Fermented Curcuma longa L. Prevents Alcoholic Fatty Liver Disease in Mice by Regulating CYP2E1, SREBP-1c, and PPAR-α.

We examined the efficacy of fermented Curcuma longa L. (FT) on the development of alcoholic fatty liver in mice and investigated the underlying mechanism. The protective potential of FT against ethanol-induced fatty liver was determined using C57BL/6 male mice allocated into four groups (8 mice/group). Control groups received either distilled water or 5 g/kg body weight (b.w.) per day ethanol for 8 days. Treatment groups were administered either 300 mg/kg b.w. per day of milk thistle or FT before receiving ethanol. FT contained a higher amount of caffeic acid and tetrahydrocurcumin than C. longa. FT pretreatment significantly suppressed the elevated hepatic lipid droplets associated with ethanol ingestion. In comparison with ethanol-treated control, FT pretreated mice showed inhibited cytochrome P4502E1 (CYP2E1), sterol regulatory element-binding protein-1 (SREBP-1c), and acetyl-CoA carboxylase production but elevated AMP-activated protein kinase, peroxisome proliferator-activated receptor-alpha (PPAR-α), and carnitine palmitoyltransferase 1 (CPT-1) levels. Taken together, FT is a promising hepatoprotectant for preventing of alcoholic fatty liver through modulating fatty acid synthesis and oxidation.

Beneficial Effects of a Combination of Curcuma longa L. and Citrus junos Against Beta-Amyloid Peptide-Induced Neurodegeneration in Mice.

Both Curcuma longa (CL) and Citrus junos Tanaka (CJ) have been used to treat various diseases due to their anti-inflammatory and antioxidative stress activities. In this study, we investigated the ameliorative effect of the combination of CL extract and CJ extract (CCC) against beta-amyloid (Aß) peptide-induced neurological damage. CCC prevented neurocytotoxicity in vitro. In addition, it was confirmed that abnormal alternation behavior and memory impairment caused by Aß peptide were reversed by treatment with CCC. Furthermore, CCC treatment led to recovery of the cholinergic system and reactive oxygen species (ROS) oxidative damage defense system. CCC induced expressions of cyclic-adenosine monophosphate response element-binding protein (CREB)-responsive element-binding protein and brain-derived neurotrophic factor were confirmed as was the significantly improved processing in the hippocampus of the mouse Aß peptides. Accordingly, these results suggest that CCC can prevent and/or reverse neurocytotoxicity and cognitive deficits in a mouse model of Alzheimer's disease.

Aucuparin Suppresses Bleomycin-Induced Pulmonary Fibrosis Via Anti-Inflammatory Activity.

Idiopathic pulmonary fibrosis (IPF) is a lung disease that results in scarring of the lungs for an unknown reason. Although many studies have been conducted on IPF, precise mechanisms and treatments have not yet been identified. In this study, we found that aucuparin, a natural product isolated from Sorbus aucuparia, inhibited pulmonary fibrosis in a bleomycin (BLM)-induced lung fibrosis mouse model. In the lung samples of mice treated with aucuparin, the gene expression of inflammation and macrophage activation markers was reduced compared to those treated with BLM alone. Moreover, aucuparin decreased the expression of profibrotic marker genes and increased the expression of antifibrotic marker genes. Finally, we observed that aucuparin significantly suppressed transforming growth factor-ß-induced activation of inflammatory cytokine production and collagen synthesis from macrophages and fibroblasts, respectively. Taken together, these data demonstrate that aucuparin inhibits lung fibrosis via its anti-inflammatory action and support its potential to be a therapeutic drug for IPF treatment.

