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Abstract Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non‐alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline‐deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl‐CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element‐binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid β‐oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.

Abstract Mulberroside F is isolated from the leaves and roots of Morus alba L. Here, we investigated whether mulberroside F could alleviate airway inflammation and eosinophil infiltration in the lungs of asthmatic mice. We also examined whether mulberroside F attenuated inflammatory responses in human tracheal epithelial BEAS‐2B cells. Female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and administered different doses of mulberroside F via intraperitoneal injection. Additionally, tumor necrosis factor (TNF)‐α‐stimulated BEAS‐2B cells were treated with various doses of mulberroside F, followed by detection of the expressions of inflammatory cytokines and chemokines. The results demonstrated that mulberroside F mitigated the levels of proinflammatory cytokines and chemokines, and CCL11, in inflammatory BEAS‐2B cells. Mulberroside F also suppressed reactive oxygen species (ROS) production and ICAM‐1 expression in TNF‐α‐stimulated BEAS‐2B cells, which effectively suppressed monocyte cell adherence. In an animal model of asthma, mulberroside F treatment attenuated airway hyperresponsiveness, eosinophil infiltration, and goblet cell hyperplasia. Mulberroside F treatment also decreased lung fibrosis and airway inflammation in OVA‐sensitized mice. Moreover, mulberroside F significantly reduced expressions of Th2‐associated cytokines (including interleukin(IL)‐4, IL‐5, and IL‐13) in bronchoalveolar lavage fluid compared to OVA‐sensitized mice. Our results confirmed that mulberroside F is a novel bioactive compound that can effectively reduce airway inflammation and eosinophil infiltration in asthmatic mice via inhibition of Th2‐cell activation.

Diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus, is primarily characterized by damage to Schwann cells caused by oxidative stress under hyperglycemic conditions. Recently, we demonstrated the ability of coumarin-rich Ficus formosana Maxim. to alleviate DPN in ovariectomized diabetic mice. However, the underlying mechanisms remain unclear. In this study, we established an in vitro DPN model using RSC96 Schwann cells exposed to high glucose levels. Daphnetin, a natural coumarin found abundantly in Ficus formosana Maxim., was co-incubated with Schwann cells in a high-glucose medium to investigate its protective effects against DPN. The free radical scavenging capacity of daphnetin was evaluated, along with assessments of cell viability, apoptosis, H2O2 levels, and the expression of proteins by the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutamate–cysteine ligase catalytic subunit (GCLC) pathway in RSC96 Schwann cells. The results showed that daphnetin was non-toxic within the tested concentration range of 6.25 μM to 50 μM in RSC96 Schwann cells. Moreover, daphnetin significantly improved cell viability, exhibited strong antioxidant activity, reduced H2O2 levels, and regulated the Nrf2/GCLC pathway protein expressions in RSC96 cells cultured in high-glucose medium. Additionally, daphnetin influenced apoptosis-related proteins by decreasing the expression levels of Bax and Caspase 3, while increasing the Bcl-2 expression level in high-glucose-treated RSC96 cells. These findings suggest that daphnetin may alleviate oxidative stress induced by high glucose levels through activation of the Nrf2/GCLC pathway and inhibition of Schwann cell apoptosis, underscoring its potential as a therapeutic agent for DPN.

Abstract Background Alzheimer’s disease (AD) is caused by many intertwining pathologies involving metabolic aberrations. Patients with metabolic syndrome (MetS) generally show hyperglycemia and dyslipidemia, which can lead to the formation of aldehydic adducts such as acrolein on peptides in the brain and blood. However, the pathogenesis from MetS to AD remains elusive. Methods An AD cell model expressing Swedish and Indiana amyloid precursor protein (APP-Swe/Ind) in neuro-2a cells and a 3xTg-AD mouse model were used. Human serum samples (142 control and 117 AD) and related clinical data were collected. Due to the involvement of MetS in AD, human samples were grouped into healthy control (HC), MetS-like, AD with normal metabolism (AD-N), and AD with metabolic disturbance (AD-M). APP, amyloid-beta (Aß), and acrolein adducts in the samples were analyzed using immunofluorescent microscopy, histochemistry, immunoprecipitation, immunoblotting, and/or ELISA. Synthetic Aß1-16 and Aß17-28 peptides were modified with acrolein in vitro and verified using LC–MS/MS. Native and acrolein-modified Aß peptides were used to measure the levels of specific autoantibodies IgG and IgM in the serum. The correlations and diagnostic power of potential biomarkers were evaluated. Results An increased level of acrolein adducts was detected in the AD model cells. Furthermore, acrolein adducts were observed on APP C-terminal fragments (APP-CTFs) containing Aß in 3xTg-AD mouse serum, brain lysates, and human serum. The level of acrolein adducts was correlated positively with fasting glucose and triglycerides and negatively with high-density lipoprotein-cholesterol, which correspond with MetS conditions. Among the four groups of human samples, the level of acrolein adducts was largely increased only in AD-M compared to all other groups. Notably, anti-acrolein-Aß autoantibodies, especially IgM, were largely reduced in AD-M compared to the MetS group, suggesting that the specific antibodies against acrolein adducts may be depleted during pathogenesis from MetS to AD. Conclusions Metabolic disturbance may induce acrolein adduction, however, neutralized by responding autoantibodies. AD may be developed from MetS when these autoantibodies are depleted. Acrolein adducts and the responding autoantibodies may be potential biomarkers for not only diagnosis but also immunotherapy of AD, especially in complication with MetS.

ABSTRACTPhillyrin is isolated from the fruit of Forsythia suspensa, and exhibits multiple pharmacological effects, including anti-tumor, anti-inflammation, and anti-oxidation activities. Here, we investigated whether phillyrin could alleviate airway hyperresponsiveness (AHR) and eosinophil infiltration in the lungs of asthmatic mice, and mitigate inflammatory responses in tracheal epithelial BEAS-2B cells. IL-4/TNF-α-stimulated BEAS-2B cells were treated with various phillyrin doses. Female BALB/c mice were sensitised and challenged with ovalbumin (OVA), and then treated with intraperitoneal injection different phillyrin doses. In IL-4/TNF-α-stimulated BEAS-2B cells, phillyrin effectively reduced proinflammatory cytokines, chemokines, and eotaxin (CCL11) levels. In the lungs of asthmatic mice, phillyrin treatment relieved AHR, airway inflammation, eosinophil infiltration, and goblet cell hyperplasia. Phillyrin also reduced serum OVA-IgE, and Th2-associated cytokine levels in splenocyte culture medium, and in bronchoalveolar lavage fluid of asthmatic mice. Our results indicate that phillyrin attenuated airway inflammation and eosinophil infiltration in asthmatic mice by suppressing Th2 cytokine production.

