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Diterpenoids from the Vietnamese medicinal plant Croton tonkinensis are rich in ent-kaurane, kaurane and the grayanane class and are valuable intermediate plant metabolites with different bioactivities. In this study, we report the antituberculosis activity of these diterpenoids against both susceptible and resistant strains of M. tuberculosis for the first time. All of the ent-kaurane, kaurane and grayanane diterpenoids showed high to moderate activity against Mycobacterium. The highest antituberculosis activity was observed for ent-1β,7α,14β-triacetoxykaur-16-en-15-one ( cpp604), with MIC values of 0.78, 1.56 and 3.12-12.5 µg/ml against H37Ra, H37Rv and all other resistant strains of Mycobacterium tuberculosis examined. In addition, other ent-kaurane-type diterpenoids also showed very high activities against mycobacterium, including cpp609 (1.56 µg/ml), cpp610 (1.56 µg/ml), cpp601 (3.12-6.25 µg/ml), cpp602 (3.12-6.25 µg/ml), cpp607 (3.12-6.25 µg/ml) and cpp608 (3.12-6.25 µg/ml). From the structure-activity relationship, functional groups R3 and R5 of the ent-kaurane skeleton were found to modulate the antimycobacterial activity. [ABSTRACT FROM AUTHOR]

Sappanchalcone, a bioactive flavonoid isolated from the heartwood of Caesalpinia sappan L. possesses anti-inflammatory effects. We studied the efficacy of sappanchalcone in attenuating collagen-induced arthritis (CIA) in a mouse model of rheumatoid arthritis. Sappanchalcone was purified to homogeneity from the chloroform fraction of the methanolic extract of C. sappan, and identified using mass spectrometry and H-nuclear magnetic resonance spectroscopy. CIA-induced male DBA/1J mice were divided into control, sappanchalcone-treated, and methotrexate-treated groups ( n = 10 per group). Paw swelling, arthritis severity, radiographic and histomorphometric changes were assessed to measure the protective role of sappanchalcone against chronic disease progression. Sappanchalcone administration significantly reduced clinical arthritis and inflammatory edema in paws. Bone mineral density and trabecular structure were maintained in CIA mice administered sappanchalcone. The levels of pro-inflammatory cytokines (TNF-α, IL-6, and 1L-1β) were significantly lower in the serum of sappanchalcone-treated mice as compared with the control group. Our results suggest that sappanchalcone could be used as an anti-inflammatory and bone-protective agent during the treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the physiological effects of different selenium (Se) levels on the growth of white-rot fungus, Pleurotus eryngii, with special reference to the regulation of ligninolytic enzymes such as laccase and versatile peroxidase. The fungus was grown in medium supplemented with 1, 10, 100, 1,000 and 10,000 μM of sodium selenite. Mycelial growth was stronger at lower Se levels, but declined significantly at higher concentrations of 1,000 and 10,000 μM, highlighting its association in mediating toxic responses. Inhibition of fungal growth was accompanied with dense and entangled hyphae taking the shape of irregular short strips. Additionally, hyphal swellings and septation were noticed which lead to a reduction in the advancement of the mycelium. Along with the inhibition of fungal biomass, the reducing sugar and protein concentrations increased to about 30.2 and 3.5 mg/ml respectively in the growth medium. Additionally, the laccase gene expression showed a twofold upregulation at higher levels of Se, although the activity of the enzyme was compromised with an inverse relationship with increased gene transcripts. The versatile peroxidase transcript showed a complete downregulation at 10,000 μM after an upregulation at lower levels of Se. We also confirmed the direct relationship of different Se levels on laccase activity of Rhus vernicifera that showed similar behavior to the fungal laccase. The results of the present study suggest that Se supplementation regulates mRNA levels of laccase and versatile peroxidase depending on exposure and may play a role in the toxicity associated with Se. [ABSTRACT FROM AUTHOR]

We prepared recombinant human interleukin-2 (rhIL-2) and studied its pretreated influence on liver regeneration and the blood profile in partially (67%) hepatectomized (PH) male Sprague-Dawley rats. Rats were injected in the tail vein with rhIL-2 three times per day for 3 consecutive days and 67% underwent a partial hepatectomy (PH). Five days after the PH, liver tissue and blood samples were analyzed for liver regeneration and hematological changes. The weight of the liver in the rhIL-2 pretreated groups increased in a dose-dependent manner; with the highest treatment (24 × 10 IU/kg), the maximum liver weight of 88.6% was exhibited. The control group showed a gradual increase to 76.3% of the original liver weight. A histological analysis of the liver showed an increase in proliferating cell nuclear antigen (PCNA)-positive cells in rhIL-2 pretreated rat livers. The rate of hepatocyte proliferation also increased significantly in primary cultured rat liver cells following rhIL-2 treatment. These results suggest that pretreatment with rhIL-2 may play adjuvant roles in liver regeneration after PH. [ABSTRACT FROM AUTHOR]

