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bioRxiv · 10.1101/2023.04.05.535784

Decoding the Cure-all Effects of Ginseng

Loo, S.·Kam, A.·Dutta, B.·Zhang, X.·Feng, N.·Sze, S. K.·Liu, C.-F.·Wang, X.·Tam, J. P.
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Abstract

Ginseng has been known as a "cure-all" traditional medicine to treat various illnesses and as an adaptogen to relieve stress. However, the known active compounds of ginseng are small-molecule metabolites. Here we report ginsentides, which are disulfide-dense, super-stable and cell-penetrating peptides with 31-33 amino acids, as active compounds and adaptogens that restore homeostasis in response to stress. Using mass spectrometry-based target identification and functional studies, we show that ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via the PI3K/Akt signaling pathway. Ginsentides were also found to alleviate 1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of the aorta, decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40, inhibit P2Y12 receptors, reduce platelet aggregation, and thrombus formation in the lung. Orally administered ginsentides were effective in anti-stress behavior using animal models of tail suspension and forced swimming tests. Together, these results suggest that ginsentides interact with multiple systems to restore homeostasis by reversing stress-induced physiological changes and provide new insights into the panacea medicinal effects of ginseng.

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Loo, S., Kam, A., Dutta, B., Zhang, X., Feng, N., Sze, S. K., Liu, C.-F., Wang, X., Tam, J. P.. 2023-04-06. Decoding the Cure-all Effects of Ginseng. https://doi.org/10.1101/2023.04.05.535784

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