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Our previous study demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) has hypo-cholesterolemic and anti-obesity activity. However, the molecular mechanisms of its effects are poorly characterized. We hypothesized that 5-uRCK and one of its major bioactive compounds, ellagic acid, decrease cellular and plasma cholesterol levels. Thus, we investigated the hypocholesterolemic activity and mechanism of 5-uRCK in both hepatocytes and a high-cholesterol diet (HCD)-induced rat model. Cholesterol in the liver and serum was significantly reduced by 5-uRCK and ellagic acid. The hepatic activities of HMG-CoA and CETP were reduced, and the hepatic activity of LCAT was increased by both 5-uRCK extract and ellagic acid, which also caused histological improvements. The MDA content in the aorta and serum was significantly decreased after oral administration of 5-uRCK or ellagic acid. Further immunoblotting analysis showed that AMPK phosphorylation in the liver was induced by 5-uRCK and ellagic acid, which activated AMPK, inhibiting the activity of HMGCR by inhibitory phosphorylation. In contrast, 5-uRCK and ellagic acid suppressed the nuclear translocation and activation of SREBP-2, which is a key transcription factor in cholesterol biosynthesis. In conclusion, our results suggest that 5-uRCK and its bioactive compound, ellagic acid, are useful alternative therapeutic agents to regulate blood cholesterol.

Dendropanax morbifera Léveille (Araliaceae) is an endemic species growing in the south-western part of South Korea and has been used in folk medicine and health functional food. Several studies have indicated that extract of D. morbifera (DP) has cytotoxic activities on a number of human cancers, such as, breast cancer, lung cancer, hepatoma, and chorioepithelioma. Recently, polyacetylene and triterpene compounds have been isolated from the DP and showed to have anti-complement activity. β-Amyrin, α-amyrin, dendropanoxide, and β-sitosterol are isolated from DP. However, its biological activities in cancer have not yet been clearly elucidated. In this study, we evaluated the anti-cancer activity of isolated triterpenoids from the DP leaves by measuring the levels of cytotoxicity against MCF-7 human breast cancer and A549 human lung cancer cells. Six triterpenoids were isolated from the n-hexane fraction of DP leaves along with the known compounds. β-amyrin (1), α-amyrin (2), olean-12-en-3,24 β-diol (3), dendropanoxide (4), β-sitosterol (5), and stigmasterol (6). Compound 3 and 6 were isolated from DP for the first time. Cytotoxic activities of six compounds were evaluated against two human cancer cell lines by using the MTT in vitro assay. Among them, five compounds (1, 2, 4, 5, and 6) showed moderate cytotoxic activities toward the tested cell lines, and were safe to normal cells. Western blot analysis showed a decreased expression of anti-apoptotic protein Bcl-2 and increased levels of pro-apoptotic protein Bax in MCF-7 and A549 cells treated by β-amyrin and α-amyrin. Flow cytometry analysis confirmed that five compounds (1, 2, 4, 5, and 6) treatment increased populations of sub-G1 (apoptosis) phase. The results of the present study revealed that triterpenoids from DP have the potential for further development as anticancer agents.

Previously, we demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) and ellagic acid has hypocholesterolemic and antiobesity activity, at least partially mediated by the downregulation of adipogenic and lipogenic gene expression in high-fat diet (HFD)-fed animals. The present study investigated the thermogenic and lipolytic antiobesity effects of 5-uRCK and ellagic acid in HFD-induced obese C57BL/6 mice and explored its mechanism of action. Mice fed an HFD received 5-uRCK or ellagic acid as a post-treatment or pretreatment. Both post-treated and pretreated mice showed significant reductions in body weight and adipose tissue mass compared to the HFD-fed mice. The protein levels of lipolysis-associated proteins, such as adipose triglyceride lipase (ATGL), phosphorylated hormone-sensitive lipase (p-HSL), and perilipin1 (PLIN1), were significantly increased in both the 5-uRCK- and ellagic acid-treated mouse epididymal white adipose tissue (eWAT). Additionally, thermogenesis-associated proteins, such as peroxisome proliferator-activated receptor &alpha, (PPAR&alpha, ), carnitine palmitoyl transferase-1 (CPT1), uncoupling protein 1 (UCP1), and peroxisome proliferator-activated receptor-&gamma, coactivator-1&alpha, (PGC1&alpha, ), in inguinal white adipose tissue (ingWAT) were clearly increased in both the 5-uRCK- and ellagic acid-treated mice compared to HFD-fed mice. These results suggest that 5-uRCK and ellagic acid are effective for suppressing body weight gain and enhancing the lipid profile.