Soy isoflavones inducing overt hypothyroidism in a patient with chronic lymphocytic thyroiditis: a case report.

BACKGROUND: Many people have thyroid conditions that make them susceptible to hypothyroidism. If the foods they eat may interfere with the production of thyroid hormone, which can lead to development of serious hypothyroidism. The danger of health drinks should always be noted. CASE PRESENTATION: A 72-year-old Japanese woman was previously diagnosed with chronic lymphocytic thyroiditis caused by a goiter and had an elevated thyroid-stimulating hormone level (6.56 µIU/ml), a high anti-thyroid peroxidase antibody level (>600 IU/ml), and a high antithyroglobulin level (> 4000 IU/ml) but normal levels of free triiodothyronine (3.08 pg/ml) and thyroxine (1.18 ng/ml). She presented to our hospital with sudden-onset general malaise, edema, and hoarseness with an elevated thyroid-stimulating hormone (373.3 µIU/ml) level and very low triiodothyronine (< 0.26 pg/ml) and thyroxine (0.10 ng/ml) levels. It was determined that for 6 months she had been consuming a processed, solved health drink ("barley young leaf") in amounts of 9 g/day, which included soybean and kale powder extract. Hypothyroidism might be affected by ingredients of health drinks. She discontinued consumption of the health drink immediately and began taking 12.5 µg of levothyroxine. The amount of levothyroxine was gradually increased every 3 days up to 100 µg. At day 61, her thyroid-stimulating hormone level had decreased (6.12 µIU/ml), her free triiodothyronine (2.69 pg/ml) and thyroxine (1.56 ng/ml) levels had increased, and her general condition was improved. Among risky foods lowering thyroid function, some experimental studies have revealed that isoflavones reduce thyroid function. Therefore, we measured the presence of isoflavones in the patient's frozen serum with thin-layer chromatography. After she discontinued consumption of the health drink, two components quickly disappeared, and the other three components gradually decreased. On the basis of developing solvent composition and a positive ferric chloride reaction in thin-layer chromatography experiment, the five ingredients that disappeared or decreased were highly suspected to be soy isoflavones. CONCLUSIONS: This case emphasizes that consuming health drinks that include soy isoflavone powder extracts can lead to severe hypothyroidism.

Structural Revision of a Naphthodipyranodione from Gentian Root and its Degradation Pathway from Gentiopicroside.

Based on NOE experiments, the structure of naphthodipyranodione from Gentianaceae plants was revised to 1,2-dihydro-4H,6H,8H-naphto[1,2-d:4,5- c'd']dipyrano-4,8-dione. Naphthodipyranodione was assumed to be formed by the degradation of gentiopicroside by enzymatic hydrolysis at low water -concentration. The degradation pathway was a unique domino-reaction triggered by enzymatic hydrolysis. Naphthodipyranodione may become an index compound for the drying and/or fermenting procedure of Gentian root.

Linkage of E2F1 transcriptional network and cell proliferation with respiratory chain activity in breast cancer cells.

Mitochondria are multifunctional organelles; they have been implicated in various aspects of tumorigenesis. In this study, we investigated a novel role of the basal electron transport chain (ETC) activity in cell proliferation by inhibiting mitochondrial replication and transcription (mtR/T) using pharmacological and genetic interventions, which depleted mitochondrial DNA/RNA, thereby inducing ETC deficiency. Interestingly, mtR/T inhibition did not decrease ATP levels despite deficiency in ETC activity in different cell types, including MDA-MB-231 breast cancer cells, but it severely impeded cell cycle progression, specifically progression during G2 and/or M phases in the cancer cells. Under these conditions, the expression of a group of cell cycle regulators was downregulated without affecting the growth signaling pathway. Further analysis suggested that the transcriptional network organized by E2F1 was significantly affected because of the downregulation of E2F1 in response to ETC deficiency, which eventually resulted in the suppression of cell proliferation. Thus, in this study, the E2F1-mediated ETC-dependent mechanism has emerged as the regulatory mechanism of cell cycle progression. In addition to E2F1, FOXM1 and BMYB were also downregulated, which contributed specifically to the defects in G2 and/or M phase progression. Thus, ETC-deficient cancer cells lost their growing ability, including their tumorigenic potential in vivo. ETC deficiency abolished the production of reactive oxygen species (ROS) from the mitochondria and a mitochondria-targeted antioxidant mimicked the deficiency, thereby suggesting that ETC activity signaled through ROS production. In conclusion, this novel coupling between ETC activity and cell cycle progression may be an important mechanism for coordinating cell proliferation and metabolism.

Novel phenolic glycosides, adenophorasides A-E, from Adenophora roots.

