# Phenolic Derivatives of Astragalus aitosensis with Selective MAO-B Inhibition and Mitochondrial Protection

## TL;DR

This study identifies new phenolic compounds in a rare Bulgarian plant that show potential for treating neurodegenerative diseases like Parkinson’s.

## Contribution

Discovery of two new and four previously unreported compounds in the genus Astragalus with selective MAO-B inhibition and mitochondrial protection.

## Key findings

- Five compounds, including maackiain, showed selective MAO-B inhibition, with maackiain reducing activity by 45%.
- Phytochemicals preserved glutathione levels and reduced lipid peroxidation in ex vivo brain models.
- Molecular docking and SAR analysis confirmed the compounds' binding to MAO-B and their structural features influencing activity.

## Abstract

Astragalus aitosensis, also known as Astracantha arnacantha (M. Bieb.) Podlech subsp. aitosensis (Ivanisch.) Réer & Podlech, a Bulgarian endemic species, was investigated for its phenolic profile and neuroprotective potential. A targeted extraction approach led to the isolation of 14 phytochemicals. According to our literature review, none of the isolated chemicals have been reported before for A. aitosensis. Two of them are previously undescribed molecules—an isomer of odoratin and 6-hydroxy-3-(2-hydroxy-4-methoxyphenyl)-7-methoxy-4H-1-benzopyran-4-one—and four of them had not been observed before our study in the genus Astragalus: 3′-methoxydaidzein, fujikinetin, sayanedine, and 6,4′-dimethoxy-7,2′-dihydroxyisoflavone. Five of the phytochemicals—maackiain, cajanin, onogenin, afrormosin, and sayanedine—exhibited selective inhibition of human monoamine oxidase-B (MAO-B), with maackiain reducing activity by 45%, nearing the effect of selegiline. The investigated phytochemicals also showed significant antioxidant and neuroprotective effects in ex vivo models using isolated rat brain synaptosomes, mitochondria, and microsomes, mitigating oxidative stress by preserving glutathione levels and reducing lipid peroxidation. Molecular docking confirmed favorable binding of active phytochemicals, particularly maackiain, within the MAO-B active site. Structure–activity relationship (SAR) analysis highlighted the role of specific substituents and fused-ring systems in MAO-B inhibition. This study expands our knowledge of the phytochemical diversity of A. aitosensis and supports the therapeutic relevance of its phenolic compounds in neurodegenerative disorders such as Parkinson’s disease.