tert-Butylhydroquinone (tBHQ) is a commonly used antioxidant additive that is approved for human use by both the Food and Agriculture Organization and the World Health Organization (FAO/WHO). In this study, we examined the effect of tBHQ on body weight gain and found that food supplementation with 0.001 % (w/w) tBHQ inhibited 61.4 % ( P < 0.01) of body weight gain in high-fat diet (HFD)-induced C57BL/6 mice, and the oral administration of tBHQ (1.5 mg/kg) reduced 47.5 % ( P < 0.05) of body weight gain in normal diet fed db/db mice. The HFD increased lipid deposit in adipocytes, but these were reduced significantly by tBHQ treatment in C57BL/6 mice. tBHQ supplementation significantly lowered the plasma triglyceride and total cholesterol, with reduced size of accumulated fat mass. The rate limiting enzyme of beta-oxidation (ACOX1) was significantly over-expressed in the liver with tBHQ treatment. These results indicate that tBHQ suppresses body weight gain in mice, possibly at least related to the up-regulation of ACOX1 gene expression. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the hepatoprotective effects of reynosin, sesquiterpenes from the leaves of Laurus nobilis, against thioacetamide (TAA)-induced apoptosis in primary hepatocyte cultures and an in vivo mouse model. Rat hepatocytes were isolated and pretreated with 0.13, 0.64, or 3.22 μM reynosin and then exposed to 100 mM TAA. Reynosin treatment significantly inhibited TAA-induced apoptosis and hepatocellular DNA damage in primary rat hepatocytes. We observed an increase in levels of antiapoptotic Bcl-2, Bcl-XL mRNA and a decrease in levels of proapoptotic Bax mRNA following reynosin treatment of hepatocytes. Apoptosis in BALB/c mice was induced with intra-peritoneal injection of 200 mg/kg TAA for 2 weeks every other day. Then reynosin (5 mg/kg) and TAA were intragastrically given for 3 weeks every other day. Aspartate aminotransferase and alanine aminotransferase levels in the blood of mice were decreased in the reynosin administration group. Bcl- 2 and Bcl- XL mRNA levels were increased, and the Bax mRNA level was decreased in reynosin-treated mice. Thus, reynosin inhibited TAA-induced apoptosis in primary hepatocytes and an in vivo mouse model. [ABSTRACT FROM AUTHOR]

Seven prenylated flavanoids, licoflavone C ( 1), cyclomulberrin ( 2), neocyclomorusin ( 3), sanggenon I ( 4), morusin ( 5), kuwanon U ( 6) and kuwanon E ( 7), and three 2-arylbenzofurans, moracin P ( 8), moracin O ( 9), and mulberrofuran Q ( 10) were isolated from the MeOH extract of Mori Cortex Radicis. Among these, compounds 2- 7 enhanced cell viability in a dose-dependent manner against sodium nitroprusside-induced cell death in neuroblastoma SH-SY5Y cells, which was measured by MTT reduction assay (EC values of 4.4, 5.6, 8.0, 6.4, 8.7, and 11.9 μg/mL, respectively). Among 10 compounds, C-3 prenylated flavones ( 2, 3, and 5) and prenylated flavanones ( 4, 6, and 7) showed cell protection. However, compound 1 which lacks the prenyl group at C-3 and three 2-arylbenzofurans ( 8- 10) did not show protective effect. The order of cell protection was as follow: C-3 prenylated flavones ( 2, 3, and 5) > prenylated flavanones ( 4, 6, and 7) > 2-arylbenzofurans ( 8- 10) and flavone ( 1). From this result, we show that some prenylated flavones and flavanones might protect neuronal cells against nitrosative stress-mediated cell death. Even though further evaluations are necessary in vitro and in vivo study, we carefully suggest that some prenylated flavonoids from Mori Cortex Radicis might protect neuronal cells from neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Dopamine (DA), as a neurotoxin, can elicit severe Parkinson's disease-like syndrome by elevating intracellular reactive oxygen species (ROS) levels and apoptotic activity. We examined the inhibitory effects of 3α-acetoxyeudesma-1,4(15),11(13)-trien-12,6α-olide (AETO), purified from the leaves of Laurus nobilis L., on DA-induced apoptosis and α-synuclein (α-syn) formation in dopaminergic SH-SY5Y cells. AETO decreased the active form of caspase-3 and the levels of p53, which were accompanied by increased levels of Bcl-2 in a dose-dependent manner. Flow cytometric and Western blot analysis showed that AETO significantly inhibited DA-induced apoptosis along with suppression of intracellular tyrosinase activity, ROS generation, quinoprotein, and α-syn formation ( P < 0.01). These results indicate that AETO inhibited DA-induced apoptosis, which is closely related to the suppression of intracellular tyrosinase activity and the formation of α-syn, ROS, and quinoprotein in SH-SY5Y cells. [ABSTRACT FROM AUTHOR]

