Hyong Joo Lee

Scope: Indole‐3‐carbinol (I3C), a derivative abundant in cruciferous vegetables such as cabbage, is well known for its various health benefits such as chemo‐preventive and anti‐obesity effects. I3C is easily metabolized to 3,3′‐diindolylmethane (DIM), a more stable form, in acidic conditions of the stomach. However, the anti‐obesity effect of DIM has not been investigated clearly. We sought to investigate the effect of DIM on diet‐induced obesity and to elucidate its underlying mechanisms.Methods and results: High‐fat diet (HFD)‐fed obese mouse and MDI‐induced 3T3‐L1 adipogenesis models were used to study the effect of DIM. We observed that the administration of DIM (50 mg/kg BW) significantly suppressed HFD‐induced obesity, associated with a decrease in adipose tissue. Additionally, we observed that DIM treatment (40 and 60 μM), but not I3C treatment, significantly inhibited MDI‐induced adipogenesis by reducing the levels of several adipogenic proteins such as PPAR‐γ and C/EBPα. DIM, but not I3C, suppressed cell cycle progression in the G1 phase, which occurred in the early stage of adipogenesis, inducing post‐translational degradation of cyclin D1 by inhibiting ubiquitin specific peptidase 2 (USP2) activities.Conclusion: Our findings indicate that cruciferous vegetables, which can produce DIM as a metabolite, have the potential to prevent or treat chronic obesity.

Ginseng (Panax ginseng C.A. Meyer) has been used as a traditional herb in the treatment of many medical disorders. Ginsenosides, which are triterpene derivatives that contain sugar moieties, are the main pharmacological ingredients in ginseng. This study was designed to investigate the effect of ginsenoside Rg3-enriched ginseng extract (Rg3GE) on scopolamine-induced memory impairment in mice. Rg3GE (50 and 100 mg/kg) were administered to C57BL/6 mice by oral gavage for 14 days (days 1–14). Memory impairment was induced by scopolamine (1 mg/kg, intraperitoneal injection) for 6 days (days 914). The Morris water maze test was used to assess hippocampus-dependent spatial memory. The effects of scopolamine with or without Rg3GE on acetylcholinesterase and nuclear factor-κB (NF-κB) in the hippocampus were also examined. Mice with scopolamine treatment alone showed impairments in the acquisition and retention of spatial memory. Mice that received Rg3GE and scopolamine showed no scopolamine-induced impairment in the acquisition of spatial memory. Oral administration of Rg3GE suppressed the scopolamine-mediated increase in acetylcholinesterase activity and stimulation of the NF-κB pathway (i.e., phosphorylation of p65) in the hippocampus. These findings suggest that Rg3GE may stabilize scopolamine-induced memory deficits through the inhibition of acetylcholinesterase activity and NF-κB signaling in the hippocampus.

Background Collagens have long been used in pharmaceuticals and food supplements for the improvement of skin. Aim We evaluated the efficacy of high advanced‐collagen tripeptide (HACP) on wound healing and skin recovery. Methods Using an in vitro model, we performed HaCaT cell migration assays and collagen gel contraction assays using HACP concentrations of 1, 10 and 100 μg/mL. In this pilot study, eight healthy volunteers were randomly divided into two groups. Both the control and experimental groups received fractional photothermolysis treatment, but in the experimental group, four subjects received 3 g/day of oral collagen peptide (CP) for 4 weeks. To assess transepidermal water loss in each patient before and after the treatment, we used a Corneometer and a Cutometer, and we also assessed the patient's Erythema Index. Results The cell migration assay showed that HACP enhanced wound closure, but not in a dose‐dependent manner. The collagen gel contraction assay showed increased contractility when patients were treated with 100 μg/mL HACP, but the results were not significantly different from those of controls. We found that post‐laser erythema resolved faster in the experimental group than in the control group (P < 0.05). In addition, the recovery of skin hydration after fractional laser treatment was greater in the experimental group than in the control group by day 3 (P < 0.05), and the experimental group showed significantly improved post‐treatment skin elasticity compared with the controls by day 14 (P < 0.05). Conclusions Collagen tripeptide treatment appears to be an effective and conservative therapy for cutaneous wound healing and skin recovery after fractional photothermolysis treatment.