Plumbagin Suppresses Pulmonary Fibrosis via Inhibition of p300 Histone Acetyltransferase Activity.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis similar to that of malignancy. The causes of IPF are not clearly known, and there is no effective therapy to date. In this study, the natural compound plumbagin, which was isolated from Plumbago rosea root extract, was screened for p300 inhibitory activity. Plumbagin specifically inhibited the activity of p300 toward histone acetyltransferases. Plumbagin treatment significantly suppressed transforming growth factor-ß-induced profibrotic target-gene expression and proliferation of fibroblast cell lines. Moreover, plumbagin significantly inhibited bleomycin-induced pulmonary fibrosis in mice. Taken together, these data demonstrate the inhibitory effects of plumbagin on lung fibrosis and its promise as a therapeutic agent for IPF.

Effects of Eriobotrya japonica Water Extract on Alcoholic and Nonalcoholic Fatty Liver Impairment.

The aim of this study was to investigate the potential protective effects of the hot water extract of Eriobotrya japonica (EJW) on EtOH- or free fatty acid (FFA)-induced fatty liver injury in vitro. HepG2/2E1 cells were exposed to EtOH and HepG2 cells were exposed to a mixture of FFAs (oleic acid:palmitic acid, 2:1) to stimulate oxidative stress and to induce lipid accumulation, respectively. Antioxidant activity was significantly increased and lipid accumulation was inhibited in cells pretreated with EJW compared to those in cells exposed to EtOH or FFA only. Also, 5'adenosine monophosphate (AMP)-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) phosphorylations were considerably increased, indicating activation of AMPK. Furthermore, EJW reduced the messenger RNA (mRNA) expression of lipogenesis-associated factors such as ACC, sterol regulatory element binding protein-1c (SREBP-1c), and fatty acid synthase (FAS), and increased mRNA expression related to components of the fatty acid ß-oxidation pathway, such as AMPK, carnitine palmitoyltransferase 1 (CPT-1), and peroxisome proliferator-activated receptor alpha (PPARα). These results suggest that EJW possessed potential preventive effects against both EtOH- and FFA-induced fatty liver disease by alleviation of oxidative stress and lipid accumulation in hepatocytes.

Dendropanax morbifera Branch Water Extract Increases the Immunostimulatory Activity of RAW264.7 Macrophages and Primary Mouse Splenocytes.

Polyacetylenes in the bark of Dendropanax morbifera trees have been reported to promote immune cell proliferation and to strengthen the innate immune system. The immunomodulatory potential of D. morbifera branch water extract (DBW) was evaluated by determining its effect on cell viability and the expression of cytokines and immune effector molecules in mouse RAW264.7 macrophages and splenocytes. Production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (interleukin [IL]-1ß, IL-2, and IFN-γ) in RAW264.7 macrophages increased after treatment with DBW. The activation of components of the NF-κB signaling pathway, including the phospho-IκBα and the expression and translocation of p65, a subunit of NF-κB, were also increased in RAW264.7 mouse macrophage cells after treatment with DBW. In addition, when mice were orally administered DBW, splenocyte cytokines and NO production were increased in a dose-dependent manner relative to control-treated mice. Furthermore, natural killer cell activity in DBW-treated mice was determined by lactate dehydrogenase (LDH) release assay. LDH release also increased in response to DBW treatment. Taken together, these results indicate that D. morbifera extract enhances innate immunity by promoting NF-κB signaling, leading to increased expression of proinflammatory cytokines and effector molecules. DBW therefore has potential therapeutic use in the context of immune stimulation.

Water Extract of Curcuma longa L. Ameliorates Non-Alcoholic Fatty Liver Disease.

