Inhibition of Photoaging by Anthocyanin Metabolites Derived from Rose Petal Extract.

SCOPE: Rose petal extract (RPE) shows a significant antioxidant effect through its anthocyanin content. However, the mechanism underlying the anti-aging effects of orally administered RPE remains unclear. This study aims to describe the anti-aging effect and mechanism of action of orally administered RPE in ultraviolet (UV)B-induced skin aging. METHODS AND RESULTS: This study evaluates the protein expression of collagen type I alpha 1 (COL1A1) and matrix metalloproteinase 1 (MMP-1) and the mRNA expression of hyaluronic synthase 2 (HAS2) in human dermal fibroblasts. In addition, the hyaluronidase and collagenase inhibitory activities of RPE are confirmed. To evaluate the anti-aging effects of RPE, SKH-1 hairless mice are administered RPE daily for 12 weeks. Wrinkle formation, transepidermal water loss (TEWL), and skin moisture loss induced by UVB irradiation are suppressed in the dorsal skin of SKH-1 hairless mice orally administered RPE. Oral administration of RPE suppresses UVB irradiation-induced collagen disruption and reduction of hyaluronic acid. To find the bioactive compound in the RPE, serum protocatechuic acid (PCA), an anthocyanin metabolite, is analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CONCLUSION: Anthocyanins in RPE are metabolized to PCA in the body and circulated through the bloodstream to exhibit anti-aging effects on the skin.

Oral administration of collagen peptide in SKH-1 mice suppress UVB-induced wrinkle and dehydration through MAPK and MAPKK signaling pathways, in vitro and in vivo evidence.

Skin aging is induced by exposure to extrinsic factors, causing various diseases and adversely affecting aesthetics. Studies have suggested that as the quality of life improves, demand for beauty and nutritional cosmetics increases. Here, the protective effects of collagen peptide against UV-induced skin damage were evaluated in vitro and in vivo. Collagen peptide inhibited water loss and UVB irradiation-induced HA degradation in the skin of SKH-1 mice. Additionally, collagen peptide dose-dependently inhibited UVB-induced wrinkle formation, epidermal thickness, and elastase activity. These results suggest that collagen peptide regulates collagen degradation through the MAPK and MAPKK pathway. In addition, collagen peptide administration did not affect changes in weight of the liver, spleen, and kidney, or enzymatic indicators of liver damage. Taken together, oral administration of collagen peptide improved the effects of UV-induced skin aging without toxicity. Therefore, this study supports the development of collagen peptide for skin aging prevention in nutricosmetic products. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01362-6.

Skin-whitening effects of Spergularia marina by suppressing MITF translocation.

Spergularia marina is a plant that grows in salty regions along the coastline and exerts radical-scavenging and anti-inflammatory effects. In this study, we investigated the skin-whitening effects of S. marina extract (SME) in B16F10 melanoma cells. SME was found to exert radical-scavenging effects. It suppressed α-melanocyte-stimulating hormone-induced melanogenesis and tyrosinase activity. We also assessed the melanin production signaling pathway to identify the inhibitory action mechanism of SME on melanogenesis. SME decreased the protein expression levels of tyrosinase-related protein (TRP)-1, TRP-2, and tyrosinase, which play important roles in melanogenesis. Furthermore, western blotting revealed that SME inhibited the nuclear translocation of melanocyte inducing transcription factor (MITF), which is a transcription factor for TRP-1, TRP-2, and tyrosinase, suggesting that SME exerts its skin-whitening effect by inhibiting MITF nuclear translocation. Therefore, SME may potentially be used in skin-whitening medicines and cosmetics.

Porcine Placenta Peptide Inhibits UVB-Induced Skin Wrinkle Formation and Dehydration: Insights into MAPK Signaling Pathways from In Vitro and In Vivo Studies.

