Miroestrol, a phytoestrogen from Pueraria mirifica, improves the antioxidation state in the livers and uteri of β-naphthoflavone-treated mice

Oxidative stress is involved in the progression of several diseases such as diabetes, hypertension, and age-related diseases. Miroestrol (MR) is a potent phytoestrogen from the tuberous root of Pueraria mirifica, a plant used in traditional Thai medicine that is claimed to have rejuvenating effects. In this study, the effects of MR on the antioxidation system, including anti-lipid peroxidation; on the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase; and on glutathione content in the livers and uteri of β-naphthoflavone (BNF)-treated mice were determined. BNF-treated mice are a model of procarcinogen-exposed mice. The results showed that MR improved the antioxidant activities of SOD and CAT in the livers and uteri of both normal and BNF-treated mice, while estradiol (E2) increased SOD activity in the uteri of normal mice and CAT activity in the livers of both normal and BNF-treated mice. In the liver, MR increased the levels of several forms of glutathione, whereas in the uteri E2 and MR reduced the level of lipid peroxidation by decreasing the level of malondialdehyde. Therefore, the use of MR as an alternative hormone replacement therapy might be beneficial due to its ability to improve antioxidation systems.     

Xanthohumol attenuates tumour cell-mediated breaching of the lymphendothelial barrier and prevents intravasation and metastasis

Health beneficial effects of xanthohumol have been reported, and basic research provided evidence for anti-cancer effects. Furthermore, xanthohumol was shown to inhibit the migration of endothelial cells. Therefore, this study investigated the anti-metastatic potential of xanthohumol. MCF-7 breast cancer spheroids which are placed on lymphendothelial cells (LECs) induce “circular chemorepellent-induced defects” (CCIDs) in the LEC monolayer resembling gates for intravasating tumour bulks at an early step of lymph node colonisation. NF-κB reporter-, EROD-, SELE-, 12(S)-HETE- and adhesion assays were performed to investigate the anti-metastatic properties of xanthohumol. Western blot analyses were used to elucidate the mechanisms inhibiting CCID formation. Xanthohumol inhibited the activity of CYP, SELE and NF-kB and consequently, the formation of CCIDs at low micromolar concentrations. More specifically, xanthohumol affected ICAM-1 expression and adherence of MCF-7 cells to LECs, which is a prerequisite for CCID formation. Furthermore, markers of epithelial-to-mesenchymal transition (EMT) and of cell mobility such as paxillin, MCL2 and S100A4 were suppressed by xanthohumol. Xanthohumol attenuated tumour cell-mediated defects at the lymphendothelial barrier and inhibited EMT-like effects thereby providing a mechanistic explanation for the anti-intravasative/anti-metastatic properties of xanthohumol.     

Climbing fibre modification of cerebellar Purkinje cell responses to parallel fibre inputs

Electrical stimulation has been used to activate, separately and independently, the climbing fibre and parallel fibre inputs to Purkinje cells of the cat cerebellum. The effects of climbing fibre impulses on Purkinje cell discharges evoked by parallel fibre stimulation has been examined. It was found that impulses in the climbing fibre could block or reduce, in a graded manner, the Purkinje cell response to parallel fibre inputs. It has previously been shown that climbing fibre inputs do not suppress the antidromic spike response of the Purkinje cell to cerebellar white matter stimulation. This suggests that the climbing fibre impulses modify the Purkinje cell response to parallel fibre inputs by reducing the excitatory action of parallel fibre impulses on the Purkinje cell.     

Thalassemia intermedia associated with complex interaction of Hb Beijing [alpha16(A14)Lys-->Asn] and Hb E [beta26(B8)Glu-->Lys] with a deletional alpha-thalassemia-1 in a Thai family

A Thai family with a complex thalassemia syndrome caused by alpha- and beta-globin defects is described. The proband was a 14-year-old boy who had chronic hypochromic microcytic anemia. Hemoglobin (Hb) and DNA analyses demonstrated that he carried Hb Beijing [alpha16(A14)Lys-->Asn], Hb E [beta26(B8)Glu-->Lys] and alpha-thalassemia-1 (alpha-thal-1). Interaction of the alphaBeijing with the betaE globin chains in the proband leads to a new Hb variant, namely Hb E Beijing with different characteristics to both Hb E and Hb Beijing. Family studies showed that his father carried Hb Beijing and Hb E, whereas his mother was a simple alpha-thal-1 carrier. The genotype-phenotype relationship observed in this Thai family with complex hemoglobinopathies is presented and a simple DNA assay based on allele specific polymerase chain reaction (ASPCR) for detection of Hb Beijing is described.     

Regulation of mouse hepatic CYP2D9 mRNA expression by growth and adrenal hormones

The constitutive expression of CYP2D9 is sexually dimorphic, namely, strong in males, but diminutive in females. Repetition of mimic growth hormone (GH) secretion pattern impressively returned the mRNA expression level to that in intact mice: the GH secretion pattern's regulation of CYP2D9 mRNA expression has been predominantly disrupted by exogenous GH-administration. The extensive decline of CYP2D9 mRNA expression becoming a sexually non-specific P450 in 9-week-old male mice exposed as neonates to monosodium L-glutamate (MSG) suggested that the male GH secretion pattern is a key to the regulation of male-specific CYP2D9 mRNA expression in adult mice. Dexamethasone (Dex) showed possibility to induce CYP2D9 mRNA expression in adult MSG-neonatally treated mice of either sex. However, the antagonism was observed by co-administration of Dex and GH in the males. Dex-administration in adrenalectomized mice significantly elevated CYP2D9 mRNA expression levels. These findings suggest that an adrenal hormone participates in the regulatory mechanism of CYP2D9 mRNA expression in association with GH.     

Vobasinyl-iboga bisindole alkaloids, potent acetylcholinesterase inhibitors from Tabernaemontana divaricata root

The roots of the Thai medicinal plant, Tabernaemontana divaricata (L.) R. Br. ex Roem. & Schult., were investigated for their content of acetylcholinesterase inhibitors. Bioassay-guided fractionation using the Ellman colorimetric method led to the isolation of two bisindole alkaloids, 19,20-dihydrotabernamine and 19,20-dihydroervahanine A. The compounds showed higher inhibitory activity on acetylcholinesterase in comparison with galanthamine, a well-known acetylcholinesterase inhibitor. The inhibitory activity of 19,20-dihydroervahanine A was proved to be specific, reversible and competitive. During the separation process, two inactive bisindole alkaloids, conodurine and tabernaelegantine A, were also isolated. The data suggest that the substitutions at the carbons 11', 12' and 16' might affect the acetylcholinesterase inhibitory activity.