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

Abstract

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-Ͼ Ͼ256 mg/l) and MR (Ͼ Ͼ256 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.

Effect of Resveratrol on <i>Helicobacter pylori</i>-Induced Interleukin-8 Secretion, Reactive Oxygen Species Generation and Morphological Changes in Human Gastric Epithelial Cells

“…13,14) Several studies have reported the anti-H. pylori activity of herbal medicines and the chemical constituents therein. [15][16][17] Furthermore, anti-adhesion activity against H. pylori binding to gastric epithelial cells has been proposed as a potential therapeutic strategy to prevent H. pylori colonization which is an initial step of the infection. 18) Resveratrol, firstly described to be the content of weed Polygoumum cuspidatum, is highly abundant in red grapes and reasonably abundant in blueberries and peanuts.…”

Mallotus species from Vietnamese mountainous areas: phytochemistry and pharmacological activities

“…Among the isolated compounds, rottlerin (98), exhibited the most potent bactericidal activity with a minimal 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. This study thus revealed the potent in vitro anti-H. pylori activity of the ethanolic extract and of rottlerin, specially against CR and MR strains, which could be gainfully utilized for the development of novel antimicrobials to prevent H. pylori related disorders (Zaidi et al 2009). …”

“…Four phloroglucinol derivatives (kamalins) were isolated from M. philippinensis, including rottlerin (98) and isoallorottlerin (99) (Lounasmaa et al 1975). Isorottlerin (100) was also mentioned in M. philippinensis (Zaidi et al 2009). …”

“…The methanolic extract of M. peltatus showed also a significant dose-dependent anti-inflammatory and antioxidant activity at nontoxic concentrations (Chattopadhyay et al 2006). The chalcones isolated from the fruits of M. philippinensis, mallotophilippens C, D and E (89-91) Isorottlerin M. philippinensis Zaidi et al (2009) inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) gene expression by a murine macrophage-like cell line (RAW 264.7), which was activated by lipopolysaccharide and recombinant mouse interferon-c (IFN-c). Furthermore, they downregulated cyclooxygenase-2 gene, interleukin-6 gene and interleukin-1b gene expression.…”

Untitled

“…Kamala 5, 7-dihydroxy-8-methyl-6-prenylflavanone, 3'-prenylrubranine, red compound, isorottlerin, rottlerin 50 .…”