Excessive exposure to ultraviolet (UV) radiation from sunlight accelerates skin aging, leading to various clinical manifestations such as wrinkles, dryness, and loss of elasticity. This study investigated the protective effects of porcine placenta peptide (PPP) against UVB-induced skin photoaging. Female hairless SKH-1 mice were orally administered PPP for 12 weeks, followed by UVB irradiation. PPP significantly reduced wrinkle formation, improved skin moisture levels, and prevented collagen degradation. Mechanistically, PPP inhibited the expression of matrix metalloproteinases (MMPs) and upregulated collagen production. Moreover, PPP elevated hyaluronic acid levels, contributing to enhanced skin hydration. Additionally, PPP demonstrated antioxidant properties by increasing the expression of the antioxidant enzyme GPx-1, thereby reducing UVB-induced inflammation. Further molecular analysis revealed that PPP suppressed the activation of p38 MAP kinase and JNK signaling pathways, crucial mediators of UV-induced skin damage. These findings highlight the potential of porcine placental peptides as a natural and effective intervention against UVB-induced skin photoaging. The study provides valuable insights into the mechanisms underlying the protective effects of PPP, emphasizing its potential applications in skincare and anti-aging formulations.

Ginsenoside Rf Enhances Exercise Endurance by Stimulating Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes and ICR Mice.

Ginsenoside Rf (G-Rf) is a saponin of the protopanaxatriol family and a bioactive component of Korean ginseng. Several ginsenosides are known to have a positive effect on exercise endurance, but there is not yet a report on that of G-Rf. Forced swimming tests were performed on G-Rf-treated mice to evaluate the effect of G-Rf on exercise endurance. Subsequently, the expression of markers related to myoblast differentiation and mitochondrial biogenesis in murine skeletal C2C12 myotubes and tibialis anterior muscle tissue was determined using Western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining to elucidate the mechanism of action of G-Rf. The swimming duration of the experimental animal was increased by oral gavage administration of G-Rf. Moreover, G-Rf significantly upregulated the myoblast differentiation markers, mitochondrial biogenesis markers, and its upstream regulators. In particular, the mitochondrial biogenesis marker increased by G-Rf was decreased by each inhibitor of the upstream regulators. G-Rf enhances exercise endurance in mice, which may be mediated by myoblast differentiation and enhanced mitochondrial biogenesis through AMPK and p38 MAPK signaling pathways, suggesting that it increases energy production to satisfy additional needs of exercising muscle cells. Therefore, G-Rf is an active ingredient in Korean ginseng responsible for improving exercise performance.

FBI-1 inhibits epithelial-to-mesenchymal transition, migration, and invasion in lung adenocarcinoma A549 cells by downregulating transforming growth factor-ß1 signaling pathway.

The factor binding inducer of short transcripts-1 (FBI-1) is a POZ-domain Kruppel-like (POK) family of transcription factors and is known as a proto-oncogene or tumor suppressor in various carcinomas. However, the role of FBI-1 on epithelial-to-mesenchymal transition (EMT) and invasiveness in lung cancer remains unknown. Preliminarily, clinical data such as tissue microarray, Kaplan-Meier, and Oncomine were analyzed to confirm the correlation between lung cancer metastasis and FBI-1. To investigate the function of FBI-1 in EMT in lung cancer, EMT was measured in FBI-1-deficient or FBI-1-overexpressing cells. FBI-1 showed decreased expression in tumors metastasized to lymph nodes than in the primary tumor. In addition, it was also associated with improved survival rates of lung cancer patients. FBI-1 knockdown improved E-to-N-cadherin switching, migration, and invasion in A549 cells, similar to the initiation of EMT stimulated by transforming growth factor- ß1 (TGF-ß1). In contrast, overexpression of FBI-1 inhibited the transcription and activation of Smad2, thereby interfering with EMT, despite stimulation by TGF-ß1. These results suggest that FBI-1 plays a negative role in EMT in lung cancer via the TGF-ß1 signaling pathway, implying its use as a new potential therapeutic target and diagnostic indicator for early stage of lung cancer metastasis.

