Improvement in Testosterone Production by Acorus gramineus for the Alleviation of Andropause Symptoms.

Acorus gramineus has a number of beneficial effects, including protective effects against age-related disorders. In this study, the effects of A. gramineus on testosterone production and andropause symptoms were evaluated. We first treated TM3 mouse Leydig cells, responsible for testosterone production, with A. gramineus aqueous extract at different concentrations. In TM3 cells, the testosterone concentration increased in a concentration-dependent manner compared with those in the control. In addition, at 400 µg/mL extract, the mRNA expression level of the steroidogenic enzyme CYP11A1 was increased. Subsequently, 23-week-old Sprague-Dawley (SD) rats exhibiting an age-related reduction in serum testosterone (approximately 80% lower than that in 7-week-old SD rats) were administered A. gramineus aqueous extract for 8 weeks. Serum total testosterone and free testosterone levels were higher and serum estradiol, prostate-specific antigen levels, and total cholesterol levels were lower in the AG50 group (A. gramineus aqueous extract 50 mg/kg of body weight/day) than in the OLD (control group). The AG50 group also showed significant elevations in sperm count, grip strength, and mRNA expression of StAR, CYP11A1, 17ß-HSD, and CYP17A1 compared with those in the OLD group. In conclusion, A. gramineus aqueous extract facilitated steroidogenesis in Leydig cells, elevated testosterone levels, lowered serum estradiol and total cholesterol levels, and increased muscle strength and sperm count, thus alleviating the symptoms of andropause. These findings suggest that A. gramineus aqueous extract is a potentially effective therapeutic agent against various symptoms associated with andropause.

Development and Validation of Deep Learning-Based Automated Detection of Cervical Lymphadenopathy in Patients with Lymphoma for Treatment Response Assessment: A Bi-institutional Feasibility Study.

The purpose is to train and evaluate a deep learning (DL) model for the accurate detection and segmentation of abnormal cervical lymph nodes (LN) on head and neck contrast-enhanced CT scans in patients diagnosed with lymphoma and evaluate the clinical utility of the DL model in response assessment. This retrospective study included patients who underwent CT for abnormal cervical LN and lymphoma assessment between January 2021 and July 2022. Patients were grouped into the development (n = 76), internal test 1 (n = 27), internal test 2 (n = 87), and external test (n = 26) cohorts. A 3D SegResNet model was used to train the CT images. The volume change rates of cervical LN across longitudinal CT scans were compared among patients with different treatment outcomes (stable, response, and progression). Dice similarity coefficient (DSC) and the Bland-Altman plot were used to assess the model's segmentation performance and reliability, respectively. No significant differences in baseline clinical characteristics were found across cohorts (age, P = 0.55; sex, P = 0.13; diagnoses, P = 0.06). The mean DSC was 0.39 ± 0.2 with a precision and recall of 60.9% and 57.0%, respectively. Most LN volumes were within the limits of agreement on the Bland-Altman plot. The volume change rates among the three groups differed significantly (progression (n = 74), 342.2%; response (n = 8), - 79.2%; stable (n = 5), - 8.1%; all P < 0.01). Our proposed DL segmentation model showed modest performance in quantifying the cervical LN burden on CT in patients with lymphoma. Longitudinal changes in cervical LN volume, as predicted by the DL model, were useful for treatment response assessment.

Protective Effects of Cudrania tricuspidata Against Helicobacter pylori-Induced Inflammation in C57BL/6 Mice.

Helicobacter pylori modulates the host inflammatory response, resulting in chronic gastritis, which contributes to gastric cancer pathogenesis. We verified the effect of Cudrania tricuspidata on H. pylori infection by inhibiting H. pylori-induced inflammatory activity. Five-week-old C57BL/6 mice (n = 8) were administered C. tricuspidata leaf extract (10 or 20 mg/kg per day) for 6 weeks. An invasive test (campylobacter-like organism [CLO]) and noninvasive tests (stool antigen test [SAT] and H. pylori antibody enzyme-linked immunosorbent assay) were performed to confirm the eradication of H. pylori. To evaluate the anti-inflammatory effect of C. tricuspidata, pro-inflammatory cytokines levels and inflammation scores were measured in mouse gastric tissue. C. tricuspidata significantly decreased the CLO score and H. pylori immunoglobulin G antibody optical density levels at both 10 and 20 mg/kg per day doses (P < .05). C. tricuspidata decreased the H. pylori antibody levels in a concentration-dependent manner, increased negative responses to SAT by up to 37.5%, and inhibited the pro-inflammatory cytokines interleukin (IL; IL-1ß, IL-6, 1L-8, and tumor necrosis factor alpha). C. tricuspidata also relieved gastric erosions and ulcers and significantly reduced the inflammation score (P < .05). We measured rutin in C. tricuspidata extract as a standard for high-performance liquid chromatography. C. tricuspidata leaf extract showed anti-H. pylori activity through the inhibition of inflammation. Our findings suggest that C. tricuspidata leaf extract is potentially an effective functional food material against H. pylori.

