Studies On The Chemical Constituents And Biological Activities Of The Leaves Of Saussurea Lappa And Artemisia Capillaris

Liver disease is a disease with high incidence rate in China.The common liver diseases include hepatitis,liver fibrosis,fatty liver,liver cancer,etc.Although there are some drugs have been approved for clinical treatment of liver diseases,such as nucleosides/nucleotide analogues（NA）and interferon-α（IFN-α）.However,due to their susceptibility to drug resistance,single target of action,significant side effects,or lack of effective drugs,they still cannot meet clinical needs.Traditional Chinese medicine,as an important resource for the development of natural drugs,plays an important role in the prevention and treatment of human diseases.These natural products have rich skeletal types and diverse biological activities,serving as natural bridges connecting target macromolecules with diseases and playing an irreplaceable role in the discovery of liver disease drugs.Therefore,this research paper is loyal to the clinical experience of folk traditional medicine in Yunnan.Based on the database constructed earlier,we selected two kinds of traditional Chinese medicines for liver diseases,Saussurea lappa and Artemisia capillaris.Using phytochemistry research methods,combined with the results of biological activity as the guide,we isolated,purified and identified the compounds of these two kinds of traditional Chinese medicines.In addition,anti HBV and anti liver cancer activity tests were conducted on the isolated compounds,and the structure-activity relationship of compounds with anti HBV activity in S.lappa was explored,providing scientific basis and support for the development and utilization of S.lappa and A.capillaris.The first chapter of this paper summarizes the research progress of Chinese herbal medicine used for treating liver diseases in Yunnan region,and analyzes the compound and single trial formulas used for treating liver diseases in ethnic medicine.Through organization and literature research,40 commonly used single trial formulas for treating liver diseases were obtained from 806 medicinal materials in Volume 1–7of Yunnan Province’s Traditional Chinese Medicine Standards.A.capillaris,a plant of the composite family,which is an essential medicine for treating liver diseases.It is the most frequently used traditional Chinese medicine in single trial formulas for treating liver diseases.Multiple compound formulas mainly composed of A.capillaris are commonly used in clinical practice to treat jaundice hepatitis,cirrhosis,liver failure,and non-alcoholic fatty liver disease.S.lappa is a plant of the composite family,it is a genuine medicinal herb in Yunnan.Muxiang type drugs have appeared in 1872 traditional Chinese medicine compound formulas,among which multiple compound formulations using Muxiang herbs as the dominant or main medicine are used to treat liver and stomach disharmony,liver and stomach qi stagnation,liver cirrhosis and ascites,and other liver diseases.Furthermore,this chapter also summarizes the natural products with anti HBV activity,providing a certain reference and reference for subsequent research.In the second chapter of this thesis,the traditional phytochemical research method,combined with LC-MS and bioactivity-guided separation,was used to study the chemical composition of the 95%ethanolic extract of S.lappa leaves,the flow components with good anti-HBV activity,and a total of 37 monomeric compounds were obtained by isolation and purification,saussulappanolide A-W（1-23）,aguerin B（24）,azuleno[4,5-b]furan,2-butenoic acid deriv（25）,subexpinnatin（26）,aguerin A（27）,cynaropicrin（28）,maximolide（29）,clementein B（30）,11α,13-dihydro-3β-methacryloyloxyzaluzanine C（31）,11α,13-dihydro-8α-methacryloyloxyzaluzanine C（32）,1,5-naphthalenediol,decahydro-4a-methyl-8-methylene-2-（1-methylethenyl）-,[1S-（1α,2β,4aβ,5β,8aα）]（33）,（3β）-eudesma-4（14）,11（13）-diene-3,12-diol（34）,3α-hydroxycostol（35）,chrysanthemol（36）,and 1β-hydroxycostol（37）were sesquiterpenoids,including 20 guaiacane-type sesquiterpenes,17 eucalyptane-type sesquiterpenes,and compounds 1-23 were new compounds.In addition,the compounds isolated from the leaves of S.lappa were further tested for anti-HBV activity using MTT and ELISA assays.The results showed that 10 compounds showed anti-HBV activity,all of them were guaiacane-type sesquiterpenes,and the IC₅₀value is in the range of 2.17–8.15μM.Finally,the conformational relationships were analyzed based on the structural characteristics and biological activity results of the compounds.In the third chapter of this paper,A.capillaris,an important medicine for treating liver diseases,was taken as the research object.Using phytochemistry research methods,a total of 10 monomer compounds were isolated and purified from the 95%ethanol extract of A.capillaris.They were identified as（R,Z）-deca-8-en-4,6-diyne-1,3-diol（1）;methyl（S）-8-（5-oxo-2,5-dihydrofuran-2-yl）octanoate（2）;gymnasterkoreayne A（3）;（S）-deca-4,6,8-triyne-1,3-diol（4）dehydrovomifoliol（5）;loliolide（6）;（3S,5R,6S,7E）3,5,6-trihydroxy-7-megastigmen-9-one（7）;（6R,9R）-3-oxo-α-ionol（8）;trans-4 hydroxylinalool 3,6-oxide（9）;methyl（S）-9-hydroxy-10-undecenoate（10）,among which compounds 1 and 2 are new compounds.In summary,this paper isolated and identified 37 compounds,including 23 new compounds,from S.lappa.Among them,10 compounds showed anti HBV activity and had a significant inhibitory effect on the secretion of HBs Ag antigen,with an IC₅₀value ranging from 2.17 to 8.15μM.Ten compounds,including two new compounds,were isolated and identified from A.capillaris.This research paper enriches the chemical components of the aboveground parts of S.lappa and A.capillaris,laying a material foundation for the pharmacological research of these two traditional Chinese medicines for treating liver diseases.