Probiotics may protect against asthma. We want to investigate whether probiotics can reverse the adverse effects of phthalate exposure on asthma. We selected the female offspring of BALB/c mice, born from pregnant female mice fed with diethylhexyl phthalate (DEHP). They were continuously administrated DEHP and Lactobacillus salivarius ssp. salicinius SA-03 when they were 5 weeks old, and ovalbumin (OVA) for asthma induction started at 6 weeks for 32 days. The mice were divided into four groups (n = 6/group): 1. control group (C), 2. OVA/DEHP group (OD), 3. OVA/DEHP/probiotics low-dose group (ODP-1X), and OVA/DEHP/probiotics high-dose group (ODP-5X). We found that the administration of probiotics significantly reduced the asthma severity of the mice, as well as serum IgE and IL-5. In the ODP-5X group, the proportion of CD4+ cells in the lung was reduced, whereas IL-10 in serum and CD8+ cells in BALF were increased. In histopathology, the ODP group showed reduced infiltration of inflammatory cells, bronchial epithelial cell hyperplasia, and tracheal mucus secretion. These results might indicate that high-dose probiotics may affect anti-inflammatory cytokines and reduce asthma-relative indicators. The above results may provide evidence that high-dose probiotics supplementation might play a modulating role in DEHP causes of allergic asthma in the pediatric animal model.

In diabetes mellitus, Ficus formosana has been reported to ameliorate blood sugar levels and inhibit inflammation through its polyphenol and flavonoid contents. However, its effect on diabetic peripheral neuropathy (DPN) remains unknown. This study aimed to investigate the effect of Ficus formosana extract (FFE) on DPN in ovariectomized diabetic mice. Ovariectomized female C57BL/6J mice fed a high-fat diet plus streptozotocin injections to induce type 2 diabetes were orally administered FEE at 20 or 200 mg/kg BW daily, for 6 weeks. To evaluate the pain responses in the paws of the mice, a von Frey filament test and a thermal hyperalgesia test were performed. Additionally, the intraepidermal and sciatic nerve sections were examined, along with an assessment of inflammation- and pain response-related mRNA expression in the paws of the mice. The results showed that the oral administration of both 20 and 200 mg/kg BW FEE significantly alleviated the hypersensitivity of the paw and the abnormal proliferation and rupture of the C fiber, and reduced the mRNA expression of interleukin-1β, interleukin-6, interferon-γ, cyclooxygenase-2, and voltage-gated sodium channel 1.8 in the sciatic nerve of ovariectomized diabetic mice. We propose that FFE ameliorates peripheral neuropathy by suppressing oxidative damage in ovariectomized diabetic mice.

Background: Ginsenoside Rg3, isolated from Panax ginseng, has anti-inflammatory and anti-tumor activities. It is known to reduce inflammation in acute lung injury in mice, and to reduce the expression of inflammatory cytokines and COX-2 in human asthmatic airway epithelium. In this study, we attempted to determine whether ginsenoside Rg3 inhibits airway inflammation, oxidative stress, and airway hyperresponsiveness (AHR) in the lungs of asthmatic mice. We also investigated its effects on oxidative stress and the inflammatory response in tracheal epithelial cells. Methods: Asthma symptoms were induced in female BALB/c mice sensitized with ovalbumin (OVA). Mice were divided into five groups: normal controls, OVA-induced asthmatic controls, and asthmatic mice treated with ginsenoside Rg3 or prednisolone by intraperitoneal injection. Inflammatory BEAS-2B cells (human tracheal epithelial cells) treated with ginsenoside Rg3 to investigate its effects on inflammatory cytokines and oxidative responses. Results: Ginsenoside Rg3 treatment significantly reduced eosinophil infiltration, oxidative responses, airway inflammation, and AHR in the lungs of asthmatic mice. Ginsenoside Rg3 reduced Th2 cytokine and chemokine levels in bronchoalveolar lavage fluids and lung. Inflammatory BEAS-2B cells treated with ginsenoside Rg3 reduced the eotaxin and pro-inflammatory cytokine expressions, and monocyte adherence to BEAS-2B cells was significantly reduced as a result of decreased ICAM-1 expression. Furthermore, ginsenoside Rg3 reduced the expression of reactive oxygen species in inflammatory BEAS-2B cells. Conclusion: Ginsenoside Rg3 is a potential immunomodulator that can ameliorate pathological features of asthma by decreasing oxidative stress and inflammation

Abstract Background Phloretin is isolated from apple trees and could increase lipolysis in 3T3-L1 adipocytes. Previous studies have found that phloretin could prevent obesity in mice. In this study, we investigated whether phloretin ameliorates non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese mice, and evaluated the regulation of lipid metabolism in hepatocytes. Methods HepG2 cells were treated with 0.5 mM oleic acid to induce lipid accumulation, and then treated with phloretin to evaluate the molecular mechanism of lipogenesis. In another experiment, male C57BL/6 mice were fed normal diet or HFD (60% fat, w/w) for 16 weeks. After the fourth week, mice were treated with or without phloretin by intraperitoneal injection for 12 weeks. Results Phloretin significantly reduced excessive lipid accumulation and decreased sterol regulatory element-binding protein 1c, blocking the expression of fatty acid synthase in oleic acid-induced HepG2 cells. Phloretin increased Sirt1, and phosphorylation of AMP activated protein kinase to suppress acetyl-CoA carboxylase expression, reducing fatty acid synthesis in hepatocytes. Phloretin also reduced body weight and fat weight compared to untreated HFD-fed mice. Phloretin also reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis in obese mice. In liver tissue from obese mice, phloretin suppressed transcription factors of lipogenesis and fatty acid synthase, and increased lipolysis and fatty acid β-oxidation. Furthermore, phloretin regulated serum leptin, adiponectin, triglyceride, low-density lipoprotein, and free fatty acid levels in obese mice. Conclusions These findings suggest that phloretin improves hepatic steatosis by regulating lipogenesis and the Sirt-1/AMPK pathway in the liver.

