Program

PO1-5-32

Oral administration of boschnaloside, a GLP-1 receptor activator from herbal medicine Boschniakia rossica (the northern groundcone), improved diabetic conditions and modulated incretin hormone levels in db/db mice

[Speaker] Hui-Kang Liu:1,2
[Co-author] Keng-Chang Tsai:1, Lie-Chwen Lin:1
1:National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taiwan, 2:Ph. D. Program in Clinical Drug Development of Chinese Herbal Medicine, College of Pharmacy, Taipei Medical University, Taiwan

Developing an oral glucagon like peptide-1 receptor (GLP-1R) agonist from small molecule is an attractive yet challenging task. Iridoid glycosides were previously found to activate GLP-1R. However, how it interacts with GLP-1R and the potential impact on endocrine hormones and islet functions deserve further investigation. By employing boschnaloside (Bos1), an iridoid glycoside isolated from Boschniakia rossica, our aims were as fellow: (1) to confirm Bos1 is a GLP-1R agonist. (2) to establish ligand-receptor pharmacophore with Bos1 mapping. (3) to evaluate the therapeutic effects of Bos1 on the glycemic control, the endocrine hormones, and the glucotoxicity against beta-cells After confirming that Bos1 is a GLP-1R agonist, pharmacophore mapping of boschnaloside reveals important hydrogen bound acceptor and hydrophobic domain features. We further demonstrated that oral administration of Bos1 to db/db mice for 4 weeks could reduce fasting blood sugar and HbA1c% below 200 mg/dl and 7%, respectively. The modulation of gut hormones and adiponectin occurred after Bos1 treatment and the modulation was affected by administration dosages. Finally, Bos1 administration improved beta-cell function against glucotoxicity. In conclusion, our results provided a novel approach for later oral GLP-1R agonist drug design and demonstrated that boschnaloside and derivatives could be effective anti-diabetic therapeutics.
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