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Climacteric symptoms, as well as postmenopausal estrogen deficiency, have been associated with many psychological problems and the risk of osteoporosis and heart disease. Therefore, in this study, we aimed to evaluate, for the first time, the dose-dependent effect of water chestnut (WC), also known as Trapa bicornis, a fruit extract, on ovariectomy (OVX)-induced menopause in ICR mice. After bilateral OVX surgery, 200, 100, and 50 mg/kg of WC and 200 mg/kg of pomegranate concentrate powder (PCP) were administered orally for 84 days from 4 weeks after OVX operation. Then, anti-climacteric activities were evaluated in five groups: (1) estrogenic, (2) anti-obesity, (3) hypolipidemic, (4) hepatoprotective, and (5) anti-osteoporosis effects. Different biochemical assays, histopathological and morphological inspections, and mRNA expression findings showed that OVX-induced estrogen deficiency-related AMPK decrease was associated with climacteric symptoms such as obesity, hyperlipidemia, hepatic steatosis, and osteoporosis in ICR mice. However, these climacteric effects were reversed in OVX rats by treating them with WC at a dose relative to the same dose of PCP in OVX-ICR mice (200 and 100 mg/kg). Water chestnut fruit extract demonstrated promise as a complementary treatment for menopausal symptoms, indicating possible uses in the health of women through supplements or prescription drugs.

Osteoarthritis (OA) is a degenerative joint disease that mainly occurs due to the cellular inflammatory response and the destruction of joint cartilage. Natural eggshell membrane (NEM), a byproduct of egg processing, might be a promising knee OA treatment because of its anti-inflammatory properties and resemblance to synovial membrane components. Therefore, we aimed to study the anti-inflammatory effects of NEM in OA, utilizing both in vitro experiments with primary chondrocytes and in vivo studies with a surgical rat model of knee OA. In vitro studies showed that NEM treatment improved cell viability in chondrocytes exposed to interleukin-1α by upregulating chondrogenic genes and inhibiting enzymes that degrade the extracellular matrix (ECM). Furthermore, the anti-inflammatory effects of NEM were observed in chondrocytes induced by lipopolysaccharide. Administering NEM orally for 56 days after OA surgery resulted in enhanced joint swelling reduction and improved mobility in animal models, as well as an increase in bone density and cartilage compressive strength in a concentration-dependent manner. It inhibited inflammatory markers (5-lipoxygenase and prostaglandin E2) and extracellular matrix (ECM)-degrading enzymes (MMP-2 and MMP-9) in both the cartilage and synovium. Simultaneously, there was an upregulation in the expression of chondrogenic genes (Sox9, aggrecan, and Col-2). The histopathological and immunohistochemical analyses demonstrated that NEM’s anti-inflammatory, anti-apoptotic, and chondrogenic properties contributed to the mitigation of joint degradation and synovial inflammation. Therefore, NEM is a potential alternative or functional food agent that addresses both anti-inflammatory and chondroprotective aspects in OA.

Deep seawater (DS), obtained from a depth over 200 m, has health benefits due to its rich nutrients and minerals, and intake of DS has shown diverse immunomodulatory effects in allergies and cancer. Therefore, the immunostimulatory effects of Korean mineral-rich seawaters were examined in a cyclophosphamide (CPA)-induced immunosuppression model. Three samples of Korean seawater, namely DS from the East Sea off the coasts of Pohang (PDS) and Uljin (UDS), and seawater from the West Sea off the coast of Boryeong (BS), were collected. The seawaters were abundant in several minerals (calcium, iron, zinc, selenium, etc.). Mice were orally administered the seawaters for 42 days, followed by CPA-induced immunosuppression. The CPA induction reduced the weight of the spleen and lymph nodes; however, the administration of seawaters increased the weight of the lymphoid organs, accompanied by stimulation of natural killer cells’ activity and NF-kB-mediated cytokine production (IFNγ, TNFα, IL1β, IL6, and IL12). The mouse-derived splenocytes showed lymphoproliferation without cytotoxicity in the seawater groups. Histopathological analysis revealed that the seawaters improved the CPA-induced atrophic changes by promoting lymphoproliferation in the spleen and lymph nodes. These results provide useful information for the use of Korean mineral-rich seawaters, particularly PDS and UDS, as alternative immunostimulants under immunosuppressive conditions.

Photoaging refers to the accumulation of skin damage which includes wrinkle formation, loss of elasticity, and epidermal thickening due to repeated ultraviolet (UV) irradiation. The present study investigated the protective effects of Elaeagnus umbellata fruit extract (Elaea) on UV-mediated photoaged skin of SKH1 hairless mice and compared the effects of Elaea with ascorbic acid. Although there was no difference in body weight between groups during experimental period, oral administration of 50–200 mg/kg Elaea once daily for 15 weeks significantly prevented an increase in skin weight, epithelial thickening of epidermis, and apoptosis caused by UV irradiation. Skin replica and histopathological analyses revealed that Elaea dose-dependently decreased wrinkle and microfold formation. In addition, Elaea administration restored UV-mediated reduction in type I collagen and hyaluronan through the inhibition of matrix metalloproteinases and p38 mitogen-activated protein kinase expression. Moreover, Elaea suppressed UV-dependent increases in superoxide anion production, fatty acid oxidation, and protein nitration by up-regulating antioxidant system. Furthermore, Elaea alleviated infiltration of inflammatory cells in UV-irradiated skin. The preventive effects of 100 mg/kg Elaea administration against UV-induced photoaging were similar to those by 100 mg/kg ascorbic acid. Collectively, the present study suggests that the E. umbellata fruit is a promising edible candidate to prevent skin photoaging.

Obesity is implicated as a factor in several serious metabolic conditions, including hypertension, cardiovascular disease, and type II diabetes. This study aimed at the development of more potent and safer alternative medications to address these metabolic diseases with minimal side effects. Following oral administration of 400, 200, and 100 of mg/kg fermented Schizandrae fructus pomace extracts (fSFP) once daily for 84 days to high-fat diet (HFD)-supplied ICR mice, respectively, we measured liver enzyme activity related to glucose metabolism, gene expression related to fat metabolism, anti-obesity effect, liver and kidney protection effect, and anti-diabetic effect to confirm the effect of fSFP on improving related complications including obesity and diabetes. In the HFD control group, significant obesity and type II diabetes symptoms were developed. However, oral administration of 200 mg/kg of fSFP showed a protective effect on kidney damage and diabetes complications related to insulin-resistant type II diabetes mellitus, as well as oxidative stress-induced abnormalities in glucose and fat metabolism, comparable to that of metformin 250 mg/kg, a positive control. The major bioactive substance in fSFP was identified as shizandrin, which was quantitated as 1.25 mg/g (w/w). Therefore, fSFP extracts can be taken as a medicinal food in combating obesity and diabetes, two current major health concerns.

The effects of coffee (Coffea arabica L.) berry pulp extracts (CBP extracts) on the improvement of diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD) were evaluated using various in vitro antioxidant activity assays and through a high-fat diet-induced mild diabetic obese mouse model. After an 84-day oral administration of CBP extracts (400–100 mg/kg), bioactivities were evaluated. The in vitro analysis showed the highest DPPH● scavenging activity of 73.10 ± 4.27%, ABTS● scavenging activity of 41.18 ± 1.14%, and SOD activity of 56.24 ± 2.81%, at a CBP extract concentration of 1000 µg/mL. The in vivo analysis of the CBP extracts showed favorable and dose-dependent anti-obesity, anti-diabetic, NAFLD, nephropathy, and hyperlipidemia refinement effects through hepatic glucose enzyme activity, 5′-AMP-activated protein kinase (AMPK) up-regulation, antioxidant activity, lipid metabolism-related gene expression, and pancreatic lipid digestion enzyme modulatory activities. This study shows that an appropriate oral dosage of CBP extracts could function as a potent herbal formulation for a refinement agent or medicinal food ingredient to control type 2 diabetes and related complications.

