Potent Bactericidal Constituents from Mallotus philippinensis against Clarithromycin and Metronidazole Resistant Strains of Japanese and Pakistani Helicobacter pylori

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  • Zaidi Syed Faisal Haider
    Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama Department of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama
  • Yoshida Ikuko
    Division of Laboratory, Toyama University Hospital
  • Butt Farhana
    Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Center
  • Yusuf Muhammed Aasim
    Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Center
  • Usmanghani Khan
    Department of Basic Clinical Sciences, Faculty of Eastern Medicine, Hamdard University
  • Kadowaki Makoto
    Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama
  • Sugiyama Toshiro
    Department of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama

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In the quest for potent anti-Helicobacter pylori agents, we found 70% EtOH extract of Mallotus philippinensis (LAM.) MUELL. (MPM) with strong bactericidal activity at the concentration of 15.6—31.2 mg/l against eight H. pylori strains. Further fractionation and purification of 70% EtOH extract of MPM led to the isolation of 5 compounds, namely 5,7-dihydroxy-8-methyl-6-prenylflavanone (1), 3′-prenylrubranine (2), red compound (3), isorottlerin (4), and rottlerin (5) which were elucidated on the basis of nuclear magnetic resonance and mass spectroscopy. Among the isolated compounds, rottlerin exhibited most potent bactericidal activity with minimum bactericidal concentration (MBC) value of 3.12—6.25 mg/l against several clinical H. pylori isolates including Japanese and Pakistani strains, nine clarithromycin resistant (CR), and seven metronidazole resistant (MR) strains. Minimum inhibitory concentration (MIC) values of CR (8—>256 mg/l) and MR (>256 mg/l) strains were analyzed by E test. Moreover, the clarithromycin resistant strains were evaluated for A2143G and A2144G point mutations of 23s rRNA gene to correlate the MBC values with mutation type. Our results revealed the potent in vitro anti-H. pylori activity of MPM and rottlerin, specially against CR and MR strains, which could be gainfully utilized for the development of novel antimicrobials to prevent H. pylori related disorders.

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