Salvia plebeia R. Br. Water Extract Ameliorates Hepatic Steatosis in a Non-Alcoholic Fatty Liver Disease Model by Regulating the AMPK Pathway.

Salvia plebeia R. Br. (SP), grown from autumn to spring, is used as a medicinal herb from roots to leaves. This herb exhibits antioxidant activities and various physiological effect, including anti-asthma, immune-promoting, anti-obesity, and anti-cholesterol effects. However, the effectiveness of SP against non-alcoholic fatty liver disease (NAFLD) and the associated mechanism have not been elucidated. In this study, alleviation of NAFLD by SP was confirmed in a mouse model of hepatic steatosis induced by a high-fat diet and in HepG2 cells administered free fatty acids (FFA). In the experimental model, intrahepatic lipid accumulation was investigated using the AdipoRedTM assay, Oil Red O staining, biomarker analysis, and hematoxylin and eosin staining. Furthermore, glucose tolerance was examined based on the fasting glucose levels and oral glucose tolerance. The molecular mechanisms related to hepatic steatosis were determined based on marker mRNA levels. Blood FFAs were found to flow into the liver via the action of fatty acid translocase, cluster of differentiation 36, and fatty acid transporter proteins 2 and 5. Salvia plebeia R. Br. water extract (SPW) suppressed the FFAs inflow by regulating the expression of the above-mentioned proteins. Notably, modulating the expression of AMP-activated protein kinase (AMPK) and liver X receptor, which are involved in the regulation of lipid metabolism, stimulated peroxisome proliferator activated receptor α in the nucleus to induce the expression genes involved in ß-oxidation and increase ß-oxidation in the mitochondria. AMPK modulation also increased the expression of sterol regulatory element binding protein-1c, which activated lipid synthesis enzymes. As a consequence of these events, triglyceride synthesis was reduced and lipid accumulation in hepatocytes was alleviated. Overall, our findings suggested that SPW could ameliorate NAFLD by inhibiting hepatic steatosis through AMPK modulation.

The Effect of a Combination of Eucommia ulmoides and Achyranthes japonica on Alleviation of Testosterone Deficiency in Aged Rat Models.

With aging, men inevitably encounter irreversible changes, including progressive loss of testosterone and physical strength, and increased fat mass. To assess the alleviatory effects of EUAJ on andropause symptoms, including in vivo testosterone deficiency, we administered EUAJ for 6 weeks in 22-week-old Sprague-Dawley rats. Before EUAJ (3:1) (E. ulmoides:A. japonica = 3:1, KGC08EA) administration, testosterone decline in 22-week-old SD rats was confirmed compared to 7-week-old SD rats (NC group). After administration of EUAJ (3:1) at 20, 40, and 80 mg/kg for 6 weeks, testosterone, free testosterone, and mRNA expression levels (Cyp11a1 and Hsd3b1) were significantly increased at 40 mg/kg EUAJ (3:1), whereas mRNA expression levels of Cyp19a1 and Srd5a2 were significantly reduced at this concentration, compared to the control group. Swimming retention time was significantly increased at both 40 mg/kg and 80 mg/kg. In summary, EUAJ (3:1) enhanced testosterone production by increasing bioavailable testosterone, sex hormone-binding globulin (SHBG), and enzymes related to testosterone synthesis at 40 mg/kg. In addition, 80 mg/kg EUAJ (3:1) also increased physical and testicular functions.

Anti-Obesity Effect of Porcine Collagen Peptide in 3T3-L1 Adipocytes and High-Fat Diet-Fed Mice by Regulating Adipogenesis.

