Studies On The Chemical Constituents And Bioactivities Of Schisandra Incarnata And Corydalis Impatiens

Schisandra incarnata,belongs to the plants of Schisandra genus,widely distributed in the west and southwest of Hubei province,China.Its wipe fruits are used in folk for the treatment of various conditions.The stems of S.incarnata have been studied by our group,but its fruits have not been investigated.In order to study the plant of S.incarnata systematically,this research was carried out.Corydalis impatiens is a plant of Papaveraceae family.It has the functions of clearing away heat and detoxifying,calming,promoting blood circulation and removing stasis.It is a commonly used medicine for Tibetan medicine.At present,the research on C.impatiens is not deep enough,and we hoped to further study its chemical composition and biological activity,and provide the basis for the development and utilization of Tibetan medicine resources.There are four chapters in the doctoral thesis.Studies on the chemical constituents and biological activities of the fruits and stems of Schisandra incarnata are discussed in chapter 1.Chapter 2 describes the alkaloids and its biological activities of the whole plant of C.impatiens.Chapter 3 presents the secondary metabolites and biological activities of the coculture of Alternaria sp.AJZ2 and Alternaria sp.XN-3-1.Chapter 4is a review about the structures,syntheses and biological activities of the new triterpenoids,lignans and sesquiterpenoids isolated from the plants in Schisandraceae from 2014 to 2019.135 compounds,including 30 new ones,were isolated from the above mentioned two medicinal plants and two fungus by various separation technologies and methods.8novel schinortriterpenoids?SNTs?with unprecedented skeletons were isolated for the first time,belonging to three different skeleton types of SNTs.Their structures with absolute configurations were determined by extensive spectroscopic analyses,single-crystal X-ray diffractions,and experimental ECD?electronic circular dichroism?.These compounds consist of triterpenoids,lignans,alkaloids,sesquiterpenoids and meroterpenoid.All the compounds isolated from the fruits and stems of Schisandra incarnata were mainly composed of triterpenoids,which were classified into schinortriterpenoids?SNTs?,lanostane type,and cycloartane type.9 novel SNTs with 4 different types of skeletons were isolated for the first time.These unprecedented SNTs consist of five ones featuring a unique 1-oxaspiro[6.6]tridecane motif,two ones possessing a unique5/5/6/11/3 ring system,one featuring a tetracyclo[6.4.0.0^2,12.0^9,11]dodecane-bridged system and one bearing a tetracyclo[6.3.0.1^1,6.0^2,4]tridecane-bridged system.The isolates from Corydalis impatiens were mainly composed of isoquinoline alkloids,which included 8 different types of skeletons.Benzo pyrones analogues were isolated as the main compounds from the the coculture of Alternaria sp.AJZ2 and Alternaria sp.XN-3-1.Some selected compounds were tested for their in vitro cytotoxic activities,immunosuppressive activities and neuroprotective effects.1.Studies on the chemical constituents and biological activities of S.incarnataThe Schisandraceae plants,containing two genera Kadsura and Schisandra,are widely used as sedative and tonic agents in folk.S.incarnata,a woody liana,is mainly distributed in the west and southwest of Hubei province,China.Over the past few years,our group has conducted a series of phytochemical investigations on the plants of Schisandra.In order to search for more structurally interesting and bioactive important components and as a continuation of our previous work,the chemical constituents of the fruits and stems of S.incarnata were investigated.As a consequence,101compounds?29 new ones?,including 63 triterpenoids,21 lignans,5 sesquiterpenoids and 12 other types were isolated from this plant.40 triterpenoids,together with 20 lignans were evaluated for their immunosuppressive activities against the proliferation of in vitro ConA-induced T-cell and LPS-induced B-cell.As a result,compounds F49 exhibited the most significant inhibition on the proliferation of T-cell and B-cell with IC₅₀ of 2.51 and 2.54?g/mL.Compounds F23,F36,F46^F48,F52 and F57 exhibited significant inhibition effects against ConA-induced T-cell proliferation(IC₅₀<10?g/mL).Compounds