Anti-trypanosomal activity of diarylheptanoids isolated from the bark of Alnus japonica.

Abstract

The crude extract of Alnus japonica bark exhibited a strong effect on the growth of Trypanosoma brucei. Subsequent chromatographic separation resulted in the isolation of two novel diarylheptanoids, known as alnuside C (2) and alnuside D (3), and three known compounds, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3(R)-O-β-D-glucopyranoside (1), oregonin (4) and hirsutanone (5). The structures of the isolates were elucidated based on the use of extensive spectroscopic and chemical methods. Among the isolated diarylheptanoids, oregonin (4) (a major component of plant bark) and hirsutanone (5) exhibited potent in vitro inhibitory activity against T. brucei growth in the bloodstream with IC50 values of 1.14 and 1.78 μM, respectively. We confirmed that oregonin (4) and hirsutanone (5) were not toxic to human normal skin fibroblast cells (NB1RGB) and colon cancer cells (HCT-15) at a concentration of 50 μM; however, lower levels of toxicity were observed for leukemia cells. To determine the structure activity relationships of the isolated components, we performed Conformation Search and found that the 3-oxo function of the heptane chain in the diarylheptanoid molecule is required for their trypanocidal activity.

• Authors: Nguyen Huu Tung, Mitsuko Suzuki, Takuhiro Uto, Osamu Morinaga, Kofi D Kwofie, Naa Ammah, Kwadwo A Koram, Frederic Aboagye, Dominic Edoh, Taizo Yamashita, Yasuchika Yamaguchi, Takao Setsu, Shoji Yamaoka, Nobuo Ohta, Yukihiro Shoyama
• Journal: The American journal of Chinese medicine (Am J Chin Med) Vol. 42 Issue 5 Pg. 1245-60 ( 2014) ISSN: 1793-6853 [Electronic] Singapore
• PMID: 25178281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diarylheptanoids
• Plant Extracts
• Trypanocidal Agents

Topics

• Alnus
• Animals
• Cells, Cultured
• Colonic Neoplasms (pathology)
• Diarylheptanoids (chemistry, isolation & purification, pharmacology)
• Dose-Response Relationship, Drug
• Fibroblasts (drug effects)
• Humans
• In Vitro Techniques
• Leukemia (pathology)
• Plant Bark
• Plant Extracts (chemistry, pharmacology, toxicity)
• Skin (cytology)
• Structure-Activity Relationship
• Trypanocidal Agents
• Trypanosoma brucei brucei (drug effects, growth & development)
• Tumor Cells, Cultured