Obesity is one of the most common diseases caused by an imbalance in the intake and expenditure of energy, and it is associated with various metabolic complications. This study aimed at investigating the anti-obesity effects and mechanisms of porcine collagen peptide (PCP) using 3T3-L1 preadipocytes and high-fat diet (HFD)-fed mice. The PCP treatment significantly inhibited the adipocyte differentiation and attenuated the mRNA expression of transcription factors (CCAAT/enhancer-binding protein alpha [C/EBPα] and peroxisome proliferator-activated receptor gamma [PPARγ]) and the lipogenic gene (fatty acid synthase [FAS]) expression in 3T3-L1 preadipocytes. In the in vivo study, HFD-fed mice were fed low- (1.5 g/kg body weight/day) and high- (4.5 g/kg body weight/day) PCP for 12 weeks and compared with the normal diet-fed group and HFD-fed control group. The PCP-fed groups showed significantly lower body weight gain, white fat weight gain, serum triglycerides, and adipocyte size compared with the HFD-fed group. The changes in body fat were associated with the upregulation of adiponectin and the downregulation of leptin, C/EBPα, PPARγ, and FAS. These results suggest that PCP has the potential to reduce obesity by suppressing adipogenesis and could be applied as a functional food material.

Effects of red ginseng oil(KGC11o) on testosterone-propionate-induced benign prostatic hyperplasia.

Background: Benign prostatic hyperplasia (BPH) is a disease characterized by abnormal proliferation of the prostate, which occurs frequently in middle-aged men. In this study, we report the effect of red ginseng oil (KGC11o) on BPH. Methods: The BPH-induced Sprague-Dawley rats were divided into seven groups: control, BPH, KGC11o 25, 50, 100, 200, and finasteride groups. KGC11o and finasteride were administered for 8 weeks. The BPH biomarkers, DHT, 5AR1, and 5AR2, androgen receptor, prostate-specific antigen (PSA), Bax, Bcl-2, and TGF-ß were determined in the serum and prostate tissue. The cell viability after KGC11o treatment was determined using BPH-1 cells, and, androgen receptor, Bax, Bcl-2, and TGF-ß were confirmed by western blotting. Results: In the in vivo study, administration of KGC11o reduced prostate weight by 18%, suppressed DHT (up to 22%) and 5AR2 (up to 12%) levels from administration of 100 mg/kg KGC11o (P < 0.05). PSA was significantly downregulated dose-dependently from at the concentration of 50 mg/kg KGC11o (P < 0.05). BPH-1 cell viability significantly reduced through the treatment with KGC11o. In vitro and vivo, AR, Bcl-2 TGF-ß levels reduced significantly but Bax was increased (P < 0.05). Conclusion: These results suggest that KGC11o may inhibit the development of BPH by significantly reducing the levels of BPH biomarkers via 5ARI, anti-androgenic effect, and anti-proliferation effect, serving as a potential functional food for treating BPH.

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.

Water Extract of Rubus coreanus Prevents Inflammatory Skin Diseases In Vitro Models.

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by immune hypersensitivity reaction. The cause of AD is unclear, but its symptoms have a negative effect on quality of life; various treatment methods to alleviate these symptoms are underway. In the present study, we aimed to evaluate in vitro antioxidant and anti-inflammatory effects of Rubus coreanus water extract (RCW) on AD. Total phenolic compounds and flavonoid content of RCW were 4242.40 ± 54.84 mg GAE/g RCE and 1010.99 ± 14.75 mg CE/g RCW, respectively. RCW reduced intracellular reactive oxygen species level and increased the action of antioxidant enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase in tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-stimulated HaCaT cells. Moreover, mRNA expression of the pro-inflammatory cytokines, including TNF-α, interleukin-1ß, and interleukin-6, was downregulated by RCW in the TNF-α/IFN-γ-stimulated cells. The levels of inflammatory chemokines (thymus- and activation-regulated chemokine; eotaxin; macrophage-derived chemokine; regulated on activation, normal T-cell expressed and secreted; and granulocyte-macrophage colony-stimulating factor) and intercellular adhesion molecule-1 were decreased in the TNF-α/IFN-γ-stimulated HaCaT cells after RCW treatment. Additionally, the mRNA expression levels of filaggrin and involucrin, proteins that form the skin, were increased by RCW. Furthermore, RCW inhibited the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway in the TNF-α/IFN-γ-stimulated HaCaT cells. Collectively, the present investigation indicates that RCW is a potent substance that inhibits AD.

Cranberry Powder Attenuates Benign Prostatic Hyperplasia in Rats.