Oral Administration of Rosa gallica Prevents UVB-Induced Skin Aging through Targeting the c-Raf Signaling Axis.

Rosa gallica is a widely used Rosa species for medicinal and culinary purposes. Rosa gallica has been reported to display antioxidant, anti-inflammatory, and antibacterial activities. However, the effect of Rosa gallica against skin aging in vivo is unknown and its active components have not been fully understood. Oral administration of Rosa gallica prevented UVB-mediated skin wrinkle formation and loss of collagen/keratin fibers in the dorsal skin of mice. Examination of biomarkers at the molecular level showed that Rosa gallica downregulates UVB-induced COX-2 and MMP-1 expression in the skin. Through a direct comparison of major compounds identified using the UHPLC-MS/MS system, we discovered gallic acid as the primary component contributing to the anti-skin aging effect exhibited by Rosa gallica. Examination of the molecular mechanism revealed that gallic acid can potently and selectively target the c-Raf/MEK/ERK/c-Fos signaling axis. In addition, both gallic acid and MEK inhibitor blocked UVB-induced MMP-1 expression and restored collagen levels in a reconstructed 3D human skin model. Collectively, Rosa gallica could be used as a functional ingredient in the development of nutraceuticals against skin aging.

Ginsenosides Rk1 and Rg5 inhibit transforming growth factor-ß1-induced epithelial-mesenchymal transition and suppress migration, invasion, anoikis resistance, and development of stem-like features in lung cancer.

BACKGROUND: Lung cancer has a high incidence worldwide, and most lung cancer-associated deaths are attributable to cancer metastasis. Although several medicinal properties of Panax ginseng Meyer have been reported, the effect of ginsenosides Rk1 and Rg5 on epithelial-mesenchymal transition (EMT) stimulated by transforming growth factor beta 1 (TGF- ß1) and self-renewal in A549 cells is relatively unknown. METHODS: We treated TGF-ß1 or alternatively Rk1 and Rg5 in A549 cells. We used western blot analysis, real-time polymerase chain reaction (qPCR), wound healing assay, Matrigel invasion assay, and anoikis assays to determine the effect of Rk1 and Rg5 on TGF-mediated EMT in lung cancer cell. In addition, we performed tumorsphere formation assays and real-time PCR to evaluate the stem-like properties. RESULTS: EMT is induced by TGF-ß1 in A549 cells causing the development of cancer stem-like features. Expression of E-cadherin, an epithelial marker, decreased and an increase in vimentin expression was noted. Cell mobility, invasiveness, and anoikis resistance were enhanced with TGF-ß1 treatment. In addition, the expression of stem cell markers, CD44, and CD133, was also increased. Treatment with Rk1 and Rg5 suppressed EMT by TGF-ß1 and the development of stemness in a dose-dependent manner. Additionally, Rk1 and Rg5 markedly suppressed TGF-ß1-induced metalloproteinase-2/9 (MMP2/9) activity, and activation of Smad2/3 and nuclear factor kappa B/extra-cellular signal regulated kinases (NF-kB/ERK) pathways in lung cancer cells. CONCLUSIONS: Rk1 and Rg5 regulate the EMT inducing TGF-ß1 by suppressing the Smad and NF-κB/ERK pathways (non-Smad pathway).

Rose (Rosa gallica) Petal Extract Suppress Proliferation, Migration, and Invasion of Human Lung Adenocarcinoma A549 Cells through via the EGFR Signaling Pathway.

We sought to investigate the effect of rose petal extract (RPE) on the proliferation, migration, and invasion of cancer cells. RPE significantly inhibited the growth of lung and colorectal cancer cell lines, with rapid suppression of A549 lung cancer cells at low concentrations. These effects occurred concomitantly with downregulation of the cell proliferation mediators PCNA, cyclin D1, and c-myc. In addition, RPE suppressed the migration and invasion of A549 cells by inhibiting the expression and activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and -9). We hypothesize that the suppressive activity of RPE against lung cancer cell proliferation and early metastasis occurs via the EGFR-MAPK and mTOR-Akt signaling pathways. These early results highlight the significant potency of RPE, particularly for lung cancer cells, and warrant further investigation.

