| Since ancient times,China has a tradition of"medicine and food have the same origin"and"the substances are both medicine and food".Traditional dual-purpose substances for medicine and food can not only be used as food,but also have good curative effect.With the improvement of people’s living standards and the deepening of the concepts of health and health preservation,dual-purpose substances for food and medicine have been widely used,and their quality and safety have also attracted much attention.Studies have shown that some dual-purpose substances for food and medicine will produce some toxic and side effects when they are consumed for a long time or in large doses.For example,it was reported that anthraquinones in Polygonum multiflorum could cause liver injury.The damage of emodin and rhein to liver is related to the phosphorylation of mitochondrial function and the abnormal transmission of TCA cycle signaling pathway.And long-term use of licorice has adverse reactions such as premature delivery and premature in children.At present,there is still a lack of studies on the toxicity assessment of endogenous components in food and drug dual-use substances,especially the effects of combined exposure of multiple components on organisms.Based on this,this paper selected the main endogenous components in some typical dual-use substances,such as Polygonum multiflorum,Semen Cassiae,Curcuma longa and Radix Puerariae（including TSG,emodin,aurantio obtusin,rhein,curcumin and puerarin）as the research objects.At the animal level,integrate a variety of analytical information to explore the biological effects of their harm to vital target organs under single or combined exposure conditions,providing a certain scientific basis for guiding people to reasonably use the above dual-purpose substances.The main research results are as follows:1.The main endogenous components emodin and TSG in Polygonum multiflorum were selected as the research objects to explore their biological effects under single and combined exposure.SPF SD rats were used as experimental animals,half male and half female,and the oral toxicity experiment was carried out for 28 days.Low,medium and high doses of emodin(1.24,49.6 and 99.2 mg·kg-1),TSG(12.4,496 and 992 mg·kg-1)and the doses of combined exposure groups（corresponding emodin dose+TSG dose）were intragastrically administered,respectively.The control groups were given equal volume of PEG 400.The results showed that compared with the control groups,there were some differences in serum biochemical indexes,including ALT,AST,T-bil,UA,UREA,CK,HBDH and LDH.The changes of serum content in high dose groups were more obvious.By histopathological analysis,medium and high doses of emodin could cause glomerular damage in rats,and some glomerular balloons disappeared.Low,medium and high doses of TSG groups and combined exposure groups had no obvious renal lesions.The medium and high doses of emodin caused congestion in the central vein of the liver or slight disorder of the liver plate in rats.Low,medium and high doses of TSG caused liver cell necrosis in rats.High dose combined exposure caused focal hepatocyte necrosis and small focal hepatocyte proliferation in male rats.And detection of oxidative stress in liver and kidney of rats,the contents of INOS and MDA in the liver of male rats exposed to low,medium and high doses of TSG and high dose of combined exposure group were increased significantly;the contents of INOS and MDA in the liver of female rats with low and high doses of TSG were also significantly higher.The contents of INOS and LPO in the kidney of male rats in the medium and high dose groups of emodin were significantly higher than those in the control group,and the content of i NOS in the kidney of female rats in the medium dose group of emodin was significantly higher,too.Rats were orally exposed to 1.24 mg·kg-1emodin,12.4mg·kg-1 TSG and combined exposure for 90 days.The results implied that compared with the control groups,there was no significant damage to the heart tissue of rats in each dose group,but it had a certain effect on the liver and kidney of rats.2 Rhein and aurantio-obtusin,the main endogenous components of Semen Cassiae,were selected as the research objects to explore their biological effects under single and combined exposure.SPF SD rats were used as experimental animals,half male and half female,and the oral toxicity experiment was carried out for 28 days.Low,medium and high doses of rhein(75,150 and 300 mg·kg-1),aurantio-obtusin(4,25 and 50 mg·kg-1)and the doses of combined exposure groups（corresponding rhein dose+aurantio-obtusin dose）were intragastrically administered,respectively.The control groups were given equal volume of corn oil.The results showed that compared with the control groups,there were some