Cranberry powder (CR) is reported to be effective against lower urinary tract symptoms (LUTS) and recurrent urinary tract infections. Benign prostatic hyperplasia (BPH) in men older than 50 years is a common cause of LUTS. Here, we attempted to evaluate if CR is also effective for treating BPH using a BPH-induced rat model, which was orally administered CR. Male Sprague-Dawley rats weighing 200-250 g were randomly divided into the following six groups (n = 9): noncastration group; castration group; BPH group; BPH and cranberry for 8-week (CR8W) group; BPH and cranberry for 4-week (CR4W) group; and BPH and saw palmetto group (saw palmetto). Compared with the BPH group, the CR8W group showed a significant decrease in prostate weight (by 33%), dihydrotestosterone (DHT) levels (by 18% in serum and 28% in prostate), 5-alpha reductase levels (18% reduction of type 1 and 35% of type 2), and histological changes. These results indicate that CR could attenuate BPH by inhibiting 5-alpha reductase and by reducing other biomarkers such as prostate weight and DHT levels. Thus, CR may be an effective candidate for the development of a functional food for BPH treatment. IACUC (USW-IACUC-R-2015-004).

Measurement of autophagy flux in benign prostatic hyperplasia in vitro.

BACKGROUND: Recent studies have suggested a novel therapeutic strategy for treatment of benign prostatic hyperplasia (BPH) via modulation of autophagy. However, it is not clear whether autophagy induction or inhibition can render better therapeutic efficacy for BPH treatment because autophagy activation in BPH tissue is not precisely known and still contradictory. The purpose of this study was to examine the levels of autophagy in BPH tissue cells. METHODS: We have analyzed and compared autophagic flux which is defined as a measure of autophagic degradation activity in two human prostate epithelial cell lines, RWPE-1 (normal prostate) and BPH-1 (BPH) using LC3-II turnover assay, to clarify the levels of autophagy in BPH. RESULTS: The in vitro autophagy flux assays showed that autophagy flux was significantly decreased in BPH-1 cell lines compared with RWPE-1 cells under all three conditions of using the original (~62%), the exchanged (~46%), and the same media (Hank's balanced salt solution (HBSS), ~40%), and these results were similar to those seen in the prostate of testosterone-induced BPH rats (~50%) (P < 0.05). CONCLUSION: It is suggested that defective autophagy, which is decreased autophagy flux in the prostate gland, may be implicated in BPH, and activating autophagy flux of the prostate with BPH may be used as a potential therapeutic target for treating and alleviating BPH disease.

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.

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.

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.

Extracts of Porphyra tenera (Nori Seaweed) Activate the Immune Response in Mouse RAW264.7 Macrophages via NF-κB Signaling.

Porphyra tenera, also known as nori, is a red algal species of seaweed. It is cultivated in Asia for culinary purposes. We report that P. tenera extract (PTE) enhances the immune response in mouse macrophages. We found that P. tenera extract regulates the NF-κB IκB kinase (IKK) signaling pathway, and we assessed the expression and translocation of p65, a subunit of NF-κB, in RAW264.7 mouse macrophage cells after treatment with PTE. We also investigated the effects of 10% ethanol PTE (PTE10) in RAW264.7 cells. The production of IL-10, IL-6, TNF-α, and IFN-γ was induced by PTE treatment of the macrophages, and PTE also enhanced p-IκB and p-AKT. PTE10 showed no cytotoxicity at 10-20 µg/mL in RAW264.7 cells. PTE10, in fact, increased cell viability at 24 h, stimulated macrophage cells, and induced the phosphorylation of Akt. Akt stimulates IKK activity through the phosphorylation of IKKα and enhances immune activity through the activation of NF-κB. In this study, NF-κB activation was induced by increasing p-NF-κB and p-IKK. A subunit of NF-κB, p65, was located in the nucleus and increased the expression of various cytokines. PTE thus enhanced the immune response through IκB-α immunostimulation signaling in RAW264.7 cells. PTE10 has potential therefore for development of future treatments requiring immune system stimulation.

Hepatoprotective effect of 10% ethanolic extract from Curdrania tricuspidata leaves against ethanol-induced oxidative stress through suppression of CYP2E1.

