KT&G Life Sciences Corp.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease caused by mutations in the mitochondrial genome. This study investigated the efficacy of β-lapachone (β-lap), a natural quinone compound, in rescuing mitochondrial dysfunction in MELAS cybrid cells. β-Lap significantly restored energy production and mitochondrial membrane potential as well as normalized the elevated ROS level in MELAS cybrid cells. Additionally, β-lap reduced lactic acidosis and restored glucose uptake in the MELAS cybrid cells. Finally, β-lap activated Sirt1 by increasing the intracellular NAD(+)/NADH ratio, which was accompanied by increased mtDNA content. Two other quinone compounds (idebenone and CoQ10) that have rescued mitochondrial dysfunction in previous studies of MELAS cybrid cells had a minimal effect in the current study. Taken together, these results demonstrated that β-lap may provide a novel therapeutic modality for the treatment of MELAS.

Calcium (Ca) is an essential element to maintain body homeostasis.However, many factors disturb calcium absorption.Aspartic acid chelated calcium (AAC) was synthesized by new methods using calcium carbonate and aspartic acid.This study was carried out to investigate the bioavailability of AAC in Ca-deficient rats.The exptl. groups were as follows: NC; normal diet control group, CD-C; untreated control group of Ca-deficient (CD) rats, CD-CaCO₃; CaCO₃ treated group of CD rats, CD-AAC; AAC treated group of CD rats, and CD-SWC; and seaweed-derived Ca treated group of CD rats.The Ca content of various types of Ca was held constant at 32 mg/day, and the four CD groups were fed for 7 days after randomized grouping.Ca content in serum, urine, and feces within feeding periods were analyzed to confirm Ca absorption.Serum Ca content was significantly higher in the CD-AAC (11.24 mg/dL) and CD-SWC (10.12 mg/dL) groups than that in the CD-C (8.6 mg/dL) group 2 h following the first administration.The Ca content in feces was significantly lower in the CD-AAC (35.4 mg/3 days) and CD-SWC (71.1 mg/3 day) groups than that in the CD-CaCO₃ (98.7 mg/3 days) group (p > 0.05).AAC had a 2.3-fold higher absorption rate of Ca than that of SWC.No differences in fibula length were observed in the NC and CD groups.The fibula weights of the CD-AAC (0.33 g) and CD-SWC (0.33 g) groups increased compared to those in the CD-C (0.27 g) group; however, no significant difference was observed between the CD groups.We conclude that bioavailability of AAC is higher than that of seaweed-derived Ca or inorganic Ca.Thus, these findings suggest the AAC has potential as a functional food material related to Ca metabolism

Lipotoxic cardiomyopathy is caused by myocardial lipid accumulation and often occurs in patients with diabetes and obesity. This study investigated the effects of β-lapachone (β-lap), a natural compound that activates Sirt1 through elevation of the intracellular NAD+ level, on acyl CoA synthase (ACS) transgenic (Tg) mice, which have lipotoxic cardiomyopathy. Oral administration of β-lap to ACS Tg mice significantly attenuated heart failure and inhibited myocardial accumulation of triacylglycerol. Electron microscopy and measurement of mitochondrial complex II protein and mitochondrial DNA revealed that administration of β-lap restored mitochondrial integrity and biogenesis in ACS Tg hearts. Accordingly, β-lap administration significantly increased the expression of genes associated with mitochondrial biogenesis and fatty acid metabolism that were down-regulated in ACS Tg hearts. β-lap also restored the activities of Sirt1 and AMP-activated protein kinase (AMPK), the two key regulators of metabolism, which were suppressed in ACS Tg hearts. In H9C2 cells, β-lap-mediated elevation of AMPK activity was retarded when the level of Sirt1 was reduced by transfection of siRNA against Sirt1. Taken together, these results indicate that β-lap exerts cardioprotective effects against cardiac lipotoxicity through the activation of Sirt1 and AMPK. β-lap may be a novel therapeutic agent for the treatment of lipotoxic cardiomyopathy.