Background and Objectives: This study evaluated the in vitro anti-adipogenic and anti-inflammatory properties of black cumin (Nigella sativa L.) seed extract (BCS extract) as a potential candidate for developing herbal formulations targeting metabolic disorders. Materials and Methods: We evaluated the BCS extract by assessing its 2,2-diphenyl-1-picrohydrazyl (DPPH) radical scavenging activity, levels of prostaglandin E2 (PGE2) and nitric oxide (NO), and mRNA expression levels of key pro-inflammatory mediators. We also quantified the phosphorylation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPK) signaling molecules. To assess anti-adipogenic effects, we used differentiated 3T3-L1 cells and BCS extract in doses from 10 to 100 μg/mL. We also determined mRNA levels of key adipogenic genes, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/BEPα), adipocyte protein 2 (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), and sterol-regulated element-binding protein 1c (SREBP-1c) using real-time quantitative polymerase chain reaction (qPCR). Results: This study showed a concentration-dependent DPPH radical scavenging activity and no toxicity at concentrations up to 30 μg/mL in Raw264.7 cells. BCS extract showed an IC50 of 328.77 ± 20.52 μg/mL. Notably, pre-treatment with BCS extract (30 μg/mL) significantly enhanced cell viability in lipopolysaccharide (LPS)-treated Raw264.7 cells. BCS extract treatment effectively inhibited LPS-induced production of PGE2 and NO, as well as the expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), interleukin (IL)-1β and IL-6, possibly by limiting the phosphorylation of p38, p65, inhibitory κBα (I-κBα), and c-Jun N-terminal kinase (JNK). It also significantly attenuated lipid accumulation and key adipogenic genes in 3T3-L1 cells. Conclusions: This study highlights the in vitro anti-adipogenic and anti-inflammatory potential of BCS extract, underscoring its potential as a promising candidate for managing metabolic disorders.

Osteoarthritis (OA) is characterized by progressive cartilage destruction and synovitis; however, there are no approved disease-modifying OA drugs. Krill oil (KO) has been reported to possess anti-inflammatory properties and alleviate joint pain in knee OA, indicating its potential to target the inflammatory mechanism of OA. Therefore, the anti-OA effects of KO were investigated in primary chondrocytes and a surgical rat model of knee OA. The oral administration of KO at 200 and 100 mg/kg for 8 weeks improved joint swelling and mobility in the animal model and led to increased bone mineral density and compressive strength in the cartilage. The oral KO doses upregulated chondrogenic genes (type 2 collagen, aggrecan, and Sox9), with inhibition of inflammation markers (5-lipoxygenase and prostaglandin E2) and extracellular matrix (ECM)-degrading enzymes (MMP-2 and MMP-9) in the cartilage and synovium. Consistently, KO treatments increased the viability of chondrocytes exposed to interleukin 1α, accompanied by the upregulation of the chondrogenic genes and the inhibition of the ECM-degrading enzymes. Furthermore, KO demonstrated inhibitory effects on lipopolysaccharide-induced chondrocyte inflammation. Histopathological and immunohistochemical analyses revealed that KO improved joint destruction and synovial inflammation, probably due to the anti-inflammatory, anti-apoptotic, and chondrogenic effects. These findings suggest the therapeutic potential of KO for knee OA.

Krill oil (KO) shows promise as a natural marine-derived ingredient for improving skin health. This study investigated its antioxidant, anti-inflammatory, anti-wrinkle, and moisturizing effects on skin cells and UVB-induced skin photoaging in hairless mice. In vitro assays on HDF, HaCaT, and B16/F10 cells, as well as in vivo experiments on 60 hairless mice were conducted. A cell viability assay, diphenyl-1-picryhydrazyl (DPPH) radical scavenging activity test, elastase inhibition assay, procollagen content test, MMP-1 inhibition test, and hyaluronan production assay were used to experiment on in vitro cell models. Mice received oral KO administration (100, 200, or 400 mg/kg) once a day for 15 weeks and UVB radiation three times a week. L-Ascorbic acid (L-AA) was orally administered at 100 mg/kg once daily for 15 weeks, starting from the initial ultraviolet B (UVB) exposures. L-AA administration followed each UVB session (0.18 J/cm2) after one hour. In vitro, KO significantly countered UVB-induced oxidative stress, reduced wrinkles, and prevented skin water loss by enhancing collagen and hyaluronic synthesis. In vivo, all KO dosages showed dose-dependent inhibition of oxidative stress-induced inflammatory photoaging-related skin changes. Skin mRNA expressions for hyaluronan synthesis and collagen synthesis genes also increased dose-dependently after KO treatment. Histopathological analysis confirmed that krill oil (KO) ameliorated the damage caused by UVB-irradiated skin tissues. The results imply that KO could potentially act as a positive measure in diminishing UVB-triggered skin photoaging and address various skin issues like wrinkles and moisturization when taken as a dietary supplement.

The use of natural products in developing respiratory-function-protective pharmaceuticals is actively progressing. However, in this context, the improvement effects of young Asian pear (Pyrus pyrifolia Nakai) extracts have not been evaluated yet. Thus, this study investigated the anti-inflammatory and lung damage improvement effects of immature Asian pear extract (IAP; 400, 200, and 100 mg/kg) using a particulate matter 2.5 μm (PM2.5)-induced sub-acute lung injury mouse model. The experimental results were compared with dexamethasone (0.75 mg/kg), used as a control drug. After two intranasal instillations of PM2.5 and ten doses of IAP extract for eight days, changes in macroscopic lung autopsy, leukocyte fractionation from bronchoalveolar lavage fluid, lung antioxidant defense system, lung histopathology, and mRNA expression in lung tissue were confirmed. Stress-induced inflammatory lung damage through the increased expression of PM2.5-induced PI3K/Akt and p38 MAPK mRNA was significantly suppressed via the administration of IAP extract (400–100 mg/kg). Furthermore, IAP extract administration promoted serous fluid production in lung tissue, increased substance P and ACh levels, and decreased mucus-production-related expression of MUC5AC and MUC5B mRNA. Interestingly, the observed effects showed a dose-dependent manner without serious hepatotoxicity. The results of this study indicate that a proper oral administration of IAP extract could be helpful in protecting against lung diseases, positioning IAP extract as a potential candidate for an alternative agent to safeguard the respiratory system.

Schizandrae Fructus (SF) and Hoveniae Semen cum Fructus (HSCF) have long been used as medicinal herbs for treating various diseases in Asian traditional medicine. In the current study, we investigated the protective effect of fermented SF pomace and HSCF extract 1:1 (w:w) combination mixture (MSH) against carbon tetrachloride (CCl4)-induced acute liver injury mice. After MSH (50–200 mg/kg) oral administration for 7 consecutive days, animals were injected intraperitoneally with CCl4 (0.5 mL/kg). Histopathological observation revealed that administration of MSH synergistically decreased the degeneration of hepatocytes and the infiltration of inflammatory cells induced by CCl4. Moreover, MSH administration reduced the activities of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase in serum, and mitigated apoptotic cell death in hepatic parenchyma. In addition, MSH alleviated CCl4-mediated lipid peroxidation by restoring endogenous antioxidants capacities including glutathione contents, superoxide dismutase, and catalase activities. In vitro assessments using tert-butyl hydroperoxide-induced oxidative stress in HepG2 cells revealed that MSH protects hepatocytes by lowering ROS generation and lipid peroxidation via upregulating the transcriptional activity of nuclear factor erythroid-2-related factor 2 and the expression of antioxidant genes. Furthermore, MSH synergistically attenuated the expression of proinflammatory cytokines in CCl4-injured liver and lipopolysaccharide-stimulated RAW 264.7 cells. Taken together, these findings suggest that MSH has the potential to prevent acute liver damage by effectively suppressing oxidative stress and inflammation.

