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

Abstract

Abstract 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 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 (LD50) was 1.37 g / kg, while the maximum tolerance 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 number of mice writhing. Based on the above findings, 10 compounds, including songoramine (1), neoline (2), bullatine C (3), dihydroatisine (4), bullatine A (5), maltol (6), 15-O-acetylsongorine (7), 15-O-acetylsongoramine (8), songorine (9), and aldohypaconitine (10) were separated and identified from the alkaloid component of PAB. Compounds 4, 6, 8, and 10 were firstly separate from Aconitum. Finally, molecular docking to anti-inflammatory analgesic target protein was carried out. The results showed that the 10 compounds and target proteins had good binding capabilities, wherein 15-O-acetylsongoramine could interact with the key protein Akt1 of Pi3k-Akt pathway and adjust the downstream NF-κB critical pathway to play an anti-inflammatory analgesic effect.