Processing Principle To Attenuate Toxicity Of Qiang Medicine Aconitum Pendulum Busch

Qiang medicine is the treasure of Chinese ethnomedicine, which processes many characteristic therapies and unique medicinal materials during the struggle against diseases for ages. Aconitum pendulum as one commonly used Qiang medicine is the radices of A. pendulum Busch. and A. flavum Hand.-Mazz., which have effects of expelling wind and moist, and relieving pains, and is widely used to treat wounds, rheumatoid arthritis, and so on. Because of intense toxicity, the plant material must be processed before use. The principles of processing are still unknown, such as the chemical changes and toxicity variation after processing.Objective:Based on the literatures and on-site investigations, the principles of Qiang medicine A. pendulum's processing have been studied in terms of changes of changes of chemical compositions and toxicological test.Method:1. Literature and on-site investigation were adapted to study the processing methods of A. pendulum in Qiang and Tibetan medicine and medication experience;2. Column chromatography and TLC, was used to isolate alkaloids from raw and processed A. pendulum and IR, ESI-MS,1H-NMR, 13C-NMR, HMBC, HSQC and NOESY for identification..3. HPLC was emplyoed to compare the compositions and contents of alkaloids between raw materials and different processed A. pendulum, and to compared alkaloidal contents with different parts of the plants of A. pendulum.4. Cardiac toxicity and myocardial cell toxicity tests were applied to evaluate the toxicity of raw materials, different processed products and alkaloids.Result:1. Among the processing methods--boiling method, sand speculation law, steaming method, roasting with branches method, boiling method was mostly used procedure.2. Fourteen components were isolated from raw materials,12 of which were identified as deoxyaconine,3-acetylaconitine, aconitine, secoaconitine, N-deethyl-deoxyaconine,N-deethyl-3-acetylaconitine,15a-OH-neoline,8-acetyl-15-hydroxy-neol ine, neoline,14-benzoyl-8-O-methylaconine, benzoylaconine, andβ-sitosterol. Secoaconitine, N-deethyl-deoxyaconine, N-deethyl-3-acetylaconitine were new ones. Twelve components were isolated from the material processed by boiled method and 2 components from the material processed by sand fried method.3. The compositions and contents of alkaloids conspicuously changed before and after processing. After processing, the contents of deoxyaconine, 3-acetylaconitine and aconitine decreased, and benzoylaconine increased obviously. Beyzoyldeoxyaconine, polyschistine-D,16-epi-pyroaconitine,16-epi-pyrodeoxy-aconitine did not exist in raw materials.4.①The acute toxicity tests revealed that was the toxicity order as follows:raw materials> boiled processed products> steaming processed products> sand fried processed products.②The toxicity from cardiac toxicity tests were raw materials>processed products.③Through cytotoxicity experiments, total alkaloids of raw materials and boiled products had a certain inhabition of the survival of cadiocyte (p<0.05), only when the concentration was 100μg/ml.5. The attenuated way of processing law are:1) Aconitine was converts into benzoylaconine, and benzoylaconine was converts into aconine.2) Deoxyaconitine was converts into dehydrobenzoylaconine.3) 3-acetylaconitine wasconverts into polyschistine-D.4) Aconitine was converts into 16-epi-pyroaconitine.5) Deoxyaconitine was converts into 16-epi-pyrodeoxyaconitine.6. The chemical components were similar in different parts of A. pendulum.Conclusive:Three processed products of A. pendulum. were much safer than raw materials, as shown by cardiac toxicity and cytotoxicity experiments. The attenuated way of processing law are different.1) After processing of boiling method or steaming method, the contents of deoxyaconine,3-acetylaconitine and aconitine decreased, and partly by way of ester hydrolysis into smaller toxic alkaloids,such as benzoylaconine, aconine, dehydrobenzoylaconine, polyschistine-D.2) In sand speculation law, except these channels, there are some alkaloids through high-temperature oxidation into less toxic alkaloids, Aconitine convert into 16-epi-pyroaconitine; deoxyaconine convert into deoxy16-epi-pyrodeoxyaconitine. Innovation:1. According to chemical compositions and toxicological test, the principles of Qiang medicine A. pendulum were elucidated.2. Three new compounds-secoaconitine, N-deethyl-deoxyaconine, N-deethyl-3-acetylaconitine were isolated from Aconitum pendulum Busch. And it is 15a-OH-neoline,8-Acetyl-15-hydroxy-neoline,14-Benzoyl-8-O-methylaconine, and so on that were firstly isolated from this plaint.