Study On Rare Ginsenosides Of Panax Notoginseng Leaves

Panax notoginseng F.H.Chen,which belongs to the ginseng genus of Araliaceae family,as an important authentic with the largest cultivated area in Yunnan Province,is a valuable traditional Chinese medicine（TCM）.Traditionally,dry roots and rhizomes of Panax notoginseng are used as medicines,while the resource coproducts,the stems and leaves,have the effects of calming,analgesic,anti-inflammatory and anti-tumor.In 2016,the Yunnan provincial government formally approved the management of Panax notoginseng flowers,stems and leaves as common local specialty food materials,and released the local food safety standards.The stems and leaves of Panax notoginseng are rich in 20（S）-protopanaxadiol saponins and a small amount of flavonoids.In recent years,a variety of rare modified saponins with side chains and other changes have been discovered,which have the activity of neuroprotection,tumor inhibition,anti diabetes,anticoagulation and so on.In order to comprehensively use the resources of Panax notoginseng,systematic chemical composition and biological activity/toxicity studies on stems and leaves will effectively promote the development of general food and the industrialization of Panax notoginseng.In this dissertation,the first chapter reviewed the literature on rare ginsenosides of Araliaceae family found in recent years.The dammarane triterpene saponins modified in the side chain,including C-25 or C-24 monooxidation,C-24 and C-25double oxidation,20-OH elimination and others,were summarized.It was found that the components derived from the leaves and stems of Panax notoginseng showed a richer molecular diversity than the roots and rhizomes.Most of them showed neuroprotective effects,while some have toxicity.Secondly,from the total saponins extract of Panax notoginseng stems and leaves,through a variety of chromatographic purification and separation methods combining the use of HPLC and TLC,totally 33 compounds of rare ginsenosides were purified,and 33 chemical structures were determined by using MS,1D-NMR,2D-NMR,IR,and UV spectroscopy techniques.The 12 new rare ginsenosides,named notoginsenoside SL1～SL12,the main feature is that the double bond at position of the side chain C-24/C-25 has undergone oxidative addition,and the double bond has been oxidized to hydroxyl,carbonyl,even peroxide,the original double bond（C-24,25）migrates to the adjacent position（C-23 or C-25 position）.The 20 known compounds are:notoginsenoside LX（1）,notoginsenoside Ng₁（2）,vina-ginsenoside R₁₃（3）,notoginsenoside E（4）,ginsenoside II（5）,majoroside E（6）,ginsenoside III（7）,Quinquenoside L₃（8）,ginsenoside Rb₃（9）,ginsenoside Rc（10）,PPT（11）,20（R）-ginsenoside Rh₁（12）,ginsenoside Rh₄（13）,ginsenoside Rk₂（14）,ginsenoside Rb₁（15）,notoginsenoside Fz（16）,notoginsenoside Fc（17）,notoginsenoside B（18）,notoginsenoside LK₄（19）,notoginsenoside A（20）,notoginsenoside Fh₅（21）.Finally,the activity/toxicity of the main compounds were tested.The potential cytotoxicity of human hepatocellular carcinoma cell line（Hep G2）was evaluated by the MTT method.Results showed no obvious cytotoxicity at a concentration of 100μM.For the neuroprotective effect,the activity of acetylcholinesterase（ACh E）was initially screened,but there was no obvious inhibitory effect,indicating that its neuroprotective effect is not directly regulated by the cholinergic system,its mechanism of action needs further study.