Five novel phenolic glycosides, adenophorasides A (1), B (2), C (3), D (4), and E (5), were isolated from commercial Adenophora roots, together with vanilloloside (6), 3,4-dimethoxybenzyl alcohol 7-O-beta-D: -glucopyranoside (7), and lobetyolin (8). The structures of the new compounds (1-5) were characterized as 4-hydroxy-3-methoxyphenylacetonitrile 4-O-beta-D: -glucopyranoside (1), 4-hydroxy-3-methoxyphenylacetonitrile 4-O-beta-D: -glucopyranosyl-(1-->6)-beta-D: -glucopyranoside (2), 4-hydroxy-3-methoxyphenylacetonitrile 4-O-alpha-L: -rhamnopyranosyl-(1-->6)-beta-D: -glucopyranoside (3), 4-hydroxyphenylacetonitrile 4-O-beta-D: -glucopyranosyl-(1-->6)-beta-D: -glucopyranoside (4), and 4-hydroxy-3-methoxybenzyl alcohol 4-O-beta-D: -glucopyranosyl-(1-->6)-beta-D: -glucopyranoside (5), respectively, by means of spectroscopic and chemical analyses.

Achyranthoside H methyl ester, a novel oleanolic acid saponin derivative from Achyranthes fauriei roots, induces apoptosis in human breast cancer MCF-7 and MDA-MB-453 cells via a caspase activation pathway.

Achyranthoside H methyl ester (AH-Me) is an oleanolic acid saponin derivative isolated from the roots of Achyranthes fauriei through diazomethane treatment. AH-Me exhibited significant cytotoxicity against human breast cancer MCF-7 and MDA-MB-453 cells, with respective ID(50) values of 4.0 and 6.5 muM: in the MTT assay. AH-Me is a unique saponin containing three methoxycarbonyl groups in the sugar moiety linked to the C-3 position of oleanolic acid. The demethylation of these methoxycarbonyl groups by alkaline hydrolysis caused a marked reduction of the cytotoxicity of AH-Me, suggesting that the methoxycarbonyl groups of AH-Me are key groups for the acquisition of cytotoxicity against human cancer cells. The staining of cancer cells with 4',6'-diamidino-2-phenylindole (DAPI) showed that the population of cells with altered nuclear morphology, for example chromatin condensation and fragmentation, increased markedly after AH-Me treatment. Exposure of MCF-7 and MDA-MB-453 cells to AH-Me resulted in a dose-dependent and time-dependent increase in the sub-G1 population, and in the cleavage of poly-ADP-ribose polymerase (PARP) followed by the formation of an 89 kD peptide. Pretreatment of the cells with the pan-caspase inhibitor z-VAD-fmk abolished the cleavage of PARP by AH-Me treatment and suppressed the antiproliferative effect of AH-Me on tumor cell growth. These results together led to the suggestion that AH-Me induces apoptosis via the caspase activation pathway in human breast cancer cells, and apoptosis is the major mode of the cytotoxic effect triggered by AH-Me.

Two new glucuronide saponins, Achyranthosides G and H, from Achyranthes fauriei root.

Two oleanolic acid saponins named achyranthosides G (1) and H (2) were newly isolated from Achyranthes fauriei root as methyl esters in addition to methyl esters of achyranthosides A - F and five oleanolic acid glucuronides (chikusetsusaponins IVa, V, 28-deglucosyl chikusetsusaponin V, pseudoginsenoside RT(1), and oleanolic acid 3-O-beta-D-glucuronopyranoside) as well as oleanolic acid 28-O-beta-D-glucopyranoside, beta-ecdysterone, and polypodine B. Their structures were characterized as follows on the basis of the chemical and spectroscopic evidences.

Anxiolytic effect of Gardeniae Fructus-extract containing active ingredient from Kamishoyosan (KSS), a Japanese traditional Kampo medicine.

Kamishoyosan (KSS), a Kampo formula used to treat menopausal psychotic syndromes in women, consists of ten crude herbal drugs. The anxiolytic effect of KSS was investigated by the social interaction (SI) test using mice, and whether the effect of KSS was due to the stimulating and/or sedating effects was examined by the open field locomotion test. Furthermore, the present study examined the effect of individual crude drugs in KSS by the SI test to clarify its active components. Oral administration of KSS increased the total SI time in a dose-dependent manner (50--200 mg/kg), but this effect was not observed over a dose of 300 mg/kg. On the other hand, there were no significant changes observed for the open field locomotion test. These results suggest that the appearance of KSS-induced SI behavior is due to an anxiolytic effect. The unaltered results of the open field test indicated that KSS was neither a stimulant nor sedative. To identify the essential herbs in KSS, the effects of "the component herbs in KSS" and "KSS minus one component herb" using the SI test were examined. An increase in the SI time was observed for hot water extracts of Menthae herba and Gardeniae Fructus, the same as for the KSS treatment. On the other hand the effect of KSS on the SI time was reduced to the control level for KSS minus Gardeniae Fructus, KSS minus Paeoniae Radix, KSS minus Glycyrrhizae Radix and KSS minus Hoelen. Oral administration of Gardeniae Fructus-extract or its common constituent, geniposide increased the SI time in a dose-dependent manner. These results indicate that Gardeniae Fructus and geniposide play a role in the anxiolytic effect of KSS.

Pharmacognostic studies on ginger and related drugs--part 1: five sulfonated compounds from Zingiberis rhizome (Shokyo).

Five sulfonated compounds, namely 4-gingesulfonic acid and shogasulfonic acids A, B, C and D, were isolated together with seven known compounds including 6-gingesulfonic acid from Zingiberis rhizome (Japanese name: Shokyo) made out of ginger. Their structures were characterized by means of spectroscopic analysis.