Polysaccharide isolated from persimmon leaves (Diospyros kaki Thunb.) suppresses TGF-ß1-induced epithelial-to-mesenchymal transition in A549 cells.

In the present study, to verify the effect of polysaccharides derived from persimmon leaves (PLE) at epithelial-to-mesenchymal transition (EMT), A549 cells were treated with TGF-ß1 alone or co-treated with TGF-ß1 and PLE (50 and 75 µg/mL). PLE-treated cells showed higher expression of E-cadherin and lower expression of N-cadherin and vimentin compared to TGF-ß1-treated cells by inhibiting the levels of transcription factors, including Snail, Slug, and ZEB1, all associated with EMT. PLE also significantly decreased migration, invasion, and anoikis resistance through TGF-ß1 mediated EMT suppression, whereby PLE inhibited the levels of MMP-2 and MMP-9 while cleaving PARP. These inhibitory effects of PLE against EMT, migration, invasion, and anoikis resistance were determined by activating the canonical SMAD2/3 and non-canonical ERK/p38 signaling pathways. Therefore, these results suggest that PLE could be used as a potential chemical therapeutic agent for early metastasis of lung cancer in vitro.

Rose Petal Extract (Rosa gallica) Exerts Skin Whitening and Anti-Skin Wrinkle Effects.

We sought to investigate the effect of extracts from Rosa gallica petals (RPE) on skin whitening and anti-wrinkle activity. Tyrosinase activity was attenuated by RPE treatment, concomitant with the reduction of melanin accumulation in human B16F10 melanoma. Treatment of the facial skin of volunteers in a clinical trial with an RPE-containing formulation enhanced skin brightness (L* value) significantly. The underlying mechanism responsible was determined to be associated with mitogen-activated protein kinase (MAPK) activation. In addition, RPE exhibited anti-wrinkle formation activity of human dermal fibroblasts by suppressing matrix metalloproteinase (MMP)-1 level. In vivo study, RPE also inhibited solar ultraviolet-stimulated MMP-1 level by c-Jun regulation. Overall, our findings indicate that RPE evokes skin whitening and anti-wrinkle formation activity by regulating intracellular signaling, supporting its utility as an ingredient for skin whitening and anti-wrinkle cosmetic products.

Acute Oral Toxicity and Genotoxicity of Polysaccharide Fraction from Young Barley Leaves (Hordeum vulgare L.).

Polysaccharides isolated from various plants are considered precious bioactive materials owing to their potent biological activities. Previously, we prepared a polysaccharide fraction (BLE0) isolated from young barley leaves (Hordeum vulgare L.), demonstrating its anti-osteoporotic and immunostimulatory activities. However, data regarding BLE0 toxicity is lacking. To establish its safety, in vitro genotoxicity (chromosomal aberration and bacterial reverse mutation assays) and acute oral toxicity assays were conducted. In the in vitro genotoxicity assays, bacterial reverse mutation and chromosomal aberration assays showed that BLE0 possessed no mutagenicity or clastogenicity. Furthermore, the median lethal dose (LD50) of BLE0 was higher than 5000 mg/kg in female and male Sprague-Dawley (SD) rats and no adverse effects were observed in terms of mortality and abnormal changes in clinical signs (body weight and necropsy). Based on these results, BLE0 was found to be safe with regards to genotoxicity under our test conditions, demonstrating no acute oral toxicity up to 5000 mg/kg in SD rats.

Catechol inhibits epidermal growth factor-induced epithelial-to-mesenchymal transition and stem cell-like properties in hepatocellular carcinoma cells.

