Search

Plants exposed to hypoxic conditions have been suggested to produce more biologically active phytochemicals than those exposed to normal oxygen levels. Previously, we investigated 314 highland crop species and showed that the flavonoid kaempferol extracted from a highland quinoa grain markedly increased mitochondrial metabolism and ATP production in a hypoxic environment in vitro. Thus, we hypothesized that kaempferol would be effective during exercise under harsh conditions, in which anaerobic metabolism occurs. This study adopted a double‐blind, placebo‐controlled, crossover design to investigate the effect of a single oral dose of kaempferol (10 mg) on the athletic performance‐related indicators of 13 male university athletes (20.8 ± 0.7 years) who performed two consecutive 400‐m runs with the shortest 90‐min interval assuming qualifying and main races. Although no significant differences were observed in the 400‐m race times between the placebo and kaempferol groups, kaempferol intake markedly reduced the respiratory and heart rates during the second run (p < 0.05). In addition, kaempferol intake reduced the levels of muscle damage markers, myoglobin, and aspartate transaminase (p < 0.05). A single oral dose of kaempferol reduced the cardiopulmonary burden and muscle damage in individuals participating in 400‐m runs. Kaempferol may be a useful supplement for relieving the physical load, particularly in individuals performing strenuous exercises with high oxygen demand. Trial Registration: UMIN Clinical Trials Registry in Japan: UMIN000049588 [ABSTRACT FROM AUTHOR]

Purpose: Exhaustive exercise induces acute liver stress; however, the precise mechanisms remain unclear. Methods: We investigated the effects of neutrophil depletion in male C57BL/6J mice. Male C57BL/6J mice were divided into four groups: sedentary with control antibody (n = 20), sedentary with antineutrophil antibody (n = 20), exhaustive exercise with control antibody (n = 20), and exhaustive exercise with antineutrophil antibody (n = 20). Antineutrophil antibodies (1A8) or control antibodies were administered intraperitoneally before running on a treadmill. Immediately and at 24 h after running to exhaustion on a treadmill at a 7% gradient and a speed of 24 m·min−1, blood neutrophil counts were measured by flow cytometry. Plasma activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also measured. Hematoxylin–eosin staining was performed to calculate the liver stress score, and hepatic tumor necrosis factor-α was measured using enzyme-linked immunosorbent assay. Results: Exercise increased blood neutrophil and neutrophil infiltration into the liver. Plasma AST and ALT activities were significantly higher immediately after exhaustive exercise than after sedentary control (AST, sedentary with control antibody: 52.2 ± 0.4, exhaustive exercise with control antibody: 210.0 ± 19.8; ALT, sedentary with control antibody: 29.8 ± 2.2, exhaustive exercise with control antibody: 87.2 ± 15.8). However, AST and ALT activities were significantly decreased with the 1A8 antibody (AST, 102.2 ± 12.9; ALT, 39.2 ± 4.0). In addition, the liver stress score increased after exercise but was significantly reduced by prior 1A8 antibody administration. The 1A8 antibody treatment also decreased hepatic tumor necrosis factor-α levels after exhaustive exercise. Conclusions: These results suggested that neutrophils play a critical role in increasing liver stress by regulating inflammation. [ABSTRACT FROM AUTHOR]

Kaempferol (KMP) has numerous important biological functions, and we recently showed that it remarkably increased intracellular adenosine triphosphate (ATP) content in C2C12 myotubes under hypoxic conditions. Since intracellular ATP is generated by aerobic energy metabolism or anaerobic glycolysis, hypoxia inducible factor-1α (HIF-1α) has been shown to be associated with metabolic remodeling and causes metabolic shift from aerobic energy metabolism to anaerobic glycolysis in response to hypoxic conditions. Here, we investigate the effects of KMP under hypoxic conditions on the stabilization of HIF-1α in C2C12 myotubes and its underlying molecular mechanisms. Constitutive HIF-1α protein expression was observed in C2C12 myotubes, and its expression under hypoxic conditions was remarkably suppressed by KMP by reducing its stability; thus, resulting in an increase in ATP content. Furthermore, KMP strikingly increased the ubiquitination of HIF-1α and promoted its degradation via the ubiquitin proteasome system. Inhibition of HIF-1α by KMP resulted in the abrogation of the expression of glycolytic enzymes such as lactate dehydrogenase A and pyruvate dehydrogenase kinase isozyme 1. In addition, the metabolome profiling showed that KMP promoted oxidative energy production, while the mitochondrial complex activity assay indicated that KMP increased the activity of mitochondrial complex IV. Finally, we showed that KMP inhibited HIF-1α expression and increased intracellular ATP content in the soleus muscle of rats. Taken together, these results suggest that KMP increases intracellular ATP content under hypoxic conditions by suppressing the HIF-1α stabilization and/or by enhancing the mitochondrial complex IV activity in muscle. [ABSTRACT FROM AUTHOR]

