Estrogenic properties of Prunus cerasoides extract and its constituents in MCF-7 cell and evaluation in estrogen-deprived rodent models.

Prunus cerasoides (PC) products contain relatively high levels of flavones and isoflavones and may be potential sources of phytoestrogens for postmenopausal symptom relief. We assessed the PC extract (PCE) and its representative constituents in vitro with assays for estrogen receptor alpha binding, estrogen response element transcriptional activity, cell proliferation, and gene expression changes for pS2 in MCF-7 cells. PCE and its compounds showed strong estrogen receptor binding affinities and estrogen response element induction. A previously undescribed compound (designated as compound 18), now identified as being gentisic acid, 5-O-ß-D-(6'-O-trans-4-coumaroyl)-glucopyranoside, also showed potent estrogenic properties and induced proliferation of MCF-7 cells. PCE was evaluated for its in vivo uterotrophic effects in immature female rats as well as for its lipid lowering effects in estrogen-deprived animals. For ovariectomized rats and aged female mice, PCE-treated groups had lower plasma triglyceride levels compared with control and, for the same comparison, had reduced serum levels of liver stress/damage markers. Our results point to strong estrogenic activities and beneficial metabolic effects for PCE, with properties that put PC and its extracts as promising sources of phytoestrogens for symptom relief in menopausal and postmenopausal cases.

Inhibitory and Inductive Effects of Opuntia ficus indica Extract and Its Flavonoid Constituents on Cytochrome P450s and UDP-Glucuronosyltransferases.

Opuntia ficus indica (OFI) is grown abundantly in arid areas and its fruits are regarded as an important food and nutrient source owing to the presence of flavonoids, minerals, and proteins. The previous report that OFI exerts phytoestrogenic activity makes it plausible for OFI-containing supplements to be used as alternative estrogen replacement therapy. In the case of polypharmacy with the consumption of OFI-containing botanicals in post- or peri-menopausal women, it is critical to determine the potential drug-OFI interaction due to the modulation of drug metabolism. In the present study, the modulating effects on the hepatic drug metabolizing enzymes (DMEs) by OFI and its flavonoid constituents (kaempferol, quercetin, isorhamnetin, and their glycosidic forms) were investigated using the liver microsomal fractions prepared from ovariectomized (OVX) rats, human liver microsomes, and human hepatocarcinoma cell line (HepG2). As a result, the oral administration of extracts of OFI (OFIE) in OVX rats induced hepatic CYP2B1, CYP3A1, and UGT2B1. OFIE, hydrolyzed (hdl) OFIE, and several flavonols induced the transcriptional activities of both CYP2B6 and CYP3A4 genes in HepG2 cells. Finally, OFIE did not inhibit activities of cytochrome P450 (CYPs) or uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), whereas hdl OFIE or flavonol treatment inhibited CYP1A2 and CYP3A1/3A4 in rat and human liver microsomes. Our data demonstrate that OFIE may induce or inhibit certain types of DMEs and indicate that drug-OFI interaction may occur when the substrate or inhibitor drugs of specific CYPs or UGTs are taken concomitantly with OFI-containing products.

Selected Phytoestrogens Distinguish Roles of ERα Transactivation and Ligand Binding for Anti-Inflammatory Activity.

Estrogen receptor α (ERα) is a ligand-activated transcriptional activator that is also involved vascular inflammation and atherosclerosis. Whether different ligands may affect this activity has not been explored. We screened a panel of phytoestrogens for their role in ERα binding and transcriptional transcription, and correlated the findings to anti-inflammatory activities in vascular endothelial cells stably expressing either a wild-type or mutant form of ERα deficient in its membrane association. Taxifolin and silymarin were "high binders" for ERα ligand binding; quercetin and curcumin were "high activators" for ERα transactivation. Using these phytoestrogens as functional probes, we found, in endothelial cells expressing wild-type ERα, the ERα high activator, but not the ERα high binder, promoted ERα nuclear translocation, estrogen response element (ERE) reporter activity, and the downstream gene expression. In endothelial cells expressing membrane association-deficient mutant ERα, the ERα nuclear translocation was significantly enhanced by taxifolin and silymarin, which still failed to activate ERα. Inflammation response was examined using the systemic or vascular inflammation inducers lipopolysaccharide or oxidized low-density lipoprotein. In both cases, only the ERα high activator inhibited nuclear translocation of nuclear factor κB, JNK, and p38, and the production of inflammatory cytokines IL-1ß and TNFα. We confirm a threshold nuclear accumulation of ERα is necessary for its transactivation. The anti-inflammatory activity of phytoestrogens is highly dependent on ERα transactivation, less so on the ligand binding, and independent of its membrane association. A pre-examination of phytoestrogens for their mode of ERα interaction could facilitate their development as better targeted receptor modifiers.