Epithelial-mesenchymal transition (EMT) is a major cellular process in which epithelial cells lose cell polarity and cell-cell adhesion and become motility and invasiveness by transforming into mesenchymal cells. Catechol is one of the natural compounds present in fruits and vegetables and has various pharmacological and physiological activities including anti-carcinogenic effects. However, the effects of catechol on EMT has not been reported. Epidermal growth factor (EGF) is one of the growth factors and is known to play a role in inducing EMT. The present study showed that catechol suppressed not only the morphological changes to the mesenchymal phenotype of epithelial HCC cells, but also the reduction of E-cadherin and the increment of Vimentin, which are typical hallmark of EMT. In addition, catechol suppressed EMT-related steps such as migration, invasion, anoikis resistance acquisition, and stem cell-like characterization through the EGFR-AKT-ERK signaling pathway during liver cancer metastasis. Therefore, these results suggest that catechol may be able to regulate the early metastasis of liver cancer in vitro.

Red Ginseng Improves Exercise Endurance by Promoting Mitochondrial Biogenesis and Myoblast Differentiation.

Red ginseng has been reported to elicit various therapeutic effects relevant to cancer, diabetes, neurodegenerative diseases, and inflammatory diseases. However, the effect of red ginseng on exercise endurance and skeletal muscle function remains unclear. Herein, we sought to investigate whether red ginseng could affect exercise endurance and examined its molecular mechanism. Mice were fed with red ginseng extract (RG) and undertook swimming exercises to determine the time to exhaustion. Animals fed with RG had significantly longer swimming endurance. RG treatment was also observed to enhance ATP production levels in myoblasts. RG increased mRNA expressions of mitochondrial biogenesis regulators, NRF-1, TFAM, and PGC-1α, which was accompanied by an elevation in mitochondrial DNA, suggesting an enhancement in mitochondrial energy-generating capacity. Importantly, RG treatment induced phosphorylation of p38 and AMPK and upregulated PGC1α expression in both myoblasts and in vivo muscle tissue. In addition, RG treatment also stimulated C2C12 myogenic differentiation. Our findings show that red ginseng improves exercise endurance, suggesting that it may have applications in supporting skeletal muscle function and exercise performance.

Delphinidin inhibits epidermal growth factor-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma cells.

Epithelial-to-mesenchymal transition (EMT), important cellular process in metastasis of primary tumors, is characterized by loss of their cell polarity, disruption of cell-cell adhesion, and gain certain properties of mesenchymal phenotype that enable migration and invasion. Delphinidin is a member of anthocyanidin belong to flavonoid groups, known as having pharmacological and physiological effects including anti-tumorigenic, antioxidative, anti-inflammatory, and antiangiogenic effects. However, the effects of delphinidin on EMT is rarely investigated. Epidermal growth factor (EGF) is known as a crucial inducer of EMT in various cancer including hepatocellular carcinoma (HCC). To determine whether delphinidin inhibits EGF-induced EMT in HCC cells, antiproliferative effect of delphinidin on Huh7 and PLC/PRF/5 cells were measured by Cell Counting Kit-8 assay. As a result, delphinidin inhibited cell proliferation in a dose-dependent manner. Based on the result of proliferation, to measure the effects of delphinidin on EGF-induced EMT, we designated a proper concentration of delphinidin, which is not affected to cell proliferation. We found that delphinidin inhibits morphological changes from epithelial to mesenchymal phenotype by EGF. Moreover, delphinidin increased the messenger RNA and protein expression of E-cadherin and decreased those of Vimentin and Snail in EGF-induced HCC cells. Also, delphinidin prevented motility and invasiveness of EGF-induced HCC cells through suppressing activation of matrix metalloproteinase 2, EGF receptor (EGFR), AKT, and extracellular signal-regulated kinase (ERK). Taken together, our findings demonstrate that delphinidin inhibits EGF-induced EMT by inhibiting EGFR/AKT/ERK signaling pathway in HCC cells.

