(Z)-6-6--7-3-a-Diligustilide and ligustilide

The increasing incidence of chronic kidney disease (CKD) urgently calls for effective nephroprotective agents. Traditional Chinese Medicine Angelica sinensis and its formula are well known for CKD therapy, but the underlying mechanisms and effective substances of reno-protective effects remain unclear. To this end, we isolated eleven ligustilide dimers (1-11) from A. sinensis and examined the molecular mechanism of their nephroprotective effects.. Because of internal RAS playing an important role in CKD, we used renin expression as a target and screened preliminarily for antifibrotic effects of ligustilide dimers (1-11) by constructing a dual luciferase reporter gene in vitro. Furthermore, the reno-protective effects of the ligustilides and their underlying mechanism were investigated in TGF-β1-stimulated HK-2 cells and 5/6 nephrectomy (Nx) mice.. The ligustilide dimers exhibited anti-fibrotic effects by inhibiting human renin (hREN) promoter activity to decrease renin expression and down-regulate the expression of fibrosis-related factors, including α-SMA, collagen I, and fibronectin in vitro. Levistolide A (LA) and angeolide keto ester (AK) were screened out to identify their ability and underlying mechanism for treating CKD. Experimental validation further indicated that LA or AK treatment inhibited the expression of key molecules in RAS, TGF-β1/Smad, and MAPK pathways to downregulate ECM deposition. Furthermore, LA obviously meliorated renal injury in 5/6 Nx mice through ameliorating oxidant stress, inflammation, apoptosis and renal fibrosis.. The experimental results demonstrated that ligustilide dimers were potential nephroprotective agents. LA might be an attractive drug candidate for renin-targeted CKD therapy.

Topics: Animals; Fibrosis; Humans; Kidney; Mice; Renal Insufficiency, Chronic; Renin; Transforming Growth Factor beta1

To study the chemical constituents from dry roots of Ligusticum glaucescens Franch.. Chromatography and spectrum analysis were employed to isolate and elucidate the chemical constituents in the plant.. 4 compounds were isolated and identified as levistolide A (I), ligustilide (II), pleuchiol (III) and ferulic acid (IV).. I-IV were isolated from this plant for the first time. The work provided evidence for the exploitation and utilization of this plant resource.

Topics: 4-Butyrolactone; Benzofurans; Coumaric Acids; Ligusticum; Methanol; Molecular Structure; Plants, Medicinal; Rhizome