Background and objectives: This study aimed to investigate the enhancing effect of vitamin-like alpha-lipoic acid (ALA) on phagocytosis of oligomeric beta-amyloid (oAβ)1–42 in BV-2 mouse microglial cells.Methods: An in vitro model was established to investigate phagocytosis of oAβ1–42 in BV-2 cells. Transmission electron microscopy images indicated that the morphology of prepared oAβ1–42 was spherical particles. BV-2 cells treated with ALA were incubated with 5(6)-carboxyfluorescein-labeled oAβ1–42 (FAM-oAβ1–42) for 24 h, followed by flow cytometer analysis, western blotting, real-time quantitative PCR, and immunocytochemistry (ICC) analysis to assess the in vitro phagocytosis ability of oAβ1–42.Results: Alpha-lipoic acid significantly increased messenger RNA (mRNA) expression of the CD36 receptor in BV-2 cells. ICC analysis showed that ALA significantly elevated CD36 protein expression in BV-2 cells both with and without oAβ1–42 treatment. Results from the flow cytometry analysis indicated that the CD36 receptor inhibitor significantly attenuated ALA-promoted phagocytosis of FAM-oAβ1–42 in BV-2 cells. Moreover, ICC analysis revealed that ALA caused the translocation of peroxisome proliferator-activated receptor-γ (PPAR-γ), which is known to regulate the expression of CD36 mRNA in BV-2 cells. ALA also elevated both the mRNA and protein expression of cyclooxygenase-2 (COX-2), which is a key enzyme involved in the synthesis of 15-deoxy-Δ12,14-prostaglandin J2 in BV-2 cells.Conclusion: We postulated that ALA enhances oAβ1–42 phagocytosis by upregulating the COX-2/15-deoxy-Δ12,14-prostaglandin J2/PPAR-γ/CD36 pathway in BV-2 cells. Finally, future studies should be conducted with an in vivo study to confirm the findings.

Background: The intricate relationship between type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) suggests that insulin is involved in modulating AD-related proteins. Alpha-lipoic acid (ALA) can improve insulin resistance (IR) in diabetic rats. However, the role of ALA in alleviating the cognitive decline of T2DM is not yet clear. This study examined the ameliorative effect of ALA on cognitive impairment, cerebral IR, and synaptic plasticity abnormalities in high-fat diet (HFD) plus streptozotocin (STZ) induced diabetic rats.Methods: The HFD/STZ-induced T2DM male Wistar rats were orally administered with ALA (50, 100, or 200 mg/kg BW) once a day for 13 weeks. Abilities of cognition were measured with a passive avoidance test and Morris water maze. Specimens of blood and brain were collected for biochemical analysis after the rats were sacrificed. Western blotting was used to determine protein expressions in the hippocampus and cortex in the insulin signaling pathways, long-term potentiation (LTP), and synaptic plasticity-related protein expressions.Results: Alpha-lipoic acid improved hyperinsulinemia and the higher levels of free fatty acids of the T2DM rats. Behavioral experiments showed that the administration of ALA improved cognitive impairment in HFD/STZ-induced T2DM rats. ALA ameliorated insulin-related pathway proteins [phosphoinositide 3-kinase (PI3K), phospho-protein kinase B (pAkt)/Akt, and insulin-degrading enzyme (IDE)] and the LTP pathway, as well as synaptic plasticity proteins (calmodulin-dependent protein kinase II, cyclic AMP response element-binding protein, and postsynaptic density protein-95) of the cerebral cortex or hippocampus in HFD/STZ-induced T2DM rats.Conclusion: Our findings suggested that ALA may ameliorate cognition impairment via alleviating cerebral IR improvement and cerebral synaptic plasticity in diabetic rats.

Our previous study found that oral administration of Gynostemma pentaphyllum extract can attenuate airway hyperresponsiveness (AHR) and reduce eosinophil infiltration in the lungs of asthmatic mice. Gypenoside A is isolated from G. pentaphyllum. In this study, we investigated whether gypenoside A can effectively reduce asthma in mice. Asthma was induced in BALB/c mice by ovalbumin injection. Asthmatic mice were treated with gypenoside A via intraperitoneal injection to assess airway inflammation, AHR, and immunomodulatory effects. In vitro, gypenoside A reduced inflammatory and oxidative responses in inflammatory tracheal epithelial cells. Experimental results showed that gypenoside A treatment can suppress eosinophil infiltration in the lungs, reduce tracheal goblet cell hyperplasia, and attenuate AHR. Gypenoside A significantly reduced Th2 cytokine expression and also inhibited the expression of inflammatory genes and proteins in the lung and bronchoalveolar lavage fluid. In addition, gypenoside A also significantly inhibited the secretion of inflammatory cytokines and chemokines and reduced oxidative expression in inflammatory tracheal epithelial cells. The experimental results suggested that gypenoside A is a natural compound that can effectively reduce airway inflammation and AHR in asthma, mainly by reducing Th2 cell activation.