Germinated Waxy Black Rice Ameliorates Hyperglycemia and Dyslipidemia in Streptozotocin-Induced Diabetic Rats.

This study aimed to examine the anti-diabetic effect of germinated waxy black rice (GWBR) using streptozotocin (STZ)-induced diabetic rats. In the diabetic rats, GWBR supplementation for 8 weeks reduced plasma blood glucose concentrations, improved glucose clearance and prevented diabetes-induced weight loss. Rats with STZ-induced diabetes who received GWBR supplementation exhibited decreased expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter (GLUT) 2 genes and proteins in the small intestine via decreases in hepatocyte nuclear factor (HNF)-1α, HNF-1ß, and HNF-4α, transcriptional factors that are involved in the regulation of SGLT1 and GLUT2, compared with the rats with STZ-induced diabetes that did not receive GWBR supplements. GWBR supplementation also enhanced the expression of GLUT4 and the genes and proteins involved in GLUT4 translocation, such as insulin receptor (IR) and insulin receptor substrate 1 (IRS1), and increased the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB, Akt) proteins in skeletal muscle. GWBR further increased glycogen synthase (GS) 1 by decreasing glycogen synthase kinase (GSK)-3ß in skeletal muscle. Interestingly, GWBR recovered STZ-impaired pancreatic ß-cells, resulting in increased insulin synthesis and secretion. In addition, GWBR reduced serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, aspartate transferase and alanine transferase concentrations and increased high-density lipoprotein cholesterol concentrations. Taken together, these findings suggest that GWBR could be a candidate for improving the diabetic condition by regulating glucose uptake in the intestine and muscle and regulating the secretion of insulin from the pancreas.

Delphinidin inhibits BDNF-induced migration and invasion in SKOV3 ovarian cancer cells.

Brain-derived neurotrophic factor (BDNF), the TrkB ligand, is associated with aggressive malignant behavior, including migration and invasion, in tumor cells and a poor prognosis in patients with various types of cancer. Delphinidin is a diphenylpropane-based polyphenolic ring structure-harboring compound, which exhibits a wide range of pharmacological activities, anti-tumor, anti-oxidant, anti-inflammatory, anti-angiogenic and anti-mutagenic activity. However, the possible role of delphinidin in the cancer migration and invasion is unclear. We investigated the suppressive effect of delphinidin on the cancer migration and invasion. Thus, we found that BDNF enhanced cancer migration and invasion in SKOV3 ovarian cancer cell. To exam the inhibitory role of delphinidin in SKOV3 ovarian cancer migration and invasion, we investigated the use of delphinidin as inhibitors of BDNF-induced motility and invasiveness in SKOV3 ovarian cancer cells in vitro. Here, we found that delphinidin prominently inhibited the BDNF-induced increase in cell migration and invasion of SKOV3 ovarian cancer cells. Furthermore, delphinidin remarkably inhibited BDNF-stimulated expression of MMP-2 and MMP-9. Also, delphinidin antagonized the phosphorylation of Akt and nuclear translocation of NF-κB permitted by the BDNF in SKOV3 ovarian cancer cells. Taken together, our findings provide new evidence that delphinidin suppressed the BDNF-induced ovarian cancer migration and invasion through decreasing of Akt activation.

Dioscin suppresses TGF-ß1-induced epithelial-mesenchymal transition and suppresses A549 lung cancer migration and invasion.

