Essential oils are generally not only antibiotic and anticarcinogenic, 1,2) but also have a sedative effect on stress. It has been shown that these essential oils contain ketone, terpene, and phenolic ether for sedation.3) Although essential oils have been regarded as useful sedatives, 4) there is little information on the antimicrobial or antifungal activities of essential oils extracted from coniferous trees. Essential oils with antimicrobial properties from medicinal as well as other edible plants have been recognized since antiquity.2) In addition, essential oils are used as food flavoring agents, and have a broad spectrum of in vitro antimicrobial activities attributed to the high content of phenolic derivatives. 5) More recently, plant extracts have been developed and proposed for use in foods as natural antioxidants. 6) In the present study, we investigated the antimicrobial and antifungal activities of several essential oils extracted from the coniferous trees Pinus densiflora, Pinus koraiensis, and Chamaecyparis obtusa against bacteria and fungi that commonly cause foot rot and other diseases. The essential oils were quantified using gas chromatography (GC) and identified in gas chromatography-mass spectrometric (GC-MS) analysis. In addition, the antibacterial effects against grampositive and gram-negative bacteria and antifungal effects against fungi were assayed using essential oils distilled from the needles of coniferous trees. MATERIALS AND METHODS Essential Oil ExtractionThe needles of the Japanese red pine (P. densiflora), Korean pine (P. koraiensis), and Japanese cypress (C. obtusa) were collected at the Reforestation Experiment Site of Chungbu Forest Experiment Station, Gyeonggi province, Korea. The essential oil from freshly cut needles of each species was obtained by steam distillation using a manufactured apparatus with a condenser. Distillation continued for 2-3 h at 100°C, and the volatile compounds containing the water-soluble fraction were allowed to settle for 20 min. The essential oil layer was separated and finally purified through a microfiltering and dehydration process.Measurement of Refractive Index The refractive index of chemical compounds is considered important because it indicates characteristic physical properties. We determined the index of the oils using an Abbe refractometer equipped with a sodium lamp (Bausch & Lomb, GD8804, U.S.A.).Quantification and Identification Each essential oil compound was quantified using a gas chromatograph (GC, Shimadzu GC-14A, Japan) equipped with a Shimadzu CPB-20 capillary column (0.2 mm inner diameterϫ50 m length). First, the calibration curves for several standard essential oils were obtained, and the calibration equation of each compound was used for quantification. GC analysis was carried out using helium carrier gas with an FID detector, and the injection and detection temperatures were 150 and 200°C, respectively. The oven temperature was increased from 50 to 200°C at intervals of 2°C/min over 75 min. Some other essential oils were id...

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Estrogen-related receptor α (ERRα) is a key regulator of mitochondrial function and metabolism essential for energy-driven cellular processes in both normal and cancer cells. ERRα has also been shown to mediate bone-derived macrophage activation by proinflammatory cytokines. However, the role of ERRα in cancer in which inflammation acts as a tumor promoter has yet to be investigated. Herein we show that global loss of ERRα accelerates the development of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Biochemical and metabolomics studies revealed that loss of ERRα promotes hepatocyte necrosis over apoptosis in response to DEN due to a deficiency in energy production. We further show that increased hepatocyte death and associated compensatory proliferation observed in DEN-injured ERRα-null livers is concomitant with increased nuclear factor κB (NF-κB)-dependent transcriptional control of cytokine expression in Kupffer cells. In particular, we demonstrate that loss of ERRα-dependent regulation of the NF-κB inhibitor IκBα leads to enhanced NF-κB activity and cytokine gene activation. Our work thus shows that global loss of ERRα activity promotes hepatocellular carcinoma by independent but synergistic mechanisms in hepatocytes and Kupffer cells, implying that pharmacological manipulation of ERRα activity may have a significant clinical impact on carcinogen-induced cancers. nuclear receptor | liver cancer H epatocellular carcinoma (HCC) is a major cause of cancer deaths worldwide, particularly in countries with high risk factors that include greater exposure to aflatoxin B1, a fungal contaminant in dietary supplies, and to the hepatitis B and C viruses (1). HCC has also been linked with exposure to toxic chemicals such as polycyclic aromatic hydrocarbons and nitrosamines and is more frequent in individuals with cirrhosis associated with chronic inflammation (2, 3). HCC that closely resembles the human disease can be induced in mice with a single postnatal injection of the tumor initiator diethylnitrosamine (DEN) (4). In this model, DNA damage induced by the carcinogen promotes cell death, which leads to an inflammatory response by resident Kupffer cells that further stimulates tumor development fueled by compensatory proliferation of hepatocytes (5). It has been shown that nuclear factor κB (NF-κB) signaling, a critical intracellular pathway in the regulation of inflammation, plays a complex role in DEN-induced hepatocarcinogenesis, displaying antitumorigenic and procarcinogenic activity in hepatocytes and Kupffer cells, respectively. In hepatocytes, NF-κB signaling protects against cell death, thus attenuating compensatory cell proliferation, while promoting the inflammatory response of Kupffer cells and production of hepatomitogens (5).Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that plays a central role in the control of energy metabolism (6). As a transcription factor, ERRα directly regulates the expression of genes required for mitochondrial biogenesis and function, including genes...

