Records of Natural Products

A new (1) and six known (2-7) monoester-type C19-diterpenoid alkaloids were isolated from the lateral roots of Aconitum carmichaelii Debx. Their structures were determined by spectroscopic techniques and calculations of NMR chemical shifts. Compound 1 (1-epi-hokbusine A) was an aconitine-type diterpenoid alkaloid possessing an unusual 1β-methoxy group. According to the main toxicity of the lateral roots of A. carmichaelii, the cardiotoxic effects of the isolates were evaluated using H9c2 rat myocardial cells and zebrafish embryos. The results showed that all the monoester-type C19-diterpenoid alkaloids exhibited cardiotoxicity, and compound 6 was found to be the most toxic compound.

Two new seco-abietanoids, 12-hydroxy-6-nor-5,6-secoabieta-8,11,13-trien-7-oic acid (1) and 7-hydroxy-7,8-secoabieta-8,12-diene-6,11,14-trione (3), together with one known seco-abietanoid, 12-hydroxy-6-nor-5-oxo-5,6-secoabieta-8,11,13-trien-7-al (2), were isolated from the methanol extract of the bark of Cryptomeria japonica. Their structures were elucidated by mean of spectroscopic analysis, as well as on  comparison of NMR data with those of known analogues. At a concentration of 50 μM, compounds 1–3 showed inhibitory activity toward xanthine oxidase by 38.2%, 55.9%, and 23.0%, respectively.

A new iridoid glycoside, (5S,7S,8S,9R)-7- hydroxy-∆4,11-dihyronepeta-1,3-diol-8-O-β-D-glucopyranosyl (1), along with 5 known compounds, dioscoridin A (2), jatamanin J (3), longiflorone (4), apigenin-8-O-β-D-glucopyranoside (5), isosakuranetin-5-O-rutinoside (6), were isolated from the Valeriana officinalis L. Their structures were determined by extensive analysis using various spectroscopic techniques. Moreover, the cytotoxic activity assay toward three human tumor cell (A549, HCT116 and SW620) lines were evaluated by the MTT method in vitro for compounds 1-2, using cisplatin as positive control. Experimental results showed that these compounds displayed weak cytotoxicity in the human cancer cell lines. Notably, compounds 2, 3 and 6 were firstly isolated from this plant, compound 4 was isolated from the genus Valeriana for the first time, compound 5 was isolated for the first time from Valerianaceae family.

Cisplatin utilization is known to be limited due to numerous side effects, especially to the ones related to kidney tissue injury. The application of antioxidants, as potential supportive drugs, to prevent oxidative cisplatin tissue damage appears intuitive. In this work, we explored the usage of caffeic acid phenethyl ester (CAPE) in this respect through the analysis of standard serum biochemical parameters and the ones related to oxidative tissue damage, the changes in arginine metabolism, and apoptosis occurrence that follow cisplatin application in rat kidneys. Additionally, pathohistological analysis and a specific TUNEL staining for the detection of apoptosis was studied. Cisplatin produced marked changes in serum parameters that reflect kidney tissue function, while at the same time produced extensive tissue oxidative damage, increased arginase activity, and depleted reduced glutathione. Moreover, both biochemical and micromorphological analyses indicated significant tubular cell apoptosis. The application of CAPE together with cisplatin prevented the disturbance in serum biochemical and tissue oxidative stress parameters, without affecting arginase activity. Interestingly, CAPE inhibited different enzymes involved in the glutathione metabolism and the apoptotic process. The results of the present study indicate that CAPE could be used as supportive therapy for oncological patients receiving cisplatin since it attenuates the nephrotoxicity of this chemotherapeutic.