Ji-Cheon Jeong

Piperine, a Component of Black Pepper, Inhibits Adipogenesis by Antagonizing PPARγ Activity in 3T3-L1 Cells

This study investigated the antiadipogenic activity of black pepper extract and its constituent piperine in 3T3-L1 preadipocytes as well as the underlying molecular mechanisms. Both black pepper extract and piperine, without affecting cytotoxicity, strongly inhibited the adipocyte differentiation of 3T3-L1 cells. The mRNA expression of the master adipogenic transcription factors, PPARγ, SREBP-1c, and C/EBPβ, was markedly decreased. Intriguingly, mRNA levels of PPARγ target genes were also down-regulated. Moreover, a luciferase reporter assay indicated that pipierine significantly represses the rosiglitazone-induced PPARγ transcriptional activity. Finally, GST-pull down assays demonstrated that piperine disrupts the rosiglitazone-dependent interaction between PPARγ and coactivator CBP. Genome-wide analysis using microarray further supports the role of piperine in regulating genes associated with lipid metabolism. Overall, these results suggest that piperine, a major component of black pepper, attenuates fat cell differentiation by down-regulating PPARγ activity as well as suppressing PPARγ expression, thus leading to potential treatment for obesity-related diseases.

Inhibitory activity of Drynariae rhizoma extracts on cathepsin having bone resorption activity.

Effects of traditional Korean (Hanbang) medicine, Drynariae rhizoma (DR), on the protease activity of bone loss‐initiation in rats and mice were investigated. Ethanol extracts‐DR (EE‐DR) and water extracts‐DR (WE‐DR) were identified as potent inhibitor of cathepsins K and L. The original WE‐DR inhibits cathepsins K and L with IC50 values of 3.7 µg/ml and 4.5 µg/ml, respectively. EE‐DR was more potent than that of WE‐DR, because the inhibitions of cathepsin K and L increased to 0.5 µg/ml and 0.8 µg/ml, respectively. The EE‐DR was proved to be the most potent. EE‐DR was found to be a potent inhibitor of cathepsins K with a Ki value of 5.0 µg/ml for cathepsin K. The activity was increased by 10‐fold when the assay is performed in the presence of glutathione at pH 7.0, which favors the formation of a GSH thiolate anion. Thus, it is suggested that this increase in potency is probably due to an enhanced chemical reactivity of the extract mixtures toward the thiolate of the active site of the enzyme. WE‐DR exhibited time‐dependet inhibition which allowed us to determine the association and dissociation rate constants with cathepsin K. Finally, EE‐DR inhibits bone resorption in an in vitro assay involving mouse osteoclasts and bovine bone with an IC50 value of 70 µg/ml. WE‐DR represents a new herbal formulation inhibiting cathepsin K and L activity and proteolysis of bone collagen. These results strongly suggest that DR is effective for preventing the development of bone loss induced by cathepsin K. This result also suggested that the DR is effective for bone resorptive action in bone cells.

Repression of LXRα by a novel member of additional sex comb-like family, ASXL3.

Among the members of the additional sex comb-like (ASXL) family, ASXL3 remains unexplored. Here, we showed that ASXL3 interacts with HP1α and LSD1, leading to transcriptional repression. We determined that ASXL3 depletion augments the ligand-induced transcriptional activities of LXRα and TRβ, which were repressed by ASXL3 overexpression. The ligand-dependent interactions of ASXL3 with LXRα and TRβ were demonstrated by the GST pull-down and immunoprecipitation analyses. We confirmed that ASXL3 suppresses the expression of LXRα target genes through its recruitment to the LXR-response elements. Finally, we observed that lipid accumulation in Hep3B cells is downregulated upon ASXL3 overexpression but upregulated upon ASXL3 depletion. Overall, our data suggest that ASXL3 is another corepressor of LXRα, promoting to the regulation of lipid homeostasis.

Inhibitory effects of Bombusae concretio Salicea on neuronal secretion of Alzheimer's β-amyloid peptides, a neurodegenerative peptide

Alzheimers disease (AD) is characterized by the age-related deposition of β-amyloid (Aβ) 40/42 peptide aggregates in vulnerable brain regions. Multiple levels of evidence implicate a central role for Aβ in the pathophysiology of AD. Aβ is generated by the regulated cleavage of a = 700 amino acid Aβ precursor protein (βAPP). Full-length βAPP can undergo proteolytic cleavage either within the Aβ domain to generate secreted sβAPPα or at the N-terminal and C-terminal domain(s) of Aβ to generate amyloidogenic Aβ peptides. Several epidemiological studies have reported that estrogen replacement therapy protects against the development of AD in postmenopausal women. The aim of this study was to elucidate the antioxidant neuroprotective mechanism of Bombusae concretio Salicea (BC). BC was effective protectants against oxidative glutamate toxicity in the murine neuroblastoma cells (N2a) and human neuroblastoma cells (SK-N-MC). BC exhibited similar protective properties against oxidative glutamate toxicity and H2O2 toxicity. BC exhibited an antioxidant activity at approximately 20 μg/ml. BC of 5 μg/ml was ineffective in preventing the oxidative modification of LDL. The half-maximal effective concentration for BC was 16 μg/ml. These results suggested that BC supplementation in elderly men may be protective in the treatment of Alzheimers disease (AD). We report here that treatment with BC increases the secretion of the nonamyloidogenic APP fragment, sβAPPα and decreases the secretion of Aβ peptides from N2a cells and rat primary cerebrocortical neurons. These results raise the possibility that BC supplementation in elderly men may be protective in the treatment of AD.