The cancer chemopreventive effect of psoralen isolated from the seeds of Psoralea corylifolia was investigated in the induction of quinone reductase (QR) activity, intracellular detoxification enzyme, inhibition of 12- O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity, a key regulatory enzyme for polyamine metabolism, and tumor promotion in mouse epidermal JB6 cells, sensitive to tumor promoters (clone 415a P+ cells), which are related to suppress multistage carcinogenesis including initiation and promotion. Psoralen was isolated and identified from the ethyl acetate-soluble fraction of the methanolic extract from the seeds. Psoralen was active in induction of QR activity, the concentration of psoralen required to induce 1.5 fold QR activity was 14.8 μg/mL. Also, this pure compound inhibited TPA-induced ODC activity by 50% (designated IC) at the concentration 15.6 μg/mL and exhibited inhibition of TPA-induced tumor promotion in mouse epidermal JB6 cells with an IC value of 17.1 μg/mL. Therefore, it is extrapolated that psoralen has the potential capable of inhibiting the initiation and/or promotion stage of carcinogenesis by induction of QR activity, inhibition of TPA-induced ODC activity and mouse epidermal JB6 cells tumor promotion. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are important mediators in many neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. This study tested the neuroprotective effects of spirafolide, a compound purified from the leaves of Laurus nobilis L. (Lauraceae), against dopamine (DA)-induced apoptosis in human neuroblastoma SH-SY5Y cells. Following a 24-h exposure of cells to DA (final conc., 0.6 mM), we observed a marked increase in apoptosis, increased generation of ROS and decreased cell viability. Pretreatment of the cells for 24 h with spirafolide (0.4, 2, and 10 μM) before exposure to DA notably increased cell survival ( p < 0.01) and lowered intracellular ROS levels ( p < 0.01). These results indicate that spirafolide has neuroprotective effects against DA toxicity. These effects may contribute to the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Energy balance is monitored by the hypothalamus, which responds to peripheral signals by releasing neuropeptides that regulate energy intake and expenditure. In this study, we constructed pro-opiomelanocortin (POMC) and 'cocaine and amphetamine-related transcript' (CART) promoter-driven luciferase plasmids and transformed them permanently into both N29-2 neuronal cells and human SHSY5Y cells. Using reporter gene assays, we identified apigenin from the seeds of Perilla frutescens Britton var crispa (Benth.) using activity-guided fractionation. The 50% promoting concentrations (EC) of apigenin on POMC and CART were 0.93 μM and 0.67 μM, respectively, in N29-2 cells, without significant cytotoxic effects. Shortterm food intake was decreased in C57BL/6J mice after an intraperitoneal injection of apigenin (10 mg/kg; p < 0.05). Food intake and body weight gain for 30 days were also reduced slightly in mice fed a high-fat diet containing apigenin (0.05%, w/w; p < 0.05). These results indicate that apigenin increased POMC and CART gene expression in neuronal cells and significantly reduced food intake in C57BL/6 mice, which may be related to the anorexigenic neuropeptides POMC and CART. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY) and agouti-related protein (AgRP) have powerful stimulatory effects on food intake, which suggests that the downregulation of brain NPY or AgRP may help reduce obesity and diabetes by inhibiting food intake. To search for active compounds that inhibit NPY and AgRP expression, we made two luciferase reporter assay systems consisting of NPY and AgRP promoter-driven luciferase genes, together with the puromycin resistance gene, in a plasmid vector. Each plasmid was permanently transfected into N29-4 neuronal cells. Using the systems, resveratrol was purified from the stem of Vitis coignetiae Pulliat by activityguided fractionation. Resveratrol downregulated NPY and AgRP promoter-driven luciferase activity in a dose-dependent manner. The inhibitory concentrations (IC50, 50% inhibition) of resveratrol against pNPY-luc and pAgRP-luc activities were 8.9 μM and 8.0 μM, respectively. Furthermore, one-time intraperitoneal injection of resveratrol (100 mg/kg) suppressed 20.0% and 17.2% of food intake during 24 and 48 h, respectively. These results indicated that resveratrol inhibited food intake, which may be related to the downregulation of NPY and AgRP gene expression. [ABSTRACT FROM AUTHOR]

