Chemical composition, pharmacodynamic activity of processed Aconitum brachypodum Diels., and molecular docking analysis of its active target

Aconitum brachypodum Diels. (AB.) is a plant of Aconitum L . The dried roots of AB have analgesic and anti-inflammatory activity. However, the processing is required to reduce toxicity before use because of its high toxicity. Studies on the toxicity, pharmacodynamics, and chemical composition of processed Aconitum brachypodum Diels. PAB. are still lacking at present. In this study, the composition changes of AB and PAB were determined by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UPLC-QE-Orbitrap-MS). The intensity of diester alkaloids was greatly reduced, while the monoester alkaloids were significantly increased. An acute toxicity experiment was used to evaluate the toxicity differences between AB and PAB, while the acetic acid-induced writhing pain experiment and croton oil-induced ear edema experiment were applied to evaluate the analgesic and anti-inflammatory properties. The acute toxicity test of AB showed that the median lethal dose (LD 50 ) was 1.37 g/kg, while the maximal feasible dose (MFD) of PAB was 30.0 g/kg. It was apparent that the toxicity of PAB was significantly reduced. The alkaloid component of PAB could significantly inhibit the mice’s ear edema and significantly reduce the writhing times of mice. Based on the above findings, ten compounds, including songoramine (1), neoline (2), bullatine C (3), dihydroatisine (4), bullatineA (5), maltol (6), 15- O -acetylsongorine (7), 15- O -acetylsongoramine (8), songorine (9), and aldohypaconitine (10) were isolated and identified from the alkaloid component of PAB. Compounds 4, 6, 8, and 10 were firstly separate from Aconitum brachypodum Diels. Finally, molecular docking to anti-inflammatory analgesic target protein was carried out. The results indicated that 15- O -acetylsongoramine has a strong binding ability with target proteins, which may interact with the target protein Akt1 of phosphatidylinositol-3-kinase/serine-threonine kinase (Pi3k/Akt) pathway, while, adjust the downstream nuclear factor kappa B (NF-κB) signaling pathway to play an anti-inflammatory analgesic effect. Graphical Abstract UPLC-QE-Orbitrap-MS, acute toxicity, analgesia, anti-inflammatory experiment, and molecular docking analysis were made to speculate the toxicity and efficacy of processed Aconitum brachypodum