Estrogenic effects of phytoestrogens derived from Flemingia strobilifera in MCF-7 cells and immature rats.

Phytoestrogen (PE) has received considerable attention due to the physiological significance of its estrogenicity. Flemingia strobilifera (FS) has been used as a folk medicine in Asia for the treatment of inflammation, cancer, and infection; however, the estrogenic effects and chemical components of FS have not yet been reported. We aimed to uncover the estrogenic properties and PEs derived from FS using phytochemical and pharmacological evaluation. PEs from FS extract (FSE) were analyzed by NMR, HPLC, and MS. To evaluate estrogenic activity, FSE and its compounds were evaluated by in vitro and in vivo assays, including human estrogen receptor alpha (hERα) binding, estrogen response element (ERE)-luciferase reporter assays, and uterotrophic assays. FSE and its compounds 1-5 showed binding affinities for hERα and activated ERE transcription in MCF-7 cells. Additionally, FSE and compounds 1-5 induced MCF-7 cell proliferation and trefoil factor 1 (pS2) expression. In immature female rats, significant increases in uterine weight and pS2 gene were observed in FSE-treated groups. We identified estrogenic activities of FSE and its bioactive compounds, suggesting their possible roles as PEs via ERs. PEs derived from FSE are promising candidates for ER-targeted therapy for post-menopausal symptoms.

A Simple and Rapid UPLC-PDA Method for Quality Control of Nardostachys jatamansi.

Nardostachys jatamansi is a well-documented herbal agent used to treat digestive and neuropsychiatric disorders in oriental medicinal systems. However, few simple, rapid, and comprehensive methods were reported for quality assessment and control of N. jatamansi. Herein, a UPLC with photodiode array detection method was developed for both fingerprint investigation of N. jatamansi and simultaneous quantitative analysis of the six serotonin transporter modulatory constituents in N. jatamansi. For chromatographic fingerprinting, 24 common peaks were selected as characteristic peaks to assess the consistency of N. jatamansi samples from different retail sources. Six of the common peaks (5, 7, 12: , and 16:  - 18: ) were identified as desoxo-narchinol A, buddleoside, isonardosinone, nardosinone, kanshone H, and (-)-aristolone, respectively, by phytochemical investigation. Five of the six compounds significantly either enhanced or inhibited serotonin transporter activity, while (-)-aristolone (18: ) didn't show any serotonin transporter activity. In quantitative analysis, the six compounds showed good linearity (r > 0.999) within test ranges. The precision, expressed as relative standard deviation, was in the range of 0.25 - 2.77%, and the recovery of the method was in the range of 92 - 105%. The UPLC-photodiode array detection-based fingerprint analysis and quantitative methods reported here could be used for routine quality control of N. jatamansi.

Prognostic Influence of BCL2 on Molecular Subtypes of Breast Cancer.

PURPOSE: We aimed to reveal the prognostic influence of B-cell CLL/lymphoma 2 (BCL2) on molecular subtypes of breast cancer. METHODS: We analyzed 9,468 patients with primary breast cancer. We classified molecular subtypes according to the National Comprehensive Cancer Network (NCCN) and St. Gallen guidelines, mainly on the basis of the expression of hormonal receptor (HR), human epidermal growth factor receptor 2 (HER2), and Ki-67. RESULTS: Regarding NCCN classification, BCL2 was a strong favorable prognostic factor in the HR(+)/HER2(-) subtype (p<0.001) and a marginally significant favorable prognosticator in the HR(+)/HER2(+) subtype (p=0.046). BCL2 had no prognostic impact on HR(-)/HER2(+) and HR(-)/HER2(-) subtypes. In relation to St. Gallen classification, BCL2 was a strong favorable prognosticator in luminal A and luminal B/HER2(-) subtypes (both p<0.001). BCL2 was a marginally significant prognosticator in the luminal B/HER2(+) subtype (p=0.046), and it was not a significant prognosticator in HER2 or triple negative (TN) subtypes. The prognostic effect of BCL2 was proportional to the stage of breast cancer in HR(+)/HER2(-), HR(+)/HER2(+), and HR(-)/HER2(-) subtypes, but not in HR(-)/HER2(+) subtype. BCL2 was not a prognostic factor in TN breast cancer regardless of epidermal growth factor receptor expression. CONCLUSION: The prognostic influence of BCL2 was different across molecular subtypes of breast cancer, and it was largely dependent on HR, HER2, Ki-67, and the stage of cancer. BCL2 had a strong favorable prognostic impact only in HR(+)/HER2(-) or luminal A and luminal B/HER2(-) subtypes, particularly in advanced stages. Further investigations are needed to verify the prognostic influence of BCL2 on molecular subtypes of breast cancer and to develop clinical applications for prognostication using BCL2.

