Studies On The Biological Effects And Metabolomics Of Some Endogenous Components In Aconiti Lateralis Radix Praeparata And Houttuyniae Herba

With the continuous development of the economy and society,as well as the continuous improvement of people’s living standards,more and more people are beginning to advocate nature,attach importance to health care and wellness.The dual-purpose substances for food and medicine are widely used in healthcare,treatment,and recuperation.But with the toxic side effects of dual-purpose substances for food and medicine has been reported,the safety of these substances is also receiving more and more widespread attention.Therefore,conducting toxicity assessment research on endogenous components in dual-purpose substances for food and medicine will have guiding significance for people’s rational use of these substances.In this paper,mesaconitine,an endogenous component of Aconiti Lateralis Radix Praeparata,and aristolactam FI,an endogenous component of Houttuyniae Herba,were selected as research objects to study their toxicity at the animal level.At the same time,the mechanism of their toxicity was preliminarily explored through urine metabonomics.The main research results are as follows:1.The 14-day acute toxicity of mesaconitine and glycyrrhizic acid were explored.The dosage of the mesaconitine administration group are as follows:male administration group（1.00 mg/kg,2.15 mg/kg,4.64 mg/kg and 10.0 mg/kg,respectively）,and female administration group（0.464 mg/kg,1.00 mg/kg,2.15 mg/kg and 4.64 mg/kg,respectively）.The dosage of glycyrrhizic acid in both male and female groups was 5.00 g/kg.The rats were orally administered at above-mentioned doses once The rats in the contral group were orally administered with equal volume of edible corn oil.The rats were observed for 14 consecutive days,and the organ coefficient,histopathological section and oxidative stress capacity were analyzed.The results showed that the LD₅₀of mesaconitine on male rats and female rats were about3.16 mg/kg and 1.26 mg/kg,respectively,and the LD₅₀of glycyrrhizic acid is>5.00g/kg.The results of histopathological analysis and oxidative stress capacity indicators showed that a certain dose of mesaconitine would cause damage to the liver of rats.Subsequently,the 28-day sub-acute toxicity of single and combined exposure to mesaconitine and glycyrrhizic acid were explored.Seventy SD rats were divided into seven groups each containing ten rats（half male and half female）.The seven groups were control group（corn oil）,low dose single exposure group of mesaconitine（0.16mg/kg mesaconitine）,medium dose single exposure group of mesaconitine（0.32mg/kg mesaconitine）,high dose single exposure group of mesaconitine（0.64mg/kg mesaconitine）,low dose combined exposure group（0.16mg/kg mesaconitine+0.32mg/kg glycyrrhizic acid）,medium dose combined exposure group（0.32mg/kg mesaconitine+0.64mg/kg glycyrrhizic acid）,and high dose combined exposure group（0.64mg/kg mesaconitine+1.28mg/kg glycyrrhizic acid）.The rats were orally administered with the above drugs continuously for 28 days.At the end of the experiment,the organ coefficient,histopathological section and serum biochemical indicators were analyzed.The results indicated that a certain dose of mesaconitine can cause damage to the heart and liver of rats.When mesaconitine is combined with glycyrrhizic acid,the damage can be significantly reduced,indicating that glycyrrhizic acid has a detoxifying effect on mesaconitine.2.Metabolomics study was conducted on the urine of rats exposed to single mesaconitine and its combination with glycyrrhizic acid.Seventy SD rats were divided into seven groups each containing ten rats（half male and half female）.The seven groups were group 1（corn oil）,group 2（0.16 mg/kg mesaconitine）,group 3（0.32 mg/kg mesaconitine）,group 4（0.64 mg/kg mesaconitine）,group 5（0.16 mg/kg mesaconitine+0.32 mg/kg glycyrrhizic acid）,group 6（0.32 mg/kg mesaconitine+0.64 mg/kg glycyrrhizic acid）,and group 7（0.64 mg/kg mesaconitine+1.28 mg/kg glycyrrhizic acid）.The rats were orally administered with the above drugs continuously for 28 days and then the urine of rats was collected.Urine metabolites were determined using Gas Chromatograph-Mass Spectrometer（GC-MS）.Determine urine metabolites using gas chromatography-mass spectrometry（GC-MS）,perform principal component analysis（PCA）and orthogonal partial least squares discriminant analysis（OPLS-DA）,and screen for differential metabolites.Relating metabolic pathways were analyzed using metabo Analyst 5.0 software and KEGG database.The results showed that mesaconitine may affect the glycerolipid metabolism,galactose metabolism,starch and sucrose metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,and pentose phosphate pathway in the liver.However,when mesaconitine is combined with glycyrrhizic acid,the impact on the pentose phosphate pathway and glycerolipid metabolism decreased.Therefore,glycyrrhizic acid can to some extent regulate metabolic disorders caused by mesaconitine.3.The 28-day sub-acute toxicity of aristolactam FI in Houttuyniae Herba was explored.Forty SD rats were divided into four groups each containing ten rats（half male and half female）.The four groups were control group（corn oil）,low dose group（2.10 mg/kg aristolactam FI）,medium dose group（4.20 mg/kg aristolactam FI）,high dose group（8.40 mg/kg aristolactam FI）.The rats were orally administered with the above drugs continuously for 28 days.At the end of the experiment,the organ coefficient,histopathological section and serum biochemical indicators were analyzed.The results indicate that a certain dose of aristolactam FI can cause damage to the liver of rats and the heart of rats.High dose of aristolactam FI can also cause certain damage to the kidney of rats.4.Metabolomics study was conducted on the urine of rats exposed to aristolactam FI.Forty SD rats were divided into four groups each containing ten rats（half male and half female）.The four groups were control group（corn oil）,low dose group（2.10 mg/kg aristolactam FI）,medium dose group（4.20 mg/kg aristolactam FI）,high dose group（8.40 mg/kg aristolactam FI）.The rats were orally administered with the above drugs continuously for 28 days and then the urine of rats was collected.Urine metabolites were determined using Gas Chromatograph-Mass Spectrometer（GC-MS）,perform principal component analysis（PCA）and screen for differential metabolites.Relating metabolic pathways were analyzed using metabo Analyst 5.0software and KEGG database.The results showed that aristolactam FI may affect the pentose phosphate pathway,biosynthesis of unsaturated fatty acid,fatty acid degradation and other metabolic pathways,which have a certain impact on the liver,heart,and kidneys.