| Objective: Traditional Chinese medicine is the treasure of the our nation. Theunderstanding of toxic Chinese medicine has been recorded in the first of our countrypharmacy monograph "Shen Nong’s herbal classic" as Shennong tasted all kinds of herbsand encountered seventy kinds of toxic substances in a single day which was detoxicatedby tea. Such understanding of toxic Chinese medicine could been found in “Zhouli” as“when Emperor was sick to drink medicine, minister need foretaste the herb to judgewhether it was poisonous; when the elder was sick to drink medicine, the younger needforetaste the herb to judge whether it was poisonous; if the doctor was not familiar withherbal medicine, acupuncture, and pulse tactic, we should not take the herbs heprescribed.” The offspring doctors had a detailed record of toxic drugs also on the basis ofit. But due to historical conditions, microscopic changes and mechanisms of toxicitycaused by the toxicity of traditional Chinese medicine has been unclear.The previous research results of our group showed that cold and hot medicinal herbshad the effects of regulatory role on the level of blood sugar and T3, T4and otherindicators of rats. Based drug effect-poison duality properties, we selected four uncontested medicine including cold medicine Coptis chinensis Franch, Gardeniajasminoides Ellis, and hot medicine Aconitum carmichaeli Debx, Curculigo orchioidesGaertn to carry out the research in which the effects and mechanisms of the fourmedicines on the pancreas and thyroid gland study and mechanisms will be studied anddiscussed.to indentify the poisonous effects of cold medicine Coptis chinensis Franch,Gardenia jasminoides Ellis, and hot medicine Aconitum carmichaeli Debx, Curculigoorchioides Gaertn from the point of view of overall, blood biochemistry, pathology andmolecule, which will provide reference for clinical use. To Explore a toxicity research ideawhich meet modern pharmacology but also reflects the characteristics of traditionalChinese medicine theory of TCM.Methods: Four herbs decoction will be prepared. Normal Wistar rats will be gavagedfor40d. The index such as weight of rats, liver and idney coefficient, function of liver andkidney, pathology, expression of the INS protein, the expression of mRNA and proteinNIS and IAPP, and the expression of TPO mRNA with methods of the whole bloodbiochemistry, tissue morphology, immunohistochemistry, real-time quantitative PCR.Statistical analysis of the data and the results will be finished with the SPSS19.0statisticalsoftware. And the poisonous effects of the four Chinese herbs mentioned above on theliver, kidney, pancreas, and thyroid gland will be identified, and the mechanisms of thepoisonous effects will be discussed.Results: After applying the medicine40d, the overall change significantly in rats.abnormal behavior can not be observed in the control group of rats. Cold medicine groupof rats are more thin, the color of hair more polluted compared to the control group. Anddecreased sensitivity to external stimuli, and occasionally diarrhea situation can beobserved in cold medicine group. There are downward trend in weight in the group of hotChinese medicines with the stool density increased. PTU group rats were skinny with dirty coat, and their sensitivity to external stimuli decreased. And the STZ rats were more thin,dirty coat, with eating more, drinking more and more urine, weight loss, a typicalsymptoms of2type of diabetes. The performance of the corresponding Chinese herbalcold and consistent trend reflected the effect of cold and heat characteristics oftraditional Chinese medicine. Blood test results of biochemical parameters changes on the40thday after application of herbs, regardless of heat or cold medicine, may result in acorresponding change in the biochemical indicators.From the perspective of relevant indicators of liver function, four herbs did not causesignificant changes in ALT and AST levels, and only Gardenia jasminoides Ellis caused arise of TBiL level. Renal function test results show, except berberine group, the rest ofChinese medicine group could cause decreased plasma Cr levels; UA levels did notchange significantly; lower levels of BUN and UREA could obtained in cold medicinegroup, otherwhile these indexes rose in hot Chinese medicine group. Compared to changesof indicators of liver and kidney function, blood sugar regulation and thyroid-relatedfunctions related indicators showed to be convergent in a decreasing trend on the40thday after the application of these herbs, whether hot or cold medicine. This shows thatfrom the perspective of blood biochemistry of the four herbs, compared to the liver andkidney function indicators, endocrine toxicity index changes were more significant andtypical.While the results from pathology showed that the structure of liver, kidney, pancreas,and thyroid gland appeared different levels of damage on the40thday after the applicationof these herbs. The results mentioned above suggested that normal indicators of liver andkidney function in toxicity studies does not mean there is no structural damage to the liverand kidney. This provides a useful reference for the study of the toxicity of these fourherbs.The results of pathology showed that there was no obvoius damage in thyroid gland. Due to the longer time span of application of these traditional Chinese medicine, the finalresults were shown to be lower plasma thyroid function indicators. Thyroid andpancreas-related mRNA and protein expression of test results show that four herbs maylead to reduced expression of IAPP mRNA and protein, lower expression level of proteinof NIS, which is relevant with the level reduction of T3and T4. In addition to thesechanges, the levels of TRH and TSH showed to be decreased. This showed that thepoisonous site of these herbs on hypothalamic-pituitary-thyroid axis was in thehypothalamus.Conclusion: The four herb decoction administered for40days may lead to changesin function and structure of liver and kidney in normal rats. The islet and thyroid functionshowed to be damaged to normal rats, which indicated there are poisonous effects onpancreas thyroid in some extend. But this damaging effects were less compared todamages of pancreas and thyroid with STZ and PTU, respectively.The damage of microstructure of rat liver, kidney, islet, and thyroid caused by thefour kinds of decoction intragastric administration for40days was not obvious, whichshowed that the damage was in mild.The expression of inhibitory effect of four Chinese herbal medicines on pancreaticendocrine function may be related to the inhibition of INS mRNA and protein expression,the promoting of IAPP mRNA and protein expression, and the inhibited PDX1mRNA;inhibition of four Chinese herb on thyroid endocrine function may be related to theinhibition of NIS mRNA and protein expression and inhibition of TPO mRNA expression. |
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