Phytochemical profiling and acetylcholinesterase inhibitory activity of fifteen Iranian Astragalus species: towards new sources of astragalosides

Astragalus L. (Fabaceae), a genus rich in bioactive triterpene saponins like astragalosides (ASTs), is recognized for its diverse biological activities. The present study aimed to quantify ASTs I, II, and IV in root extracts of fifteen Iranian Astragalus species. The acetylcholinesterase inhibitory activity of root extracts from astragaloside-rich species was also evaluated, and their neuroprotective effects were estimated using molecular docking analysis. Additionally, total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity in root and aerial parts of species were evaluated. A. michauxianus and A. gossypinus yielded the highest ASTs I and IV content (2.49 ± 0.03 and 6.27 ± 0.89 mg/g DW, respectively), among Astragalus species examined in this study. TPC and TFC of roots were higher than that of aerial parts for all species, and the highest TPC and TFC were obtained for A. verus (12.12 ± 1.05 mg GAE/g DW) and A. floccosus (115.48 ± 1.54 mg RUE /g DW), respectively. Furthermore, the aerial parts extracts of A. remotijugus and A. aduncus showed the best free radical scavenging ability with the lowest IC50 values (28.83 ± 0.64 and 28.86 ± 0.64 μg/mL, respectively), while for A. gossypinus and A. floccosus, the best scavenging ability (IC50) was displayed in root extracts (23.32 ± 0.79 and 23.45 ± 0.74 μg/mL, respectively). The highest AChE inhibitory activity was exhibited by A. aduncus with the lowest IC50 (200 ± 14.02 µg/ mL), followed by A. gossypinus and A. michauxianus. Moreover, molecular docking studies revealed that astragaloside I exhibits the strongest binding affinity to AChE (− 7.610 kcal/mol), forming multiple stabilizing interactions within the active site, suggesting its superior inhibitory potential compared to astragalosides II and IV. These findings highlight the potential of selected Astragalus species as valuable resources for pharmaceutical applications and provide a foundation for future breeding programs aimed at maximizing ASTs production.