Characterization of Phase I and Phase II Hepatic Metabolism and Reactive Intermediates of Larrea nitida Cav. and Its Lignan Compounds.

Larrea nitida Cav. (LNC), which belongs to the family Zygophyllaceae, is widely indigenous and used in South America to treat various pathological conditions. It contains the antioxidant and antiinflammatory but toxic nordihydroguaiaretic acid (NDGA) as well as O-methylated metabolite of NDGA (MNDGA) as bioactive compounds. The hepatic metabolism-based toxicological potential of extracts of LNC (LNE), NDGA, and MNDGA has not previously been reported. The present study aimed to characterize the phase I and phase II hepatic metabolism and reactive intermediates of LNE, NDGA, and MNDGA and their effects on the major drug-metabolizing enzymes in vitro and ex vivo. A methanol extract of LNC collected from Chile as well as NDGA and MNDGA isolated from LNE were subjected to metabolic stability assays in liver microsomes in the presence of the cofactors reduced nicotinamide dinucleotide phosphate (NADPH) and/or uridine 5'-diphosphoglucuronic acid (UDPGA). Cytochrome P450 (CYP) inhibition assays were performed using CYP isozyme-specific model substrates to examine the inhibitory activities of LNE, NDGA, and MNDGA, which were expressed as % inhibition and IC50 values. Ex vivo CYP induction potential was investigated in the liver microsomes prepared from the rats intraperitoneally administered with LNE. Glutathione (GSH) adduct formation was monitored by LC-MS3 analysis of the microsomal incubation samples with either NDGA or MNDGA and an excess of GSH to determine the formation of electrophilic reactive intermediates. Both NDGA and MNDGA were stable to NADPH-dependent phase I metabolism, but labile to glucuronide conjugation. LNE, NDGA, and MNDGA showed significant inhibitory effects on CYP1A2, 2C9, 2D6, and/or 3A4, with IC50 values in the micromolar range. LNE was found to be a CYP1A2 inducer in ex vivo rat experiments, and mono- and di-GSH adducts of both NDGA and MNDGA were identified by LC-MS3 analysis. Our study suggests that hepatic clearance is the major elimination route for the lignans NDGA and MNDGA present in LNE. These lignans may possess the ability to modify biomacromolecules via producing reactive intermediates. In addition, LNE, NDGA, and MNDGA are found to be inhibitors for various CYP isozymes such as CYP2C9 and 3A4. Thus, the consumption of LNC as an herbal preparation or NDGA may cause metabolism-driven herb-drug interactions. Copyright © 2016 John Wiley & Sons, Ltd.

Chemical Constituents from the Flowers of Wild Gardenia jasminoides J.Ellis.

Four new iridoids, 2'-O-(E)-coumaroylshanzhiside (1), 6'-O-(E)-coumaroylshanzhiside (2), 8α-butylgardenoside B (3), 6α-methoxygenipin (4), and one new phenylpropanoid glucoside, 5-(3-hydroxypropyl)-2-methoxyphenyl ß-d-glucopyranoside (5), together with sixteen known compounds, were isolated from the edible flowers of wild Gardenia jasminoides J.Ellis. Their chemical structures were characterized by extensive spectroscopic techniques, including 1D- and 2D-NMR, HR-ESI-MS, and CD experiments. The absolute configurations of the new isolates' sugar moiety were assigned by HPLC analysis of the acid hydrolysates. Furthermore, the antioxidant activities of those isolates were preliminarily evaluated by DPPH scavenging experiment. And comparison of 1 H-NMR spectra for the EtOH extract of G. jasminoides J.Ellis, gardenoside B and geniposide revealed that the flowers of this plant have a considerable content of gardenoside B instead of geniposide in the fruits, indicating different activities and applications in people's daily life.

