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1.
FEBS Open Bio ; 6(1): 64-76, 2016 Jan.
Article in English | MEDLINE | ID: mdl-27047743

ABSTRACT

Recent findings on the association of gut microbiota with various diseases, including obesity, prompted us to investigate the possibility of using a certain type of gut bacteria as a safe therapeutic for obesity. Lactobacillus mutants with enhanced capacity in absorption of free fatty acids (FFAs) were isolated to show reduced absorption of FFAs by the administered host, attributing to inhibition of body weight gain and body fat accumulation as well as amelioration of blood profiles. Consequently, high throughput screening of natural FFAs-absorbing intestinal microbes led to the isolation of Lactobacillus reuteri JBD30 l. The administration of Lactobacillus JBD30l lowered the concentration of FFAs in the gut fluid content of small intestine, thus reducing intestinal absorption of FFAs whereas promoting fecal excretion of FFAs. Animal data also confirmed that the efficacy of Lactobacillus JBD30l on body weight similar to that of orlistat, an FDA-approved pharmaceutical for long-term use to treat obesity. In a subsequent random, double-blind, placebo-controlled clinical trial (KCT0000452 at Clinical Research Information Service of Korea), there was a statistically significant difference in the percentage change in body weight between the Lactobacillus JBD301 and the placebo group (P = 0.026) as well as in the BMI (P = 0.036) from the 0-week assessment to the 12-week assessment. Our results show that FFA-absorbing Lactobacillus JBD301 effectively reduces dietary fat absorption, providing an ideal treatment for obesity with inherent safety.

2.
J Cell Mol Med ; 17(5): 672-80, 2013 May.
Article in English | MEDLINE | ID: mdl-23551430

ABSTRACT

Multiple lines of evidence suggest that natural compounds can prevent skin ageing induced by ultraviolet light. Luteolin, a bioactive compound found in chilli, onion, broccoli, celery and carrot, has been reported to exhibit anti-photoageing effects in vitro. However, the molecular targets and mechanisms of luteolin are still poorly understood. In this study, we sought to investigate the effects of luteolin on UVB-induced photoageing and the molecular mechanisms involved, using HaCaT human keratinocytes and SKH-1 hairless mice. Luteolin was found to inhibit UVB-induced MMP-1 expression in HaCaT cells, as well as UVB-induced activation of AP-1, a well-known transcription factor targeting the MMP-1 promoter region, as well as c-Fos and c-Jun, which comprise the AP-1 complex. In contrast, Western blot data showed that UVB-induced phosphorylation of JNK, ERK and p90RSK was not inhibited by luteolin. In vitro kinase assay data revealed that luteolin significantly suppressed JNK1 and p90RSK activity, but not that of JNK2 and ERK2. Pull-down assays showed that luteolin binds JNK1 in an ATP-competitive manner and p90RSK2 in an ATP-independent manner. Luteolin also inhibited UVB-induced wrinkle formation and MMP-13 expression, a rodent interstitial collagenase in mouse skin, in vivo. Taken together, our observations suggest that luteolin exhibits anti-photoageing effects in vitro and in vivo and may have potential as a treatment for the prevention of skin ageing.


Subject(s)
Luteolin/pharmacology , Mitogen-Activated Protein Kinase 8/antagonists & inhibitors , Ribosomal Protein S6 Kinases, 90-kDa/antagonists & inhibitors , Skin Aging/radiation effects , Ultraviolet Rays , Adenosine Triphosphate/pharmacology , Animals , Binding, Competitive/drug effects , Binding, Competitive/radiation effects , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Keratinocytes/drug effects , Keratinocytes/enzymology , Keratinocytes/radiation effects , Luciferases/metabolism , Luteolin/chemistry , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 13/metabolism , Mice , Mice, Hairless , Mitogen-Activated Protein Kinase 8/metabolism , Models, Biological , Phosphorylation/drug effects , Phosphorylation/radiation effects , Promoter Regions, Genetic/genetics , Protein Binding/drug effects , Protein Binding/radiation effects , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-jun/metabolism , Ribosomal Protein S6 Kinases, 90-kDa/metabolism , Skin Aging/drug effects , Transcription Factor AP-1/genetics , Transcription Factor AP-1/metabolism , Transcriptional Activation/drug effects , Transcriptional Activation/radiation effects
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