Our aim was to investigate whether hot water extract (CLW) of Curcuma longa L. could prevent non-alcoholic fatty liver disease (NAFLD). HepG2 cells were treated with free fatty acid (FFA) mixture (oleic acid: palmitic acid, 2:1) for 24 h to stimulate in vitro fatty liver. In addition, C57BL/6 mice were fed 60 kcal% high-fat (HF) diet for eight weeks to induce fatty liver in vivo. Intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) productions were increased by FFA and HF-diet, but supplementation with CLW significantly decreased these levels. CLW treatment ameliorated antioxidant activities that were suppressed by exposure to the FFA and HF-diet. Cluster of differentiation 36 (CD36) and fatty acid transport proteins (FATP2 and FATP5) were increased in HF-diet groups, while CLW suppressed their expression levels. Moreover, sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-coenzyme A carboxylase (ACC), and fatty acid synthase (FAS) expression levels were down-regulated in the CLW groups compared to HF-diet groups. On the other hand, 5' adenosine monophosphate-activated protein kinase (AMPK), Peroxisome proliferator-activated receptor alpha (PPAR-α), and carnitine palmitoyltransferase 1 (CPT-1) expressions were up-regulated in the CLW groups. HF-diet fed mice showed high hepatic triglycerides (TG) content compared to the normal diet mice. However, the administration of CLW restored the hepatic TG level, indicating an inhibitory effect against lipid accumulation by CLW. These results suggest that CLW could be a potentially useful agent for the prevention of NAFLD through modulating fatty acid uptake.

Ameliorative Effects of Dendropanax morbifera on Cognitive Impairment Via Enhancing Cholinergic Functions and Brain-Derived Neurotrophic Factor Expression in ß-Amyloid-Induced Mice.

Alzheimer's disease accounts for the majority of dementia and shows hallmarks such as sequential cognitive dysfunction and abnormal behavior. Dendropanax morbifera (DM) has traditionally been used to treat a variety of diseases in East Asia. The aim of this study was to assess the therapeutic effects of DM on brain neuron damage and on cognitive deficit in neuronal cell induced by Aß1-42 in mice. Treatment with DM reduced the levels of intracellular reactive oxygen species and protected against the death of neuronal cells induced by Aß1-42 peptide. In addition, it was also found that pretreatment with DM decreased cognitive damage induced by Aß peptide via enhancing the cholinergic system and antioxidant defense system in mice. Furthermore, the study verified that the change in the expression of both cyclic-adenosine monophosphate response element binding protein and of brain-derived neurotrophic factor in the hippocampus in Aß peptide-treated mice was significantly ameliorated after treatment with DM. Accordingly, these results suggest that pretreatment with DM defends against oxidative stress and cognitive impairment caused by Aß peptide.

A Blend of Extracts from Houttuynia cordata, Nelumbo nucifera, and Camellia sinensis Protects Against Ethanol-Induced Liver Damage in C57BL/6 Mice.

The protective activity of a mixture of aqueous and ethanolic extracts from Houttuynia cordata Thunb, Nelumbo nucifera G. leaves, and Camellia sinensis seed (HNC) was evaluated in C57BL/6 mice. Pretreatment with HNC prevented the elevation of serum aspartate aminotransferase and alanine aminotransferase caused by ethanol-induced hepatic damage. The HNC-treated mice showed significantly lower triglyceride levels, reduced CYP2E1 activity, and increased antioxidant enzyme activities and lipogenic mRNA levels. These results suggest that HNC might be a candidate agent for liver protection against ethanol-induced oxidative damage, through enhancement of antioxidant and antilipogenic activity.

Effect of Ethanol Extract of Canavalia gladiata on Endurance Swimming Capacity in Mice.

The effects of Canavalia gladiata ethanolic extract on endurance swimming capacity were evaluated in a mouse model. The mice were orally administered distilled water (CON), hot water extract (CGW), or 80% ethanol extract (CGE). The swimming time to exhaustion was significantly prolonged in the CGE group. Of the three groups, the CGE showed the lowest blood lactate and the highest nonesterified fatty acid and muscle glycogen levels. These results suggest that the administration of CGE could improve endurance swimming capacity by enhancing lipid catabolism and thereby preserving glycogen stores.

Delphinidin induces apoptosis via cleaved HDAC3-mediated p53 acetylation and oligomerization in prostate cancer cells.

