Evaluating the Anti-Osteoarthritis Potential of Standardized Boswellia serrata Gum Resin Extract in Alleviating Knee Joint Pathology and Inflammation in Osteoarthritis-Induced Models.

Osteoarthritis is a widespread chronic degenerative disease marked by the deterioration of articular cartilage, modifications in subchondral bone, and a spectrum of symptoms, including pain, stiffness, and disability. Ultimately, this condition impairs the patient's quality of life. This study aimed to evaluate the therapeutic efficacy of standardized Boswellia serrata gum resin extract (BSRE) in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. A total of 60 rats were allocated into six groups: normal control group (NC), osteoarthritis control (injected with MIA, OC), O + B50 (injected with MIA and treated with 50 mg/kg body weight (BW) BSRE), O + B75 (injected with MIA and treated with 75 mg/kg BW BSRE), O + B100 (injected with MIA and treated with 100 mg/kg BW BSRE), and O + M (injected with MIA and treated with 150 mg/kg BW methyl sulfonyl methane). Several parameters, including knee joint swelling, histopathological changes, and the expression of collagen type II alpha 1 (COL2A1) and aggrecan, were comprehensively assessed. Concurrently, the serum levels and mRNA expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) were analyzed in both the serum and knee joint synovium. The results demonstrated that BSRE significantly mitigated knee joint swelling, cartilage destruction, and tissue deformation. Notably, BSRE administration markedly upregulated the expression of COL2A1 and aggrecan while concurrently reducing levels of nitric oxide, prostaglandin E2, leukotriene B4, interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Furthermore, a substantial decrease was observed in the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-6, TNF-α and MMP-3 and -13, thereby indicating promising therapeutic implications for osteoarthritis. In conclusion, BSRE exhibited anti-inflammatory properties and inhibited cartilage matrix degradation in a rat model of MIA-induced osteoarthritis, with the O + B100 group showing significant reductions in swelling and notable improvements in joint cartilage damage. These findings illuminate the preventive and therapeutic potential of BSRE for osteoarthritis treatment, emphasizing the criticality of exhaustive evaluation of novel compounds.

The Impact of Ulmus macrocarpa Extracts on a Model of Sarcopenia-Induced C57BL/6 Mice.

Aging leads to tissue and cellular changes, often driven by oxidative stress and inflammation, which contribute to age-related diseases. Our research focuses on harnessing the potent anti-inflammatory and antioxidant properties of Korean Ulmus macrocarpa Hance, a traditional herbal remedy, to address muscle loss and atrophy. We evaluated the effects of Ulmus extract on various parameters in a muscle atrophy model, including weight, exercise performance, grip strength, body composition, muscle mass, and fiber characteristics. Additionally, we conducted Western blot and RT-PCR analyses to examine muscle protein regulation, apoptosis factors, inflammation, and antioxidants. In a dexamethasone-induced muscle atrophy model, Ulmus extract administration promoted genes related to muscle formation while reducing those associated with muscle atrophy. It also mitigated inflammation and boosted muscle antioxidants, indicating a potential improvement in muscle atrophy. These findings highlight the promise of Ulmus extract for developing pharmaceuticals and supplements to combat muscle loss and atrophy, paving the way for clinical applications.

Effects of Probiotic Culture Supernatant on Cariogenic Biofilm Formation and RANKL-Induced Osteoclastogenesis in RAW 264.7 Macrophages.

