| Backgrounds:There is a herb pair Sargassum(Haizao,HZ)and Glycyrrhizae Radix et Rhizoma(Gancao,GC),one of the so-called "eighteen antagonistic medicaments" in TCM documents,indicating that the two herbs shouLd not be applied simuLtaneously.Whereas,the herb pair HZ-GC has been widely used in HYD for the treatment of thyroid dysfunction,galactophore hyperplasia and ovarian cyst.In recent decades,a number of literature research,clinical study and animal experiment have been carried out to evaluate the efficacy and safety of the combination.However,their respective curative effects and mechanisms remain controversial and there is limited scientific evidence to establish the safety and efficacy of these herbal products.Haizao Yuhu Decoction has been widely used to treat thyroid-related diseases especially goiter with few side effects in TCM,including herb pair Sargassum(Haizao,HZ)and Glycyrrhizae Radix et Rhizoma(Gancao,GC),as one of "eighteen antagonistic medicaments" The two different species of Sargassum,Sargassum fusiforme(Yangqicai,Sf)and Sargassum pallidum(Haihaozi,Sp),are not clearly differentiated in clinical use,so that herb pair Sf-GC and Sp-GC couLd show different effect and toxicity,which might related to the antagonistic medicament.Objects:To compare the effect and toxicity of Sf and Sp of different Haizao Yuhu Decoction groups,we proposed the present study to evaluate anti-goitrous effect,toxicity systematically and clarify the underlying mechanism of the two different species of Sargassum in HYD in PTU-reduced goiter rats at molecuLar,celluLar and whole level.Methods:1.We have compared the acute toxicity of Sargassum pallidum,Sargassum fusiforme,Radix Glycyrrhiaze and different Haizao Yuhu Decoction groups in mice.Different groups were prepared,and comparisons were made in accordance with the classical acute toxicity test methods.2.And then we investigated the anti-goitrous effect(FT3,FT4,thyroid weight and histological changes),toxicity(liver/renal function parameters)and clarify the potential underlying mechanism(TSH,TRH,Tg mRNA and TPO mRNA,CYP3A1/3A2/2E1 mRNA)of the two different species of Sargassum in HYD(HYDf and HYDp)in PTU-reduced goiter rats.Results:1.The acute toxicity of different groups in mice is:Sargassum pallidumda>Sargassum pallidum with Radix Glycyrrhiaze>the Haizao Yuhu Decoction removed Radix Glycyrrhiaze(Sargassum pallidumda)>the Haizao Yuhu Decoction(Sargassum pallidumda)>the Haizao Yuhu Decoction removed Sargassum and Radix Glycyrrhiaze>the Haizao Yuhu Decoction removed Radix Glycyrrhiaze(Sargassum fusiforme).Conclusion:Sargassum pallidumda,Sargassum pallidum with Radix Glycyrrhiaze have low toxitity to mice with LD50 of 35.73g/kg body weight,LD50(6)of 40.83g/kg body weight.Sargassum fusiforme has no toxitity to mice.2.The resuLts demonstrated that both HYDf and HYDp couLd exhibit anti-goitrous effect through alterations in hypothalamus-pituitary-thyroid(HPT)axis and inhibition the TPO gene expression,there are no difference in the anti-goitrous effects between the two different species of Sargassum application in HYD.HYDp showed the non-toxic and liver/kidney protection effect,but HYDf couLd cause celluLar constriction in both liver and kidney.3.RT-PCR showed an increased mRNA level of CYP2E1 and CYP3A2 in PTU-induced goiter rats as compared with the normal control group(p<0.05);compared to model group,the expression of CYP2E1 mRNA was inhibited in group Haizao Yuhu Decoction(Sargassum pallidumda)and group group Haizao Yuhu Decoction(Sargassum fusiforme)(p<0.05);the protein expression of CYP2E1 was inhibited in group Haizao Yuhu Decoction removed Sargassum.Conclusion:This study evaluated the safety and efficacy of herb pair HZ-GC applied in HYD in goiter rats at molecuLar,celluLar and whole level and compared the two species of Sargassum further.We provide a reliable way to clarify the possible mechanism of the antagonistic medicament herb pair HZ-GC for its application. |
PDF Full Text Request