Human milk oligosaccharides (HMOs) belong to a group of multifunctional glycans that are abundantly present in human breast milk. While health effects of neutral oligosaccharides have been investigated extensively, a lot remains unknown regarding health effects of acidic oligosaccharides, such as the two sialyllactoses (SLs), 3′sialyllactose (3′SL), and 6′sialyllactose (6′SL). We utilized Caenorhabditis elegans (C. elegans) to investigate the effects of SLs on exercise performance. Using swimming as an endurance‐type exercise, we found that SLs decrease exhaustion, signifying an increase in endurance that is strongest for 6′SL. Through an unbiased metabolomics approach, we identified changes in energy metabolism that correlated with endurance performance. Further investigation suggested that these metabolic changes were related to adaptations of muscle mitochondria that facilitated a shift from beta oxidation to glycogenolysis during exercise. We found that the effect of SLs on endurance performance required AMPK‐ (aak‐1/aak‐2) and adenosine receptor (ador‐1) signaling. We propose a model where SLs alter the metabolic status in the gut, causing a signal from the intestine to the nervous system toward muscle cells, where metabolic adaptation increases exercise performance. Together, our results underline the potential of SLs in exercise‐associated health and contribute to our understanding of the molecular processes involved in nutritionally‐induced health benefits.
Predictions on bioactivities of herbs and herbal compounds could greatly aid drug development, but require integration of available information on herb and compound effects from various databases. We present Herb-paths, an integrated network connecting information on health-beneficial effects of herbs and herbal constituents. The statistical models included in Herb-paths allow for the calculation of the association strength of herbal (constituents) with health-beneficial effects, for both known and novel effects, and give insight into the major bioactive compounds and molecular mechanisms driving the effects. Herb-paths' predictions were tested and validated using a case-study of Panax notoginseng and its derived medicinal extract of Panaxatriol saponins (PTS), used in traditional Chinese medicine to treat stroke and other cardiovascular and cerebrovascular thromboembolic (CCT) disorders. Results showed that Herb-paths predicted known and novel associations between PTS/Notoginseng and CCT phenotypes and diseases, including stroke. Predicted novel associations, such as MoyaMoya disease, are promising putative leads for treatment with PTS/Notoginseng, to be tested in further studies.
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