Postbiotics are a promising functional ingredient that can overcome the limitations of viability and storage stability that challenge the production of probiotics. To evaluate the effects of postbiotics on oral health, eight spent culture supernatants (SCSs) of probiotics were prepared, and the effects of SCSs on Streptococcus mutans-induced cariogenic biofilm formation and the receptor activator of the nuclear factor κB ligand (RANKL)-induced osteoclastogenesis were evaluated in RAW 264.7 macrophages. SCS of Lactobacillus salivarius MG4265 reduced S. mutans-induced biofilm formation by 73% and significantly inhibited tartrate-resistant acid phosphatase (TRAP) activity, which is a biomarker of mature osteoclasts in RAW 264.7 macrophages. The suppression of RANKL-induced activation of mitogen activated the protein kinases (c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38) and nuclear factor κB pathways, as well as the upregulation of heme oxygenase-1 expression. The suppression of RANK-L-induced activation of mitogen also inhibited the expression of transcriptional factors (c-fos and nuclear factor of activated T cells cytoplasmic 1) and, subsequently, osteoclastogenesis-related gene expression (tartrate-resistant acid phosphatase-positive (TRAP), cathepsin K, and matrix metalloproteinase-9).Therefore, SCS of L. salivarius MG4265 has great potential as a multifunctional oral health ingredient that inhibits biofilm formation and suppresses the alveolar bone loss that is associated with periodontitis.

Anti-inflammatory activity of palmitoylethanolamide ameliorates osteoarthritis induced by monosodium iodoacetate in Sprague-Dawley rats.

Novel treatment strategies are urgently required for osteoarthritis (OA). Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and elucidate the molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague-Dawley rats. The experimental animals were divided into normal control group (injected with saline + treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA + treated with PBS, CON), 50 or 100 mg/kg body weight (BW)/day PEA-treated group (injected with MIA + treated with 50 or 100 mg of PEA/kg BW/day, PEA50 or PEA100), and positive control group (injected with MIA + treated with 6 mg of diclofenac/kg BW/day, DiC). The changes in blood parameters, body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. Oral administration of PEA had no adverse effects on the BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and prostaglandin E2 considerably reduced in the PEA100 group compared with those in the CON group. In the synovia of knee joints, the mRNA expression of iNOS, 5-Lox, Cox-2, Il-1ß, Tnf-α, and Mmp-2, -3, -9, and -13 apparently increased with MIA administration. Meanwhile, Timp-1 mRNA expression apparently decreased in the CON group but increased to the normal level with PEA treatment. Thus, PEA can be an effective therapeutic agent for OA.

Development of RNA aptamer that inhibits methyltransferase activity of dengue virus.

OBJECTIVES: To develop an RNA aptamer specific for the methyltransferase (MTase) of dengue virus (DENV) which is essential for viral genome replication and translation acting directly on N-7 and 2'-O-methylation of the type-I cap structure of the viral RNA. RESULTS: We identified 2'-fluoro-modified RNA aptamers that can specifically bind DENV serotype 2 (DENV2) MTase using systematic evolution of ligands by exponential enrichment technology. We truncated the chosen aptamer into a 45-mer RNA sequence that can bind DENV2 MTase with K d  ~ 28 nM and inhibit N-7 methylation activity of the protein. Moreover, the 45-mer truncated aptamer could not only bind with an K d  ~ 15.6 nM but also inhibit methylation activity of DENV serotype 3 (DENV3) MTase. The 45-mer aptamer competitively impeded binding of both DENV2 and DENV3 genomic RNA to MTase of each serotype. CONCLUSION: The selected 45-mer truncated RNA aptamer specifically and avidly bound DENV MTase and competitively inhibited its methylation activity, and thus could be useful for the development of anti-DENV agents.

ß-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice.