Schizandrae Fructus (SF), fruits of Schisandra chinensis (Turcz.) Baill. and Hoveniae Semen cum Fructus (HSCF), the dried peduncle of Hovenia dulcis Thunb., have long been used for alcohol detoxification in the traditional medicine of Korea and China. In the current study, we aimed to evaluate the potential synergistic hepatoprotective effect of a combination mixture (MSH) comprising fermented SF pomace (fSFP) and HSCF hot water extracts at a 1:1 (w:w) ratio against ethanol-induced liver toxicity. Subacute ethanol-mediated hepatotoxicity was induced by the oral administration of ethanol (5 g/kg) in C57BL/6J mice once daily for 14 consecutive days. One hour after each ethanol administration, MSH (50, 100, and 200 mg/kg) was also orally administered daily. MSH administration significantly reduced the serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase. Histological observation indicated that MSH administration synergistically and significantly decreased the fatty changed region of hepatic parenchyma and the formation of lipid droplet in hepatocytes. Moreover, MSH significantly attenuated the hepatic triglyceride accumulation through reducing lipogenesis genes expression and increasing fatty acid oxidation genes expression. In addition, MSH significantly inhibited protein nitrosylation and lipid peroxidation by lowering cytochrome P450 2E1 enzyme activity and restoring the glutathione level, superoxide dismutase and catalase activity in liver. Furthermore, MSH synergistically decreased the mRNA level of tumor necrosis factor-α in the hepatic tissue. These findings indicate that MSH has potential for preventing alcoholic liver disease through inhibiting hepatic steatosis, oxidative stress, and inflammation.

Allergic asthma is a chronic inflammatory disease characterized by the infiltration of leukocytes, particularly eosinophils, into the airways, resulting in respiratory dysfunction. To develop new asthma treatment materials with minimal side effects and excellent bioactivities, we evaluated the efficacy of immature Asian pear extract (IAP extract; 400–100 mg/kg) in alleviating ovalbumin (OVA)-induced asthma in female C57BL/6J mice. This study assesses various parameters associated with OVA-induced allergic asthma including lung weight, macroscopic necropsy findings, the total cell count in bronchoalveolar lavage fluid (BALF), the total leukocyte count and leukocyte differential count, serum ovalbumin-specific Ig E (OVA-sIg E) levels, interleukin (IL)-4 and IL-5 contents in BALF, histopathological changes in the lungs, and alterations in oxidative stress and inflammation-related mRNA expressions. The results of this study demonstrate clear asthma-related findings in the OVA control group. However, the oral administration of IAP extract (at doses ranging from 400 to 100 mg/kg) significantly suppressed the anti-inflammatory and antioxidant activities by regulating the expressions of phosphoinositide 3-kinase/protein kinase B/phosphatase and TENsin homolog deleted on chromosome 10 (PI3K/Akt/PTEN), p38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in a dose-dependent manner. These effects are comparable to those observed with dexamethasone at a concentration of 0.75 mg/kg. As a result, the oral administration of an appropriate dose of IAP extract holds promise as a potential natural drug or health-functional food material for improving respiratory function.

This study was performed to identify the effect of synovium graft on conjunctiva in rabbits after dry eye induction. Six New Zealand White rabbits were used as dry eye models. Both eyes were divided to two groups as control and synovium graft group. The synovium graft was performed in fourth week after dry eye modeling. Quantitative change of tears through Schirmer tear test (STT), qualitative change of tear film through tear film break up time (TFBUT), and damage of cornea through fluorescein staining were observed for 10 weeks at intervals of two weeks. Histological examination was performed to evaluate cornea and conjunctiva at tenth week. In both groups, STT and TFBUT were significantly decreased in 4 weeks after modeling compared to 0 weeks (p < 0.05) . After synovium graft, there were increases in STT value at 4 weeks and TFBUT at 4 and 6 weeks in graft group (p < 0.05). Corneal fluorescein staining showed no significant difference between the two groups. In histopathological examination, grafted synovium was detected as round to ovoid ingression folds, well attached to grafted regions with 0.11 ± 0.04 mm2 (range, 0.05- 0.16 mm2). These results indicated that the synovium graft on the conjunctiva had an effect on the qualitative and quantitative improvement of the tear film even though there was no histological change.

Adenophora stricta Miq. (Campanulaceae family) is a traditional herb used for relieving cough and phlegm in East Asia. This study explored the effects of A. stricta root extract (AsE) in ovalbumin (OVA)-induced allergic asthma and lipopolysaccharide (LPS)-stimulated macrophages. Administration of 100–400 mg/kg AsE dose-dependently decreased pulmonary congestion and suppressed the reduction of alveolar surface area in mice with OVA-mediated allergic asthma. Histopathological analysis of lung tissue and cytological analysis of bronchioalveolar lavage fluid showed that AsE administration significantly attenuated inflammatory cell infiltration into the lungs. In addition, AsE also alleviated OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5 production, which are essential for OVA-dependent activation of T helper 2 lymphocytes. In Raw264.7 macrophage cells, AsE significantly blocked nitric oxide, tumor necrosis factor-α, IL-1β, IL-6, and monocyte chemoattractant factor-1 production in response to LPS. Results from an immunoblot assay revealed that AsE inhibited the phosphorylation of c-jun N-terminal kinase, inhibitory-κB kinase α/β, and p65 in LPS-stimulated cells. Furthermore, 2-furoic acid, 5-hydroxymethylfurfural, and vanillic acid 4-β-D-glucopyranoside in AsE were shown to inhibit the production of proinflammatory mediators by LPS. Taken together, the present results suggest that A. stricta root will be a useful herb for relieving allergic asthma through managing airway inflammation.

To deal with the adverse effects associated with the use of currently available treatments for metabolic disorders, such as type 2 diabetes, there is a need to find an alternative drug compound. In the present study, we investigated the therapeutic potential of black cumin (Nigella sativa L.) seeds extract (BCS extract) for type 2 diabetes using a 45% Kcal-fed obese mouse model. The BCS extract at different doses (400–100 mg/kg) showed a dose-dependent improvement tendency in high-fat diet (HFD)-induced obesity, non-alcoholic fatty liver disease (NAFLD), hyperlipidemia, and diabetic nephropathy compared to the metformin (250 mg/kg). In particular, BCS extract at a dose of 200 mg/kg significantly inhibited the HFD-induced metabolic conditions. The oral administration of BCS extract (200 mg/kg) significantly inhibited the oxidative stress through lipid peroxidation, normalized the activity of sugar metabolism-related enzymes and the expression of genes involved in fat metabolism, and inhibited insulin resistance through glucose and fat metabolism by regulating the 5’-AMP-activated protein kinase (AMPK) expression. Furthermore, BCS extract (200 mg/kg) showed renal damage improvement effects compared to the metformin (250 mg/kg). The results clearly show that BCS aqueous extract at an appropriate concentration could help in the treatment of metabolic disorders, and BCS aqueous extract can be used as a functional food for various diabetic complications, such as obesity, diabetes, and NAFLD.

