Discovery Of Chemical Constituents And Biological Evaluation Of Paeonia Suffruticosa And Marsdenia Tenacissima(Roxb.) Moon

This doctoral dissertation is comprised of four chapters,in which studies on chemical constituents and biological evaluation of Paeonia suffruticosa’Feng Dan’and Marsdenia tenacissima.The first and second chapters systematically investigate the chemical and biological activities of the root bark of Paeonia suffruticosa’Fengdan’and the stem of Marsdenia tenacissima,respectively.The chapter three apply on structural similarity algorithms to analyze the biological activities of new compounds in’Fengdan’and reverse docking to find possible targets.The progress of research on the unique natural products in Paeonia suffruticosa were summarized in chapter four.A total number of 136 non-duplicated natural products,including 56 new compounds,were isolated and identified from the root bark of Paeonia suffruticosa and the stem of Marsdenia tenacissima.The classes of these main types of chemical constituents include monoterpenes and glycosides,phenolic acids and phenolic glycosides,flavonoids,triterpenes,sesquiterpenes,lignans,and so on.The structures were analyzed by spectroscopic analysis,including 1D,2D NMR,HRESIMS,and IR spectroscopic analysis.The new compounds were analyzed separately for in vitro antitumor and anti-inflammatory activities,and 23 natural products with outstanding activities were identified.1.Chemical Constituents from Paeonia suffruticosaThe root bark of Paeonia suffruticosa is the dried root bark,family Ranunculaceae,which was first published in the Shen Nong Ben Cao Jing.Fengdan’s root bark is an authentic medicinal herb in Anhui Provence.In this doctoral dissertation,a total of 111compounds were isolated from Fengdan,including 46 new compounds,and The structure type of the new compound involves monoterpenes,monoterpene glycosides,phenols,phenolic glycosides,and lignans.2.Chemical and Bioactive Constituents from Marsdenia tenacissima（Roxb.）The plant Marsdenia tenacissima（Roxb.）Moon.（M.tenacissima）mainly grows in Yunnan,Guizhou,Sichuan,Guangxi Provinces in China,and other tropical regions,such as India,Myanmar,Sri Lanka,Indonesia,Vietnam,Laos,and Cambodia in Southeastern Asia[1].In China,it was named“Tong Guang Teng”and was first recorded in Dian Nan Ben Cao,a medicinal classic published during the Ming dynasty in 1436 A.D.This plant,belonging to the Asclepiadaceae family,is a medicinal herb used in traditional Chinese Medicine as recorded in the 1977,2010,2015,and 2020editions of Chinese Pharmacopoeia,and is also widely used in ethnic Dai Medicine by Dai people living in Laos,Myanmar,and the Yunnan Province in China as detoxification,decreasing swelling,and alleviating pain agents.A total of 25constituents were isolated from the stem of M.tenacissima,including 10 new compounds,all of which were the type of pregnane glycosides.One new8,14-seco-pregnane glycosides harboring a new hemiketal formed at C-11 and C-8positions.The new compounds were tested for in vitro anti-inflammatory activity.Compounds LMB 06a,22,and 24 showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7 with IC₅₀values 37.5,38.8,and42.8μM(L-NMMA was used as a positive control,IC₅₀39.3μM),respectively.3.Biological Activity of New Constituents from Paeonia suffruticosaTo further explore the diversity of the new compounds in terms of bio-activity,the bio-activity of the new constituents in Paeonia suffruticosa was predicted using network pharmacology based on structural similarity algorithms.The new compounds are predicted to have possible anti-tumor activity based on activity assays.However,the anti-tumor activity and anti-inflammatory activity of all compounds were analyzed,and the results showed that a total of three compounds exhibited anti-inflammatory activity superior to that of the positive control at 40μM concentration,16 compounds had exhibited anti-tumor cell（HL-60,SMMC-7721,A-549,SW480 and MDA-MB-231）activity with IC₅₀values comparable to the positive control.Compounds TP 68、TP 46、TP 105b and TP 122 displayed cytotoxic activities against HL-60 cells with IC₅₀values of 2.746±0.099、6.784±0.105、5.670±0.206 and 4.375±0.203μM（DDP 23.51±0.77μM）;Compound TP 68 displayed cytotoxic activities against A549 cell with IC₅₀values of4.688±0.031μM（DDP 30.36±1.42μM）;Compound TP 68 displayed cytotoxic activities against SMMC-7721 cell with IC₅₀values of 1.947±0.072μM（DDP8.098±0.882μM）;Compound TP 68 displayed cytotoxic activities against MDA-MB-23 cell with IC₅₀values of 6.089±0.180μM（DDP 16.90±1.19μM）;Compound TP 47a、TP 68、TP 105b、TP 122、TP 123、TP 132a、TP 146 and TP 150displayed cytotoxic activities against SW480 cell with IC₅₀values of 8.858±0.402、3.389±0.077、7.661±0.318、6.176±0.56、11.64±0.47、12.73±0.72、12.40±0.23和10.12±0.43μM（DDP 25.06±1.26μM）.The relevant diseases and targets with high association with the compounds were predicted by multi-target enrichment analysis.The binding sites of targets and compounds were mapped by reverse docking.4.Biological Activity of Cortex MoutanAs a traditional Chinese herb,Cortex Moutan is commonly used in various classical and famous prescriptions by Chinese medicine practitioners.With modern advances in analysis,separation techniques,and structural identification,the material basis of the medicinal effects of compounds in Cortex Moutan bark is further revealed.This chapter provides a review of the research on the classification,traditional applications and biological activities of Cortex Moutan in the past ten years.