Ginkgolide C, isolated from Ginkgo biloba, is a diterpene lactone that has multiple biological functions and can improve Alzheimer disease and platelet aggregation. Ginkgolide C also inhibits adipogenesis in 3T3-L1 adipocytes. The present study evaluated whether ginkgolide C reduced lipid accumulation and regulated the molecular mechanism of lipogenesis in oleic acid-induced HepG2 hepatocytes. HepG2 cells were treated with 0.5 mM oleic acid for 48 h to induce a fatty liver cell model. Then, the cells were exposed to various concentrations of ginkgolide C for 24 h. Staining with Oil Red O and the fluorescent dye BODIPY 493/503 revealed that ginkgolide C significantly reduced excessive lipid accumulation in HepG2 cells. Ginkgolide C decreased peroxisome proliferator-activated receptor γ and sterol regulatory element-binding protein 1c to block the expression of fatty acid synthase. Ginkgolide C treatment also promoted the expression of adipose triglyceride lipase and the phosphorylation level of hormone-sensitive lipase to enhance the decomposition of triglycerides. In addition, ginkgolide C stimulated CPT-1 to activate fatty acid β-oxidation, significantly increased sirt1 and phosphorylation of AMP-activated protein kinase (AMPK), and decreased expression of acetyl-CoA carboxylase for suppressed fatty acid synthesis in hepatocytes. Taken together, our results suggest that ginkgolide C reduced lipid accumulation and increased lipolysis through the sirt1/AMPK pathway in oleic acid-induced fatty liver cells. Keywords: AMPK, Anti-obesity, Ginkgolide C, Lipogenesis, Lipolysis

Tomatidine, which is isolated from green tomato, can ameliorate inflammation and oxidative stress in cells and animal experiments and has been shown to improve airway inflammation in a murine model of asthma. Here, we investigated whether tomatidine can ameliorate acute lung injury in mice. Mice were given tomatidine by intraperitoneal injection for 7 consecutive days, and then, lung injury was induced via intratracheal instillation of lipopolysaccharide (LPS). Tomatidine reduced inflammatory cytokine expressions in bronchoalveolar lavage fluid (BALF), attenuated neutrophil infiltration in the BALF and lung tissue, increased superoxide dismutase activity and glutathione levels, and alleviated myeloperoxidase expression in the lung tissue of mice with lung injury. Tomatidine also decreased inflammatory cytokine and chemokine gene expression in inflammatory lungs and attenuated the phosphorylation of mitogen-activated protein kinase and nuclear factor kappa B. Furthermore, tomatidine enhanced the production of heme oxygenase-1, decreased the secretion of inflammatory cytokines and chemokines in LPS-stimulated lung epithelial cells, and attenuated THP-1 monocyte adhesion. Our findings suggest that tomatidine attenuates oxidative stress and inflammation, improving acute lung injury in mice.

Sophoraflavanone G (SG), isolated from Sophora flavescens, has anti-inflammatory and anti-tumor bioactive properties. We previously showed that SG promotes apoptosis in human breast cancer cells and leukemia cells and reduces the inflammatory response in lipopolysaccharide-stimulated macrophages. We investigated whether SG attenuates airway hyper-responsiveness (AHR) and airway inflammation in asthmatic mice. We also assessed its effects on the anti-inflammatory response in human tracheal epithelial cells. Female BALB/c mice were sensitized with ovalbumin, and asthmatic mice were treated with SG by intraperitoneal injection. We also exposed human bronchial epithelial BEAS-2B cells to different concentrations of SG to evaluate its effects on inflammatory cytokine levels. SG treatment significantly reduced AHR, eosinophil infiltration, goblet cell hyperplasia, and airway inflammation in the lungs of asthmatic mice. In the lungs of ovalbumin-sensitized mice, SG significantly promoted superoxide dismutase and glutathione expression and attenuated malondialdehyde levels. SG also suppressed levels of Th2 cytokines and chemokines in lung and bronchoalveolar lavage samples. In addition, we confirmed that SG decreased pro-inflammatory cytokine, chemokine, and eotaxin expression in inflammatory BEAS-2B cells. Taken together, our data demonstrate that SG shows potential as an immunomodulator that can improve asthma symptoms by decreasing airway-inflammation-related oxidative stress.

In Taiwan, the root extract of Vitis thunbergii Sieb. et Zucc. (Vitaceae, VT) is rich in stilbenes, with resveratrol (Res) and its derivatives being the most abundant. Previously, we showed that the effect of Res derivatives against tumor necrosis factor-α (TNF-α)-stimulated inflammatory responses occurs via cPLA2/COX-2/PGE2 inhibition. This study compared and explored the underlying anti-inflammatory pharmacological mechanisms. Before stimulation with TNF-α, RMCs were treated with/without pharmacological inhibitors of specific protein kinases. The expression of inflammatory mediators was determined by Western blotting, gelatin zymography, real-time PCR, and luciferase assay. Cellular and mitochondrial ROS were measured by H2DHFDA or DHE and MitoSOX™ Red staining, respectively. The RNS level was indirectly measured by Griess reagent assay. Kinase activation and association were assayed by immunoprecipitation followed by Western blotting. TNF-α binding to TNFR recruited Rac1 and p47phox, thus activating the NAPDH oxidase-dependent MAPK and NF-κB pathways. The TNF-α-induced NF-κB activation via c-Src-driven ROS was independent from the EGFR signaling pathway. The anti-inflammatory effects of Res derivatives occurred via the inhibition of ROS derived from mitochondria and NADPH oxidase; RNS derived from iNOS; and the activation of the ERK1/2, JNK1/2, and NF-κB pathways. Overall, this study provides an understanding of the various activities of Res derivatives and their pharmacological mechanisms. In the future, the application of the active molecules of VT to health foods and medicine in Taiwan may increase.

We previously demonstrated that acacetin reduces adipogenesis in adipocytes, and decreases lipid accumulation in visceral adipocyte tissue. Here we investigated whether acacetin regulated the mechanisms of lipogenesis and inflammation in non-alcoholic fatty liver disease (NAFLD) in obese mice. Male C57BL/6 mice were fed a high-fat diet (HFD), and then administered acacetin by intraperitoneal injection. Acacetin reduced body weight and liver weight in obese mice. Acacetin-treated obese mice exhibited decreased lipid accumulation, increased glycogen accumulation, and improved hepatocyte steatosis. Acacetin regulated triglycerides and total cholesterol in the liver and serum. Acacetin decreased low-density lipoprotein and leptin concentrations, but increased high-density lipoprotein and adiponectin levels in obese mice. Acacetin effectively weakened the gene expressions of transcription factors related to lipogenesis, and promoted the expressions of genes related to lipolysis and fatty acid β-oxidation in liver. Acacetin also reduced expressions of inflammation-related cytokines in the serum and liver. Oleic acid induced lipid accumulation in murine FL83B hepatocytes, and the effects of acacetin treatment indicated that acacetin may regulate lipid metabolism through the AMPK pathway. Acacetin may protect against hepatic steatosis by modulating inflammation and AMPK expression.

