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PP-49

Anti-hyperglycemic and Bacteroides ovatus-modulating effects of

galactomannans from Cordyceps militaris and Trigonella foenum-graecum

enhanced by microbial transformation and cordycepin co-administration

1
1
5,6
2,3
3,4
Ching-Yi Lu, Wen-Yu Hsieh, Hui-Kang Liu, Mei-Kuang Lu, Shoei-Sheng Lee,
Chia-Chuan Chang*
,1

1 School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan
2 Biomedical Industry Ph.D. program, National Yang Ming Chiao Tung University, Taipei
11221, Taiwan
3 Natural Research Institute of Chinese Medicine, Taipei 10050, Taiwan
4 Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 10031, Taiwan
5 School of Chinese Medicine, National Yang Ming Chiao Tung University, Taipei 11221,

Taiwan
6 Traditional Chinese Medicine Glycomics Research Center, National Yang Ming Chiao Tung
University, Taipei 11221, Taiwan
* E-mail: chiachang@ntu.edu.tw

Abstract
Regulation of gut microbiota by polysaccharides is a promising strategy for the treatment of
metabolic disorders, such as diabetes. Galactomannans have been reported to exhibit anti-
diabetic and immunomodulatory effects. Therefore, this study evaluated the interaction between
galactomannans and specific gut microbe and their in vitro activities in order to find their
biological potentials. Isolation of two galactomannan-rich herbs, Trigonella foenum-graecum
(TF) and Cordyceps militaris (CM & CF), gave a total of twenty-three purified polysaccharides.
Among these, two (CF-1b03 and TF-5; 2.4- and 2.1- fold in GLP-1 secretion, respectively) and
one (CM-1a02, with an EC50 = 0.76 μM against DPP-4) polysaccharides demonstrated
significant in vitro anti-hyperglycemia-related effects. Therefore, polysaccharides with diverse
linkages (CM-1a02 & CF-1b03) had better anti-hyperglycemia-related activities. Moreover, all
three polysaccharides promoted the growth of Bacteroides ovatus (a representative gut microbe
for the digestion of galactomannans) about 1.5-fold, and one polysaccharide (CM-1a02)
remarkably induced the production of short-chain fatty acid (2~5-fold). The same microbe was
used to partially digest these polysaccharides. One oligosaccharide, TF_BO, demonstrated
similar activities to those of the most potent polysaccharides. Molecular docking confirmed the
DPP-4 active site, providing structural insight into its mode of action. In addition, co-
administration of cordycepin with CM-1a02 or CF-1b03, enhanced the DPP-4 inhibition. This
work highlights the therapeutic potential of galactomannans have in the treatment of
hyperglycemia.

Keywords: Fenugreek; Cordyceps militaris; Galactomannans; Gut microbiota; Anti-diabetic
effects