The rapid discovery, target preparation, and bioactivity evaluation of 5-lipoxygenase and acetylcholinesterase inhibitors from the flowers of Astragalus membranaceus (Fisch) Bge
Bibliographic record
Abstract
This study investigated the bioactive components of Astragalus membranaceus flowers that target 5-lipoxygenase (5-LOX) and acetylcholinesterase (AChE), enzymes linked to inflammation and Alzheimer’s disease. Using receptor-ligand affinity ultrafiltration combined with HPLC-MS, seven active compounds were identified with purities exceeding 98 %. Among them, 9,10-dimethoxy-pterocarpan-3-O-β-D-glucoside (DMPTG) exhibited the strongest dual inhibition of 5-LOX and AChE, with IC50 values of 5.69 × 10⁻⁵ mol/L and 3.97 × 10⁻⁵ mol/L, respectively. Enzyme-catalyzed reaction kinetics confirmed the reversible inhibition of both enzymes. Extraction conditions were optimized using response surface methodology, achieving a target compound yield of 5.96 % under simplified parameters. Efficient isolation was accomplished using semi-preparative liquid chromatography and high-speed countercurrent chromatography, overcoming the limitations of single techniques. Molecular docking and dynamics simulations revealed stable interactions between DMPTG and the target enzymes, supported by strong binding energies and minimal structural fluctuations. Biological assays demonstrated that DMPTG significantly protected glutamate-injured PC12 cells by modulating the expression of apoptosis-related proteins, restoring Bcl-2 levels, and reducing Bax and Bad expression. This regulatory effect underscores the neuroprotective potential of the compound. This comprehensive strategy integrates advanced screening, extraction, and bioactivity evaluation, providing a robust foundation for developing dual-target inhibitors. The findings highlight the industrial and pharmacological value of A. membranaceus flowers in treating inflammation and neurodegenerative disorders. • A binary target was employed to screen for highly bioactive components. • A “two in one” extraction and targeted preparation methodology was established. • A complex separation protocol was optimized for high yield and purity. • Compounds with potent molecular and cellular level bioactivities were identified. • A quaternary bioactivity evaluation process helps avoid false-positive results.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".