Urolithin A is an active compound of gut-microbiota-derived metabolites of polyphenol ellagic acid that has anti-aging, antioxidative, and anti-inflammatory effects. However, the effects of urolithin A on polyinosinic acid-polycytidylic acid (poly(I:C))-induced inflammation remain unclear. Poly(I:C) is a double-stranded RNA (dsRNA) similar to a virus and is recognized by Toll-like receptor-3 (TLR3), inducing an inflammatory response in immune cells, such as macrophages. Inflammation is a natural defense process of the innate immune system. Therefore, we used poly(I:C)-induced RAW264.7 cells and attenuated the inflammation induced by urolithin A. First, our data suggested that 1–30 μM urolithin A does not reduce RAW264.7 cell viability, whereas 1 μM urolithin A is sufficient for antioxidation and the decreased production of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and C-C chemokine ligand 5. The inflammation-related proteins cyclooxygenase-2 and inducible nitric oxide synthase were also downregulated by urolithin A. Next, 1 μM urolithin A inhibited the levels of interferon (INF)-α and INF-β. Urolithin A was applied to investigate the blockade of the TLR3 signaling pathway in poly(I:C)-induced RAW264.7 cells. Moreover, the TLR3 signaling pathway, subsequent inflammatory-related pathways, and antioxidation pathways showed changes in nuclear factor-κB (NF-κB) signaling and blocked ERK/mitogen-activated protein kinase (MAPK) signaling. Urolithin A enhanced catalase (CAT) and superoxide dismutase (SOD) activities, but decreased malondialdehyde (MDA) levels in poly(I:C)-induced RAW264.7 cells. Thus, our results suggest that urolithin A inhibits TLR3-activated inflammatory and oxidative-associated pathways in macrophages, and that this inhibition is induced by poly(I:C). Therefore, urolithin A may have antiviral effects and could be used to treat viral-infection-related diseases.

Fisetin is isolated from many fruits and vegetables and has been confirmed to improve airway hyperresponsiveness in asthmatic mice. However, whether fisetin reduces inflammatory response and oxidative stress in bronchial epithelial cells is unclear. Here, BEAS-2B human bronchial epithelial cells were treated with various concentrations of fisetin and then stimulated with tumor necrosis factor-α (TNF-α) or TNF-α/interleukin-4. In addition, ovalbumin-sensitized mice were treated with fisetin to detect inflammatory mediators and oxidative stress expression. Fisetin significantly reduced the levels of inflammatory cytokines and chemokines in TNF-α-stimulated BEAS-2B cells. Fisetin also attenuated intercellular adhesion molecule-1 expression in TNF-α-stimulated BEAS-2B cells, suppressing THP-1 monocyte adhesion. Furthermore, fisetin significantly suppressed airway hyperresponsiveness in the lungs and decreased eosinophil numbers in the bronchoalveolar lavage fluid of asthmatic mice. Fisetin decreased cyclooxygenase-2 expression, promoted glutathione levels, and decreased malondialdehyde levels in the lungs of asthmatic mice. Our findings indicate that fisetin is a potential immunomodulator that can improve the pathological features of asthma by decreasing oxidative stress and inflammation.

Cytokine-induced endothelial dysfunction leads to inflammation and vascular adhesion molecule production in retinal pigment epithelium (RPE) cells. Inflammation is a critical mediator in retinal degeneration (RD) diseases, including age-related macular degeneration (AMD), and RD progression may be prevented through anti-inflammatory activity in RPE cells. The flavonoid polyphenol luteolin (LU) has anti-inflammatory and antidiabetes activities, but its effects regarding retinal protection remain unknown. Here, we examined the ability of luteolin to alleviate markers of inflammation related to RD in cytokine-primed APPE-19 cells. We found that luteolin decreased the levels of interleukin- (IL-) 6, IL-8, soluble intercellular adhesion molecule-1 (sICAM-1), and monocyte chemoattractant protein-1 (MCP-1) and attenuated adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. Luteolin also increased anti-inflammatory protein heme oxygenase-1 (HO-1) levels. Interestingly, luteolin induced protein kinase B (AKT) phosphorylation, thus inhibiting nuclear factor- (NF-) κB transfer from cytoplasm into the nucleus and suppressing mitogen-activated protein kinase (MAPK) inflammatory pathways. Furthermore, cotreatment with MAPK inhibitors and luteolin decreased inflammatory cytokine and chemokine levels, and further suppressed THP-1 adhesion. Overall, these results provide evidence that luteolin protects ARPE-19 cells from IL-1β-stimulated increases of IL-6, IL-8, sICAM-1, and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways, thus ameliorating the inflammatory response.

Helminthostachys zeylanica is a traditional folk herb used to improve inflammation and fever in Taiwan. Previous studies showed that H. zeylanica extract could ameliorate lipopolysaccharide-induced acute lung injury in mice. The aim of this study was to investigate whether H. zeylanica water (HZW) and ethyl acetate (HZE) extracts suppressed eosinophil infiltration and airway hyperresponsiveness (AHR) in asthmatic mice, and decreased the inflammatory response and oxidative stress in tracheal epithelial cells. Human tracheal epithelial cells (BEAS-2B cells) were pretreated with various doses of HZW or HZE (1 μg/ml–10 μg/ml), and cell inflammatory responses were induced with IL-4/TNF-α. In addition, female BALB/c mice sensitized with ovalbumin (OVA), to induce asthma, were orally administered with HZW or HZE. The result demonstrated that HZW significantly inhibited the levels of proinflammatory cytokines, chemokines, and reactive oxygen species in activated BEAS-2B cells. HZW also decreased ICAM-1 expression and blocked monocytic cells from adhering to inflammatory BEAS-2B cells in vitro. Surprisingly, HZW was more effective than HZE in suppressing the inflammatory response in BEAS-2B cells. Our results demonstrated that HZW significantly decreased AHR and eosinophil infiltration, and reduced goblet cell hyperplasia in the lungs of asthmatic mice. HZW also inhibited oxidative stress and reduced the levels of Th2 cytokines in bronchoalveolar lavage fluid. Our findings suggest that HZW attenuated the pathological changes and inflammatory response of asthma by suppressing Th2 cytokine production in OVA-sensitized asthmatic mice.

Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

Fucoxanthin is isolated from brown algae and was previously reported to have multiple pharmacological effects, including anti-tumor and anti-obesity effects in mice. Fucoxanthin also decreases the levels of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. The purpose of the present study was to investigate the effects of fucoxanthin on the oxidative and inflammatory responses in inflammatory human tracheal epithelial BEAS-2B cells and attenuated airway hyperresponsiveness (AHR), airway inflammation, and oxidative stress in asthmatic mice. Fucoxanthin significantly decreased monocyte cell adherence to BEAS-2B cells. In addition, fucoxanthin inhibited the production of pro-inflammatory cytokines, eotaxin, and reactive oxygen species in BEAS-2B cells. Ovalbumin (OVA)-sensitized mice were treated by intraperitoneal injections of fucoxanthin (10 mg/kg or 30 mg/kg), which significantly alleviated AHR, goblet cell hyperplasia and eosinophil infiltration in the lungs, and decreased Th2 cytokine production in the BALF. Furthermore, fucoxanthin significantly increased glutathione and superoxide dismutase levels and reduced malondialdehyde (MDA) levels in the lungs of asthmatic mice. These data demonstrate that fucoxanthin attenuates inflammation and oxidative stress in inflammatory tracheal epithelial cells and improves the pathological changes related to asthma in mice. Thus, fucoxanthin has therapeutic potential for improving asthma.

Sesamol, isolated from sesame seeds (Sesamum indicum), was previously shown to have antioxidative, anti-inflammatory, and anti-tumor effects. Sesamol also inhibited lipopolysaccharide (LPS)-induced pulmonary inflammatory response in rats. However, it remains unclear how sesamol regulates airway inflammation and oxidative stress in asthmatic mice. This study aimed to investigate the efficacy of sesamol on oxidative stress and airway inflammation in asthmatic mice and tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin, and received oral sesamol on days 14 to 27. Furthermore, BEAS-2B human bronchial epithelial cells were treated with sesamol to investigate inflammatory cytokine levels and oxidative responses in vitro. Our results demonstrated that oral sesamol administration significantly suppressed eosinophil infiltration in the lung, airway hyperresponsiveness, and T helper 2 cell-associated (Th2) cytokine expressions in bronchoalveolar lavage fluid and the lungs. Sesamol also significantly increased glutathione expression and reduced malondialdehyde levels in the lungs of asthmatic mice. We also found that sesamol significantly reduced proinflammatory cytokine levels and eotaxin in inflammatory BEAS-2B cells. Moreover, sesamol alleviated reactive oxygen species formation, and suppressed intercellular cell adhesion molecule-1 (ICAM-1) expression, which reduced monocyte cell adherence. We demonstrated that sesamol showed potential as a therapeutic agent for improving asthma.

Casticin has been isolated from Vitex trifolia and found to have anti-inflammatory and anti-tumor properties. We also previously discovered that casticin can reduce pro-inflammatory cytokines and ICAM-1 expression in inflammatory pulmonary epithelial cells. In the present study, we evaluated whether casticin reduced airway hyper-responsiveness (AHR), airway inflammation, and oxidative stress in the lungs of a murine asthma model and alleviated inflammatory and oxidative responses in tracheal epithelial cells. Female BALB/c mice were randomly divided into five groups: normal controls, ovalbumin (OVA)-induced asthma, and OVA-induced asthma treated with intraperitoneal injection of casticin (5 or 10 mg/kg) or prednisolone (5 mg/kg). Casticin reduced AHR, goblet cell hyperplasia, and oxidative responses in the lungs of mice with asthma. Mechanistic studies revealed that casticin attenuated the levels of Th2 cytokine in bronchoalveolar lavage fluids and regulated the expression of Th2 cytokine and chemokine genes in the lung. Casticin also significantly regulated oxidative stress and reduced inflammation in the lungs of mice with asthma. Consequently, inflammatory tracheal epithelial BEAS-2B cells treated with casticin had significantly suppressed levels of pro-inflammatory cytokines and eotaxin, and reduced THP-1 monocyte cell adherence to BEAS-2B cells via suppressed ICAM-1 expression. Thus, casticin is a powerful immunomodulator, ameliorating pathological changes by suppressing Th2 cytokine expression in mice with asthma.

Acacetin, a flavone that can be isolated from the Saussurea involucrata plant, has anti-tumor and anti-inflammatory properties that ameliorate airway hyperresponsiveness in asthmatic mice. This study investigated whether acacetin has anti-adipogenic effects in 3T3-L1 adipocytes and whether it regulates the inflammatory response in adipocytes and macrophages. It also investigated whether acacetin ameliorates lipid accumulation in high-fat diet- (HFD) induced obese mice. Differentiated 3T3-L1 cells were treated with acacetin. The glycerol levels in the culture medium were measured, and the expression of proteins and genes involved in adipogenesis and lipolysis were assayed by Western blot and real-time PCR, respectively. Inflammatory cytokine signaling pathway activity was assessed in macrophages that were treated with acacetin and cultured with differentiated medium from 3T3-L1 cells. Intraperitoneal injections of acacetin were administered to HFD-induced obese mice twice a week for 10 weeks. Acacetin significantly increased the levels of glycerol in the culture medium and significantly inhibited lipid accumulation in adipocytes. Acacetin reduced the expression of adipogenesis-related transcription factors, including the expression of the CCAAT/enhancer-binding protein; it also increased sirtuin 1 expression and AMPK phosphorylation in adipocytes. In macrophages cultured with differentiated media from 3T3-L1 adipocytes, acacetin reduced the levels of inflammatory mediators and the activity of the mitogen-activated protein kinase and NF-κB pathways. In obese mice, acacetin reduced both body weight and visceral adipose tissue weight. These results demonstrate that acacetin inhibited adipogenesis in adipocytes and in obese mice. Acacetin also reduced the inflammatory response of macrophages that were stimulated with differentiated media from 3T3-L1 cells.