Delphinidin is a major anthocyanidin compound found in various fruits. It has anti-inflammatory, anti-oxidant, and various other biological activities. In this study, we identified the epigenetic modulators that mediate the apoptotic effect of delphinidin in human prostate cancer cells. We found that treatment of LNCaP cells (a p53 wild-type, human prostate cancer cell line) with delphinidin increased caspase-3, -7, and -8 activity, whereas it decreased histone deacetylase activity. Among class I HDACs, the activity of HDAC3 was specifically inhibited by delphinidin. Moreover, the induction of apoptosis by delphinidin was dependent on caspase-mediated cleavage of HDAC3, which results in the acetylation and stabilization of p53. We also observed that delphinidin potently upregulated pro-apoptotic genes that are positively regulated by p53, and downregulated various anti-apoptotic genes. Taken together, these results show that delphinidin induces p53-mediated apoptosis by suppressing HDAC activity and activating p53 acetylation in human prostate cancer LNCaP cells. Therefore, delphinidin may be useful in the prevention of prostate cancer.

Immunomodulatory and Antioxidant Effects of Purple Sweet Potato Extract in LP-BM5 Murine Leukemia Virus-Induced Murine Acquired Immune Deficiency Syndrome.

The immunomodulatory effects of a dietary supplement of purple sweet potato extract (PSPE) in LP-BM5 murine leukemia virus (MuLV)-induced immune-deficient mice were investigated. Mice were divided into six groups: normal control, infected control (LP-BM5 MuLV infection), positive control (LP-BM5 MuLV infection+dietary supplement of red ginseng 300 mg/kg), purple sweet potato water extract (PSPWE) (LP-BM5 MuLV infection+dietary supplement of PSPE 300 mg/kg), PSP10EE (LP-BM5 MuLV infection+dietary supplement of 10% ethanol PSPE 300 mg/kg), and PSP80EE (LP-BM5 MuLV infection+dietary supplement of 80% ethanol PSPE 300 mg/kg). Dietary supplementation began on the day of LP-BM5 MuLV infection and continued for 12 weeks. Dietary supplementation of PSPE inhibited LP-BM5 MuLV-induced splenomegaly and lymphadenopathy and attenuated the suppression of T- and B-cell proliferation and T helper 1/T helper 2 cytokine imbalance in LP-BM5 MuLV-infected mice. Dietary supplement of PSPE increased the activity of the antioxidant enzymes, superoxide dismutase and glutathione peroxidase. The data suggest that PSPE may ameliorate immune dysfunction due to LP-BM5 MuLV infection by modulating antioxidant defense systems.

Rosa rugosa Aqueous Extract Alleviates Endurance Exercise-Induced Stress.

This study was performed to investigate the effect of water extract from Rosa rugosa (RRW) on endurance exercise-induced stress in mice. The mice were orally administered with distilled water or RRW, respectively. The endurance capacity was evaluated by exhaustive swimming using an adjustable-current water pool. Mice administered RRW swam longer before becoming exhausted. Also, RRW administration resulted in less lipid peroxidation, lower muscular antioxidant enzyme activities, and lower cortisol level. The results suggest that RRW can prevent exercise-induced stress by decreasing oxidative stress levels.

Sasa borealis Extract Efficiently Enhanced Swimming Capacity by Improving Energy Metabolism and the Antioxidant Defense System in Mice.

This study was conducted to determine the effects of 50% ethanolic extract from Sasa borealis leaves (SBE) on swimming capacity and oxidative metabolism in mice. The mice were divided into 2 groups with similar swimming times and body weights; Ex-Control and Ex-SBE were orally administered with distilled water and 250 mg/kg body weight/d of SBE. Exhaustive swimming times were prolonged by 1.5-fold in the Ex-SBE group compared to the Ex-Control. The Ex-SBE group displayed lower lactate and higher non-esterified fatty acid levels 15 min after swimming and the hepatic and muscle glycogen levels were significantly higher than that in the Ex-Control. SBE potentially enhanced mRNA expression of citrate synthase (CS), carnitine palmitoyltransferase (CPT-1), and ß-hydroxyacyl coenzyme A dehydrogenase (ß-HAD) in skeletal muscle. The activities and mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were elevated in the Ex-SBE compared with the Ex-Control after exhaustive swimming. These results suggest that SBE might be used as an effective agent to enhance swimming capacity by utilization of energy substrates and might ameliorate physical exhaustion by facilitating energy-generating metabolic genes and enhancing endogenous antioxidants.