The hepatoprotective effect of 10% ethanolic extract of Curdrania tricuspidata (CTE) was investigated in HepG2/2E1 cells and C57BL/6 J mice. When compared ethanol-only treated HepG2/2E1 cells, pretreatment of CTE prevented increased intra-cellular reactive oxygen species levels and decreased antioxidant activities by ethanol-induced oxidative stress. In C57BL/6 J mice, CTE at a dose of 250 mg/kg/day was administered for 10 days, with ethanol (5 g/kg/day) administered for the final 3 days. Pretreatment with CTE prevented the elevated activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase caused by ethanol-induced hepatic damage. CTE-treated mice displayed a reduced level of malondialdehyde and increased antioxidant activities of catalase, glutathione S-transferase, glutathione peroxidase, and superoxide dismutase, as well as a reduced level of glutathione as compared with ethanol-only-treated mice. CTE-treated mice exhibited significant inhibition of CYP2E1 activities and expression. These results suggest that CTE could be a useful agent for the prevention of ethanol-induced oxidative damage in the liver, elevating antioxidative potentials and alleviating oxidative stress by suppressing CYP2El.

Protein serine/threonine phosphatase PPEF-1 suppresses genotoxic stress response via dephosphorylation of PDCD5.

Programmed cell death 5 (PDCD5) is believed to play a crucial role in p53 activation; however, the underlying mechanism of how PDCD5 function is regulated during apoptosis remains obscure. Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser-119, which leads to PDCD5 destabilization. Overexpression of wild-type PPEF-1, but not inactive PPEF-1D172N, efficiently suppressed CK2α-mediated stabilization of PDCD5 and p53-mediated apoptosis in response to etoposide (ET). Conversely, PPEF-1 knockdown further enhanced genotoxic stress responses. Notably, PPEF-1 suppressed p53-mediated genotoxic stress response via negative regulation of PDCD5. We also determined that overexpression of wild-type PPEF-1, but not inactive PPEF-1D172N, significantly increased tumorigenic growth and chemoresistance of A549 human lung carcinoma cells. Collectively, these data demonstrate that PPEF-1 plays a pivotal role in tumorigenesis of lung cancer cells by reducing PDCD5-mediated genotoxic stress responses.

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.

Antistress Effects of Rosa rugosa Thunb. on Total Sleep Deprivation-Induced Anxiety-Like Behavior and Cognitive Dysfunction in Rat: Possible Mechanism of Action of 5-HT6 Receptor Antagonist.

Our previous results suggest that the Rosa rugosa Thunb. (family Rosaceae) alleviates endurance exercise-induced stress by decreasing oxidative stress levels. This study aimed to screen and identify the physiological antistress effects of an extract of R. rugosa (RO) on sleep deprivation-induced anxiety-like behavior and cognitive tests (in vivo) and tested for hippocampal CORT and monoamine levels (ex vivo), corticosterone (CORT)-induced injury, N-methyl-d-aspartate (NMDA) receptor, and serotonin 6 (5-hydroxytryptamine 6, 5-HT6) receptor activities (in vitro) in search of active principles and underlying mechanisms of action. We confirmed the antistress effects of RO in a sleep-deprived stress model in rat and explored the underlying mechanisms of its action. In conclusion, an R. rugosa extract showed efficacy and potential for use as an antistress therapy to treat sleep deprivation through its antagonism of the 5-HT6 receptor and resulting inhibition of cAMP activity.

SUMOylation of TBL1 and TBLR1 promotes androgen-independent prostate cancer cell growth.

Chronic inflammation is strongly associated with prostate cancer pathogenesis. Transducin ß-like protein (TBL1) and Transducin ß-like 1X-linked receptor 1 (TBLR1) have been identified recently as a coactivator for NF-κB-mediated transcription; however, the underlying mechanism by which TBL1 and TBLR1 activate NF-κB function during inflammation remains unknown. Here, we demonstrate that cytokine production is significantly elevated in androgen-independent PC-3 prostate cancer cells compared with androgen-dependent LNCaP prostate cancer cells. Elevated cytokine production positively correlates with the TBL1 and TBLR1 SUMOylation level in PC-3 cells. We show that both TBL1 and TBLR1 are SUMOylated in response to TNF-α treatment, and this increases formation of the TBL1-TBLR1-NF-κB complex, which leads to NF-κB-mediated transcriptional activation of cytokine gene expression. Conversely, SENP1-mediated deSUMOylation of TBL1 and TBLR1 inhibits NF-κB-target gene expression by dissociating TBL1 and TBLR1 from the nuclear hormone receptor corepressor (NCoR) complex. TBL1 knockdown substantially suppresses inflammatory signaling and PC-3 cell proliferation. Collectively, these results suggest that targeted SUMOylation of TBL1 and TBLR1 may be a useful strategy for therapeutic treatment of androgen-independent prostate cancer.