1β-Hydroxy-2-oxopomolic acid isolated from Agrimonia pilosa extract inhibits adipogenesis in 3T3-L1 cells

In order to determine anti-adipogenic effect, this study investigated 1β-hydroxy-2-oxopomolic acid (HOA) isolated from Agrimonia pilosa inhibits adipocyte differentiation and expression of adipogenic marker genes, such as peroxisome proliferator activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), glucose transporter 4 (GLUT4), adiponectin, adipocyte fatty acid-binding protein 2 (aP2), adipocyte determination and differentiation factor 1/sterol regulatory element binding protein 1c (ADD1/SREBP1c), resistin, and fatty acid synthase (Fas) in 3T3-L1 preadipocyte. We demonstrated that HOA induced a significant decrease in lipid accumulation and expression of adipogenic marker genes in a dose-dependent manner. In addition, HOA reduced the transcripitional activity of PPARγ induced by troglitazone, a potent diabetes agent; it also suppressed expression of PPARγ and C/EBPα protein levels. Our data suggest that HOA isolated from Agrimonia pilosa inhibits adipocyte differentiation through downregulation of various adipocytokines by blocking PPARγ and C/EBPα expression.     

Phenylpropanoid ester from <Emphasis Type="Italic">Zingiber officinale</Emphasis> and their inhibitory effects on the production of nitric oxide

A new phenylpropanoid ester mixture, (E)-geranylferulic acid (1a) and (Z)-geranylferulic acid (1b), along with 13 known compounds, [6]-gingerol (2), [8]-gingerol (3), [10]-gingerdione (4), 1-dehydro-[6]-gingerdione (5), 1-dehydro-[8]-gingerdione (6), [6]-paradol (7), [8]-paradol (8), [6]-gingeroldiacetate (9), 6-hydroxy-[6]-shogaol (10), galanolactone (11), trans-®-sesquiphellandrol (12), trans-sesquipiperitol (13), and 4α,5β-dihydroxybisabola-2,10-diene (14) were isolated from ethanol extract of Zingiber officinale. Their structures were determined based on the spectroscopic (1D, 2D-NMR and MS) and chemical evidence. All of the isolates were evaluated for their potential to inhibit LPS-induced production of nitric oxide in murine macrophage RAW264.7 cells. Compounds 1–12 were found to inhibit nitric oxide production with IC₅₀ values ranging from 5.5 to 28.5 μM.     

Interleukin‐27 suppresses osteoclastogenesis via induction of interferon‐γ

Interleukin (IL)‐27 is a heterodimeric cytokine that is known to have both stimulatory and inhibitory functions during immune responses. We investigated the effects of IL‐27 on arthritis and bone erosion in the murine collagen‐induced arthritis (CIA) model. We demonstrate that the inhibitory effect of IL‐27 on osteoclastogenesis is associated with interferon‐γ (IFN‐γ) production by using an IFN‐γ knockout mouse model. The IL‐27‐Fc was injected into both CIA and IFN‐γ‐deficient mice. The effects of IL‐27‐Fc on osteoclast differentiation were evaluated both in vitro and in vivo. The IL‐27‐Fc‐injected mice showed significantly lower arthritis indices and fewer tartrate‐resistant acid‐phosphatase‐positive osteoclasts in their joint tissues than untreated mice. Interleukin‐27 inhibited osteoclastogenesis from bone marrow‐derived mononuclear cells in vitro, which was counteracted by the addition of anti‐IFN‐γ antibody. The IL‐27‐Fc did not affect arthritis in IFN‐γ knockout mice. Interleukin‐27 also suppressed osteoclast differentiation in human and intriguingly, it could promote the expression of IFN‐γ on priming osteoclasts. These results imply that IL‐27 suppressed the generation of CIA and osteoclastogenesis, which were mediated by the induction of IFN‐γ.     

Successful Conservative Treatment: Multiple Atypical Fractures in Osteoporotic Patients After Bisphosphate Medication: A Unique Case Report

Bisphosphonates have been commonly used for the treatment of osteoporosis. However, there have been recent case reports of atypical fractures citing their long-term use, which inhibits the turnover of bone components.A 64-year-old woman visited the outpatient clinic with pain in her right thigh and ambulation difficulty. We found fractures at both pedicles of L4 vertebra. subtrochanteric region of right femur, and left femoral shaft upon a radiologic examination. She had taken intravenous ibandronic sodium for osteoporosis over 3 years.We changed the bishophonates to a parathyroid hormone because it was suspected that the multiple fractures were caused by the medication. Further, rehabilitation, including progressive weight bearing, was started. After 3 months of the conservative treatment, she was able to walk independently.In conclusion, it is necessary to evaluate the possibility of atypical fractures in osteoporotic patients when they complain of lower extremity pain and to consider alternative treatments instead of bisphosphonates.