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Toxic And Active Material Basis Of Aconitum Sinomontanum Nakai Based On Biological Activity Guidance And Uplc-Q/Tof-Ms Technology

文献类型： 外文期刊

作者： Fan, Qin;Li, Yun;Hu, Fangdi;Dai, Hairong;Miao, Xiaolou;Zhang, Lijun;Shang, Xiaofei;Zhang, Lijun

作者机构：

关键词： Aconitum Sinomontanum; Nakai; Acute Toxicity; Antinociceptive; Anti-Inflammatory; Alkaloids; Uplc-Q/Tof-Ms

期刊名称： JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

ISSN： 0731-7085

年卷期： 2020 年 188 卷

页码：

摘要： Background: As a folk medicine, Aconitum sinomontanum Nakai (Ranunculaceae, Gaowutou, in Chinese) is used by traditional healers to treat many disorders, including pain and inflammatory diseases, but it exhibits the toxic side effects. This study aimed to obtain toxic extract parts from A. sinomontanum roots and to further evaluate the antinociceptive and anti-inflammatory effects of toxic extract parts on mice. This work also aimed to identify various chemical compositions of the toxic and active extract parts and evaluate the safety profile of this plant. Methods: Experimental drugs (petroleum ether, chloroform, ethyl acetate, n-butanol, alcohol and water extracts) were obtained through systematic solvent extraction from 95 % ethanol extract from A. sinomontanum roots. An acute toxicity test was conducted to compare the toxicity of different extracts administered at the maximum dose to screen a highly toxic extract. In pharmacodynamic activity analysis, the antinociceptive activity of the A. sinomontanum toxic extract was assessed using an acetic acidinduced abdominal writhing model and a hot plate test. Anti-inflammatory activity was assessed in terms of xylene-induced inflammation. Ultraperformance liquid chromatography-quadrupole time-offlight mass spectrometry (UPLC-QJTOF-MS) was performed to establish a chromatographic fingerprint and to identify various chemical components of the toxic and active extract. Results: Chloroform, water and n-butanol extracts elicited significant toxic effects and had LD50 of 89.65, 1805.40 and 24409.41 mg/kg, respectively. Antinociceptive and anti-inflammatory activities indicated that the chloroform extract significantly alleviated (p < 0.01) the pain induced by acetic acid with an inhibition rate of 44.7 % (5.9 mg/kg) and 50.4 % (17.7 mg/kg). The chloroform extract also significantly (p < 0.01) increased the latency time during the hot plate test. The latency time at 5.9 and 17.7 mg/kg increased from 15.6 +/- 4.1 s to 47.3 +/- 6.4 s and from 16.3 +/- 3.8 s to 49.8 +/- 7.6 s (p < 0.01), respectively, 2 h after treatment. In the inflammatory test, the chloroform extract significantly reduced (p < 0.01) the xylene-induced mouse ear oedema with an inhibition rate of 45.48 % (5.9 mg/kg) and 51.46 % (17.7 mg/kg), respectively. This result indicated that A. sinomontanum chloroform extract was also the active extract part of A. sinomontanum. Phytochemical analysis revealed the presence of alkaloids in the chloroform extract. A total of 30 compounds were detected, and 23 compounds, including lappaconine, ranaconidine, 8-O-acetylexcelsine, sinomontanine H, finaconitine, lappacontine, N-dacetyllappaconitine, ranaconitine and isolappaconitine, were identified. Conclusions: A. sinomontanum chloroform extract possesses antinociceptive and anti-inflammatory activities and exhibits significant toxic effects. Phytochemical analysis indicated that some alkaloids may be the main bioactive ingredient responsible for the toxicity and efficacy of A. sinomontanum. This work contributes to the determination of the safety of the medicinal use of A. sinomontanum roots. (C) 2020 Elsevier B.V. All rights reserved.

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