Studies On Chemical Constituents Of The Roots Of Bergenia Purpurascens And The Structural Modification Of Its Effective Constituent Ursolic Acid

Bergenia purpurascens,which belongs to the genus Bergenia?Saxifragaceae?,is widely distributed in Tibet,Sichuan and Yunnan.B.purpurascens is used as a Chinese medicine for the treatment of cough,pyogenic infections,chronic bronchitis,dysentery,diarrhea,pain from rheumatism,internal and external bleeding and so on.In order to study the chemical constituents and medical value of B.purpurascens,this research investigates the chemical constituents of ethanol extracts of the roots of B.purpurascens comprehensively.The research mainly used repeated chromatography on silica gel colum and other separation material like MCI,Sephadex LH-20 to obtain 27 compounds from the ethanol extracts of B.purpurascens'roots.The structures of 27 compounds were identified on the basis of their chemical properties and spectrum data:?-taraxerol?Q1?,?-sitosterol?Q2?,betulinic acid?Q3?,ursolic acid?Q4?,?2S?-1-O-heptatriacontanoyl glycerol?Q5?,luteolin?Q6?,quercetin?Q7?,bergenin?Q8?,?-daucosterol?Q9?,kaempferol?Q10?,hydroquinone?Q11?,oleanolic acid?Q12?,2?-hydroxyursolic acid?Q13?,gallic acid?Q14?,apigenin?Q15?,methylgallate?Q16?,?+?-catechin?Q17?,?+?-catechin-3-O-gallate?Q18?,11-O-galloylbergenin?Q19?,11-O-?4'-O-methylgalloyl?-bergenin?Q20?,ellagic acid?Q21?,quercetin-3-O-?-D-glucoside?Q22?,luteolin-5-O-?-D-glucoside?Q23?,arbutin?Q24?,11-O-?4'-hydroxybenzoyl?bergenin?Q25?,rutin?Q26?,luteolin-7-O-?-D-glucoside?Q27?.These compounds contain different types of compounds,such as terpenoid,phenols,flavonoids,steroids,tannins and so on.Among them,Q5,Q6,Q20,Q21,Q23,Q27 were firstly found from the ethanol extracts of this plant and even firstly found from the genus Bergenia.Ursolic Acid is a pentacyclic triterpenoid and widely found in natural plants.It is widely distributed in the plant kingdom and is also one of the B.purpurascens'important chemical constituents.Ursolic acid has a variety of biological activities,the most important of which is anti-tumor activity.Ursolic acid and its derivatives exhibited potent cytotoxic effects against various types of cancer cell lines,as well as induced tumor cell differentiation and apoptosis.What is more,they were found to be potent inhibitors of NF-?B.In this research,a series of inhibitors of NF-?B based on ursolic acid?UA?derivatives containing long-chain diamine moieties were designed,synthesized and evaluated in terms of anti-tumor effects.Pharmacological results indicated that these compounds exhibited significant inhibitory activity to the NF-?B with IC₅₀ values at micromolar concentrations in A549 lung cancer cell line.Among them,compound 8c exerted potent activity against the test tumor cell lines including multidrug resistant human cancer lines,with the IC₅₀ values ranged from 5.22 to8.95?M.Moreover,compound 8c successfully suppressed the migration of A549 cells.Related mechanism study indicated compound 8c caused cell cycle arrest at G1 phase and triggered apoptosis in A549 cells through blockage of NF-?B signalling pathway.Molecular docking study revealed that key interactions between compound 8c and the active site of NF-?B in which the bulky and strongly electrophilic group of long-chain diamine moieties were important for improving activity.Based on the discovery and structural optimization of natural active lead compounds,it is an important approach for the development of new drugs.In this research,the structural modification of ursolic acid which is an active lead compound was also carried out based on the study of the chemical constituents of B.purpurascens'roots.The results of this research provided a theoretical basis for the in-depth development,utilization and new drugs creation of the medicinal plant B.purpurascens.