Alleviation of weight-gain in mice by an ethanolic extract from Rubus coreanus under conditions of a high-fat diet and exercise.

The administration of an ethanolic extract (RCE) from Rubus coreanus significantly reduced the body weight and epididymal fat tissue of mice under conditions of a high-fat diet (HFD) and exercise. The mice also displayed enhanced muscular carnitine palmitoyltransferase 1 (CPT1) expression and increased superoxide dismutase and glutathione levels. These results suggest that RCE exerted an anti-obesity effect by up-regulating CPT1 and elevating the level of antioxidants.

Isothiocyanates ameliorate the symptom of heart dysfunction and mortality in a murine AIDS model by inhibiting apoptosis in the left ventricle.

Cardiac involvement has been reported in as many as 45-55% of patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), and significant cardiac morbidity is reported in 6-7% of HIV patients. We investigated the inhibitory effects of isothiocyanates (ITCs) on heart dysfunction and mortality by regulating apoptosis in the left ventricle of the heart in a murine AIDS model. Mice were divided into six groups: an uninfected group, an untreated LP-BM5 retrovirus-infected group, and four LP-BM5 retrovirus-infected groups treated with one of four ITCs (sulforaphane [SUL], indolo[3,2-b]carbazole, benzyl isothiocyanate [BITC], or phenethyl isothiocyanate [PEITC]). After 16 weeks, the median survival time of the LP-BM5 retrovirus-infected mice was 87 days, whereas that of the uninfected control group and all ITC treatment groups was over 112 days. SUL, PEITC, and BITC significantly inhibited apoptosis in the left ventricle by increasing the Bcl-2/Bax ratio compared with LP-BM5-infected mice. In addition, SUL and PEITC suppressed inducible nitric oxide synthase (iNOS) expression at both the mRNA and protein levels in the left ventricle of heart tissue infected with the LP-BM5 retrovirus by inactivating cytoplasmic nuclear factor κB (NF-κB). In conclusion, LP-BM5 retrovirus infection was related to survival of murine AIDS mice, and NF-κB-mediated iNOS expression may be an important mediator of left ventricle dysfunction of the heart. Furthermore, certain ITCs may have the potential to improve AIDS-related heart dysfunction due to their inhibition of apoptosis by decreasing iNOS and Bax expression through suppression of NF-κB.

Inhaled essential oil from Chamaecyparis obtuse ameliorates the impairments of cognitive function induced by injection of ß-amyloid in rats.

CONTEXT: Chamaecyparis obtusa Sieb. & Zucc., Endlicher (Cupressaceae) forest bathing or aromatherapy has been shown in various studies to have biological functions such as anticancer, antiallergies, antiinflammatory, and antioxidant activity. However, no reports exist on the pharmacological or biological activities of the essential oil of C. obtusa (EOCO) or its effects on central nervous system. OBJECTIVE: The aggregation and formation of ß-amyloid peptides (Aß) into fibrils are central events in the pathogenesis of Alzheimer's disease (AD), and overproduction and aggregation of Aß into oligomers have been known to trigger neurotoxicity. In this study, we investigated the effects of inhaled EOCO on cognitive function and neuronal apoptosis in rats intrahippocampally injected with Aß. MATERIALS AND METHODS: To model AD, 4 µg of aggregated Aß was injected into the hippocampus. To test the effects of EOCO, behavioral performance in the Morris water maze was tested 4 days after injection. After behavioral testing, brain sections were prepared for TTC staining and TUNEL assay. RESULTS: Inhaled EOCO protected spatial learning and memory from the impairments induced by Aß(1-40) injection. In addition, the behavioral deficits accompanying Aß(1-40)-induced AD were attenuated by inhalation of EOCO. Furthermore, acetylcholinesterase (AChE) activity and neuronal apoptosis were significantly inhibited in rats treated with Aß(1-40) and EOCO compared to rats treated only with Aß(1-40). DISCUSSION AND CONCLUSION: EOCO suppressed both AD-related neuronal cell apoptosis and AD-related dysfunction of the memory system. Thus, the results of this study support EOCO as a candidate drug for the treatment of AD.