Context Kyeongok-go (KOG) is a traditional mixed herb preparation consisting of Panax ginseng CA Meyer (Araliaceae), Poria cocos Wolf (Polyporaceae), Rehmannia glutinosa (Gaertner) Liboschitz ex Steudel (Orobanchaceae), and honey. Various pharmacological effects of KOG are reported, but the efficacy on respiratory diseases has not been evaluated. Objective The anti-inflammatory, expectorant, and antitussive properties of KOG were examined using animal models of respiratory diseases. Materials and methods KOG (100, 200, and 400 mg/kg) was orally administered to ICR mice (n = 8) once a day for 11 days. Anti-inflammatory effects of vehicle, xylene, KOG and DEXA (1 mg/kg) were determined by monitoring edoema and redness of treated ears, and measuring the relative and absolute weight of each ear. Expectorant properties of vehicle, KOG and AM (250 mg/kg) were evaluated by observing body surface redness, and the amount of mucous secreted by the trachea. The antitussive potential of vehicle, NH4OH, KOG and TB (50 mg/kg) was evaluated by monitoring changes in the number of coughs (for 6 min). Results KOG (400 mg/kg) treated mice showed 31.29% and 30.72% (p

The purpose of the current study was to observe the anti-diabetic and anti-obesity effects of blue honeysuckle (BH; Lonicera caerulea L.) extracts on obese diabetic mice. BH extracts dose-dependently and significantly inhibited abnormal endocrine pancreas histopathological changes. Moreover, favorable anti-diabetic effects and non-alcoholic fatty liver disease, nephropathy, and hyperlipidemia refinement activities in BH extracts were shown to be dose dependent. Particularly, BH extract 200 mg/kg showed favorable modulatory activities on PPAR γ and AMPK in hepatic and adipose tissues as comparable to those of positive control, conjugated linoleic acid (CLA) administration. Results from the current study suggest that BH extracts could be a potential functional ingredient for anti-obesity and anti-diabetic effects through the inhibition of lipogenesis and hepatic glucose production by regulating lipid metabolism-related mRNA expressions.

Although the immunomodulatory effects of Astragali Radix extract (AR) have been documented, its anti-mutagenic activity, a problem arising from chemotherapeutic agents, is rarely reported. Therefore, the anti-mutagenic and immunomodulatory effects of AR were investigated using a cyclophosphamide (CPA)-induced immunosuppressed mouse model to develop an alternative immunomodulatory agent. The fluid-bed-dried aqueous extract of AR containing 37.5% dextrin and exopolymers purified from Aureobasidium pullulans SM-2001 (EAP) were used in this study. The therapeutic potentials of AR at doses ranging from 100 mg/kg to 400 mg/kg was estimated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based cytotoxicity and splenocyte proliferation assay, body weight and lymphatic organ weight measurements, hematological measurements, serum and spleen cytokine level measurements, natural killer (NK) cell activity measurements, real-time RT-PCR expressions of splenic mRNA, a micronucleus test, histopathological observations, and immunohistochemical measurements. In CPA-treated mice, a clear immunosuppressive effect was observed for all tested parameters. However, the oral administration of AR (100, 200, and 400 mg/kg) showed dose-dependent and favorable inhibitory activities on CPA-induced immunosuppression and mutagenicity as compared to 200 mg/kg EAP. Furthermore, AR (100–400 mg/kg) up-regulated the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) which are related to NK-, T-, and B-cell activation, with no critical cytotoxicity. The results of this study clearly demonstrate that AR at an appropriate oral dose could act as a potential alternative agent with significant anti-mutagenicity and immunomodulatory properties.

Chronic exposure of particulate matter of less than 2.5 μm (PM2.5) has been considered as one of the major etiologies for various respiratory diseases. Adenophora stricta Miq. is a medicinal herb that has been used for treating respiratory diseases in East Asia. The present study investigated the effect of A. stricta root extract (AsE) on PM2.5-induced lung injury in mice. Oral administration of 100–400 mg/kg AsE for 10 days significantly reduced the PM2.5-mediated increase in relative lung weight, but there was no difference in body weight with AsE administration. In addition, AsE dose-dependently decreased congested region of the lung tissue, prevented apoptosis and matrix degradation, and alleviated mucus stasis induced by PM2.5. Moreover, cytological analysis of bronchioalveolar lavage fluid revealed that AsE significantly inhibited the infiltration of immune cells into the lungs. Consistently, AsE also decreased expression of proinflammatory cytokines and chemokines in lung tissue. Furthermore, AsE administration blocked reactive oxygen species production and lipid peroxidation through attenuating the PM2.5-dependent reduction of antioxidant defense system in the lungs. Therefore, A. stricta root would be a promising candidate for protecting lung tissue from air pollution such as PM2.5.

Obesity increases the risks of metabolic syndromes including nonalcoholic fatty liver disease (NAFLD), diabetic dyslipidemia, and chronic kidney disease. Dietary krill oil (KO) has shown antioxidant and anti-inflammatory properties, thereby being a therapeutic potential for obesity-induced metabolic syndromes. Thus, the effects of KO on lipid metabolic alteration were examined in a high-fat diet (HFD)-fed mice model. The HFD model (n = 10 per group) received an oral gavage with distilled water as a control, metformin at 250 mg/kg, and KO at 400, 200, and 100 mg/kg for 12 weeks. The HFD-induced weight gain and fat deposition were significantly reduced in the KO treatments compared with the control. Blood levels were lower in parameters for NAFLD (e.g., alanine aminotransferase, and triglyceride), type 2 diabetes (e.g., glucose and insulin), and renal dysfunction (e.g., blood urea nitrogen and creatinine) by the KO treatments. The KO inhibited lipid synthesis through the modification of gene expressions in the liver and adipose tissues and adipokine-mediated pathways. Furthermore, KO showed hepatic antioxidant activities and glucose lowering effects. Histopathological analyses revealed that the KO ameliorated the hepatic steatosis, pancreatic endocrine/exocrine alteration, adipose tissue hypertrophy, and renal steatosis. These analyses suggest that KO may be promising for inhibiting obesity and metabolic syndromes.

We recently reported that varying combination ratios of lemon balm (Mellissa officinalis L.) and corn silk extracts (Stigma of Zea mays L. fruit) could reduce the obesity caused by a high-fat diet (HFD). The present study investigated the dose-dependent effect of a 1:1 (w:w) mixture of lemon balm and corn silk extracts (M-LB/CS) on HFD-mediated metabolic disorders and compared the effect with metformin. Oral administration of 50–200 mg/kg of M-LB/CS for 84 days significantly inhibited HFD-induced body weight gain, adipocyte hypertrophy, and lipogenic gene induction without affecting food consumption in mice. Biochemical analyses showed that M-LB/CS blocked abnormal lipid accumulation in the blood by escalating fecal lipid excretion. In addition, M-LB/CS prevented HFD-mediated pancreatic atrophy, decreased the number of insulin- and glucagon-immunoreactive cells, and inhibited increases in glycated hemoglobin, glucose, and insulin. Moreover, M-LB/CS also reduced hepatic injury, lipid accumulation, gluconeogenesis, and lipid peroxidation in parallel with the induction of AMP-activated protein kinase and antioxidant enzymes. Furthermore, M-LB/CS protected the kidney by inhibiting tubular vacuolation and reducing serum creatinine and blood urea nitrogen levels. The prophylactic effect of 100 mg/kg M-LB/CS-administration was comparable to that of metformin. Therefore, M-LB/CS may be an alternative option for managing obesity and its related metabolic disorders.

