Dihydroisotanshinone I Protects Against Menadione-Induced Toxicity in a Primary Culture of Rat Hepatocytes

Abstract

Dihydroisotanshinone I is a phenanthrenequinone derivative isolated from the roots of Salvia trijuga Diels. The present study demonstrated the hepatoprotective effect of dihydroisotanshinone I against menadione-induced cytotoxicity in a primary culture of rat hepatocytes. Pretreating the cells with dihydroisotanshinone I at concentrations ranging from 2.5 microM to 20 microM for 24 hours caused dose-dependent protection against hepatotoxicity induced by menadione. Intracellular glutathione level and activity of DT-diaphorase have been suggested to play important roles in menadione-induced cytotoxicity. However, treating the hepatocytes with 20 microM dihydroisotanshinone I for 24 hours did not cause a significant change in glutathione level and DT-diaphorase activity. On the contrary, adding dihydroisotanshinone I to freshly isolated hepatocytes at concentrations between 50 nM to 200 nM inhibited NADH-induced superoxide production dose-dependently as indicated by the decrease of lucigenin-amplified chemiluminescence. In addition, dihydroisotanshinone I at concentrations ranging from 5 microM to 20 microM inhibited tert-butyl hydroperoxide-induced lipid peroxidation dose-dependently in isolated hepatocytes as indicated by the level of malondialdehyde. These results suggest that the protective action of dihydroisotanshinone I against menadione-induced hepatotoxicity is attributed to its antioxidant properties including the free radical scavenging activity and inhibition of lipid peroxidation. Abbreviations. DTD:DT-diaphorase GSH:glutathione LDH:lactate dehydrogenase MDA:malondialdehyde MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide TBHP: tert-butyl hydroperoxide

Anti-cancer effect of danshen and dihydroisotanshinone I on prostate cancer: targeting the crosstalk between macrophages and cancer cells via inhibition of the STAT3/CCL2 signaling pathway

“…Specifically, T1 has inhibited the growth of leukemia and lung and colorectal cancer cells in vitro [29–31], T2A has inhibited the growth of breast cancer, glioma, leukemia, and hepatocellular carcinoma cells in vitro [32–35], and CT inhibited the growth of hepatocarcinoma cells in vitro [36]. Moreover, DT, which contains an abietane-type diterpene quinone (Supplementary Figure 1A), has a protective effect against menadione-induced hepatotoxicity because of its antioxidant properties and its ability to inhibit lipid peroxidation [37]. However, the clinical effects of danshen and the underlying mechanisms of DT on prostate cancer remain unclear.…”

Induction of ferroptosis by natural products in non-small cell lung cancer: a comprehensive systematic review

“…Salvia miltiorrhiza has been widely used in traditional Chinese medicine and possess diverse pharmacological activities and therapeutic potential (XD et al, 2019;He et al, 2024). Research studies have demonstrated that DTIDTI exhibits anti-oxidant (Ip et al, 2002), and anti-cancer properties (Wu et al, 2017;Lin et al, Frontiers in Pharmacology frontiersin.org 2019). Wu (Wu et al, 2021)have shown that DTI inhibits the growth of A549 cells and H460 cells via inducing ferroptosis.…”