Quebrachitol:Global Status and Basic Research

Recently,there has been a renewed interest in the natural-products-inspired drugs.Quebrachitol(QCT)is one of naturally occurring optically active cyclitols that has now received considerable attention.Until the last decade,it came to be a starting point for the lead discovery.In this review,we had a discussion on the basic research of QCT,including its source,structure,properties,and the recent advances on its application.The biological activities and QCT-inspired leads that are potentially effective for treating human diseases were also discussed.

Anti-atherosclerotic effect of extract of traditional Chinese medicine formula Dan-yi-lian in ApoE^(-/-) mice

OBJECTIVE To explore the anti-atherosclerotic effect of the extract of traditional Chinese medicine formula Dan-yi-lian(DYL) and the related mechanism.METHODS Atherosclerosis(AS) mod.el was established in ApoE(-/-) mice with a western diet.The mice were orally administered with differ.ent doses of DYL or vehicle daily for 28 d.The anti-atherosclerotic effect was evaluated by measuring the aortic atherosclerotic lesion area and media thickness with ultrasound imaging and histological sec.tions staining method.The effect on blood lipid was investigated by determining TC,TG,LDL,HDL,Apo-A1,Apo-B,etc.The anti-oxidative activity as assessed by determining the level of SOD,CAT,GSH,GSH-Px and MDA.Western blot analysis was used to determine the effect on ICAM-1,VCAM-1,MMP-2 and TNF-α.RESULTS In Dan-yi-lian administered ApoE(-/-) mice,the plaque area and media thickness were significantly reduced.Meanwhile,serum TC,TG,LDL and Apo-B were decreased,in contrast to the increased level of HDL and Apo-A1.On the other hand,SOD,CAT,GSH and GSH-Px were increased,while MDA was reduced in liver homogenate.In addition,the expression of ICAM-1,VCAM-1,MMP-2 and TNF-α was obviously inhibited by Dan-yi-lian.CONCLUSION Dan-yi-lian exhibit.ed potent anti-athero-sclerotic efficacy,in which the lipid-regulating,anti-oxidative and anti-inflammato.ry mechanism might be involved.

Multifaceted anti-colorectal tumor effect of digoxin on HCT8 and SW620 cells in vitro

Background Colorectal cancer(CRC)is one of the leading causes of cancer death worldwide.Novel drugs for CRC therapy are urgently needed.Digoxin has been in clinical use for treatment of heart failure and atrial arrhythmias for many years.Fragmentary reports suggested that digoxin might have antitumor efficacy on CRC.Here,we aimed to investigate the antitumor effect of digoxin on human CRC cells and the underlying mechanism.Methods Cell viability was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT)assay and plate colony formation assay.The effects of digoxin on cell-cycle distribution and apoptosis were analysed by flow cytometry.The anti-metastatic effect on tumor cells was determined by wound-healing assay and transwell assay.Anti-angiogenic effect was examined by determining the inhibition against proliferation,migration,and tube formation of human umbilical vein endothelial cells(HUVECs).Mechanism study was performed by Western blot,enzyme-linked immunosorbent assay(ELISA),and gelatin-zymography assay.Results Digoxin potently inhibited cell proliferation,induced G1-phase and G2/M-phase arrest in colorectal-cancer HCT8 and SW620 cells,respectively.No obvious apoptosis was observed in the treated cells.Anti-metastatic activities were shown on HCT8 cells by inhibiting the migration and invasion.Meanwhile,the expression of MMP2,MMP9,and phosphorylated Integrinb1 were decreased.Digoxin inhibited the proliferation,migration,and tube formation of HUVECs and reduced HIF1a expression and vascular endothelial growth factor A(VEGF-A)secretion in HCT8 cells,suggesting anti-angiogenic activity.Furthermore,digoxin significantly reversed ABCB1-mediated multidrug resistance on SW620/Ad300 cells.Conclusion Our findings suggest that digoxin has the potential to be applied as an antitumor drug via inhibiting proliferation and metastasis as well as reversing the ABCB1-mediated multidrug resistance of colorectal cancer.