Bioactivity‑Guided Isolation of Totarane‑Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3‑Deoxy‑2α‑hydroxynagilactone E

Bioactivity-guided phytochemical investigation of Podocarpus neriifolius D.Don.(Podocarpaceae)has led to the isolation of one new(2)and three known(1,3,and 4)B-type podolactones,along with three totarane-type diterpenes(5-7).Their structures were determined by interpretation of High Resolution ElectroSpray Ionization Mass Spectrometry(HRESIMS)and 1D and 2D NMR data,and comparison with the values reported in the literature.The structure of compound 1,previously identifed as 3-deoxy-2α-hydroxynagilactone E(8),was revised as its 2β-epimer,which has been reported recently as a new compound.All of the isolates were evaluated for their antiproliferative activity against a panel of four human cancer cell lines,namely,ovarian(OVCAR3),breast(MDA-MB-231),colon(HT-29),and melanoma(MDA-MB-435),and compounds 1 and 3 were found to be cytotoxic with IC_(50) values in the low micromolar range for most of the cell lines used.The major compound,inumakilactone A(3),was further tested in vivo using the HT-29,MDA-MB-435,and OVCAR3 cells in a murine hollow fber model,for the frst time.

Inhibitory Effects of 2,3,4',5-tetrahydroxystilbene-2-O-β-D-glucoside on Angiotensin Ⅱ-Induced Proliferation of Vascular Smooth Muscle Cells

Objective：To investigate the effect of 2,3,4’,5-tetrahydroxystilbene-2-0- p-D-glucoside（TSG）,an active component extracted from the root of Polygonum multiflorum,on angiotensin Ⅱ（Ang Ⅱ）-induced proliferation of cultured rat vascular smooth muscle cells（VSMCs） and to identify the potential mechanism.Methods：Cell proliferation and cell cycle were determined by cell counting,5-bromo-2’-deoxyuridine incorporation assay,proliferating cell nuclear antigen protein expression and flow cytometry.Levels of phosphorylated extracellular signal-regulated kinase 1/2（ERK1/2）,mitogenic extracellular kinase 1/2（MEK1/2） and Src in VSMCs were measured by Western blot.The expression of c-fos,c-jun and c-myc mRNA were measured by reverse transcription polymerase chain reaction（RT-PCR）.Intracellular reactive oxygen species（ROS） was measured by fluorescence assay.Results：TSG significantly inhibited Ang Ⅱ-induced VSMCs proliferation and arrested cells in the G1/S checkpoint（P〈0.05 or P〈0.01）.TSG decreased the levels of phosphorylated ERK1/2,MEK1/2 and Src in VSMCs（P〈0.05 or P〈0.01）.TSG also suppressed c-fos,c-jun and c-myc mRNA expression（P〈0.05 or P〈0.01）.In addition,the intracellular ROS was reduced by TSG（P〈0.01）.Conclusions：TSG inhibited Ang Ⅱ-induced VSMCs proliferation.Its antiproliferative effect might be associated with down-regulation of intracellular ROS,followed by the suppression of the Src-MEK1/2-ERK1/2 signal pathway,and hence,blocking cell cycle progression.

Screening and Identifying Hepatotoxic Components in Polygoni multiflori Radix and Polygoni multiflori Radix Praeparata

Objective: In this study, the hepatotoxic components of Polygoni multiflori Radix and Polygoni multiflori Radix Praeparata(known as Heshouwu [HSW] and Zhiheshouwu [ZHSW] in China, respectively) were screened, isolated, and identified. Materials and Methods: The ethanol extracts of HSW and ZHSW were separated into 80 fractions according to their polarity in the preparation liquid phase. Chang liver cell line was used to screen the toxic components of HSW and ZHSW in vitro. The obtained toxic mixture was further collected, isolated, and identified to confirm the hepatotoxic compounds of HSW and ZHSW. Results: The identifid hepatotoxic compounds include 2,3,5,4’-tetrah ydroxystilbene-2-O-β-D-glucoside, emodin, physcion-8-O-β-d-glucoside, physcion, and citreorosein, the fist two among them were the main components of HSW and ZHSW. After processing of HSW, the contents of 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside and emodin in ZHSW were signifiantly decreased. Conclusions: The traditional processing with herb has signifiant effects on the components, especially the toxic components, in the extract of HSW and is an effective method to reduce its toxicity.

New Isoflavonoid Glycosides from the Rhizomes of Iris leptophylla Lingelsh.

Two new isoflavonoid glucosides, 5-hydroxy-6,7-methylenedioxy-isoflavone-4＇-O-D-glucopyranosyl （2→〉l）-L-rhamnoside （irilone-bioside） （compound 1） and 5,4＇-methoxy-6,7-methylenedioxyisoflavone-3＇-O-β-D-glucoside （irisleptophyllidin） （compound 2）, together with five known compounds, nigricanin- 4＇-O-β-D-glucoside （compound 3）, irifloside （compound 4）, irigenin （compound 5）, 5, 3＇, 4＇-trimethoxy-6,7-methylenedioxyisoflavone （compound 6）, and nigricanin （compound 7） were isolated from the alcoholic extract of rhizomes of Iris leptophylla Lingelsh. Their structures were elucidated by spectroscopic methods.