Study On The Chemical Components And Biological Activities Of Euphorbia Chamaejasm

As the traditional Chinese medicine,"Lang-du" was original from Shengnong’s Herbal,has the effects of promoting diuresis,expelling phlegm,and resolving toxin,which has been used for the treatment of superfical scrofula,psoriasis,and insecticide for many years.The lacking of ancient literature about Langdu led to the phenomenon of multi-sources.Nowadays,Land-du has been classified for thirteen types,including Euphorbia fischeriana Steud.,Euphorbia ebracteolata Hayata.,Euphorbia prolifera Buch.Ham.,Euphorbia wallichii Hook.f.,Euphorbiae nematocypha Hand.-Mazz.,Euphorbiae nematocypha var.induta.,Euphorbia pinus.,Euphorbia bupleuroides.,Euphorbia chrysocoma.,Stellera chamaejasme L.,Stellera chamaejasme f.chrysantha.,Alocasia macrorrhiza L.Schott.,Gypsophila oldhamiana Miq.Euphorbia fischeriana and Euphorbia ebracteolata was recorded for the standard medicinal materials by 1977,2010,and 2015 editions of Chinese pharmacopoeia.Euphorbia fischeriana is an herbaceous plant belongs to the genus of Euphorbia,which was widely distributed in Heilongjiang,Jilin province,and the eastern Mongolia.With the aim of further exploring the traditional Chinese medicine,the 95%ethanol extract of the roots of E.fischeriana was investigated for the chemical studies after reviewed the literatures about the chemical and pharmacological reseaches of Langdu.By means of various chromatographic methods,such as silica gel,opening ODS column chromatography,semi-preparative HPLC,43 compounds were isolated,and the structures were elucidated on the basis of spectroscopic data,such as UV,IR,HRESIMS,NMR,X-ray,and calculated ECD methods.The structures of isolated compound including six meroterpenoids,twenty-eight diterpenoids,three phloroglucinol derivatives,and three phenolic compounds,and the new structures were named as fischernolide A(1**),fischernolide B(2**),fischernolide C(3**),fischernolide D(4**),fischernolide D(5*),langduin D(6),euphorbiabietane A(7*),euphorbiabietane B(8*),euphorbiabietane C(9*),euphorbiabietane D(10*),Euphorbiabietane E(11*),euphorbiabietane F(12*),3α-hydroxy-17-oxo-ent-stroba8(15),12(13)-diene(26*),17-acetoxy-3α-hydroxy-ent-pimara-8(14),15-diene(27*).Notably,compounds 1-4 featured an unprecedented carbon skeleton,and compounds 5,7-12,26-27 were new structures.The known compounds were identified as langduin D(6),fischeriolide D(13),fischeriolide A(14),8β,14β-epoxy-13,15-abiatene-16,12α-olide(15)，11β-hydroxy-8,14epoxy-ent-abieta-13(15)-en-16,12-olide(16),ent-11α-hydroxyabieta-8(14),13(15)-dien-16,12α-olide(17),jolkinolide B(18),17-hydroxyjolkinolide B(19),8β,11β,14β-trihydroxy-entabieta-13(15)-en-16,12-olide(20),jolkinolide A(21),17-hydroxyjolkinolide A(22),7β,11β,12β-trihydroxy-ent-abieta-8(14),13(15)-dien-16,12-olide(23),13β-hydroxy-7-oxo-abiet-8(14)-en-19,6β-olide(24),13α-hydroxy-ent-abiet-8(14)-en-7-one(25),maniesculentins(28),jolkinol A’(29),jolkinol A(30),ent-3β,13α-hydroxyatis-16-ene-14-one(31),ent-13α-hydroxyatis-16-ene-3,14-dione(32),ent-kaurane-3-oxo-16a,17-diol(33),prostratin(34),2,4-dihydroxy-6-methoxyacetophenone(35),2,4-dihydroxy-6-methoxy-3methyl-acetophenone(36),6-hydroxy-2-methoxy-4-O-α-L-arabinofurano-syl(→6)-β-D-gluco-pyranoside(37),1,6-di-O-galloyl-β-D-glucose(38),isolariciresinol-9-O-β-D-glucopyrano-side(40),scopoletin(41),fraxidin(42),indole-3-carboxaldehyde(43),respectively.The inhibitory effects againsit pancreatic carcer Panc-28,liver cancer Bel-7402,colon cancer HT-29,lung cancer A549,breast cancer MCF-7,cervical cancer HeLa cell lines of the isolated compounds were evaluated by MTS method.The results revealed that compounds 1-5,8,9 displayed the remarkable cytotoxic activities against the cancer cells.What’s more,compounds 2 and 4 with an α-pyrone ring have better inhibitory effect than compound 1 with an α-furaneol ring,and the cytotoxic activities of meroterpenoids(2 and 4)were better than the probable biogenetic precursor(8).The Annexin V-FITC/PI double staining assays showed compounds 1 and 2 have the effects of promoting late apoptosis of MCF-7 and Bel-7402 cells,and the cells of MCF-7 were more sensitive.In the meantime,the effects on the STAT3 pathway of compounds 1,2,5,6,8,18,and 35 were tested,by measuring IL-6-induced STAT3 promoter activity in HepG2 cells.The results showed compounds 1,2,6,and 18 had potent inhibitory effects.Compounds 1-2,5-6,9,13,18,26,28,and 29-35 were evaluated for the viability of anti-inflammatory for RAW264.7 cells stimulated by LPS.The results showed that compound 9 has the excellent inhibitory effects to the secretion of TNF-α and IL-6 at the concentration of 5 μM.Besides,compound 18 inhibited the secretion of TNF-α from RAW264.7 cells with an IC50 value of 1.36 μg/mL,which was superior to dexamethasone.