Epithelial-to-mesenchymal transition (EMT), an important cellular process, occurs during cancer development and progression, has a crucial role in metastasis by enhancing the motility of tumor cells. Dioscin is a polyphenolic component isolated from Phyllanthus amarus, which exhibits a wide range of pharmacological and physiological activities, such as anti-tumor, anti-inflammatory, anti-obesity, anti-fungal, and anti-viral activities. However, the possible role of dioscin in the EMT is unclear. We investigated the suppressive effect of dioscin on the EMT. Transforming growth factor-beta 1 (TGF-ß1) is known to induce EMT in a number of cancer cell types and promote lung adenocarcinoma migration and invasion. To verify the inhibitory role of dioscin in lung cancer migration and invasion, we investigated the use of dioscin as inhibitors of TGF-ß1-induced EMT in A549 lung cancer cells in vitro. Here, we found that dioscin prominently increased expression of the epithelial marker E-cadherin and expression of the mesenchymal marker N-cadherin and Snail during the TGF-ß1-induced EMT. In addition, dioscin inhibited the TGF-ß1-induced increase in cell migration and invasion of A549 lung cancer cells. Also, dioscin remarkably inhibited TGF-ß1-regulated activation of MMP-2/9, Smad2, and p38. Taken together, our findings provide new evidence that dioscin suppresses lung cancer migration, and invasion in vitro by inhibiting the TGF-ß1-induced EMT.

Kefir prevented excess fat accumulation in diet-induced obese mice.

Excessive body fat accumulation can result in obesity, which is a serious health concern. Kefir, a probiotic, has recently shown possible health benefits in fighting obesity. This study investigated the inhibitory effects of 0.1 and 0.2% kefir powder on fat accumulation in adipose and liver tissues of high-fat diet (HFD)-induced obese mice. Kefir reduced body weight and epididymal fat pad weight and decreased adipocyte diameters in HFD-induced obese mice. This was supported by decreased expression of genes related to adipogenesis and lipogenesis as well as reduced proinflammatory marker levels in epididymal fat. Along with reduced hepatic triacylglycerol concentrations and serum alanine transaminase and aspartate transaminase activities, genes related to lipogenesis and fatty acid oxidation were downregulated and upregulated, respectively, in liver tissue. Kefir also decreased serum triacylglycerol, total cholesterol, and low-density lipoprotein-cholesterol concentrations. Overall, kefir has the potential to prevent obesity.

Combined treatment with zingerone and its novel derivative synergistically inhibits TGF-ß1 induced epithelial-mesenchymal transition, migration and invasion of human hepatocellular carcinoma cells.

The epithelial-mesenchymal transition (EMT) is an important cellular process during which polarized epithelial cells become motile mesenchymal cells, which promote cancer metastasis. Ginger, the rhizome of Zingiber officinale, is extensively used in cooking worldwide and also as a traditional medicinal herb with antioxidant, anti-inflammatory and anticancer properties. Several pungent compounds have been identified in ginger, including zingerone, which has anticancer potential. However, the role of zingerone in EMT is unclear. We investigated the synergistic effect of zingerone and its derivative on EMT. Transforming growth factor-beta 1 (TGF-ß1) induces the EMT to promote hepatocellular carcinoma metastasis, including migration and invasion. To understand the repressive role of the combination of zingerone and its derivative (ZD 2) in hepatocellular carcinoma metastasis, we investigated the potential use of each compound of ginger, such as zingerone, ZD 2 and 6-shogaol, or the mixture of zingerone and ZD 2 (ZD 2-1) as inhibitors of TGF-ß1 induced EMT development in SNU182 hepatocellular carcinoma cells in vitro. We show that ZD 2-1, but not zingerone, ZD 2 and 6-shogaol significantly increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker N-cadherin during initiation of the TGF-ß1 induced EMT. In addition, ZD 2-1 inhibited the TGF-ß1 induced increase in cell migration and invasion of SNU182 hepatocellular carcinoma cells. Furthermore, ZD 2-1 significantly inhibited TGF-ß1 regulated matrix metalloproteinase-2/9 and activation of Smad2/3. We also found that ZD 2-1 inhibited nuclear translocation of NF-κB, activation of p42/44 MAPK/AP1 signaling pathway in the TGF-ß1 induced EMT. Our findings provide new evidence that combined treatment with ZD 2, novel zingerone derivative, and zingerone synergistically suppresses hepatocellular carcinoma metastasis in vitro by inhibiting the TGF-ß1 induced EMT.