We reported previously that high-fat diet (HFD) feeding stimulated solid tumor growth and lymph node (LN) metastasis in C57BL/6N mice injected with B16F10 melanoma cells. ß-caryophyllene (BCP) is a natural bicyclic sesquiterpene found in many essential oils and has been shown to exert anti-inflammatory activities. To examine whether BCP inhibits HFD-induced melanoma progression, 4-weeks old, male C57BL/6N mice were fed a control diet (CD, 10 kcal% fat) or HFD (60 kcal% fat + 0, 0.15 or 0.3% BCP) for the entire experimental period. After 16 weeks of feeding, B16F10s were subcutaneously injected into mice. Three weeks later, tumors were resected, and mice were killed 2 weeks post-resection. Although HFD feeding increased body weight gain, fasting blood glucose levels, solid tumor growth, LN metastasis, tumor cell proliferation, angiogenesis and lymphangiogenesis, it decreased apoptotic cells, all of which were suppressed by dietary BCP. HFD feeding increased the number of lipid vacuoles and F4/80+ macrophage (MΦ) and macrophage mannose receptor (MMR)+ M2-MΦs in tumor tissues and adipose tissues surrounding the LN, which was suppressed by BCP. HFD feeding increased the levels of CCL19 and CCL21 in the LN and the expression of CCR7 in the tumor; these changes were blocked by dietary BCP. In vitro culture results revealed that BCP inhibited lipid accumulation in 3T3-L1 preadipocytes; monocyte migration and monocyte chemoattractant protein-1 secretion by B16F10s, adipocytes and M2-MΦs; angiogenesis and lymphangiogenesis. The suppression of adipocyte and M2-cell accumulation and the inhibition of CCL19/21-CCR7 axis may be a part of mechanisms for the BCP suppression of HFD-stimulated melanoma progression.

High-fat diet-induced obesity increases lymphangiogenesis and lymph node metastasis in the B16F10 melanoma allograft model: roles of adipocytes and M2-macrophages.

To examine the effects of high-fat diet (HFD) on melanoma progression, HFD-fed C57BL/6N mice were subcutaneously injected with syngeneic B16F10 melanoma cells. At 3 weeks post-injection, the tumors were resected; the mice were then sacrificed at 2 weeks post-resection. HFD stimulated melanoma growth and lymph node (LN) metastasis as well as tumor and LN lymphangiogenesis. Lipid vacuoles in the tumor and M2-macrophage (MΦ)s in the adipose and tumor tissues were increased in HFD-fed mice. CCL19 and CCL21 contents were higher in LNs than in tumors. HFD increased both CCL19 and CCL21 levels in LNs and CCR7 in tumors. Adipose tissue-conditioned media (CM) from HFD-fed mice enhanced lymphangiogenesis, and mature adipocyte (MA)/M2-MΦ co-culture CM markedly stimulated the tube formation of lymphatic endothelial cell (LEC)s and B16F10 migration. Monocyte migration was moderately stimulated by B16F10 or MA CM, but tremendously stimulated by B16F10/M2-MΦ co-culture CM, which was enhanced by MA/B16F10/M2-MΦ co-culture CM. The co-culture results revealed that MAs increased CCL2, M-CSF and CCR7 mRNAs in B16F10s; vascular endothelial growth factor (VEGF)-D mRNA in M2-MΦs; and CCL19, CCL21 and VEGF receptor (VEGFR)3 mRNA in LECs. M2-MΦs increased CCL2, M-CSF and VEGF-A mRNAs in B16F10s, whereas B16F10s increased VEGF-C mRNAs in M2-MΦs and VEGFR3 mRNA in LECs. These results indicate that in HFD-fed mice, MA-induced CCL2 and M-CSF in tumor cells increase M2-MΦs in tumor; the crosstalk between tumor cells and M2-MΦs further increases cytokines and angiogenic and lymphangiogenic factors. Additionally, MA-stimulated CCL19, CCL21/CCR7 axis contributes to increased LN metastasis in HFD-fed mice.

Berteroin present in cruciferous vegetables exerts potent anti-inflammatory properties in murine macrophages and mouse skin.

Berteroin (5-methylthiopentyl isothiocyanate) is a sulforaphane analog present in cruciferous vegetables, including Chinese cabbage, rucola salad leaves, and mustard oil. We examined whether berteroin exerts anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin inflammation models. Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages. Berteroin inhibited LPS-induced degradation of inhibitor of κBα (IκBα) and nuclear factor-κB p65 translocation to the nucleus and DNA binding activity. Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor ß activated kinase-1. Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT. In the mouse ear, berteroin effectively suppressed TPA-induced edema formation and down-regulated iNOS and COX-2 expression as well as phosphorylation of AKT and ERK1/2. These results demonstrate that berteroin exhibits potent anti-inflammatory properties and suggest that berteroin can be developed as a skin anti-inflammatory agent.