Phloretin (PT), isolated from the apple tree, was previously demonstrated to have antioxidative and anti-inflammatory effects in macrophages and anti-adiposity effects in adipocytes. Inflammatory immune cells generate high levels of reactive oxygen species (ROS) for stimulated severe airway hyperresponsiveness (AHR) and airway inflammation. In this study, we investigated whether PT could reduce oxidative stress, airway inflammation, and eosinophil infiltration in asthmatic mice, and ameliorate oxidative and inflammatory responses in tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin (OVA) to induce asthma symptoms. Mice were randomly assigned to the five experimental groups: normal controls; OVA-induced asthmatic mice; and OVA-induced mice injected intraperitoneally with one of the three PT doses (5, 10, or 20 mg/kg). In addition, we treated inflammatory human tracheal epithelial cells (BEAS-2B cells) with PT to assess oxidative responses and the levels of proinflammatory cytokines and chemokines. We found that PT significantly reduced goblet cell hyperplasia and eosinophil infiltration, which decreased AHR, inflammation, and oxidative responses in the lungs of OVA-sensitized mice. PT also decreased malondialdehyde levels in the lung and reduced Th2 cytokine production in bronchoalveolar lavage fluids. Furthermore, PT reduced ROS, proinflammatory cytokines, and eotaxin production in BEAS-2B cells. PT also suppressed monocyte cell adherence to inflammatory BEAS-2B cells. These findings suggested that PT alleviated pathological changes, inflammation, and oxidative stress by inhibiting Th2 cytokine production in asthmatic mice. PT showed therapeutic potential for ameliorating asthma symptoms in the future.

Tomatidine is isolated from the fruits of tomato plants and found to have anti-inflammatory effects in macrophages. In the present study, we investigated whether tomatidine suppresses airway hyperresponsiveness (AHR) and eosinophil infiltration in asthmatic mice. BALB/c mice were sensitized with ovalbumin and treated with tomatidine by intraperitoneal injection. Airway resistance was measured by intubation analysis as an indication of airway responsiveness, and histological studies were performed to evaluate eosinophil infiltration in lung tissue. Tomatidine reduced AHR and decreased eosinophil infiltration in the lungs of asthmatic mice. Tomatidine suppressed Th2 cytokine production in bronchoalveolar lavage fluid. Tomatidine also blocked the expression of inflammatory and Th2 cytokine genes in lung tissue. In vitro, tomatidine inhibited proinflammatory cytokines and CCL11 production in inflammatory BEAS-2B bronchial epithelial cells. These results indicate that tomatidine contributes to the amelioration of AHR and eosinophil infiltration by blocking the inflammatory response and Th2 cell activity in asthmatic mice.

Licochalcone A was isolated from Glycyrrhiza uralensis and previously reported to have antitumor and anti-inflammatory effects. Licochalcone A has also been found to inhibit the levels of Th2-associated cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. However, the molecular mechanism underlying airway inflammation and how licochalcone A regulates oxidative stress in asthmatic mice are elusive. In this study, we investigated whether licochalcone A could attenuate inflammatory and oxidative responses in tracheal epithelial cells, and whether it could ameliorate oxidative stress and airway inflammation in asthmatic mice. Inflammatory human tracheal epithelial (BEAS-2B) cells were treated with licochalcone A to evaluate oxidative responses and inflammatory cytokine levels. In addition, BALB/c mice were sensitized with ovalbumin (OVA) and injected intraperitoneally with licochalcone A (5 or 10 mg/kg). Licochalcone A significantly inhibited reactive oxygen species, eotaxin, and proinflammatory cytokines in BEAS-2B cells. Licochalcone A also decreased intercellular adhesion molecule 1 levels in inflammatory BEAS-2B cells, blocking monocyte cell adherence. We also found that licochalcone A significantly decreased oxidative responses, reduced malondialdehyde levels, and increased glutathione levels in the lungs of OVA-sensitized mice. Furthermore, licochalcone A decreased airway hyper-responsiveness, eosinophil infiltration, and Th2 cytokine production in the BALF. These findings suggest that licochalcone A alleviates oxidative stress, inflammation, and pathological changes by inhibiting Th2-associated cytokines in asthmatic mice and human tracheal epithelial cells. Thus, licochalcone A demonstrated therapeutic potential for improving asthma.

Quercetin, a bioflavonoid derived from vegetables and fruits, exerts anti-inflammatory effects in various diseases. Our previous study revealed that quercetin could suppress the expression of matrix metalloprotease-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) to achieve anti-inflammatory effects in tumor necrosis factor-α (TNF-α)-stimulated human retinal pigment epithelial (ARPE-19) cells. The present study explored whether quercetin can inhibit the interleukin-1β (IL-1β)-induced production of inflammatory cytokines and chemokines in ARPE-19 cells. Prior to stimulation by IL-1β, ARPE-19 cells were pretreated with quercetin at various concentrations (2.5−20 µM). The results showed that quercetin could dose-dependently decrease the mRNA and protein levels of ICAM-1, IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1). It also attenuated the adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. We also demonstrated that quercetin inhibited signaling pathways related to the inflammatory process, including phosphorylation of mitogen-activated protein kinases (MAPKs), inhibitor of nuclear factor κ-B kinase (IKK)α/β, c-Jun, cAMP response element-binding protein (CREB), activating transcription factor 2 (ATF2) and nuclear factor (NF)-κB p65, and blocked the translocation of NF-κB p65 into the nucleus. Furthermore, MAPK inhibitors including an extracellular signal-regulated kinase (ERK) 1/2 inhibitor (U0126), a p38 inhibitor (SB202190) and a c-Jun N-terminal kinase (JNK) inhibitor (SP600125) decreased the expression of soluble ICAM-1 (sICAM-1), but not ICAM-1. U0126 and SB202190 could inhibit the expression of IL-6, IL-8 and MCP-1, but SP600125 could not. An NF-κB inhibitor (Bay 11-7082) also reduced the expression of ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1. Taken together, these results provide evidence that quercetin protects ARPE-19 cells from the IL-1β-stimulated increase in ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways to ameliorate the inflammatory response.