Metformin, the first-line drug for type 2 diabetes mellitus (T2DM), has additional effects on improvements of nonalcoholic fatty liver disease (NAFLD); however, there are no treatments for both T2DM and NAFLD. Previous studies have shown hepatoprotective effects of a mixture of lemon balm and dandelion (LD) through its antioxidant and anti-steatosis properties. Thus, combination effects of metformin and LD were examined in a high-fat diet (HFD)-induced metabolic disease mouse model. The model received an oral administration of distilled water, monotherapies of metformin and LD, or a metformin combination with LD for 12 weeks. The HFD-induced weight gain and body fat deposition were reduced more by the combination than either monotherapy. Blood parameters for NAFLD (i.e., alanine aminotransferase and triglyceride), T2DM (i.e., glucose and insulin), and renal functions (i.e., blood urea nitrogen and creatinine) were reduced in the combination. The combination further enhanced hepatic antioxidant activities, and improved insulin resistance via the AMP-activated protein kinase and lipid metabolism pathways. Histopathological analyses revealed that the metformin combination ameliorated the hepatic hypertrophy/steatosis, pancreatic endocrine/exocrine alteration, fat tissue hypertrophy, and renal steatosis, more than either monotherapy. These results suggest that metformin combined with LD can be promising for preventing and treating metabolic diseases involving insulin resistance.

Atopic dermatitis (AD) is a chronic and allergic skin disease; however, there is no cure for the disease. Red ginseng is well known to have anti-AD potential, while red ginseng marc (RGM) remaining after ginseng extraction is regarded as useless and discarded. However, it has recently been reported that RGM, particularly fermented RGM (fRGM), still contains bioactive properties. Thus, the anti-allergic effects of fRGM were examined in a 2,4-dinitrochlorobenzene-induced AD-like mice model. The model was topically treated with distilled water (control), dexamethasone, or fRGM for six weeks. Treatments of fRGM alleviated skin lesions and reduced serum IgE levels, compared with the control. The fRGM also reduced skin levels of lipid peroxidation and superoxide anion; however, it increased glutathione contents, with downregulated gene expression for inflammatory mediators. Histopathological analyses demonstrated that fRGM suppressed epidermal thickening, collagen deposition, and inflammatory cell and mast cell infiltration, which involved anti-inflammatory, antioxidant, and anti-apoptotic effects. Further, fRGM suppressed hypertrophic changes and inflammatory responses in the spleen and lymph nodes. The beneficial effects were observed in the dexamethasone and fRGM groups; however, the antioxidant effects were evident only in the fRGM treatments. These results provide useful information for developing fRGM as a therapeutic source for AD.

The aim of the study was to elucidate the protective action of roasted Lycium chinense (rLF) enhanced kaempferol glycosides as bioactive components from obese-induced type 2 diabetes mice by investigating the histopathological, biochemical, and transcriptional analyses in blood, liver, and adipose tissue. The rLF extract significantly decreased the hypertrophy of fat deposition, pancreatic hyperplasia, hyperinsulinemia, hepatocellular steatosis, and nephropathy in a dose dependent manner (p

This study was initiated to determine whether 2 structurally related flavonoids found in Cyclopia subternata-vicenin-2 (VCN) and scolymoside (SCL)-could modulate renal functional damage in a mouse model of sepsis, and to elucidate the relevant underlying mechanisms. The potential of VCN and SCL treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured via assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with either VCN or SCL resulted in elevated plasma levels of BUN and creatinine, and of protein in the urine of mice with CLP-induced renal damage. Moreover, both VCN and SCL inhibited nuclear factor κB activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. VCN and SCL treatment also reduced the plasma levels of interleukin-6, and tumor necrosis factor-α, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. The present results suggest that VCN and SCL protect mice from sepsis-triggered renal injury.

Osteoarthritis (OA), the most prevalent articular disease with the clinical syndrome of joint pain accompanied by varying degrees of functional limitation, reduces the quality of elderly life. In this study, the effects of Plebeian sage extract (PS) on anti-inflammatory and anti-articular cartilage degradation activities were evaluated in rats with surgically induced OA. PS supplement for 12 weeks significantly decreased Mankin scores, including inflammatory cell numbers, and improved surface cartilage damage and mean femur and tibia articular cartilage (AC) thicknesses in OA rats. PS diminished IL-1β, IL-6, TNF-α, MMP-2, MMP-3, and MMP-9, as well as lipocalin-2 levels in serum or cartilage, which were increased due to OA. The results suggested that PS decreased joint inflammation and loss of articular cartilage by suppressing provocative responses and synovial tissue decimation in the OA model. Thus, PS may be used as a novel potential therapeutic regime for OA in the elderly.

Background and Objectives: The currently used pharmacological agents for metabolic disorders such as type II diabetes have several limitations and adverse effects; thus, there is a need for alternative therapeutic drugs and health functional foods. Materials and Methods: This study investigated the pharmacological effects of water chestnut (fruit of Trapa japonica) extracts (WC: 50–200 mg/kg) for type II diabetes using a 45% Kcal high-fat diet (HFD)-fed type II obese diabetic mice model for a period of 84 days, and the effects were compared to those of metformin (250 mg/kg). Results: Increases in body weight, serum biochemical indices such as triglycerides, low-density lipoprotein, and blood urea nitrogen, increases in antioxidant defense system enzymes such as catalase, superoxide dismutase, and glutathione, and mRNA expressions (such as AMPKα1 and AMPKα2) in the liver tissue and mRNA expressions (such as AMPKα2 mRNA, leptin, and C/EBPα) in the adipose tissue were observed in the HFD control group. The WC (50 mg/kg)-administered group showed no significant improvements in diabetic complications. However, HFD-induced obesity and diabetes-related complications such as hyperlipidemia, diabetic nephropathy, nonalcoholic fatty liver disease (NAFLD), oxidative stress, activity of antioxidant defense systems, and gene expressions were significantly and dose-dependently inhibited and/or normalized by oral administration of WC (100 mg/kg and 200 mg/kg), particularly at a dose of 100 mg/kg. Conclusions: The results of this study suggest that WC at an appropriate dose could be used to develop an effective therapeutic drug or functional food for type II diabetes and various associated complications, including NAFLD.

Cluster of differentiation 44 (CD44) is the most common cancer stem cell (CSC) marker and high CD44 expression has been associated with anticancer drug resistance, tumor recurrence, and metastasis. In this study, we aimed to investigate the molecular mechanism by which CD44 and nuclear factor erythroid 2-like 2 (NFE2L2; NRF2), a key regulator of antioxidant genes, are linked to CSC resistance using CD44high breast CSC-like cells. NRF2 expression was higher in CD44high cell populations isolated from doxorubicin-resistant MCF7 (ADR), as well as MCF7, MDA-MB231, and A549 cells, than in corresponding CD44low cells. High NRF2 expression in the CD44highCD24low CSC population (ADR44P) established from ADR cells depended on standard isoform of CD44. Silencing of CD44 or overexpression of CD44 resulted in the reduction or elevation of NRF2, respectively, and treatment with hyaluronic acid, a CD44 ligand, augmented NRF2 activation. As functional implications, NRF2 silencing rendered ADR44P cells to retain higher levels of reactive oxygen species and to be sensitive to anticancer drug toxicity. Moreover, NRF2-silenced ADR44P cells displayed tumor growth retardation and reduced colony/sphere formation and invasion capacity. In line with these, CD44 significantly colocalized with NRF2 in breast tumor clinical samples. The molecular mechanism of CD44-mediated NRF2 activation was found to involve high p62 expression. CD44 elevation led to an increase in p62, and inhibition of p62 resulted in NRF2 suppression in ADR44P. Collectively, our results showed that high CD44 led to p62-associated NRF2 activation in CD44high breast CSC-like cells. NRF2 activation contributed to the aggressive phenotype, tumor growth, and anticancer drug resistance of CD44high CSCs. Therefore, the CD44-NRF2 axis might be a promising therapeutic target for the control of stress resistance and survival of CD44high CSC population within breast tumors. Keywords: CD44, Cancer stem cell (CSC), NFE2L2/NRF2, Reactive oxygen species (ROS), Stress resistance, p62