Novel antidepressant-like activity of caffeic Acid phenethyl ester is mediated by enhanced glucocorticoid receptor function in the hippocampus.

Caffeic acid phenethyl ester (CAPE) is an active component of propolis that has a variety of potential pharmacological effects. Although we previously demonstrated that propolis has antidepressant-like activity, the effect of CAPE on this activity remains unknown. The present study assessed whether treatment with CAPE (5, 10, and 20 µmol/kg for 21 days) has an antidepressant-like effect in mice subjected to chronic unpredictable stress via tail suspension (TST) and forced swim (FST) tests. CAPE administration induced behaviors consistent with an antidepressant effect, evidenced by decreased immobility in the TST and FST independent of any effect on serum corticosterone secretion. Western blots, conducted subsequent to behavioral assessment, revealed that CAPE significantly decreased glucocorticoid receptor phosphorylation at S234 (pGR(S234)), resulting in an increased pGR(S220/S234) ratio. We also observed negative correlations between pGR(S220)/(S234) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation, which was decreased by CAPE treatment. These findings suggest that CAPE treatment exerts an antidepressant-like effect via downregulation of p38MAPK phosphorylation, thereby contributing to enhanced GR function.

Activation of Estrogen Receptor by Bavachin from Psoralea corylifolia.

In this study, we examined the estrogenic activity of bavachin, a component of Psoralea corylifolia that has been used as a traditional medicine in Asia. Bavachin was purified from ethanolic extract of Psoralea corylifolia and characterized its estrogenic activity by ligand binding, reporter gene activation, and endogenous estrogen receptor (ER) target gene regulation. Bavachin showed ER ligand binding activity in competitive displacement of [(3)H] E2 from recombinant ER. The estrogenic activity of bavachin was characterized in a transient transfection system using ERα or ERß and estrogen-responsive luciferase plasmids in CV-1 cells with an EC50 of 320 nM and 680 nM, respectively. Bavachin increased the mRNA levels of estrogen-responsive genes such as pS2 and PR, and decreased the protein level of ERα by proteasomal pathway. However, bavachin failed to activate the androgen receptor in CV-1 cells transiently transfected with the corresponding receptor and hormone responsive reporter plasmid. These data indicate that bavachin acts as a weak phytoestrogen by binding and activating the ER.

Anti-inflammatory, anti-angiogenic, and anti-nociceptive activities of the chloroform fraction of a methanol extract from Rosa davurica Pall. leaves in experimental animal models.

Rosa davurica Pall. has been traditionally used to treat inflammatory diseases and tumors. Its dried leaves were extracted with absolute methanol, and the methanol extract was successively fractionated into n-hexane, chloroform, ethyl acetate, n-butanol, and aqueous fractions. Anti-angiogenic and anti-nociceptive activities were determined using the chick embryo chorioallantoic membrane (CAM) assay and acetic acid-induced writhing response, respectively. Anti-inflammatory activity was evaluated using two in vivo mouse models, acetic acid-induced vascular permeability and carrageenan-induced inflammation in the air-pouch. The methanol extract gave rise to significant inhibition in the CAM angiogenesis, and showed marked 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Among the fractions prepared from the methanol extract, the chloroform fraction exhibited highest inhibitory effect in the CAM angiogenesis. The chloroform fraction displayed anti-inflammatory activities in vascular permeability and air-pouch models. In the air-pouch model, it was able to diminish exudate volume, number of polymorphonulcear leukocytes, and nitrite content. It also showed anti-nociceptive activity in the writhing response model in mice. The leaves of R. davurica possess anti-angiogenic and related anti-inflammatory and anti-nociceptive activities, which would provide some therapeutic support on its traditional use.

New estrogenic compounds isolated from Broussonetia kazinoki.

Two new and two known compounds were identified as estrogenic constituents from Broussonetia kazinoki. Their structures were elucidated as broussonin A (1), tupichinol C (2), kazinol U (3), and (+)-(2R) kazinol I (4). They showed estrogenic activity with ligand-binding activity of estrogen receptor, transcriptional activity of estrogen-responsive element-luciferase reporter genes. They also control the cellular gene expression levels of estrogen-responsive genes. Phytoestrogens from B. kazinoki may have beneficial effects in the treatment of menopausal symptoms.

Caffeic acid phenethyl ester, a component of beehive propolis, is a novel selective estrogen receptor modulator.