Anti-osteoporotic effects of Boswellia serrata gum resin extract in vitro and in vivo.

BACKGROUND/OBJECTIVES: This study evaluated the beneficial effects of an ethanol extract of Boswellia serrata gum resin (FJH-UBS) in osteoporosis. MATERIALS/METHODS: MC3T3-E1 osteoblastic cells and RAW 264.7 osteoclastic cells were treated with FJH-UBS. The alkaline phosphatase (ALP) activity, mineralization, collagen synthesis, osteocalcin content, and Runt-related transcription factor 2 (RUNX2) and Osterix expression were measured in MC3T3-E1 cells. The actin ring structures, tartrate-resistant acid phosphatase (TRAP) activity, and the nuclear factor of activator T-cells, cytoplasm 1 (NFATc1) expression were evaluated in RAW 264.7 cells. Ovariectomized ICR mice were orally administered FJH-UBS for eight weeks. The bone mineral density (BMD) and the serum levels of osteocalcin, procollagen 1 N-terminal propeptide (P1NP), osteoprotegerin, and TRAP 5b were analyzed. RESULTS: FJH-UBS increased the ALP activity, collagen, osteocalcin, mineralization, and RUNX2 and osterix expression in MC3T3-E1 osteoblastic cells, whereas it decreased the TRAP activity, actin ring structures, and NFATc1 expression in RAW 264.7 osteoclastic cells. In ovariectomy-induced osteoporosis mice, FJH-UBS positively restored all of the changes in the bone metabolism biomarkers (BMD, osteocalcin, P1NP, osteoprotegerin, and TRAP 5b) caused by the ovariectomy. CONCLUSION: FJH-UBS has anti-osteoporotic activity by promoting osteoblast activity and inhibiting osteoclast activity in vitro and in vivo, suggesting that FJH-UBS is a potential functional food ingredient for osteoporosis.

Peanut sprout tea extract inhibits lung metastasis of 4T1 murine mammary carcinoma cells by suppressing the crosstalk between cancer cells and macrophages in BALB/c mice.

BACKGROUND/OBJECTIVES: As peanuts germinate, the content of the components beneficial to health, such as resveratrol, increases within the peanut sprout. This study examined whether the ethanol extract of peanut sprout tea (PSTE) inhibits breast cancer growth and metastasis. MATERIALS/METHODS: After orthotopically injecting 4T1 cells into BALB/c mice to induce breast cancer, 0, 30, or 60 mg/kg body weight/day of PSTE was administered orally. Angiogenesis-related protein expression in the tumors and the degree of metastasis were analyzed. 4T1 and RAW 264.7 cells were co-cultured, and reverse transcription polymerase chain reaction was performed to measure the crosstalk between breast cancer cells and macrophages. RESULTS: PSTE reduced tumor growth and lung metastasis. In particular, PSTE decreased matrix metalloproteinase-9, platelet endothelial cell adhesion molecule-1, vascular endothelial growth factor-A, F4/80, CD11c, macrophage mannose receptor, macrophage colony-stimulating factor, and monocyte chemoattractant protein 1 expression in the tumors. Moreover, PSTE prevented 4T1 cell migration, invasion, and macrophage activity in RAW 264.7 cells. PSTE inhibited the crosstalk between 4T1 cells and RAW 264.7 cells and promoted the macrophage M1 subtype while inhibiting the M2 subtype. CONCLUSIONS: These results suggest that PSTE blocks breast cancer growth and metastasis to the lungs. This may be because the PSTE treatment inhibits the crosstalk between mammary cancer cells and macrophages and inhibits the differentiation of macrophages into the M2 subtype.

Effects of Lactobacillus reuteri MG5346 on Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL)-Induced Osteoclastogenesis and Ligature-Induced Experimental Periodontitis Rats.