Lemon balm and corn silk are valuable medicinal herbs, which exhibit variety of beneficial effects for human health. The present study explored the anti-obesity effects of a mixture of lemon balm and corn silk extracts (M-LB/CS) by comparison with the effects of single herbal extracts in high-fat diet (HFD)-induced obesity in mice. HFD supplementation for 84 days increased the body weight, the fat mass density, the mean diameter of adipocytes, and the thickness of fat pads. However, oral administration of M-LB/CS significantly alleviated the HFD-mediated weight gain and adipocyte hypertrophy without affecting food consumption. Of the various combination ratios of M-LB/CS tested, the magnitude of the decreases in weight gain and adipocyte hypertrophy by administration of 1:1, 1:2, 2:1, and 4:1 (w/w) M-LB/CS was more potent than that by single herbal extracts alone. In addition, M-LB/CS reduced the HFD-mediated increases in serum cholesterol, triglyceride, and low-density lipoprotein, prevented the reduction in serum high-density lipoprotein, and facilitated fecal excretion of cholesterol and triglyceride. Moreover, M-LB/CS mitigated the abnormal changes in specific mRNAs associated with lipogenesis and lipolysis in the adipose tissue. Furthermore, M-LB/CS reduced lipid peroxidation by inhibiting the HFD-mediated reduction in glutathione, catalase, and superoxide dismutase. Therefore, M-LB/CS is a promising herbal mixture for preventing obesity.

Ferroptosis is a type of programmed necrosis triggered by iron-dependent lipid peroxidation. We investigated the role of B-cell translocation gene 1 (BTG1) in cystine and methionine deficiency (CST/Met (−))-mediated cell death. CST/Met (−) depleted reduced and oxidized glutathione in hepatocyte-derived cells, increased prostaglandin-endoperoxide synthase 2 expression, and promoted reactive oxygen species accumulation and lipid peroxidation, as well as necrotic cell death. CST/Met (−)-mediated cell death and lipid peroxidation was specifically inhibited by pretreatment with ferroptosis inhibitors. In parallel with cell death, CST/Met (−) blocked global protein translation and increased the expression of genes associated with the integrated stress response. Moreover, CST/Met (−) significantly induced BTG1 expression. Using a BTG1 promoter-harboring reporter gene and siRNA, activating transcription factor 4 (ATF4) was identified as an essential transcription factor for CST/Met (−)-mediated BTG1 induction. Although knockout of BTG1 in human HAP1 cells did not affect the accumulation of reactive oxygen species induced by CST/Met (−), BTG1 knockout significantly decreased the induction of genes associated with the integrated stress response, and reduced lipid peroxidation and cell death in response to CST/Met (−). The results demonstrate that CST/Met (−) induces ferroptosis by activating ATF4-dependent BTG1 induction.

Background and Objectives: The present study investigated the beneficial effects of tart cherry (fruit of Prunus cerasus) concentrated powder (TCcp) on glucocorticoid (GLU)-induced catabolic muscular atrophy in the skeletal muscle of mice. Furthermore, its potential mechanism was also studied. Materials and Methods: Changes in calf thickness, calf muscle weight, calf muscle strength, body weight, gastrocnemius muscle histology, immunohistochemistry, serum creatinine, creatine kinase, lactate dehydrogenase, and antioxidant defense systems were measured. Malondialdehyde, reactive oxygen species, glutathione content, catalase, and superoxide dismutase activities in the gastrocnemius muscle, and muscle-specific mRNA expressions were evaluated. Results: After 24 days, GLU control mice showed muscular atrophy at all criteria of indexes. The muscular atrophy symptoms were significantly inhibited by oral treatment with 250 mg/kg and 500 mg/kg of TCcp through antioxidative and anti-inflammatory modulated expression of genes involved in muscle protein degradation (myostatin, atrogin-1, SIRT1, and MuRF1) and synthesis (A1R, Akt1, TRPV4, and PI3K). Conclusions: This study shows that the TCcp (500 mg/kg and 250 mg/kg) could improve muscular atrophies caused by various etiologies.

The purpose of the current study was to investigate antioxidant and anti-inflammatory effects of spray dry powder containing 40% curcumin (CM-SD) in C2C12 myoblast cells. CM-SD increased DPPH radical scavenging activity in a dose-dependent manner, and up to 30 μg/mL of CM-SD did not express cytotoxicity in C2C12 cells. Exposure to hydrogen peroxide (H2O2) drastically decreased the viability of C2C12 cells, but pre-treatment of CM-SD significantly increased the cell viability (p < 0.01). CM-SD significantly transactivated the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent luciferase activity in a dose-dependent manner and enhanced the levels of heme oxygenase (HO)-1, glutamate cysteine ligase catalytic subunit (GCLC), and NAD(P)H-dependent quinone oxidoreductase (NQO)-1. CM-SD also significantly reduced reactive oxygen species (ROS) production and lipid peroxidation and restored glutathione (GSH) depletion in H2O2-treated C2C12 cells. Moreover, CM-SD significantly reduced lipopolysaccharides (LPS)-mediated interleukin (IL)-6 production in the conditioned medium. Results from the current study suggest that CM-SD could be a useful candidate against oxidative stress and inflammation-related muscle disorders.

In this paper, we hypothesized that ShashamKyeongok-go (SKOG) is a mixed preparation of Adenophorae Radix powder (AR) and Kyeongok-go (KOG). SKOG may be served as a novel preventive and/or therapeutic agent for various respiratory diseases. SKOG were orally administered to ICR mice at 400, 200, and 100 mg/kg once a day for 11 days to examine antitussive, expectorant, and anti-inflammatory effects. The NH4OH exposure-induced allergic acute inflammation with coughing responses was dose-dependently and significantly (p < 0.01) inhibited by pretreatment with SKOG at doses of 400, 200, and 100 mg/kg. With these concentrations of SKOG, the thickness of intrapulmonary secondary bronchus mucosa and the number of periodic acid Schiff stain-positive mucous-producing cells were significantly (p < 0.05 or p < 0.01) increased, as a result of the increased amount of phenol red secretion. Subsequently, SKOG showed significant (p < 0.01) anti-inflammatory activities as characterized by reducing the effects of xylene-induced increases of ear weight, thickness of total ear and ear dermis, and number of infiltrated inflammatory cells in the ear dermis, in a dose-dependent manner. These results supported that SKOG might have potential therapeutic effects to be used as an antitussive, expectorant, and anti-inflammatory agents in the prevention or treatment of chronic bronchitis and asthma.

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.

An abnormal hair-growth cycle induces hair loss, which affects psychological distress and impairs life quality. Red ginseng marc (RGM) is usually discarded as a byproduct after extracting red ginseng, but several studies have shown that the RGM still has bioactive components including ginsenosides. Therefore, the hair-growth effects of fermented RGM (fRGM) and traditional polyherb formula (PH) were examined in C57BL/6 mice. The dorsal hairs of mice were depilated, and they were topically treated with fRGM or PH at 400, 200 and 100 mg/kg or the combination of both middle doses (combi) once a day for two weeks. The hair-covering regions were significantly increased with higher doses of fRGM and PH and in combi groups, compared with the control treated with distilled water. Hair length, thickness and weight also increased in the treatment groups. In particular, the fRGM and PH increased the anagen-phased hair follicles, the follicular diameters and the dermal thickness. Immunostains for Ki-67 showed the anagen-phased cell division in the treatment groups. The beneficial effects were greater in the high doses of fRGM and PH and the combi groups. These suggest hair-growth-promoting effects of fRGM, PH and the combination by enhancing the hair-growth cycle.