Caffeic acid phenethyl ester (CAPE) is an active ingredient of beehive propolis with a structure similar to phenolic acid. The estrogenic effects of propolis were previously demonstrated through the activation of an estrogen receptor. To identify the estrogenic properties of propolis, CAPE was evaluated using in vitro and in vivo methods. CAPE showed selective binding affinity to human estrogen receptor beta (hERbeta) rather than hERalpha. CAPE also reduced ERalpha expression in MCF-7 and MDA 231 cells. In the yeast estrogen receptor transcription assay, CAPE produced the transcriptional activity of estrogen-responsive element with EC(50) values of 3.72 x 10(-6) M. CAPE did not increase the growth of MCF-7 estrogen receptor-positive breast cancer cells in doses ranging from 10(-7) to 10(-5) M. In order to understand how CAPE acts in animals, CAPE was tested by a uterotrophic bioassay. Treatment with CAPE (100, 500 mg/kg) did not increase the uterine weight relative to 3 microg/kg 17beta-estradiol treatment. The results indicate that CAPE, which is a selective agonist to hERbeta, but does not show any estrogenic effect on estrogen receptor-positive breast cancer cells and in immature rat uterine tissue, is a potential selective estrogen receptor modulator.

Evaluation of the antiangiogenic, anti-inflammatory, and antinociceptive activities of morin.

Morin displayed significant inhibition of chick chorioallantoic membrane (CAM) angiogenesis and was able to increase the endostatin level in human umbilical vein endothelial cells (HUVECs). Morin was shown to contain an in vivo anti-inflammatory activity using a carrageenan-induced air pouch model in mice. Antinociceptive activity of morin was also assessed using an acetic acid-induced writhing test in mice. Collectively, morin possesses antiangiogenic, in vivo anti-inflammatory, and antinociceptive activities.

Anti-inflammatory, anti-angiogenic and anti-nociceptive activities of an ethanol extract of Salvia plebeia R. Brown.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia plebeia R. Brown has been used for the treatment of a variety of inflammatory diseases, cold and tumors in many countries, including Korea and China. AIM OF THE STUDY: This study aimed to assess anti-inflammatory and related activities of an ethanol extract (SPEE) prepared from the dried whole parts of Salvia plebeia. MATERIALS AND METHODS: Anti-angiogenic and anti-nociceptive activities of SPEE were analyzed using the chick chorioallantoic membrane (CAM) assay and acetic acid-induced writhing response, respectively. Anti-inflammatory activity of SPEE was evaluated using acetic acid-induced vascular permeability, carrageenan-induced inflammation in the air pouch and analyses of nitrite content and induced nitric oxide synthase (iNOS) level in the macrophage cells. RESULTS: SPEE gave rise to a significant inhibition in chick chorioallantoic membrane angiogenesis. SPEE exhibited anti-inflammatory activities in vascular permeability and air-pouch models. In the air-pouch model, SPEE was able to diminish exudate volume, number of polymorphonulcear leukocytes and nitrite content. SPEE also displayed anti-nociceptive activity in the writhing response model in mice. SPEE significantly decreased nitrite content and induced nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells, while it could not modulate cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 levels in the stimulated phages. SPEE decreased reactive oxygen species (ROS) level in the stimulated macrophages. CONCLUSION: The ethanol extract (SPEE) of Salvia plebeia possesses anti-inflammatory and related anti-angiogenic, anti-nociceptive and antioxidant activities, which offers partial support to its folkloric use.

Anti-angiogenic, antinociceptive and anti-inflammatory activities of Lonicera japonica extract.

This study aimed to elucidate some novel pharmacological activities of Lonicera japonica (Caprifoliaceae), which is widely used in Oriental folk medicine. The ethanolic extract of L. japonica (LJ) dose dependently inhibited chick chorioallantoic membrane angiogenesis. The antinociceptive activity of LJ was assessed using the acetic acid-induced constriction model in mice. LJ showed anti-inflammatory activity in two in-vivo models: the vascular permeability and air pouch models. LJ suppressed the production of nitric oxide via down-regulation of inducible nitric oxide synthase in lipopolysaccharide-stimulated RAW264.7 macrophage cells. However, LJ was unable to suppress induction of cyclooxygenase-2 in the stimulated macrophage cells. LJ decreased the reactive oxygen species level in the stimulated macrophage cells. In brief, the flowers of L. japonica possess potent anti-angiogenic and antinociceptive activities, in addition to anti-inflammatory activity, which partly supports its therapeutic efficacy.