differences in serum biochemical indexes,including ALT,AST,T-bil,UA,UREA,CK,HBDH and LDH.The levels of ALT,AST and UA in serum of rats in high dose groups increased significantly.Histopathological analysis showed that multiple focal spot necrosis occurred in the liver of male and female rats exposed to high dose rhein,high dose hesperidin and high dose combined exposure.High dose of rhein reduced individual glomerular volume of kidney in male rats,but had little effect on female rats.Medium dose of aurantio-obtusin reduced the volume of individual glomeruli in male rats,and high dose of aurantio-obtusin caused atrophy of individual glomeruli in male and female rats.In the combined high-dose group,some glomerular atrophy was observed in male and female rats.All drug administration groups had little effect on the heart of male and female rats.The results of oxidative stress analysis of rat liver and kidney indicated that the contents of MDA and INOS in liver of rats in all high dose groups were significantly increased.The content of INOS in the kidney of male rats exposed to high dose rhein,medium and high doses aurantio-obtusin and high dose combined exposure was significantly higher,and the content of LPO in the kidney of male rats exposed to high dose aurantio-obtusin and combined exposure groups was significantly higher than that of the control group.The contents of INOS and LPO in kidney of female rats exposed to high dose of aurantio-obtusin and the content of LPO in kidney of female rats exposed to high dose of combined exposure group were significantly increased.The above results showed that single and combined exposure to high doses of rhein and aurantio-obtusin caused serious damage to liver and kidney of rats.3.Based on curcumin,the main endogenous component of Curcuma,as the research object,to explore its biological effects.SPF SD rats were used as experimental animals,half male and half female,and the oral toxicity experiment was carried out for 28 days.Low,medium and high doses of curcumin(10.35,258.75 and517.50 mg·kg-1)were administered by intragastrically administered,respectively.The control groups were given equal volume of PEG 400.The results showed that compared with the control groups,there were some differences in serum biochemical indexes,including ALT,AST,T-bil,UA,UREA,CK,HBDH and LDH.The T-bil content in the serum of male and female rats in the high-dose curcumin groups was significantly higher,and the UA content in the serum of female rats in the high-dose groups was significantly increased,too.Through histopathological analysis,it was found that the liver of male and female rats with medium dose and high dose of curcumin had hyperemia,and the heart had scattered eosinophilia and a little capillary hyperemia.High dose of curcumin could make glomerulus disappear in female rats,and cause glomerular fibrosis and focal glomerular hyperemia in male rats.The results of oxidative stress analysis of rat liver and kidney showed that the content of i NOS in the kidney of rats in the high dose curcumin groups was significantly higher,and the content of LPO in the kidney of female rats in the high dose curcumin group was also significantly higher.The results indicated that high dose curcumin had a serious effect on rat kidney.4.Based on puerarin,the main endogenous component of Radix Puerariae,as the research object,to explore its biological effects.SPF SD rats were used as experimental animals,half male and half female,and the oral toxicity experiment was carried out for 28 days.Low,medium and high doses of puerarin(37.20,1488.00 and2976.00 mg·kg-1)were intragastrically administered,respectively.The control groups were given equal volume of PEG 400.The results showed that compared with the control groups,there were some differences in some biochemical indexes of serum in the drug administration groups,including ALT,AST,T-bil,UA,UREA,CK,HBDH and LDH.The contents of ALT and AST in serum of male rats in high dose group were significantly higher than those in control group,and the contents of UA and UREA in serum of rats in high dose groups were significantly higher.Histopathological analysis showed that low,medium and high doses of puerarin had little effect on the heart of rats;high dose puerarin caused focal degeneration,necrosis of hepatocytes and individual glomerular atrophy in male rats.The analysis of oxidative stress ability showed that high dose puerarin significantly increased the contents of i NOS and MDA in the liver of male rats,and the contents of i NOS in the kidney of high dose rats and LPO in the kidney of high dose female rats.The above results show that puerarin has little effect on rat heart,while high dose puerarin has certain damage to rat liver and kidney. |
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