Acute kidney injury (AKI) is a disease caused by sudden renal dysfunction, which is an important risk factor for chronic renal failure. However, there is no effective treatment for renal impairment. Although some traditional polyherbs are commercially available for renal diseases, their effectiveness has not been reported. Therefore, we examined the nephroprotective effects of polyherbs and their relevant mechanisms in a cisplatin-induced cell injury model. Rat NRK-52E and human HK-2 subjected to cisplatin-induced AKI were treated with four polyherbs, Injinhotang (IJ), Ucha-Shinki-Hwan (US), Yukmijihwang-tang (YJ), and UrofenTM (Uro) similar with Yondansagan-tang, for three days. All polyherbs showed strong free radical scavenging activities, and the treatments prevented cisplatin-induced cell death in both models, especially at 1.2 mg/mL. The protective effects involved antioxidant effects by reducing reactive oxygen species and increasing the activities of superoxide dismutase and catalase. The polyherbs also reduced the number of annexin V-positive apoptotic cells and the expression of cleaved caspase-3, along with inhibited expression of mitogen-activated protein kinase-related proteins. These findings provide evidence for promoting the development of herbal formulas as an alternative therapy for treating AKI.

Many studies have reported the biological activities of retrofractamide C (RAC). However, few studies have investigated the anti-inflammatory effect of RAC. In the present study, we investigated the anti-inflammatory effect of RAC using lipopolysaccharide (LPS)-induced J774A.1 cells and a xylene-induced mouse ear edema model. Treatment with RAC decreased LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) secretion and inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. It also downregulated the LPS-induced production of interleukin-1β (IL-1β) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). In the LPS-induced signaling pathway, RAC inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) but not c-Jun N-terminal kinase (JNK) or p38. In a xylene-induced mouse ear edema model, RAC treatment alleviated edema formation and inflammatory cell infiltration. In conclusion, the present study indicates that RAC has the potential to have anti-inflammatory effects and could be a prospective functional food.

The present study examined the effects of Wasabi leaf (WL) on 45% Kcal high-fat diet (HFD)-fed mild diabetic obese mice. In particular, the hepatoprotective (i.e., liver weight, histopathology of liver, serum aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase) effects of 12 weeks of continuous oral administration of 250 mg/kg metformin, and 200, 100, or 50 mg/kg WL were investigated. In addition, the hypolipidemic (i.e., serum triglyceride, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein levels), hypoglycemic (i.e., glycated hemoglobin, blood glucose and insulin levels, pancreatic weight, and immunohistochemical-histopathological analysis of the pancreas), and anti-obesity effects (i.e., body weight, mean food consumption, total and abdominal body fat mass, periovarian fat weight, and histopathology of the periovarian and abdominal wall adipocytes) were monitored. The liver and general antioxidant defense systems were also assessed by lipid metabolism-related gene expression. All diabetes manifestations and related complications, including obesity and non-alcoholic fatty liver disease (NAFLD), were dose-dependently reduced after 84 days of oral treatment with metformin or each of the three dosages of WL. In particular, 50 mg/kg WL showed effective suppression effects against HFD-induced diabetes and related complications of obesity, NAFLD, and hyperlipidemia, comparable to the effects of metformin.

Chronic and excessive inflammation can destroy host organs and cause inflammatory diseases such as inflammatory bowel disease, asthma, and rheumatoid arthritis. In this study, we investigated the anti-inflammatory effects of Alpinia katsumadai seed-derived 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (PHT) using lipopolysaccharide (LPS)-stimulated J774 cells and a formalin-induced chronic paw inflammation mouse model. The in vitro results showed that PHT exhibited no cytotoxicity and decreased LPS-induced NO secretion. Additionally, PHT inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. The quantitative real-time PCR results showed that PHT downregulated the gene expression of the proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). PHT inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). In a mouse model, oral administration of 50 mg/kg PHT significantly alleviated both mouse paw thickness and volume. These results indicate that PHT has potential anti-inflammatory effects and should be considered a possible functional material.

In this study, we aimed to determine the synergistic effects of a formula consisting of dried pomegranate concentrate powder, Eucommiae Cortex, and Achyranthis Radix 5:4:1 (g/g) (PCP:EC:AR) in a surgically induced osteoarthritis (OA) rabbit model. PCP:EC:AR was orally administered once per day. Knee thickness, maximum extension of the knee joint, gross articular defect area, and the histopathological appearance of the cartilage were monitored, along with serum collagen type II C-telopeptide (CTX-II), cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-3, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and subchondral IL-1β and TNF-α levels. Roentgenographic images were also evaluated. PCP:EC:AR significantly inhibited the surgically induced increase in knee thickness, maximum extension of both knees, knee thickness after capsule exposure, gross femoral and tibial articular defect areas, loss of the knee joint area, serum and synovial COMP, CTX-II, and MMP expression, and synovial IL-1β, and TNF-α expression. In addition, surgically induced narrowing of the knee bones, loss of the joint area, cartilage damage, and osteophyte formation were reduced. PCP:EC:AR suppressed the surgically induced increases in the Mankin score, and subchondral IL-1β and TNF-α immunolabeled cell numbers. PCP:EC:AR exerted potent OA protective effects in a surgically induced OA rabbit model.

Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of sepsis. Here, we examined the effects of three phenolic glycosides (1–3) found in Rhododendron brachycarpum, which has been used as food and medicinal resources for anti-rheumatic agent, diuretic, and anti-inflammatory in Asia, on inflammatory responses by monitoring the effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1, and on the modulation of HMGB1-mediated inflammatory responses. The anti-inflammatory activities of phenolic glycosides 1–3 were determined by measuring permeability, monocyte adhesion and migration, and the activation of pro-inflammatory proteins in HMGB1-activated HUVECs and mice. All three phenolic glycosides inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. Phenolic glycosides 1–3 also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with compounds 1–3 reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury. Our results indicate that phenolic glycosides 1–3 could be candidate therapeutic agents for various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.

Piperlonguminine (PL), an important component of Piperlongum fruits, is known to exhibit anti-hyperlipidemic, antiplateletand anti-melanogenic activities. Here, the anticoagulantactivities of PL were examined by monitoring activatedpartial-thromboplastin-time (aPTT), prothrombin-time (PT), andthe activities of thrombin and activated factor X (FXa). Theeffects of PL on the expressions of plasminogen activatorinhibitor type 1 (PAI-1) and tissue-type plasminogen activator(t-PA) were also tested in tumor necrosis factor-α (TNF-α)activated HUVECs. The results showed that PL prolonged aPTTand PT significantly and inhibited the activities of thrombin andFXa. PL inhibited the generation of thrombin and FXa inHUVECs. In accordance with these anticoagulant activities, PLprolonged in vivo bleeding time and inhibited TNF-α inducedPAI-1 production. Furthermore, PAI-1/t-PA ratio was significantlydecreased by PL. Collectively, our results suggest that PLpossesses antithrombotic activities and that the current studycould provide bases for the development of new anticoagulantagents. [BMB Reports 2013; 46(10): 484-489]

