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Title: SELECTIVE GROWTH-INHIBITING EFFECTS OF COMPOUNDS IDENTIFIED IN TABEBUIA IMPETIGINOSA INNER BARK ON HUMAN INTESTINAL BACTERIA

Author
item PARK, BYEOUNG-SOO - SEOUL NAT'L UNIV., KOREA
item KIM, JUN-RAN - SEOUL NAT'L UNIV., KOREA
item LEE, SUNG-EUN - SEOUL NAT'L UNIV., KOREA
item KIM, KYOUNG SOON - SEOUL NAT'L UNIV., KOREA
item Takeoka, Gary
item AHN, YOUNG-JOON - SEOUL NAT'L UNIV., KOREA
item KIM, JEONG-HAN - SEOUL NAT'L UNIV., KOREA

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/23/2004
Publication Date: 1/29/2005
Citation: Park, B.-S., Kim, J.-R., Lee, S.-E., Kim, K.-S., Takeoka, G.R., Ahn, Y.-J., Kim, J.-H. 2005. Selective Growth-Inhibiting Effects of Compounds Identified in Tabebuia impetiginosa Inner Bark on Human Intestinal Bacteria. Journal of Agricultural and Food Chemistry. Vol. 53, p. 1152-1157.

Interpretive Summary: The intestinal microbiota in healthy subjects remains relatively constant but is known to be greatly influenced by physical, biological, chemical, environmental or host factors. Accordingly, alterations to the microbiota may cause abnormal physical conditions or disease. Infectious diseases caused by clostridia have a broad spectrum of clinical severity that ranges from mild outpatient illness to sudden death. Among the clostridia, C. perfringens has been associated with sudden death, toxicity and gastrointestinal disease in man. On the contrary, bifidobacteria are often taken as useful indicators of human health under most environmental conditions because they play important roles in metabolism such as amino acid and vitamin production, aid in the defense against infections, are associated with longevity, exhibit antitumor activities, pathogen inhibition and immunopotentiation. Accordingly, it would be desirable to both inhibit the growth of potential pathogens such as clostridia and increase the number of bifidobacteria in the human gut. Selective growth promoters for bifidobacteria or inhibitors of harmful bacteria are especially important for human health because intake of these materials may normalize disturbed physiological functions, resulting in the prevention and treatment of various diseases caused by pathogens in the gastrointestinal tract. Recently, attention has been focused on the inhibitory roles of natural compounds in suppressing the carcinogenic and mutagenic effects of clostridia. Plants are potential alternatives to synthetic antibacterial agents because they exhibit selective growth inhibition effects on Clostridium sp. with no inhibitory effects on the other human intestinal bacteria and may be applied to humans in the same way as other commercially available antibiotics. In the present study, taheebo extract exhibited growth inhibition of C. paraputrificum and C. perfringens. The growth-inhibiting constituents of T. impetiginosa inner bark were identified as anthraquinone 2-carboxylic acid and lapachol with species selective activity. These compounds had potent growth-inhibiting activities against C. paraputrificum and C. perfringens, whereas no growth inhibition was observed against five lactic acid-producing bacteria (B. adolescentis, B. bifidum, B. infantis, L. acidophilus, and L. casei). However, growth of B. longum was slightly inhibited. This is the first report on the growth-inhibiting activity of anthraquinone 2-carboxylic acid and lapachol against C. paraputrificum and C. perfringens. As naturally occurring growth-inhibiting agents, anthraquinone-2-carboxylic acid and lapachol, could be useful as new preventive agents against various diseases caused by harmful intestinal bacteria such as clostridia. Further work is necessary to establish whether this activity is exerted in vivo after consumption of taheebo by humans.

Technical Abstract: The growth-inhibiting activity of anthraquinone-2-carboxylic acid and lapachol (identified in the inner bark of Tabebuia impetiginosa) toward 10 human intestinal bacteria was evaluated by using a paper disk diffusion bioassay and compared to those of seven lapachol congeners (1,4-naphthoquinone, naphthazarin, menadione, lawsone, plumbagin, juglone, and dichlone) as well as two commercially available antibiotics, chloramphenicol and tetracycline. Anthaquinone-2-carboxylic acid exhibited very strong growth inhibition of Clostridium paraputrificum at 1 µg/disk while 100 µg/disk of lapachol was needed for moderate growth inhibition of the same organism. These two isolates exhibited weak inhibition of Clostridium perfringens and Escherichia coli at 100 µg/disk while no adverse effects were observed on the growth of Bifidobacterium adolescentis, B. bifidum, B. infantis, Lactobacillus acidophilus, and L. casei at 1000 µg/disk. Both compounds caused weak inhibition of B. longum at 10 to 1000 µg/disk. Tetracycline and chloramphenicol showed strong to moderate growth inhibition of two clostridia, E. coli, and two lactobacilli at 10 µg/disk. The antibiotics did not affect the growth of B. bifidum, and B. infantis at 1000 µg/disk while moderate to weak activity was observed toward B. adolescentis at 100 mg/disk. Structure-activity relationships indicate that a methyl group in the C-2 position of 1,4-naphthoquinone derivatives might play an important role in antibacterial activity. Naturally occurring Tabebuia bark-derived compounds, particularly lapachol, merit further study as potential antibacterial agents or as lead compounds.