F36,F46^F48,F52 and F57 showed significant inhibition effects against LPS-induced B-cell proliferation(IC₅₀<10?g/mL).Compound F64 presented moderate inhibition effects against ConA-induced T-cell proliferation with IC₅₀ of 9.38?g/mL,while compound F63,F64 and F72 presented moderate inhibition effects against LPS-induced B-cell proliferation with IC₅₀ of 13.10,13.40 and 14.93?g/mL.43 triterpenoids,together with 20 lignans were tested for their in vitro cytotoxicty against human hepatoma cell HepG2,human breast cancer cell MCF-7 and human colorectal cancer cell HT-29.The results showed that F36 and F57 exhibited very weak cytotoxicity against HepG2.The other compounds showed no significant activities.Additionally,the neuroprotective activities in SH-SY5Y cells of the isolates were also studied.Compounds F79 in the CoCl₂-induced hypoxic injury model,and compounds F69,F70,F78 and F79 in the H₂O₂-induced oxidative injury model,showed significant neuroprotective activities at 50?M,respectively.However,at a low concentration?5?M?,the neuroprotective activities of the tested lignans were not obvious.2.The chemical constituents and biological activities of C.impatiensThe genus of Corydalis belonging to the Papaveraceae family,contains approximately 428 species in the word,about 298 of which are widespread in China.As reported,the genus of Corydalis has been widely used for detoxification,dehumidification and pain relief,treatment of cold,fever,sore,swollen,ulceration and other symptoms in traditional Chinese medicine.Corydalis impatiens is widely distributed in Tibet,China.To search for more interesting components,we explored the chemical compositions of the whole plant of C.impatiens collected from Tibet,China.As a consequence,26 compounds,including 25 alkaloids were obtained from this species.Compounds C22 and C23 were isolated from Corydalis genus for the first time.Compounds C1^C7,C9^C11,C17,C20 and C24 isolated from C.impatiens,were firstly discovered.Firstly,in vitro immunosuppressive activities of selected alkaloids were investigated for the first time.Compounds C11,C15,C16 and C18 exhibited significant inhibition effects against LPS-induced B-cell proliferation(IC₅₀<10?g/mL).Secondly,the alkaloids C1⁶,C8^C21,C23 and C25 were tested for their in vitro cytotoxic activities against HepG2 and MCF-7.The results showed that C13 and C23 exhibited significant cytotoxicities against human hepatoma cell HepG2 with IC₅₀0 of 18.92 and2.14?g/mL,respectively.The tested compounds C13 and C23 showed no effects against MCF-7 cancer cell line.Thirdly,C3^C8,C10^C14,C16^C19,C21 and C23were investigated for their neuroprotective effects against CoCl₂-induced hypoxic injury and H₂O₂-induced oxidative damage of human neuroblastoma cells SH-SY5Y.Some of selected compounds in the CoCl₂-induced hypoxic injury and the H₂O₂-induced oxidative injury model,showed significant neuroprotective activities at50?M,respectively.However,the neuroprotective activities of the tested alkaloids were not obvious at the low concentration?5?M?.3.The secondary metabolites and biological activities of the coculture of Alternaria sp.AJZ2 and Alternaria sp.XN-3-1Our group has conducted the phytochemical investigations on the plant of Schisandra sphenanthera and obtained some new triterpenoids and lignans.In order to explore the relationship between the fungus and the plant of Schisandra sphenanthera,as well as search for more structurally interesting and bioactive important components,we investigated the secondary metabolites and biological activities of the coculture of Alternaria sp.AJZ2 and Alternaria sp.XN-3-1.As a result,8 compounds including a new meroterpenoid were isolated.In vitro cytotoxicty against human breast cancer cell MCF-7 and human hepatoma cell HepG2 and immunosuppressive activities were tested for seaveral compounds,but no significant cytotoxic activity was detected.Compounds ST2,ST4 and ST5 exhibited significant inhibition effects against LPS-induced B-cell proliferation,while the tested compounds showed weak inhibition effects against ConA-induced T-cell.4.Studies on the chemical constituents from the Schisandraceae familyChapter 4 is a review about the structures,syntheses and biological activities of the new triterpenoids,lignans and sesquiterpenoids isolated from the plants in Schisandraceae from 2014 to 2019.