Non-alcoholic fatty liver disease (NAFLD) results from triglyceride accumulation within the liver and some of them advances to non-alcoholic steatohepatitis (NASH). It is important to note that in NAFLD development, hepatic de novo lipogenesis (DNL) derives from excess carbohydrates and fats under a condition of excess energy through β-oxidation. As a main regulator for DNL, sterol regulatory element-binding protein 1 (Srebp-1) forms complex with progesterone receptor membrane component 1 (Pgrmc1). To investigate whether Pgrmc1 may have a notable effect on DNL via SREBP-1 activation, we generated Pgrmc1 knockout (KO) mice and fed a high fat diet for one month. High-fat-fed Pgrmc1 KO mice showed a substantial increase in levels of hepatic TG accumulation, and they were predisposed to NAFLD when compared to WT mice. Loss of Pgrmc1 increased mature SREBP-1 protein level, suggesting that induction of hepatic steatosis in Pgrmc1 KO mice might be triggered by de novo lipogenesis. Moreover, Pgrmc1 KO mice were also more vulnerable to early stage of NASH, showing high levels of alanine aminotransferase, obesity-linked pro-inflammatory cytokines, and fibrosis markers. This is interesting because Pgrmc1 involves with the first step in regulating the hepatic de novo lipogenesis under an excess energy condition.

Polycystic ovarian syndrome (PCOS) is an endocrine, metabolic, and systemic disease. It is mainly characterized by hyperandrogenism, oligomenorrhea, and high levels of luteinizing hormone (LH). There is no obvious therapy for PCOS, so patients have received symptomatic therapy. Welsh onion (Allium fistulosum) is well-known in Asian countries for its usage in food ingredients and traditional medicines. It is also studied for its many effects. These include activation of immune responses, antihypertensive effects, and antioxidant effects. Using letrozole-induced PCOS rats, we focused on herbal therapy using extract of Allium fistulosum (AF; A. fistulosum) roots to improve ovarian functions. As a nonsteroidal aromatase inhibitor, letrozole blocks conversion of testosterone to estrogen and subsequently induces PCOS phenomenon. We divided six-week-old female rats into four groups, including control, letrozole, letrozole + AF extract, and temporary letrozole groups. In our study, treatment with AF extract shows a low plasma LH/FSH ratio, and reveals high estrogen levels, ovarian morphology, folliculogenesis-related genes, and aromatase expression under PCOS mimic conditions. We concluded that AF extract administration influenced aromatase production, enhanced the estrogen steroid synthesis, and consequently restored the estrogenic feedback mechanism on the pituitary-ovary system.

Abstract.Phthalates are suspected to disrupt the endocrine system, especially through estrogenic effects. In the present study, we investigated the effects of various phthalates and compared them with those of estrogenic compounds that disrupt the female reproductive system. To assess the effects of these phthalates, alteration of the Calbindin-D9k (CaBP-9k) gene was measured as a biomarker because rat CaBP-9k gene carries an estrogen response element (ERE) which is involved in estrogen responsiveness of the gene during the estrous cycle. In this study, phthalates were tested for estrogenic properties in in vitro and in vivo models. First, the E-Screen assay was used to measure the proliferation of MCF-7 cells, a human breast cancer cell line. Treatments with 17β-estradiol (E2; 9-fold) and 17α-estradiol (EE; 9-fold) induced MCF-7 cell proliferation at concentrations of 10 -9 M. Phthalates induced an increase in MCF-7 proliferation at concentration of 10 -6 M up to 10 -4 M. Nbutyl benzyl phthalate (BBP; 6-fold vs. vehicle), dicyclohexyl phthalate (DCHP; 8-fold), 2-ethylhexyl phthalate (DEHP; 6-fold) and di-n-butyl phthalate (DBP; 7-fold) at the concentration of 10 -4 M induced in an increase in MCF-7 proliferation after 6 d of treatment compared to vehicle. However, significant increase in MCF-7 proliferation was induced by diethyl phthalate (DEP). Second, we investigated the expression of CaBP-9k in the uterus of immature rats after oral treatment with BBP, DCHP, DEHP, DBP or DBP (600 mg/kg per day) in this in vivo model, because the immature rat model is highly sensitive to exposure to estrogenic chemicals. None of the phthalates induced the expression of CaBP9k mRNA and its protein in the neonatal uterus as analysed by Northern and Western blot analyses, respectively. Although phthalates induced an increase in MCF-7 cell proliferation by an estrogenic effect, they could not induce CaBP-9k expression in the in vivo system, suggesting that the assays of estrogenic effects of various phthalates conducted in vitro and in vivo expression of CaBP-9k may produce conflicting results.

Methylene blue (MB), which has antioxidant, anti-inflammatory, neuroprotective, and mitochondria protective effects, has been widely used as a dye and medication. However, the effect of MB on inflammasome activation has not yet been studied. Inflammasomes are multi-protein complexes that induce maturation of interleukins (ILs)-1β and -18 as well as caspase-1-mediated cell death, known as pyroptosis. Dysregulation of inflammasomes causes several diseases such as type 2 diabetes, Alzheimer’s disease, and gout. In this study, we assess the effect of MB on inflammasome activation in macrophages. As the result, MB attenuated activation of canonical inflammasomes such as NLRP3, NLRC4, and AIM2 as well as non-canonical inflammasome activation. In addition, MB inhibited upstream signals such as inflammasome assembly, phagocytosis, and gene expression of inflammasome components via inhibition of NF-κB signaling. Furthermore, MB reduced the activity of caspase-1. The anti-inflammasome properties of MB were further confirmed in mice models. Thus, we suggest that MB is a broad-spectrum anti-inflammasome candidate molecule.

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