Background: Kaempferol (KMP), a flavonoid in edible plants, exhibits diverse pharmacological effects. Growing body of evidence associates extended lifespan with physical activity (PA) and sleep, but KMP's impact on these behaviors is unclear. This double-blind, placebo-controlled, crossover trial assessed KMP's effects on PA and sleep., Methods: A total of 33 city workers (17 males and 16 females) participated in this study. They were randomly assigned to take either 10 mg of KMP or placebo for 2 weeks in the order allocated, with a 7-day washout period in between. All participants wore an accelerometer-based wearable device (Fitbit Charge 4), which monitored daily PA, heart rate (HR), and HR variability during sleep., Results: The duration of wearing the device was 23.73 ± 0.04 h/day. HR decreased in each PA level, and the mean daily step count and distance covered increased significantly during KMP intake compared to placebo. The outing rate, number of trips, number of recreational activities, and time spent in recreation on weekends increased. Sleep quality improved following KMP intake. The decrease in HR and increase in RMSSD may be important in mediating the effects of these KMPs., Conclusion: KMP leads to behavioral changes that subsequently improve sleep quality and potentially improve long-term quality of life., Clinical Trial Registration: https://center6.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000048447, UMIN000042438., Competing Interests: YI, AG-K and TM were employed by Otsuka Pharmaceutical Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ikeda, Gotoh-Katoh, Okada, Handa, Sato, Mizokami and Saito.)

Moderate exercise is effective for maintaining or improving overall health. However, excessive exercise that exhausts the adaptive reserve of the body or its ability to positively respond to training stimuli can induce tissue damage and dysfunction of multiple organs and systems. Tissue injury, inflammation, and oxidative stress are reportedly induced in the skeletal muscles, liver, and kidneys after exercise. However, the precise mechanisms underlying acute tissue injury after intense exercise have not yet been fully elucidated. Studies using various experimental models of acute tissue injury, other than intense exercise, have demonstrated infiltration of inflammatory cells, including neutrophils and macrophages. These cells infiltrate injured tissues and induce inflammatory and oxidative stress responses by producing inflammatory cytokines and reactive oxygen species, thereby exacerbating tissue injury. In addition to the activation of blood neutrophils and increase in their levels during and/or after prolonged or intense exercise, chemokines that contribute to leukocyte migration are released, facilitating the migration of neutrophils and monocytes into tissues. Therefore, neutrophils and macrophages, activated by exhaustive exercise, may infiltrate tissues and contribute to exhaustive exercise-induced tissue injury. Recently, the contributions of neutrophils and macrophages to various tissue injuries caused by exhaustive exercise have been reported. In this review, we summarize the involvement of neutrophils and monocytes/macrophages in exhaustive exercise-induced non-skeletal muscle tissue injury. In addition, we present novel data demonstrating the contribution of neutrophils and macrophages to exhaustive exercise-induced cardiac and pulmonary injuries. Our study findings and the evidence presented in this review suggest that neutrophils and macrophages may play pivotal roles in exhaustive exercise-induced tissue injuries., (Copyright © 2016 International Society of Exercise and Immunology. All rights reserved.)

Exhaustive exercise promotes muscle injury, including myofiber lesions; however, its exact mechanism has not yet been elucidated. In this study, we tested the hypothesis that macrophage depletion by pretreatment with clodronate liposomes alters muscle injury and inflammation following exhaustive exercise. Male C57BL/6J mice were divided into four groups: rest plus control liposome ( n =8), rest plus clodronate liposome ( n =8), exhaustive exercise plus control liposome ( n =8), and exhaustive exercise plus clodronate liposome ( n =8). Mice were treated with clodronate liposome or control liposome for 48 h before undergoing exhaustive exercise on a treadmill. Twenty-four hours after exhaustive exercise, the gastrocnemius muscles were removed for histological and PCR analyses. Exhaustive exercise increased the number of macrophages in the muscle; however, clodronate liposome treatment reduced this infiltration. Although exhaustive exercise resulted in an increase in injured myofibers, clodronate liposome treatment following exhaustive exercise reduced the injured myofibers. Clodronate liposome treatment also decreased the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the skeletal muscle after exhaustive exercise. These results suggest that macrophages play a critical role in increasing muscle injury by regulating inflammation.