Four previously undescribed ent-abietane diterpenoids(1—4),along with eleven known analogues(5—15),were isolated from the roots of wild Euphorbia fischeriana.Their gross structures were determined via extensive spec...Four previously undescribed ent-abietane diterpenoids(1—4),along with eleven known analogues(5—15),were isolated from the roots of wild Euphorbia fischeriana.Their gross structures were determined via extensive spectroscopic data,and the absolute configurations were elucidated by means of single-crystal X-ray diffraction analysis,Rh2(OCOCF3)4-induced CD spectrum and ECD calculations.Their cervical carcinoma inhibition activities counteract HeLa cells were screened by MTT assay,and the structure-activity relationships were further examined.The results demonstrated that 2(IC50 value at 3.75μmol/L)was more potent than cisplatin.The underlying mechanism study revealed that 2 could distinctly induce apoptosis accompanied by increasing reactive oxygen species(ROS)production,Ca^(2+)influx and decreasing mitochondrial membrane potential.Furthermore,signal pathways including MAPKs/AKT might play a significant role in 2-induced cervical cancer cells death.展开更多
Chromatographic purification of Sigesbeckia glabrescens extracts led to three undescribed ent-pimarane diterpenoid dimers,named glabreside A—C(1-3).Their structures were confirmed by comprehensive spectroscopic analy...Chromatographic purification of Sigesbeckia glabrescens extracts led to three undescribed ent-pimarane diterpenoid dimers,named glabreside A—C(1-3).Their structures were confirmed by comprehensive spectroscopic analyses,and the structures of compound 1 and 3 were confirmed by X-ray crystallography.The results of anti-inflammatory activity assay showed that glabreside C(3)exhibited the most potent inhibition activity on nitric oxide(NO)production induced by lipopolysaccharide(LPS)in BV2 microglia compared with the other two compounds.Glabreside C also increased the protein expression level of heme oxygenase-1(HO-1),and suppressed inducible nitric oxide synthase(iNOS)and cyclooxygenase 2(COX2)in LPS-stimulated BV2 cells.Mechanistically,glabreside C exerts its anti-inflammatory effect by inhibiting AKT/MAPKs signaling pathway.These findings indicate the vital role of ent-pimarane diterpenoid dimers in explaining the anti-inflammatory activity of S.glabrescens and provide important evidence for further development and utilization of Sigesbeckiae Herba.These results also suggest that glabreside C is a potential lead compound for anti-inflammatory drugs.展开更多
基金This work was supported by the National Key R&D Program of China(2017YFC1701200)the National Natural Science Foundation of China(81903789)。
文摘Four previously undescribed ent-abietane diterpenoids(1—4),along with eleven known analogues(5—15),were isolated from the roots of wild Euphorbia fischeriana.Their gross structures were determined via extensive spectroscopic data,and the absolute configurations were elucidated by means of single-crystal X-ray diffraction analysis,Rh2(OCOCF3)4-induced CD spectrum and ECD calculations.Their cervical carcinoma inhibition activities counteract HeLa cells were screened by MTT assay,and the structure-activity relationships were further examined.The results demonstrated that 2(IC50 value at 3.75μmol/L)was more potent than cisplatin.The underlying mechanism study revealed that 2 could distinctly induce apoptosis accompanied by increasing reactive oxygen species(ROS)production,Ca^(2+)influx and decreasing mitochondrial membrane potential.Furthermore,signal pathways including MAPKs/AKT might play a significant role in 2-induced cervical cancer cells death.
基金This work was supported by the National Natural Science Foundation of China(No.81903789)the China Postdoctoral Science Foundation(Nos.2020M670675,2020M680988)In addition,the collection of medicinal materials was guided and assisted by the staff from Anhui YATAI Pharmaceutical Co.,Ltd.Thanks to the above organizations and individuals.
文摘Chromatographic purification of Sigesbeckia glabrescens extracts led to three undescribed ent-pimarane diterpenoid dimers,named glabreside A—C(1-3).Their structures were confirmed by comprehensive spectroscopic analyses,and the structures of compound 1 and 3 were confirmed by X-ray crystallography.The results of anti-inflammatory activity assay showed that glabreside C(3)exhibited the most potent inhibition activity on nitric oxide(NO)production induced by lipopolysaccharide(LPS)in BV2 microglia compared with the other two compounds.Glabreside C also increased the protein expression level of heme oxygenase-1(HO-1),and suppressed inducible nitric oxide synthase(iNOS)and cyclooxygenase 2(COX2)in LPS-stimulated BV2 cells.Mechanistically,glabreside C exerts its anti-inflammatory effect by inhibiting AKT/MAPKs signaling pathway.These findings indicate the vital role of ent-pimarane diterpenoid dimers in explaining the anti-inflammatory activity of S.glabrescens and provide important evidence for further development and utilization of Sigesbeckiae Herba.These results also suggest that glabreside C is a potential lead compound for anti-inflammatory drugs.