Effects of culture supernatants of Lactobacillus reuteri MG5346 (CS-MG5346) on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis were examined. CS-MG5346 treatment up to 400 µg/mL significantly reduced tartrate-resistant acid-phosphatase (TRAP) activity, the phenotype biomarker of osteoclast, without affecting cell viability. CS-MG5346 inhibited the expression of osteoclast specific transcriptional factors (c-fos and nuclear factor-activated T cells c1) and their target genes (TRAP, cathepsin, and matrix metallo-proteinase-9) in a dose-dependent manner (p<0.05). The administration of L. reuteri MG5346 (2×108 CFU/day) for 8 wks significantly improved furcation involvement, but no difference was observed in alveolar bone loss in ligature-induced experimental periodontitis rats. The elevated RANKL/ osteoprotegerin ratio, the biomarker of periodontitis, was significantly lowered in the gingival tissue by administration of L. reuteri MG5346 (p<0.05). L. reuteri MG5346 showed excellent stability in simulated stomach and intestinal fluids and did not have antibiotic resistance. Based on the results, L. reuteri MG5346 has the potential to be a promising probiotic strain for oral health.

Immune-enhancing effect of hydrolyzed and fermented Platycodon grandiflorum extract in cyclophosphamide-induced immunosuppressed BALB/c mice.

BACKGROUND/OBJECTIVES: The immunomodulatory effect of Platycodon grandiflorum (PG) has been reported, but studies on its mechanism are still lacking. This study was undertaken to confirm whether the hydrolyzed and fermented PG extract (HFPGE) obtained by adding hydrolysis and fermentation to the extraction process has an immune-enhancing effect in the in vivo system. MATERIALS/METHODS: Five-week-old BALB/c mice were divided into 4 groups: normal control group (NOR), control group (CON), 150 mg/kg body weight (BW)/day HFPGE-treated group (T150), and 300 mg/kg BW/day HFPGE-treated group (T300). The mice were administered HFPGE for 4 weeks and intraperitoneally injected with cyclophosphamide (CPA, 80 mg/kg BW/day) on day 6, 7, and 8, respectively, to induce immunosuppression. The levels of immunoglobulins (Igs) and cytokines were measured in the serum. In splenocytes, proliferation and cytokine levels were measured. RESULTS: Serum IgA, IgG, and IgM levels were observed to decrease after CPA treatment, which was recovered by HFPGE administration. The levels of serum interleukin (IL)-12, tumor necrosis factor (TNF)-α, IL-8, and transforming growth factor (TGF)-ß were also decreased after exposure to CPA but increased after HFPGE administration. Decreased splenocyte proliferation was seen in CPA-treated mice, but was observed to increase in the T150 and T300 groups as compared to the NOR group. Compared to the CON group, splenocyte proliferation stimulated with concanavalin A (ConA) or lipopolysaccharide (LPS) in the HFPGE-treated groups was significantly increased. The cytokines secreted by ConA-stimulated splenocytes (IL-2, IL-12, interferon-γ, TNF-α) were increased in the T150 and T300 groups, and cytokines secreted by LPS-stimulated splenocytes (IL-4, IL-8, TGF-ß) were also increased by HFPGE administration. CONCLUSION: These results suggest that HFPGE stimulates the immunity in immunosuppressed conditions, thereby enhancing the immune response. Therefore, it is expected that HFPGE has the potential to be used as functional food and medicine for immune recovery in various immunocompromised situations.

Agaricus bisporus Extract Exerts an Anti-Obesity Effect in High-Fat Diet-Induced Obese C57BL/6N Mice by Inhibiting Pancreatic Lipase-Mediated Fat Absorption.

