Studies On The Diterpenoids Constituents And Their Bioactivities Of Three Species Salvia Plant

The dissertation is composed of five chapters.Chapters 1-4 described the studies on the chemical constituents and their bioactivities of three speices of Salvia,Salvia farinacea Benth,Salvia hispanica L.and Salvia tiliifolia Vahland,respectively.In Chapter 5,we summarized the progress in the research of the chemical constituents and pharmacological activities of ten exotic speices of Salvia.By the means of chromatography methods,spectroscopic evidences,crystal X-ray methods and chemical derivatization,150 neo-clerodane diterpenoids were isolated and identified from the above three Salvia species,among which 66 compounds were new,including a compound possessed unprecedented skeleton with a 6/5/7 tricyclic ring skeleton fused with?-lactone ring and furan ring.Some of the isolated compounds were evaluated for the effect on steatosis hepatocytes,protective effects against H₂O₂-induced cardiomyocytes injury,cytotoxicity against five human cancer cell lines,and their neurite outgrowth-promoting activity on PC12 cells.As a result,one new neo-clerodane diterpenoid displayed potent effect on reducing hepatic steatosis.Seven compounds significantly increased the viability of cardiomyocytes injured by H₂O₂.Moreover,three compounds exhibited the moderate activities of potentiating NGF-induced neurite outgrowth in PC12 cells.Chapter 1.The Chemical Constituents and Their Bioactivities in Salvia farinacea BenthSalvia farinacea Benth is native to the America,belonging to the Labiatae family.It has been introduced into our country due to its beautiful flowers for decorating flower bed.Our investigation of the chemical constituents of the leaves and stems of this plant,which was collocted in a garden of Kunming city,resulted in the isolation of 47 neo-clerodane diterpenoids including 21 new ones.Notably,salvifarinin A?1?possessed unprecedented skeleton with a 6/5/7 tricyclic ring skeleton fused with?-lactone ring and furan ring.Compounds 22-24 were seco-clerodanes,and 43-47 were diterpenoid glycosides.The effects of compounds 1-3 on steatosis hepatocytes were evaluated.The result showed that compound 2 significantly reduced the lipid accumulation and the triglyceride level in HL7702 cells.Chapter 2.The Chemical Constituents and Their Bioactivities in Salvia hispanica Collected in OctoberSalvia hispanica is native to southern Mexico and northern Guatemala.Its seeds were used for regulating blood lipid,blood glucose,and blood pressure,assisting weight loss,preventing cardiovascular and cerebrovascular disease.The chemical constituents of the aerial parts of this plant have not been reported so far.In a continuation of our research work on the diterpenoids from Salvia species,we examined the constituents of S.hispanica collected in October.27 new diterpenoids were isolated together with 13known diterpenoids.Among them,salvihispin A-2-O-?-D-3-keto-glucopyranoside?2?possessed an unusual 3-keto-glucopyranoside moiety,whose absolute configuration was confirmed by single crystal X-ray diffraction.Moreover,hispanin A?5?and hispanin B?6?represented the first neo-clerodane diterpenoids with a unique oxygen bridge between C-19 and C-20.Compounds 1 and 2 had obviously increasing activity of neuronal differentiation after72 h at the concentration of 10?M with the differentiation rate of 9.30%and 10.96%,respectively,compared with 4.29%of the negative control.Compounds 8,10,14,17,21,23,35 significantly had protective effects against H₂O₂-induced cardiomyocytes injury with the cell viability ranging from 73.26±1.72%to 87.44±6.28%(10^-4 mol/L),showing remarkable cardioprotective activities.Chapter 3.The Chemical Constituents and Their Bioactivities in Salvia hispanica Collected in JulyIn view of the different harvest time,especially the flowering and without blossom time,the diterpenoids of the same plant may be different in type and content.We examined the constituents of S.hispanica collected in July which were also collected from Kunming Botanical Garden.44 diterpenoids including 12 new compounds were isolated from the plant.It is noted that the compounds isolated from samples with different harvest time showed differences not only in the content of the large number of compounds,but also the proportion of different types of diterpenoids.The sugar unit of diterpenoid glycosides was all glucopyranoside described in this chapter,and the sugar unit of diterpenoid glycosides in second chapter was all 3-keto-glucopyranoside moiety.Hispanin T?1?represented the first neo-clerodane diterpenoids with 9,10-seco-clerodane skeleton.Hispanin U?2?was the first compound with 1,10-seco-clerodane skeleton.Hispanin V?3?represented the first neo-clerodane diterpenoids with 12,17-seco-clerodane skeleton.Chapter 4.The Chemical Constituents and Their Bioactivities in Salvia tiliifoliaSalvia tiliifolia Vahl is native to southern America and Mexico.It had been incorrectly identified as S.dugesii?a synonym of S.melissodora?in China.It was probably introduced into Kunming,Yunnan in the 1990s.With the aim of searching for useful metabolites from this invasive plant and continuing our systematic studies of this genus,six new neo-clerodane diterpenoids,tiliifolins A-F?1-6?,were obtained,along with 13 known compounds.Tiliifolin A?1?and tiliifolin B?2?represented 5,6-seco-clerodanes with a furofuran moiety.All the new compounds were evaluated for their neurite outgrowth-promoting activity on PC12 cells,and compound 5 was found to have moderate increasing activity of neuronal differentiation.Chapter 5.Studies on the progress of exotic speices of SalviaThis review described the recent studies on the chemical constituents and pharmacological activities of ten exotic speices of Salvia,S.splendens,S.farinacea,S.coccinea,S.tiliifolia,S.officinalis,S.uliginosa,S.leucantha,S.nipponica,S.sclarea,S.hispanica.Up to now,102 compounds were reported.The classes of these compounds included diterpenoids,sesterterpenoids,triterpenoids,phenolic acids and so on.Pharmacological activities included lipid-lowering effect,hypoglycemic activity,cytotoxic activity,cardiovascular activity,anti-inflammatory activity,antiviral activity,anti-diarrhea,antispasmodic and stomach protection activities,etc.