The sex-dependent differences in serum levels of complement components have been reported concerning C4 (1), C5 (2, 3), C6 (3), C4-binding protein (C4-bp) ~ (4), and sex-limited protein (Slp) (5) in the mouse complement system. The serum levels of these components in adult mice are always higher in males than in females within each inbred strain and are strongly under hormonal control. With regard to C5, young male and female mice have the same serum levels of C5, and the levels increase with age, most markedly in males and less in females (2). After sexual maturity, the ratio of C5 in serum of males vs. females is greater than 2:1. Injection of testosterone increases the levels of C5 in both males and females, whereas castration or injection of estradiol decreases the levels in males to those in females (3, 6). These reports, however, reveal only the quantitative difference but not the qualitative one.During attempts to detect polymorphism of mouse C5 by isoelectric focusing (IEF), we found the difference in electrophoretic patterns of C5 between males and females. Females of all strains tested had one C5 band, but males had two C5 bands, one of which was identical to the female band. The expression of the other C5 band in males was shown to be influenced by sex hormones, indicating that this C5 is actually responsible for the sex-dependent difference.
Edaravone increases antioxidant potency and reduces seizure susceptibility in EL mice, making it a promising novel antiepileptic agent.
It has been reported that oxidative stress is closely related to the development of seizure susceptibility. To investigate if the redox condition shifts to an oxidized state during ictogenesis in epilepsy-prone EL mice, which shows the first seizure episode at 8 to 10 weeks of age, changes in the activities in the hippocampus or parietal cortex of reduced glutathione (GSH), oxidized glutathione, glutathione peroxidase, and nitric oxide were examined. This study showed that GSH activities were lower and oxidized glutathione activities were higher in EL mice than in ddY mice, mother strain control of EL, even though glutathione peroxidase activities were higher in EL mice between the ages of 3 and 8 weeks. Similarly, nitric oxide activities were higher in EL mice. The study also showed that GSH-mediated scavenger potency was lower not only in the hippocampus but also in the parietal cortex of EL mice at an early age. This reduction in GSH-mediated scavenger potency may be related to the acquisition of epileptogenesis in both the primary (parietal cortex) and secondary (hippocampus) epileptogenic centers of EL mice.
Background and objective: Chrysanthemum flowers are consumed as fresh condiments, herbal teas, and processed foods in Japan and Taiwan. They contain luteolin as a major polyphenol and are traditionally used for eye care. We previously demonstrated that the ingestion of Chrysanthemum flower extract (CFE) for 1 month reduced serum uric acid levels. However, the findings obtained were considered to be biased because the study was performed by a CFE manufacturer. Therefore, we herein conducted a clinical trial on CFE on a larger scale and examined its effects on purine base absorption from the intestines, which represents an effective approach for reducing serum uric acid levels. Methods: Both studies were performed as randomized, double-blind, placebo-controlled trials and CFE (100 mg) containing 1 mg of luteolin was used as the active sample. We enrolled 44 healthy Japanese men and women with 6.0 to 7.9 mg/dL serum uric acid. All subjects were randomly allocated to an active group (n=22) or placebo group (n=22) using a computerized random number generator. In the purine base absorption study, CFE was ingested with a purine base-rich diet and serum uric acid levels were measured chronologically. In the 12-week consecutive ingestion study, CFE or placebo was administered between January and April 2021. Serum uric acid levels after 12 weeks were assessed as the primary outcome, and uric acid were measured before and after 4 weeks of the intervention as secondary outcomes. Blood, urine and body parameters were examined to evaluate the safety of CFE. Results: Thirty-nine subjects completed the trial, and the per protocol set comprised 18 and 21 subjects in the active and placebo groups, respectively. In the single dosing study of CFE on subjects loaded by the purine base-rich diet, no significant changes were observed between the CFE and placebo groups. On the other hand, in the 12-week ingestion study, serum uric acid levels were significantly lower in the CFE group than in the placebo group. Laboratory tests revealed no abnormalities to suggest any side effects of CFE.Conclusions: CFE (100 mg/day) containing 1 mg of luteolin reduced serum uric acid levels. CFE may be beneficial for improving hyperurichemia. Trial Registration: UMIN-CTR: UMIN000042327Foundation: The present study was funded by Oryza Oil & Fat Chemical Co., Ltd. Keywords: Chrysanthemum, luteolin, uric acid, purine base
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