Agaricus bisporus is well known as a source of polysaccharides that could improve human health. The objective of this study was to explore the anti-obesity effect of A. bisporus extract (ABE), abundant in polysaccharides, and its underlying mechanism. Pancreatic lipase inhibitory activity in vitro was determined after treatment with ABE and chitosan. Treatment with ABE and chitosan significantly decreased pancreatic lipase activity. Five-week-old male SD rats were randomly divided into three groups for acute feeding with vehicle, ABE at 80 mg/kg body weight (BW)/day, and ABE at 160 mg/kg BW/day. ABE dose-dependently increased plasma lipid clearance in an oral lipid tolerance test. Five-week-old male C57BL/6N mice were fed a control diet (CD), a high-fat diet (HFD), an HFD with ABE at 80 mg/kg BW/day, ABE at 160 mg/kg BW/day, or chitosan at 160 mg/kg BW/day for eight weeks. HFD-fed mice showed significant increases in body weight, fat mass, white adipose tissue, average lipid droplet size, and serum levels of glucose, triglyceride, ALT, and AST compared to those in the CD group. However, ABE or chitosan administration ameliorated these increases. ABE or chitosan significantly reduced dietary efficiency and increased fecal excretion levels of lipids, triglycerides, and total cholesterol. These in vitro and in vivo findings suggest that ABE might act as an anti-obesity agent by inhibiting pancreatic lipase-mediated lipid absorption, at least in part.

Protective effects of red orange (Citrus sinensis [L.] Osbeck [Rutaceae]) extract against UVA-B radiation-induced photoaging in Skh:HR-2 mice.

BACKGROUND/OBJECTIVES: The skin is the outermost organ of the human body and plays a protective role against external environmental damages, such as sunlight and pollution, which affect anti-oxidant defenses and skin inflammation, resulting in erythema or skin reddening, immunosuppression, and epidermal DNA damage. MATERIALS/METHODS: The present study aimed to investigate the potential protective effects of red orange complex H extract (ROC) against ultraviolet (UV)-induced skin photoaging in Skh:HR-2 mice. ROC was orally administered at doses of 20, 40, and 80 mg/kg/day for 13 weeks, along with UV irradiation of the mice for 10 weeks. RESULTS: ROC improved UV-induced skin barrier parameters, including erythema, melanin production, transepidermal water loss, elasticity, and wrinkle formation. Notably, ROC inhibited the mRNA expression of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor α) and melanogenesis. In addition, ROC recovered the UV-induced decrease in the hyaluronic acid and collagen levels by enhancing genes expression. Furthermore, ROC significantly downregulated the protein and mRNA expression of matrix metalloproteinases responsible for collagen degradation. These protective effects of ROC against photoaging are associated with the suppression of UV-induced phosphorylation of c-Jun NH2-terminal kinase and activator protein 1 activation. CONCLUSIONS: Altogether, our findings suggest that the oral administration of ROC exerts potential protective activities against photoaging in UV-irradiated hairless mice.

Cydonia oblonga Miller fruit extract exerts an anti-obesity effect in 3T3-L1 adipocytes by activating the AMPK signaling pathway.

BACKGROUND/OBJECTIVES: The fruit of Cydonia oblonga Miller (COM) is used traditionally in Mediterranean region medicine to prevent or treat obesity, but its mechanism of action is still unclear. Beyond a demonstrated anti-obesity effect, the fruit was tested for the mechanism of adipogenesis in 3T3-L1 preadipocytes. MATERIALS/METHODS: 3T3-L1 preadipocytes were cultured for 8 days with COM fruit extract (COME) at different concentrations (0-600 µg/mL) with adipocyte differentiation medium. The cell viability was measured using an MTT assay; triglyceride (TG) was stained with Oil Red O. The expression levels of the adipogenesis-related genes and protein expression were analyzed by reverse transcription polymerase chain reaction and Western blotting, respectively. RESULTS: COME inhibited intracellular TG accumulation during adipogenesis. A COME treatment in 3T3-L1 cells induced upregulation of the adenosine monophosphate-activated protein kinase (AMPK)α phosphorylation and downregulation of the adipogenic transcription factors, such as sterol regulatory element-binding protein 1c, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer binding protein α. The COME treatment reduced the mRNA expression of fatty acyl synthetase, adenosine triphosphate-citrate lyase, adipocyte protein 2, and lipoprotein lipase. It increased the mRNA expression of hormone-sensitive lipase and carnitine palmitoyltransferase I in 3T3-L1 cells. CONCLUSIONS: COME inhibits adipogenesis via the AMPK signaling pathways. COME may be used to prevent and treat obesity.

