0.05) than the other two strains at 200 μM. 7-O-Butylnaringenin also showed the highest inhibitory effect against urease activity of H. pylori. Morphological changes of H. pylori 26695 treated with these flavonoids indicated that both hesperetin and 7-O-butylnaringenin at 200 μM damaged the cell membranes.