Senescence marker protein-30 (SMP30) is a redox-responsive protein involved in the biosynthesis of ascorbic acid that has been established to have cytoprotective effects in rodents. Previously, we reported that SMP30 is released into extracellular vesicle (EV) fractions in osteogenic disorder Shionogi (ODS) model rats. In the present study, we examined changes in hepatic SMP30 expression patterns and EV-associated SMP30 levels in acetaminophen (APAP)-induced acute liver injury. APAP administration was found to significantly reduce hepatic SMP30 expression at the mRNA and protein levels, whereas we detected marked SMP30 elevations in EV fractions. In addition, APAP treatment was observed to induce oxidative stress–associated liver injury, as evidenced by hepatomegaly, a depletion of hepatic total glutathione, increases in malondialdehyde levels, and an elevated AST and ALT activities. Although we detected an approximate 1.45-fold increase in serum ascorbic acid levels and modest elevation in hepatic ascorbic acid levels, hepatic SMP30 expression was not restored. This indicates that regulation is independent of ascorbic acid availability. Furthermore, APAP markedly induced the phosphorylation of ERK1/2 and STAT3. Rather than a passive leakage from necrotic hepatocytes, the reciprocal reduction in hepatic SMP30 and increase in EV-associated SMP30 are considered to be indicative of a signaling-dependent selective release process. These findings provide the first evidence linking EV-associated SMP30 expression with the serum ascorbic acid levels in APAP-induced acute liver injury, and contribute new insights into redox-responsive protein trafficking under conditions of acute hepatic injury.

Kaempferia parviflora has long been used in traditional medicine because of its various health benefits, including the promotion of longevity and vitality. SIRTMAX^®, a rhizome extract of K. parviflora standardized for polymethoxyflavones, is widely used as an ingredient in functional foods and dietary supplements. However, comprehensive safety data generated in accordance with internationally recognized regulatory guidelines remain limited. To comprehensively evaluate the safety of SIRTMAX^®, we conducted a battery of genotoxicity and oral toxicity studies in accordance with Good Laboratory Practice (GLP) and Organisation for Economic Co-operation and Development (OECD) guidelines. Genotoxicity was assessed using a bacterial reverse mutation test, in vitro chromosomal aberration test, and in vivo mammalian erythrocyte micronucleus test. Oral toxicity was evaluated in Sprague-Dawley rats using a 90-day repeated-dose oral toxicity study. SIRTMAX^® did not exhibit genotoxic effects in any of the assays conducted. In the 90-day repeated-dose oral toxicity study, daily oral administration of SIRTMAX^® at doses up to 1000 mg/kg body weight/day was not associated with adverse effects. Accordingly, the no-observed-adverse-effect level (NOAEL) was determined as 1000 mg/kg body weight/day. These findings provide scientific evidence supporting the safety of SIRTMAX^® for daily consumption.

Anserine (β-alanyl-1-methyl-L-histidine) is a kind of imidazole dipeptide (IMDP) contained abundantly in skeletal muscles of chickens, salmon, tuna, bonito, and other species. IMDPs possess antioxidant activity, and their consumption confers several health benefits. We prepared a highly purified anserine (approximately 75% purity) from salmon using hot water extraction, followed by ion exchange treatment and membrane separation technology. We report the results of different safety tests conducted using the purified salmon anserine. No deaths were observed in a single-dose toxicity test in mice, and the LD₅₀ value of purified salmon anserine was estimated to be >5,000 mg/kg body weight. In a 90-day repeated-dose toxicity study in rats at 1,300 mg/kg body weight/day, no toxicological changes were observed between treated and control rats regarding body weight, food intake, urinalysis, blood biochemistry, pathological examination, or organ weights. Furthermore, no mutagenicity was observed in the Ames test using Salmonella typhimurium (S. typhimurium) and Escherichia coli (E. coli). Together, these findings indicate that purified salmon anserine is a safe food ingredient under all the conditions tested.