| Objective:To study the toxic side effects of water extraction, alcohol extractioncomponent from Menispermum dauricum DC. accompanied by the effect ofanti-inflammatory, and to investigate its mechanism, as well as to provide experimentalbasis for revealing the “toxicity–efficacy” relationship of toxic drugs.To research and evaluate the “dose-time-toxicity” relationship of toxic target organs atpharmacodynamic dose, in order to provide basis for the elucidation of the toxicalmechanism, and reveal the range of toxic dose, as well as establish foundation for thequality control of Menispermum dauricum DC. and its preparation of manufacturetechnology and the safe application of Menispermum dauricum DC.Methods:The extract technology of water extraction, alcohol extraction componentfrom Menispermum dauricum DC. were screened based on the literature; its acute toxicityof intragastric administration in mice was researched by the classical acute toxicity testmethod; the croton oil induced ear edema model and granuloma model were established tostudy the anti-inflammatory effects of water extraction, alcohol extraction component fromMenispermum dauricum DC. the side effects during the administration were observed. Theresearch on “dose-time-toxicity” relationship of acute and chronic toxicity caused by singleor multiple intragastric administration to mice or rats were carried on, and then the level ofALT, AST in serum were tested, and pathohistological changes were observed with opticalmicroscope or electron microscope.Results:The Menispermum dauricum DC. has certain toxicity, which is consistentwith the clinical adverse effect. Alkaloids are the main chemical components inMenispermum dauricum DC. as well as the material basis of the expression of efficacy andtoxicity. The content of dauricine was determined by HPLC, its concentration was waterextraction>alcohol extraction component. The intragastric administration of water extraction and alcohol extraction component can cause fairly acute toxicity to mice. The allcomponents、water extraction components in Menispermum dauricum DC. are unable tomake LD50, MLD、MTD results calculated in accordance with crude drug content wererespectively15.96g·kg-1·d-1、92.12g·kg-1·d-1. The LD50and its95%confident limit ofalcohol extraction components was75.116（72.389-77.885）g·kg-1. The croton oil inducedear swelling and agar induced granulomas were inhibited after ig water extractioncomponent and ethanol extract components repeatedly to mice. With the dose increased theeffect of inhibition being stronger, which shows a certain dose dependent relationship. Theeffects of swelling inhibition: alcohol extraction component>water extraction component,the level of PGE2in serum was significantly reduced; the activity of ALT、AST in serumincreased, and the contents of Cr, BUN increased too. The level of SOD, MDA, NO, NOS,GSH and GSH-PX in serum shows significant changes. The liver and kidneys ratioincreased as the liver pathological changes obviously. The above indicators of granulomamice increased greater than the ear swelling model mice. The target organ is theliver.Compared with the control group, ALT, AST level in serum of water extractedcomponents and alcohol extraction components are peaked after4hours’ administration.The water extracted components of （46.05～61.40） g· kg-1and alcohol extractedcomponents of （8.45～15.02） g·kg-1have obvious damage to the liver organization, andALT, AST in serum increased significantly with the dose increasing.Multiple intragastricadministration of water extracted components and alcohol extracted components fromMenispermum dauricum DC. with dosage （1.2～7.2）g·kg-1、（1.2～26.1）g·kg-1for7days may induce chronic hepatotoxical injury in mice the level of ALT, AST in serum andhepar index increased significantly after3d and the toxical expression reach to extremefrom3d to7d after administration.Conclusion:The acute toxicity of different components in Menispermum dauricumDC. on mice is: alcohol extraction components>water extraction components> allcomponents. It shows that the toxic components mainly present in the alcohol-soluble parts.The total alkaloids are the major alcohol–soluble components, which is consistent with theliterature. The alcohol extraction components and water extraction components haveobvious anti-inflammatory effects. Its anti-inflammatory mechanisms related to reducinginflammatory mediator released and inhibiting oxidative damaged. Chronic or acutehepatotoxical injury can be induced by multiple or single intragastric administration of alcohol extraction components and water extraction components from Menispermumdauricum DC. with certain dosage and the level of ALT,AST in serum have a most obviouschange. The change showed significant “dose-time-toxicity” relationship in a certain range.Per oxidation injury is one of the main hepatotoxical mechanisms. The research canprovide experimental basis for the elucidation of target and mechanism of toxicity andestablish foundation for the quality control of Menispermum dauricum DC. optimization ofmanufacture technology and the safe application of Menispermum dauricum DC. |
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