Aqueous extract of Laurus nobilis leaf accelerates the alcohol metabolism and prevents liver damage in single-ethanol binge rats.

BACKGROUND/OBJECTIVES: Excessive alcohol consumption has harmful health effects, including alcohol hangovers and alcohol-related liver disease. Therefore, methods to accelerate the alcohol metabolism are needed. Laurus nobilis is a spice, flavoring agent, and traditional herbal medicine against various diseases. This study examined whether the standardized aqueous extract of L. nobilis leaves (LN) accelerates the alcohol metabolism and protects against liver damage in single-ethanol binge Sprague-Dawley (SD) rats. MATERIALS/METHODS: LN was administered orally to SD rats 1 h before ethanol administration (3 g/kg body weight [BW]) at 100 and 300 mg/kg BW. Blood samples were collected 0.5, 1, 2, and 4 h after ethanol administration. The livers were excised 1 h after ethanol administration to determine the hepatic enzyme activity. The alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in the liver tissue were measured. RESULTS: LN decreased the serum ethanol and acetaldehyde levels in ethanol-administered rats. LN increased the hepatic ADH and ALDH activities but decreased the alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase activities in the ethanol-administered rats. In addition, LN inhibited lipid peroxidation and increased the activities of SOD and GPx. CONCLUSIONS: LN modulates the mediators of various etiological effects of excessive alcohol consumption and enhances the alcohol metabolism and antioxidant activity, making it a potential candidate for hangover treatments.

AGEs Blocker™ (Goji Berry, Fig, and Korean Mint Mixed Extract) Inhibits Skin Aging Caused by Streptozotocin-Induced Glycation in Hairless Mice.

Glycation is a cause of skin aging. This study investigated in a glycation-induced skin aging mouse model the effects on skin and mechanism of action of AGEs Blocker™ (AB), which contains goji berry, fig, and Korean mint mixed extract. This study sought to demonstrate the antiglycation effect of streptozotocin, thereby improving skin aging, by measuring advanced glycation end products (AGEs) and various skin parameters, including collagen; matrix metalloproteinases (MMPs); inflammatory cytokines; activities of oxidative enzymes; and skin wrinkles, elasticity, and hydration. This study found that skin wrinkles, elasticity, and hydration improved with AB. Particularly, the oral administration of AB suppressed AGEs, receptors of AGEs, and carboxymethyl lysine in blood and skin tissue. In addition, AB increased the activities of antioxidative enzymes, reduced inflammatory cytokines, suppressed MMP-9 expression, and increased the contents of collagen and hyaluronic acid, ultimately suppressing skin wrinkles and increasing skin elasticity and hydration. Therefore, AB can inhibit skin aging through its antiglycation effect and is thus considered a good ingredient for skin care products.

Bone marrow-derived, alternatively activated macrophages enhance solid tumor growth and lung metastasis of mammary carcinoma cells in a Balb/C mouse orthotopic model.

