Studies On Chemical Constituents And Bioactivities Of Chloranthus Japonicus Sieb

Chloranthus,a genus of the Chloranthaceae family,comprises about 17 species distributed in subtropical and tropical Asia,with 13 species and 5 varieties occurring in China.This genus is a perennial herbaceous plant and is distributed widely in southwest region of China.As Chinese folk medicine,some plants have long been applied for treatment of rheumatic arthralgia,fractures,traumatic injuries,etc.So far,previous phytochemical investigations of Chloranthus indicated that sesquiterpenes and sesquiterpene lactone dimers are the major secondary metabolites,some of which were reported to exhibit potent and selective inhibition on the delayed rectifier(Ik)K+ current,anti-HIV-1 activity,antiinflammatory,anti-tumour,antifungal activity,etc.Chloranthus japonicus Sieb,with a Chinese name “yinxiancao”,is mainly distributed in Jilin,Heilongjiang,Shanxi,Gansu,Hebei provinces in China,and also has distribution in Japan and Korea.As a part of our program searching for structurally novel bioactive sesquiterpenes and sesquiterpene dimers from medicinal plants,thus,the chemical constituents of Chloranthus japonicus Sieb were investigated.Meanwhile,sesquiterpene compounds from Chloranthus japonicus Sieb were evaluated for in vitro anti-tumor and antiinflammatory activities.1.Chemical constituents from C.japonicusIn our investigation,chemical investigation of the Et OH extract of the whole plant of C.japonicus afforded fifty-five compounds,consisting of forty-two sesquiterpenes,five other terpenoids and their glycosides,four flavones,two steroids,and two others,by column chromatography(silica gel,ODS,Sephadex LH-20,HPLC).And their structures were established by interpretation of the spectroscopic data(HRESIMS?NMR?CD?OR?Xray).Among all identified compounds,thirty-one compounds were isolated from this plant for the first time,and compounds Y-1 ~ Y-4,Y-19 ~ Y-21,Y-25 and Y-30 were identified to be new compounds.Y-1 is the first 8,9-seco eudesmane sesquiterpenoid and Y-30 is a new lindenane sesquiterpenoid dimer with a rare hydroperoxy group.Compounds Y-2,3,20 and Y-21 configurations were determined by single crystal X-ray diffraction experiment2.Biological activities of C.japonicusThe cytotoxic activity of the sesquiterpene compounds against five human tumor cell lines,including MGC803,Hep G2,HL-60,HCT116 and A549 was investigated by CCK-8 method.Among the tested compounds,only compound Y-39 exhibited potent cytotoxicity against three human tumor cell lines MGC803,Hep G2,and HL-60 with the IC50 values of 4.60±1.05,3.17 ± 0.66,and 1.57 ± 0.27 ?M,respectively.Moreover,compounds Y-35,36 had weak cytotoxicity against two tumor cell lines MGC803 and HL-60 cell line with the IC50 value of 10 to 18 ?M.Compound Y-2 with two ?,?-unsaturated ketone fragments showed significant inhibition against nitric oxide(NO)release in LPS-induced RAW264.7 macrophages with IC50 values of 9.56 ± 0.71 ?M,comparable to that of positive control amino guanidine(8.50 ± 0.35 ?M).