Chronic kidney disease (CKD) is a major complication of metabolic disorders such as diabetes mellitus, obesity, and hypertension. Comorbidity of these diseases is the factor exacerbating CKD progression. Statins are commonly used in patients with metabolic disorders to decrease the risk of cardiovascular complications. Sarpogrelate, a selective antagonist of 5-hydroxytryptamine (5-HT) 2A receptor, inhibits platelet aggregation and is used to improve peripheral circulation in diabetic patients. Here, we investigated the effects of sarpogrelate and rosuvastatin on CKD in mice that were subjected to a high fat diet (HFD) for 22 weeks and a single low dose of streptozotocin (STZ, 40 mg/kg). When mice were administrated sarpogrelate (50 mg/kg, p.o.) for 13 weeks, albuminuria and urinary cystatin C excretion were normalized and histopathological changes such as glomerular mesangial expansion, tubular damage, and accumulations in lipid droplets and collagen were significantly improved. Sarpogrelate treatment repressed the HFD/STZ-induced CD31 and vascular endothelial growth factor receptor-2 expressions, indicating the attenuation of glomerular endothelial proliferation. Additionally, sarpogrelate inhibited interstitial fibrosis by suppressing the increases in transforming growth factor-β1 (TGF-β1) and plasminogen activator inhibitor-1 (PAI-1). All of these functional and histological improvements were also seen in rosuvastatin (20 mg/kg) group and, notably, the combinatorial treatment with sarpogrelate and rosuvastatin showed additive beneficial effects on histopathological changes by HFD/STZ. Moreover, sarpogrelate reduced circulating levels of PAI-1 that were elevated in the HFD/STZ group. As supportive in vitro evidence, sarpogrelate incubation blocked TGF-β1/5-HT-inducible PAI-1 expression in murine glomerular mesangial cells. Taken together, sarpogrelate and rosuvastatin may be advantageous to control the progression of CKD in patients with comorbid metabolic disorders, and particularly, the use of sarpogrelate as adjunctive therapy with statins may provide additional benefits on CKD.

Curcumin, a polyphenol responsible for the yellow color ofthe curry spice turmeric, possesses antiinflammatory, antiproliferativeand antiangiogenic activities. However, anticoagulantactivities of curcumin have not been studied. Here,the anticoagulant properties of curcumin and its derivative(bisdemethoxycurcumin, BDMC) were determined by monitoringactivated partial thromboplastin time (aPTT), prothrombintime (PT) as well as cell-based thrombin and activated factor X(FXa) generation activities. Data showed that curcumin andBDMC prolonged aPTT and PT significantly and inhibitedthrombin and FXa activities. They inhibited the generation ofthrombin or FXa. In accordance with these anticoagulant activities,curcumin and BDMC showed anticoagulant effect invivo. Surprisingly, these anticoagulant effects of curcuminwere better than those of BDMC indicating that methoxygroup in curcumin positively regulated anticoagulant functionof curcumin. Therefore, these results suggest that curcuminand BDMC possess antithrombotic activities and daily consumptionof the curry spice turmeric might help maintain anticoagulantstatus. [BMB reports 2012; 45(4): 221-226]

Enzymatic oxidation of commercially available pyrogallol wasefficiently transformed to an oxidative product, purpurogallin.Purpurogallin plays an important role in inhibiting glutathioneS-transferase, xanthine oxidase, catechol O-methyltransferaseactivities and is effective in the cell protection of several celltypes. However, the anti-inflammatory functions of purpurogallinare not well studied. Here, we determined the effectsof purpurogallin on lipopolysaccharide (LPS)-mediated proinflammatoryresponses. The results showed that purpurogallininhibited LPS-mediated barrier hyper-permeability, monocyteadhesion and migration and such inhibitory effects weresignificantly correlated with the inhibitory functions ofpurpurogallin on LPS-mediated cell adhesion molecules(vascular cell adhesion molecules, intracellular cell adhesionmolecule, E-selectin). Furthermore, LPS-mediated nuclearfactor-κB (NF-κB) and tumor necrosis factor-α (TNF-α) releasesfrom HUVECs were inhibited by purpurogallin. Given theseresults, purpurogallin showed its anti-inflammatory activitiesand could be a candidate as a therapeutic agent for varioussystemic inflammatory diseases. [BMB reports 2012; 45(3):200-205]

Ultraviolet (UV) B exposure induces DNA damage and production of reactive oxygen species (ROS), which causes skin photoaging through signaling pathways of inflammation and modulation of extracellular matrix remodeling proteins, collagens, and matrix metalloproteinase (MMP). As low molecular-weight fucoidan (LMF) has potential antioxidant and anti-inflammatory properties, we examined the protective effects of LMF against UVB-induced photoaging. A UVB-irradiated mouse model was topically treated with myricetin or LMF at 2.0, 1.0 and 0.2 mg/cm2 (LMF2.0, LMF1.0 and LMF0.2, respectively) once a day for 15 weeks. Wrinkle formation, inflammation, oxidative stress, MMP expression, and apoptosis in the treated regions were compared with those in a distilled water-treated photoaging model (UVB control). LMF treatments, particularly LMF2.0 and LMF1.0, significantly inhibited the wrinkle formation, skin edema, and neutrophil recruitment into the photo-damaged lesions, compared with those in the UVB control. While LMF decreased interleukin (IL)-1β release, it increased IL-10. The LMF treatment inhibited the oxidative stresses (malondialdehyde and superoxide anion) and enhanced endogenous antioxidants (glutathione). Additionally, LMF reduced the mRNA expression of MMP-1, 9, and 13. The histopathological analyses revealed the anti-photoaging effects of LMF exerted via its antioxidant, anti-apoptotic, and MMP-9-inhibiting effects. These suggest that LMF can be used as a skin-protective remedy for photoaging.

The aim of this study was to observe whether Polycal has inhibitory activity on ligation-induced experimental periodontitis and related alveolar bone loss in rats following topical application to the gingival regions. One day after the ligation placements, Polycal (50, 25, and 12.5 mg/mL solutions at 200 μL/rat) was topically applied to the ligated gingival regions daily for 10 days. Changes in bodyweight, alveolar bone loss index, and total number of buccal gingival aerobic bacterial cells were monitored, and the anti-inflammatory effects were investigated via myeloperoxidase activity and levels of the pro-inflammatory cytokines IL-1β and TNF-α. The activities of inducible nitric oxide synthase (iNOS) and lipid peroxidation (MDA) were also evaluated. Bacterial proliferation, periodontitis, and alveolar bone loss induced by ligature placements were significantly inhibited after 10 days of continuous topical application of Polycal. These results indicate that topical application of Polycal has a significant inhibitory effect on periodontitis and related alveolar bone loss in rats mediated by antibacterial, anti-inflammatory, and anti-oxidative activities.

Background: Achilles tendon is composed of dense connective tissue and is one of the largest tendons in the body. In veterinary medicine, acute ruptures are associated with impact injury or sharp trauma. Healing of the ruptured tendon is challenging because of poor blood and nerve supply as well as the residual cell population. Platelet-rich plasma (PRP) contains numerous bioactive agents and growth factors and has been utilized to promote healing in bone, soft tissue, and tendons. Objective: The purpose of this study was to evaluate the healing effect of PRP injected into the surrounding fascia of the Achilles tendon after allograft in rabbits. Methods: Donor rabbits (n = 8) were anesthetized and 16 lateral gastrocnemius tendons were fully transected bilaterally. Transected tendons were decellularized and stored at -80°C prior to allograft. The allograft was placed on the partially transected medial gastrocnemius tendon in the left hindlimb of 16 rabbits. The allograft PRP group (n = 8) had 0.3 mL of PRP administered in the tendon and the allograft control group (n = 8) did not receive any treatment. After 8 weeks, rabbits were euthanatized and allograft tendons were transected for macroscopic, biomechanical, and histological assessment. Results: The allograft PRP group exhibited superior macroscopic assessment scores, greater tensile strength, and a histologically enhanced healing process compared to those in the allograft control group. Conclusions: Our results suggest administration of PRP on an allograft tendon has a positive effect on the healing process in a ruptured Achilles tendon. [ABSTRACT FROM AUTHOR]