Astratides: Insight into bioactive compounds in Chinese Medicine from Astragalus membranaceus (#154)
Plant-derived cysteine-rich peptides (CRPs) are natural products with high resistance to thermal, acid and enzymatic degradation. Among which, plant defensins are cationic peptides consisting of 45 to 54 amino acids, which belong to a large superfamily of antimicrobial peptides [1]. Therapeutically, they are reported to be antifungical therapeutics and potential anticancer drugs. Astragalus membranaceus is a medicinal herb has been used in traditional Chinese medicine (TCM) in treatment of weakness, wounds and allergies. Currently the compounds be responsible for this crude drug has not been elucidated. In our program of TCM screening, results indicated that CRPs are widely distributed and postulated to be the bioactive components. Herein, we report the discovery and characterization of a plant defensin, astratide bM1 from the root of A. membranaceus. Proteomic analysis revealed that it contains four disulfide bonds, and have >50% sequence similarity with other reported defensins. Stability assays showed that bM1 is resistant to thermal, chemical and proteolytic degradation. Antifungal susceptibility assays revealed that bM1 possesses potent anti-fungal activity against four phyto-pathogenic fungi at submicromolar level. Phylogenetic analysis reveals that bM1 together with a group of plant defensins discovered from Fabaceae family, contain a unique CXCXC motif at the C-terminal, which may contribute to their functions. Together, the study gives insight into the discovery of bioactive compounds in Chinese Medicine as exemplified by astratide. In addition, it reveals that the hyper-stable CRP could be used as a potential scaffold for developing orally active peptidyl therapeutics.
- Tam, J.P., et al., Antimicrobial Peptides from Plants. Pharmaceuticals (Basel), 2015. 8(4): p. 711-57.