Anti-inflammatory, anti-angiogenic and anti-nociceptive activities of Sedum sarmentosum extract.

This study aimed to assess some novel pharmacological activities of Sedum sarmentosum Bunge, a perennial herb widely distributed on the mountain slopes in Oriental countries and traditionally used for the treatment of certain inflammatory diseases. Sedum sarmentosum was extracted with absolute methanol to generate the methanol extract (SS). SS exhibited a significant inhibitory activity in the chick embryo chorioallantoic membrane (CAM) angiogenesis in a dose-dependent manner (IC(50)=2.29 microg/egg). The anti-nociceptive activity of SS was demonstrated using acetic acid-induced writhing model in mice. SS reduced the levels of anti-inflammatory markers, such as volume of exudates, number of polymorphonuclear leukocytes and nitrite content, in the air pouch model. It dose-dependently exhibited an inhibitory activity in the acetic acid-induced vascular permeability in mice. It suppressed production of nitric oxide in the lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Additionally, it suppressed induction of inducible nitric oxide synthase (iNOS) in the activated macrophages. In brief, the results provide some pharmacological basis for the therapeutic use of Sedum sarmentosum.

Anti-angiogenic activity of the methanol extract and its fractions of Ulmus davidiana var. japonica.

This study aimed to elucidate anti-angiogenic activity of Ulmus davidiana var. japonica that has been widely used in folk medicine. The methanol extract (UDE) of Ulmus davidiana var. japonica concentration-dependently displayed a strong inhibition in the chick chorioallantoic membrane (CAM) angiogenesis. The n-butanol fraction of UDE and subsequent 30% MeOH subfraction were identified to be most responsible for the anti-angiogenic activity.

Reduced oxidative stress promotes NF-kappaB-mediated neuroprotective gene expression after transient focal cerebral ischemia: lymphocytotrophic cytokines and antiapoptotic factors.

Nuclear factor-kappa B (NF-kappaB) is activated by oxidative stress such as that induced by transient focal cerebral ischemia (tFCI). Whether NF-kappaB has a role in cell survival or death in stroke is a matter of debate. We proposed that the status of oxidative stress may determine its role in cell death or survival after focal ischemia. To characterize the coordinated expression of genes in NF-kappaB signaling after mild cerebral ischemia, we investigated the temporal profile of a NF-kappaB-pathway-focused DNA array after 30 mins of tFCI in wild-type (WT) mice and human copper/zinc-superoxide dismutase transgenic (SOD1 Tg) mice that had a significantly reduced level of superoxide. Differentially expressed genes among 96 NF-kappaB-related genes were further confirmed and compared in the WT and SOD1 Tg mice using quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. Persistent upregulation of NF-kappaB seen at 7 days in the WT mice was decreased in the SOD1 Tg mice. Lymphocytotrophic cytokine genes such as interleukin-2, interleukin-12, and interferon-alpha1 were increased in the SOD1 Tg mice compared with the WT mice after tFCI. In addition, antiapoptosis factors bcl-2 and tumor necrosis factor receptor-associated factor 1 rapidly increased in the SOD1 Tg mice compared with the WT mice. This study indicates that reduced oxidative stress by SOD1 overexpression increased NF-kappaB-related rapid defenses, such as immune response and antiapoptosis factors, and prevented brain damage after tFCI-induced oxidative stress.

Anti-inflammatory and related pharmacological activities of the n-BuOH subfraction of mushroom Phellinus linteus.

This study aimed to elucidate the anti-inflammatory and related activities of mushroom Phellinus linteus. The results show that the EtOH extract of Phellinus linteus (PLE) dose-dependently inhibited the mouse ear edema induced by croton oil. Among PLE subfractions, the n-BuOH subfraction showed highest anti-inflammatory activity in croton oil-induced ear edema test. The n-BuOH subfraction also showed highest inhibitory activity on the chick embryo chorioallantoic membrane (CAM) angiogenesis in a dose-dependent manner. PLE could significantly reduce the number of writhing induced by acetic acid in mice, indicating that PLE possesses potent antinociceptive effect mediated by its anti-inflammatory activity. Mycelial extract of six different Phellinus strains were found to contain anti-angiogenic activity in the CAM assay. These results suggest that Phellinus linteus has anti-inflammatory and antinociceptive activities, in addition to its anti-angiogenic activity.