Multiple mechanisms are involved in exercise-induced fatigue, including energy depletion, metabolite accumulation, and oxidative stress, etc. The mechanistic findings provide a rationale for a multi-targeted approach to exercise-induced fatigue management. This study created a multi-ingredient formula mixed with valine, isoleucine, leucine, β-alanine, creatine, l-carnitine, quercetin, and betaine, based on the functional characteristics of these agents, and evaluated the preventive effect of this mechanism-based formula on exercise-induced fatigue. Results showed that the 7-d formula supplement significantly increased the running duration time of mice by 14% and the distance by 20% in an exhaustive treadmill test, indicating that the formula could delay fatigue appearance and improve exercise performance. Mechanistically, the formula enhanced fatty acid oxidation and spared liver glycogen by regulating the fat/glucose metabolism-related signaling pathways, including phospho-adenosine monophosphate-activated protein kinase α (p-AMPKα), phospho-acetyl CoA carboxylase (p-ACC), carnitine palmitoyl-transferase 1B (CPT1B), fatty acid translocase (CD36), and glucose transporter type 4 (GLUT4), and increased antioxidant capacity. The findings suggested that the formula tested in this study effectively ameliorated exercise-induced fatigue by targeting multi-signaling pathways, showing promise as a regimen to fight exercise-induced fatigue.

Combination of intermittent fasting and chemotherapy has been drawn an increasing attention because of the encouraging efficacy. In this study, we evaluated the anti-cancer effect of combination of glucose limitation and selenite (Se), a representative inorganic form of selenium, that is preferentially accumulated in tumors. Results showed that cytotoxic effect of selenite on cancer cells, but not on normal cells, was significantly enhanced in response to the combination of selenite and glucose limitation. Furthermore, in vivo therapeutic efficacy of combining selenite with fasting was dramatically improved in xenograft models of lung and colon cancer. Mechanistically, we found that SLC7A11 expression in cancer cells was up-regulated by selenite both in vitro and in vivo. The elevated SLC7A11 led to cystine accumulation, NADPH depletion and the conversion of cystine to cysteine inhibition, which in turn boosted selenite-mediated reactive oxygen species (ROS), followed by enhancement of selenite-mediated cytotoxic effect. The findings of the present study provide an effective and practical approach for increasing the therapeutic window of selenite and imply that combination of selenite and fasting holds promising potential to be developed a clinically useful regimen for treating certain types of cancer.

This study aimed to prepare Artemisia capillaris Thunb. leaf protein peptide selenium chelates (AP‐Se) employing sodium selenite as a selenium (Se) source, with a focus on their structure and biological activities. Artemisia capillaris Thunb. leaf protein (AP) was extracted from Artemisia capillaris Thunb. leaf (AC) and enzymatically digested to obtain AP peptide (AP‐P). The results exhibited that the maximum Se chelating capacity of 52.78 ± 0.74 (mg/g) was obtained at a peptide‐Se mass ratio of 1:3.3, pH 9, and temperature of 49°C condition. The N‐terminal amino group and C‐terminal carboxyl group of AP‐P were the main binding sites of selenium ions. The chelation reaction caused folding and curling of the peptide chain in AP‐P, which produced folds and crystal in AP‐Se microstructure. Furthermore, at certain dosages, AP‐Se demonstrated an ABTS ⁺ clearance rate comparable with that of Vitamin C (VC), along with outstanding gastrointestinal permeability. Furthermore, AP‐Se was proven to be less hazardous to cells than sodium selenite. Overall, the study indicated that AP‐Se may have a promising usage as an effective natural selenium supplement in the medical and food industries.