Various health effects have been attributed to the ginsenoside metabolite 20‐O‐β‐D‐glucopyranosyl‐20(S)‐protopanaxadiol (GPD); however, its effect on ultraviolet (UV)‐induced matrix metalloproteinase (MMP)‐1 expression and the mechanism underlying this effect are unknown. We examined the inhibitory effect of GPD on UV‐induced MMP‐1 expression and its mechanisms in human dermal fibroblasts (HDFs). GPD attenuated UV‐induced MMP‐1 expression in HDFs and suppressed the UV‐induced phosphorylation of mammalian target of rapamycin (mTOR) and p70^S6K without inhibiting the activity of phosphatidylinositol 3‐kinase and Akt, which are well‐known upstream kinases of mTOR. GPD augmented the phosphorylation of liver kinase B1 (LKB1) and adenosine monophosphate‐activated protein kinase (AMPK), which are inhibitors of mTOR, to a greater extent than UV treatment alone. Similar to GPD, 5‐aminoimidazole‐4‐carboxamide‐1‐β‐d‐ribofuranosyl 5′‐monophosphate (AICAR), an activator of AMPK, augmented UV‐induced AMPK phosphorylation to a greater extent than UV treatment alone, resulting in the inhibition of MMP‐1 expression. AICAR also decreased the phosphorylation of mTOR and p70^S6K. However, compound C, an antagonist of AMPK, increased MMP‐1 expression. In HDF cells with AMPK knock‐down using shRNA, MMP‐1 expression was increased. These results indicate that AMPK activation plays a key role in MMP‐1 suppression. Additionally, the cAMP‐dependent protein kinase (PKA) inhibitor, H‐89, antagonized GPD‐mediated MMP‐1 suppression via the inhibition of LKB1. Our results suggest that the suppressive activity of GPD on UV‐induced MMP‐1 expression is due to the activation of AMPK as a downstream of the PKA‐LKB1 pathway. J. Cell. Biochem. 115: 1702–1711, 2014.

In the present study, we aimed to investigate the antiobesity effect of CAPE in vivo, and the mechanism by which CAPE regulates body weight in vitro. To confirm the antiobesity effect of CAPE in vivo, mice were fed with a high fat diet (HFD) with different concentrations of CAPE for 5 weeks. CAPE significantly reduced body weight gain and epididymal fat mass in obese mice fed a HFD. In accordance with in vivo results, Oil red O staining results showed that CAPE significantly suppressed MDI-induced adipogenesis of 3T3-L1 preadipocytes. FACS analysis results showed that CAPE delayed MDI-stimulated cell cycle progression, thereby contributing to inhibit mitotic clonal expansion (MCE), which is a prerequisite step for adipogenesis. Also, CAPE regulated the expression of cyclin D1 and the phosphorylation of ERK and Akt, which are upstream of cyclin D1. These results suggest that CAPE exerts an antiobesity effect in vivo, presumably through inhibiting adipogenesis at an early stage of adipogenesis.

Cellular oxidative damage mediated by reactive oxygen species has been reported to inhibit gap‐junctional intercellular communication (GJIC). In turn, the inhibition of GJIC can be attenuated by functional food compounds with antioxidant properties. In this study, we compared the protective effects of onion peel extract (OPE) and onion flesh extract (OFE) on oxidative stress‐mediated GJIC inhibition, and investigated the mechanisms of action responsible. OPE restored H ₂ O ₂ ‐induced GJIC inhibition to a higher degree than OFE in WB‐F344 rat liver epithelial cells. OPE was found to inhibit H ₂ O ₂ ‐induced phosphorylation of ERK1/2 and Cx43. A radical scavenging assay demonstrated superiority of OPE over OFE, suggesting that the observed effects might be mediated via an antioxidant mechanism. Quercetin is the major compound that is likely to be responsible for the protective effect against H ₂ O ₂ ‐mediated GJIC inhibition. This study suggests that OPE, a material often discarded, may be of value for the future development of functional food products. Practical Application: This study demonstrates that onion peel extract (OPE) exhibits a protective effect against the inhibition of gap‐junctional intercellular communication (GJIC) mediated by H ₂ O ₂ , which is likely to occur via its antioxidant activity. OPE contains significant concentrations of bioactive phenolic compounds. Reductions in oxidative stress can lead to recovery of GJIC, which has been reported to be implicated in the prevention and treatment of cancers. These findings suggest that onion peel, a common waste product, could be used as potential resources for functional food development. Onion peel could be processed into a quercetin‐rich powder or a pill for the prevention of cancer and other oxidative stress‐related diseases.