INTRODUCTION: Tumor-associated macrophages, which are derived from the infiltration of circulating bone marrow-derived monocytes, consist primarily of a polarized M2 macrophage (M2-Mϕ) population and are associated with poor prognosis in various cancers. In the present study, we attempted to assess whether M2-Mϕs derived from bone marrow stimulate the promotion and progression of mammary tumors. METHODS: 4T1 murine mammary carcinoma cells were injected either alone or coupled with M2-Mϕs into the mammary fat pads of syngeneic female Balb/C mice. M2-Mϕs were prepared by treating monocytes isolated from female Balb/C mouse bone marrow with IL-4. Tumor cell growth was determined using an in vivo imaging system and the expression of cell proliferation-related, angiogenesis-related, and lymphangiogenesis-related proteins in tumor tissues was immunohistochemically analyzed. To evaluate the effects of the crosstalk between 4T1 cells and M2-Mϕs on the secretion and mRNA expression of cytokines and the migration of monocytes, 4T1 cells and M2-Mϕs were co-cultured and cytokine antibody array, real-time RT-PCR, and trans-well migration assays were conducted. RESULTS: The co-injection of M2-Mϕs into the mammary fat pads of mice increased solid tumor growth and lung metastasis of 4T1 cells as well as the infiltration of CD45+ leukocytes into tumor tissues. The proportions of Ki-67+ proliferating cells and the expression of hypoxia inducible factor-1α, vascular endothelial cell growth factor A, CD31, vascular endothelial cell growth factor C, and lymphatic vessel endothelial receptor-1 were increased significantly in the tumor tissues of mice co-injected with 4T1 cells and M2-Mϕs. The in vitro results revealed that the proliferation of 4T1 cells, the migration of monocytes, and the secretion of granulocyte colony-stimulating factor, IFNγ, IL-1α, IL-2, IL-16, IFNγ-induced protein-10, keratinocyte-derived chemokine, macrophage colony-stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein-1α, and RANTES were increased when 4T1 cells were co-cultured with M2-Mϕs, as compared with when the 4T1 cells were cultured alone. CONCLUSION: The crosstalk between 4T1 cells and M2-Mϕs increased the production of cytokines, which may have induced immune cell infiltration into tumor tissues, tumor cell proliferation, angiogenesis, and lymph angiogenesis, thereby increasing solid tumor growth and lung metastasis.

The synergistic therapeutic effect of cisplatin with Human papillomavirus E6/E7 short interfering RNA on cervical cancer cell lines in vitro and in vivo.

Human papillomavirus (HPV) types 16 and 18 are the major etiologic factors in the development of cervical epithelial neoplasia. Our study was designed to validate antiviral short interfering RNA (siRNA) targeting the E6 and E7 oncogenes as a potential chemosensitizer of cisplatin (cis-diaminedichloroplatinum II; CDDP) in cervical carcinoma. Specifically, the therapeutic efficacy of combination of CDDP and E6/E7-specific siRNA was assessed in an in vivo cervical cancer xenograft models. The combination of CDDP and E6/E7-specific siRNA had greater efficacy than the combination of CDDP and E6-specific siRNA especially in terms of inducing cellular senescence. Through in vitro and in vivo experiments, the mechanism of synergy between these two treatments was revealed, demonstrating that the combination of E6/E7-specific siRNA and CDDP therapy was significantly superior to either modality alone. In vitro, long-term exposure of HeLa cells to the combination of CDDP and E6/E7-specific siRNA induced apoptosis and cellular senescence. In vivo, E6/E7-specific siRNA potentiated the antitumor efficacy of CDDP via induction of apoptosis, senescence and antiangiogenesis. Our results suggest that E6/E7-specific siRNA may be an effective sensitizer of CDDP chemotherapy in cervical cancer.

Effects of Lactobacillus curvatus MG5246 on inflammatory markers in Porphyromonas gingivalis lipopolysaccharide-sensitized human gingival fibroblasts and periodontitis rat model.

This study investigated the effects of Lactobacillus curvatus MG5246 on periodontitis inflammation. Cell-free supernatants (CFS) prepared from L. curvatus MG5246 decreased prostaglandin E2 production and cyclooxygenase-2 gene expression by 60% and 78% in Porphyromonas gingivalis-lipopolysaccharide stimulated human gingival fibroblasts at 400 µg/mL. Gene expressions of tumor necrosis factor-α, interleukin-6, matrix metalloproteinases, and chemokines were significantly downregulated by CFS treatment (p < 0.05). L. curvatus MG5246 (2 × 108 CFU/day, 8 weeks) administration significantly improved alveolar bone loss in the ligature-induced periodontitis rat model. Elevated mRNA expression of the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio in the gingival tissue was significantly decreased by L. curvatus MG5246 administration (p < 0.05). Moreover, L. curvatus MG5246 showed sufficient tolerance in simulated gastrointestinal conditions (gastric tolerance: 89.48%, intestinal tolerance: 98.62%) and did not show antibiotic resistance and hemolytic activity. Therefore, L. curvatus MG5246 has the potential as novel oral probiotics.