Quinone reductase (QR) is a protective phase II enzyme against mutagens and carcinogens which is inducible by a number of chemical compounds in plants. This study was carried out to investigate effects of the fractions from the seeds of Psoralea corylifolia on the induction of QR with Hepa 1c1c7 murine hepatoma cell line. The ethyl acetate-soluble fraction of the methanolic extract from the seeds was found to induce QR and the concentration of 1.5 fold QR induction (1.5 FIC) was 1.2 μg/mL. We obtained as an active compound, psoralidin, isolated from the ethyl acetate-soluble fraction after further sequential fractionation with column chromatography and 1.5 FIC of psoralidin was 0.5 μg/mL. The seeds of Psoralea corylifolia and psoralidin might be a candidate for developing QR inducers. [ABSTRACT FROM AUTHOR]

Eight furoquinoline alkaloids were purified from two plants belonging to the Rutaceae family. Kokusaginine, skimmianine, evolitrine, and confusameline were purified from Melicope confusa, and haplopine, robustine, dictamine, and γ-fagarine from Dictamnus albus. In this study, the eight furoquinoline alkaloids were examined for, inhibitory potency against human phosphodiesterase 5 (hPDE5A) in vitro. DNA encoding the catalytic domain of human PDE5A was amplified from the mRNA of T24 cells by RT-PCR and was fused to GST in an expression vector. GST-tagged PDE5A was then purified by glutathione affinity chromatography and used in inhibition assays. Of the eight alkaloids, γ-fagarine was the most potent inhibitor of PDE5A, and its single methoxy group at the C-8 position was shown to be critical for inhibitory activity. These results clearly illustrate the relationship between PDE5A inhibition and the methoxy group position in furoquinoline alkaloids. [ABSTRACT FROM AUTHOR]

Endosulfan is one of the organochlorine pesticides, which are well-known endocrine disrupters (EDs), and it acts as an estrogen agonist. Estrogen is a group of hormones that play an important role in mammary gland function and are implicated in mammary carcinogenesis. In the present study, we studied the effects of endosulfan on nodule like alveolar lesion (NLAL) formation in mouse mammary gland development using a mouse mammary gland organ culture (MMOC) system. Although endosulfan-treated mammary glands did not form NLALs, more alveolar buds were formed in this group than in the negative control (vehicle-treated) group. In addition, telomerase reverse transcriptase (TERT) mRNA expression levels were increased in endosulfan-treated mammary glands in a dose-dependent manner. Telomerase can be activated by estrogen, therefore, we examined the effects of endosulfan on telomerase activity, and found that the telomerase activity in estrogen receptor-positive MCF-7 cells was up-regulated by endosulfan treatment. Moreover, this activation was accompanied by the upregulation of the TERT mRNA expression. Also, transient expression assays using CAT reporter plasmids containing various fragments of the TERT promoter showed that this imperfect palindromic estrogen-responsive element is almost certainly responsible for the transcriptional activation by endosulfan. These results may help elucidate the endocrine disrupting mechanism of endosulfan. [ABSTRACT FROM AUTHOR]

Bee venom is used as a traditional medicine for treatment of arthritis. The anti-inflammatory activity of the n-hexane, ethyl acetate, and aqueous partitions from bee venom ( Apis mellifera) was studied using cyclooxygenase (COX) activity and pro-inflammatory cytokines (TNF-α and IL-1β) production, in vitro. COX-2 is involved in the production of prostaglandins that mediate pain and support the inflammatory process. The aqueous partition of bee venom showed strong dose-dependent inhibitory effects on COX-2 activity (IC50 = 13.1 μg/mL), but did not inhibit COX-1 activity. The aqueous partition was subfractionated into three parts by molecular weight differences, namely, B-F1 (above 20 KDa), B-F2 (between 10 KDa and 20 KDa) and B-F3 (below 10 KDa). B-F2 and B-F3 strongly inhibited COX-2 activity and COX-2 mRNA expression in a dose-dependent manner, without revealing cytotoxic effects. TNF-α and IL-1β are potent pro-inflammatory cytokines and are early indicators of the inflammatory process. We also investigated the effects of three subfractions on TNF-α and IL-1β production using ELISA method. All three subfractions, B-F1, B-F2 and B-F3, inhibited TNF-α and IL-1β production. These results suggest the pharmacological activities of bee venom on anti-inflammatory process include the inhibition of COX-2 expression and the blocking of pro-inflammatory cytokines (TNF-α, and IL-1β) production. [ABSTRACT FROM AUTHOR]

A correction to the article " Effects of different selenium levels on growth and regulation of laccase and versatile peroxidase in white-rot fungus, Pleurotus eryngii" in the April 23, 2014 is presented.