Licochalcone A is a chalcone isolated from Glycyrrhiza uralensis. It showed anti-tumor and anti-inflammatory properties in mice with acute lung injuries and regulated lipid metabolism through the activation of AMP-activated protein kinase (AMPK) in hepatocytes. However, the effects of licochalcone A on reducing weight gain and improving nonalcoholic fatty liver disease (NAFLD) are unclear. Thus, the present study investigated whether licochalcone A ameliorated weight loss and lipid metabolism in the liver of high-fat diet (HFD)-induced obese mice. Male C57BL/6 mice were fed an HFD to induce obesity and NAFLD, and then were injected intraperitoneally with licochalcone A. In another experiment, a fatty liver cell model was established by incubating HepG2 hepatocytes with oleic acid and treating the cells with licochalcone A to evaluate lipid metabolism. Our results demonstrated that HFD-induced obese mice treated with licochalcone A had decreased body weight as well as inguinal and epididymal adipose tissue weights compared with HFD-treated mice. Licochalcone A also ameliorated hepatocyte steatosis and decreased liver tissue weight and lipid droplet accumulation in liver tissue. We also found that licochalcone A significantly regulated serum triglycerides, low-density lipoprotein, and free fatty acids, and decreased the fasting blood glucose value. Furthermore, in vivo and in vitro, licochalcone A significantly decreased expression of the transcription factor of lipogenesis and fatty acid synthase. Licochalcone A activated the sirt-1/AMPK pathway to reduce fatty acid chain synthesis and increased lipolysis and β-oxidation in hepatocytes. Licochalcone A can potentially ameliorate obesity and NAFLD in mice via activation of the sirt1/AMPK pathway.

Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.

Spilanthol (SP) is a bioactive compound found in Spilanthes acmella, giving the flowers and leaves a spicy taste. Studies found that phyto-ingredients stored in spice plants act against obesity-related diseases. SP has antimicrobial, anti-inflammatory, and analgesic properties, but the effects on obesity are not yet known. We investigated the effects of SP in differentiated adipocytes (3T3-L1 cells) and mice fed a high-fat diet (HFD). SP significantly inhibited intracellular lipid accumulation and significantly reduced the expression of lipogenesis-related proteins, including acetyl-CoA carboxylase (ACC) and fatty-acid synthase (FAS). In contrast, SP increased the expression of carnitine palmitoyltransferase (CPT)1 and AMP-activated protein kinase (AMPK) in adipocytes. However, SP suppressed the levels of cyclooxygenase-2 (COX-2), phospho-p38 (pp38), and phospho-JNK (c-Jun N-terminal kinase) (pJNK) in LPS (lipopolysaccharide)-stimulated murine pre-adipocytes. SP administered to HFD-induced obese mice via intraperitoneal injections twice a week for 10 weeks decreased body weight gain, visceral adipose tissue weight, and adipocyte size. SP inhibited lipogenic proteins FAS and ACC, and suppressed adipogenic transcription factors, enhancing lipolysis and AMPK protein expression in the liver. SP has anti-obesity effects, upregulating AMPK to attenuate lipogenic and adipogenic transcription factors.

A compound isolated from Glycyrrhiza uralensis, licochalcone A (LA) exhibits anti-inflammatory and anti-tumor properties in various cell lines. LA has been found to promote autophagy and suppress specificity protein 1, inducing apoptosis in breast cancer cells. However, the regulation of breast cancer cell invasion and migration by LA is elusive. Thus, the present study investigated whether LA induces apoptosis and cellular motility in MDA-MB-231 breast cells, and investigated the underlying molecular mechanisms. MDA-MB-231 cells treated with LA and cell viability measured by cell counting kit-8 assay. Apoptotic signal proteins checked by flow cytometry, fluorescent staining, and Western blot. LA effectively suppressed cell migration, and modulated E-cadherin and vimentin expression by blocking MAPK and AKT signaling. LA inhibited cell proliferation and cell cycle, modulated mitochondrial membrane potential and DNA damage, and reduced oxidative stress in MDA-MB-231 cells. LA also activated cleaved-caspase 3 and 9, significantly decreased Bcl-2 expression, ultimately causing the release of cytochrome c from the mitochondria into the cytoplasm. Overall, our findings suggest that LA decreases cell proliferation and increases reactive oxygen species production for induced apoptosis, and regulates E-cadherin and vimentin by reducing MAPK and AKT signaling, resulting in suppressed MDA-MB-231 cell migration and invasion.

Matrine is isolated from Sophora flavescens and shows anti-inflammatory effects in macrophages. Here we evaluated matrine’s suppressive effects on cyclooxygenase 2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1) expressions in lipopolysaccharide- (LPS-) stimulated human lung epithelial A549 cells. Additionally, BALB/c mice were given various matrine doses by intraperitoneal injection, and then lung injury was induced via intratracheal instillation of LPS. In LPS-stimulated A549 cells, matrine inhibited the productions of interleukin-8 (IL-8), monocyte chemotactic protein-1, and IL-6 and decreased COX-2 expression. Matrine treatment also decreased ICAM-1 protein expression and suppressed the adhesion of neutrophil-like cells to inflammatory A549 cells. In vitro results demonstrated that matrine significantly inhibited mitogen-activated protein kinase phosphorylation and decreased nuclear transcription factor kappa-B subunit p65 protein translocation into the nucleus. In vivo data indicated that matrine significantly inhibited neutrophil infiltration and suppressed productions of tumor necrosis factor-α and IL-6 in mouse bronchoalveolar lavage fluid and serum. Analysis of lung tissue showed that matrine decreased the gene expression of proinflammatory cytokines, chemokines, COX-2, and ICAM-1. Our findings suggest that matrine improved lung injury in mice and decreased the inflammatory response in human lung epithelial cells.

In this paper, a novel signal processing circuit which can be used for the measurement of H+ ion and urea concentration is presented. A potentiometric method is used to detect the concentrations of H+ ions and urea by using H+ ion-selective electrodes and urea electrodes, respectively. The experimental data shows that this measuring structure has a linear pH response for the concentration range within pH 2 and 12, and the dynamic range for urea concentration measurement is in the range of 0.25 to 64 mg/dL. The designed instrumentation circuit possesses a calibration function and it can be applied to different sensing electrodes for electrochemical analysis. It possesses the advantageous properties of being multi-purpose, easy calibration and low cost.