Hong Pyo Kim

LCC, a cerebroside from Lycium chinense, protects primary cultured rat hepatocytes exposed to galactosamine.

Primary cultures of rat hepatocytes exposed to galactosamine (GalN) were used as a screening system to assess whether a new cerebroside, LCC, isolated from the fruits of Lycium chinense, exhibits hepatoprotective activity. Cultured rat hepatocytes injured with GalN routinely release glutamic pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) into the culture medium. Treatment of these GalN‐injured primary cultures with LCC markedly blocked the release of both GPT and SDH in a dose‐dependent manner over concentrations of LCC ranging from 1 µM to 10 µM. To investigate the mechanism of action for the hepatoprotective activity of LCC, the extent of [3H]‐uridine incorporation into RNA was measured in GalN‐injured cultures of rat hepatocytes. [3H]‐Uridine incorporation was significantly decreased in injured hepatocytes. LCC, however significantly restored the incorporation of [3H]‐uridine into RNA in a dose‐dependent manner over concentrations ranging from 1 µM to 10 µM. LCC also blocked the suppression of RNA synthesis caused by actinomycin D in a dose‐dependent manner. These data suggest that LCC may have prominent hepatoprotective activity and that its therapeutic value should be investigated further. Copyright

Antihepatotoxic zeaxanthins from the fruits ofLycium chinense

A CHCl3: MeOH extract of the fruit ofLycium chinense Mill. (Solanaceae) was found to afford significant protection against carbon tetrachloride-induced toxicity in primary cultures of rat hepatocytes. Subsequent activity-guided fractionation resulted in the isolation of zeaxanthin and zeaxanthin dipalmitate as antihepatotoxic components. Incubation of injured hepatocytes with zeaxanthin dipalmitate reduced the levels of glutamic pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) released from damaged cells to 60.5% and 76.3% of those released from untreated controls, respectively. Zeaxanthin also reduced the levels of GPT and SDH to 68.5% and 61.3% of the levels of those released from the untreated control. The results confirm the hepatoprotective activities of zeaxanthins. Antihepatotoxic activities of zeaxanthins are comparable to that of silybin.

Salicortin-Derivatives from Salix pseudo-lasiogyne Twigs Inhibit Adipogenesis in 3T3-L1 Cells via Modulation of C/EBPα and SREBP1c Dependent Pathway

Obesity is reported to be associated with excessive growth of adipocyte mass tissue as a result of increases in the number and size of adipocytes differentiated from preadipocytes. To search for anti-adipogenic phytochemicals, we screened for inhibitory activities of various plant sources on adipocyte differentiation in 3T3-L1 preadipocytes. Among the sources, a methanolic extract of Salix pseudo-lasiogyne twigs (Salicaceae) reduced lipid accumulation in a concentration-dependent manner. During our search for anti-adipogenic constituents from S. pseudo-lasiogyne, five salicortin derivatives isolated from an EtOAc fraction of this plant and bearing 1-hydroxy-6-oxo-2-cyclohexene-carboxylate moieties, namely 2′,6′-O-acetylsalicortin (1), 2′-O-acetylsalicortin (2), 3′-O-acetylsalicortin (3), 6′-O-acetylsalicortin (4), and salicortin (5), were found to significantly inhibit adipocyte differentiation in 3T3-L1 cells. In particular, 2′,6′-O-acetylsalicortin (1) had the most potent inhibitory activity on adipocyte differentiation, with an IC50 value of 11.6 μM, and it significantly down-regulated the expressions of CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element binding protein 1 (SREBP1c). Furthermore, 2′,6′-O-acetylsalicortin (1) suppressed mRNA expression levels of C/EBPβ during the early stage of adipocyte differentiation and stearoyl coenzyme A desaturase 1 (SCD-1), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) expression, target genes of SREBP1c. In the present study, we demonstrate that the anti-adipogenesis mechanism of 2′,6′-O-acetylsalicortin (1) may be mediated via down-regulation of C/EBPα and SREBP1c dependent pathways. Through their anti-adipogenic activity, salicortin derivatives may be potential novel therapeutic agents against obesity.

Selective Apoptosis in Hepatic Stellate Cells Mediates the Antifibrotic Effect of Phenanthrenes from Dendrobium nobile

Regardless of the etiology, cellular death of the liver parenchymal hepatocyte seems to be a primary event of hepatic fibrogenesis, which ultimately results in hepatic stellate cell (HSC) activation and the synthesis of extracellular matrix proteins. Recently it has been demonstrated that hepatic fibrosis can be a reversible process when the stimulus is properly eliminated. Apoptotic removal of active HSC is considered an essential part of the resolution. By employing the HSC cell line, HSC‐T6, it was found that the methanol extract of Dendrobium nobile stem significantly inhibited the proliferation of HSC‐T6 cells. Three phenanthrenes, denbinobin, fimbriol B and 2,3,5‐trihydroxy‐4,9‐dimethoxyphenanthrene isolated from D. nobile were proven to inhibit HSC proliferation. Growth arrest of HSCs by these compounds was accompanied by cellular loss via autophagy‐linked apoptosis. The maximal dose of these compounds, however, had little effect on primary cultured hepatocytes in rats. Collagen deposition in HSC‐T6 cells was attenuated by these phenanthrenes. Collectively, the above results demonstrated that denbinobin, fimbriol B and 2,3,5‐trihydroxy‐4,9‐dimethoxyphenanthrene exhibited antifibrotic activities possibly by the induction of selective cell death in HSCs but not in hepatocytes, implying that these compounds may be useful candidates for developing therapeutic agents for the prevention and treatment of hepatic fibrosis. Copyright