Anti-obesity effect of a standardised ethanol extract from Curcuma longa L. fermented with Aspergillus oryzae in ob/ob mice and primary mouse adipocytes.

BACKGROUND: We examined the anti-obesity effect of fermented Curcuma longa L. (turmeric) standardised ethanol extract (FTE) in the C57BL/6J ob/ob mouse model. Mice were fed a chow diet containing FTE (0, 200, or 500 mg kg⁻¹ body weight) for 9 weeks. RESULTS: Supplementation with FTE significantly reduced body weight gain and retroperitoneal and epididymal adipose tissue weights compared to the ob/ob control group. Additionally, total cholesterol and triglyceride levels in serum and liver were significantly decreased in FTE-200 and FTE-500 groups when compared to those of the ob/ob control group, whereas the high-density lipoprotein-cholesterol level was significantly increased. The levels of serum adiponectin as well as mRNA expression of lipases, such as hormone sensitive lipase and adipose triglyceride lipase, were clearly increased. In primary adipocytes of C57BL/6J mice, FTE treatment caused a significant increase glycerol release and hormone sensitive lipase levels and decreased perilipin A levels. CONCLUSION: These results suggest that supplementation of FTE has potent anti-obesity effects by controlling body weight, fat mass, serum lipids, and hepatic lipids. Moreover, FTE could be considered a potential resource for the treatment of obesity through its promotion of lipolysis via the protein kinase A pathway.

Fatigue-alleviating effect on mice of an ethanolic extract from Rubus coreanus.

The fatigue-alleviating effects on mice of Rubus coreanus were investigated by using an adjustable-current water pool. The mice were exhaustively exercised for 2 consecutive days, and those administered with the 80% ethanol extract (RCE) of R. coreanus displayed a lower reduction (20%) in swimming time on day 2 than the control group (41% reduction). RCE significantly prevented the depletion of hepatic antioxidants during exercise-induced fatigue. These results suggest that RCE alleviated fatigue by elevating the antioxidative potential.

Grape seed extract regulates androgen receptor-mediated transcription in prostate cancer cells through potent anti-histone acetyltransferase activity.

Histone acetylation, which is regulated by histone acetyltransferases (HATs) and deacetylases, is an epigenetic mechanism that influences eukaryotic transcription. Significant changes in histone acetylation are associated with cancer; therefore, manipulating the acetylation status of key gene targets is likely crucial for effective cancer therapy. Grape seed extract (GSE) has a known protective effect against prostate cancer. Here, we showed that GSE significantly inhibited HAT activity by 30-80% in vitro (P < .05). Furthermore, we demonstrated significant repression of androgen receptor (AR)-mediated transcription by GSE in prostate cancer cells by measuring luciferase activity using a pGL3-PSA construct bearing the AR element in the human prostate cancer cell line LNCaP (P < .05). GSE treatment also decreased the mRNA level of the AR-regulated genes PSA and NKX 3.1. Finally, GSE inhibited growth of LNCaP cells. These results indicate that GSE potently inhibits HAT, leading to decreased AR-mediated transcription and cancer cell growth, and implicate GSE as a novel candidate for therapeutic activity against prostate cancer.