The effects of high-intensity exercise training and detraining with and without active recovery on postexercise hypotension in young men.

Whether high-intensity exercise training and detraining combined with skeletal muscle pump (MP) could alter the magnitude of postexercise hypotension has not been investigated. We therefore sought to determine whether the combination of MP (unloaded back-pedaling) with 4 weeks of high-intensity exercise training and detraining could alter the magnitude of postexercise hypotension. Fourteen healthy men underwent 4 weeks of high-intensity exercise training (5 consecutive days per week for 15 min per session at 40% of the difference between the gas exchange threshold and maximal oxygen uptake [i.e., Δ40%]) followed by detraining for 4 weeks. Assessments were conducted at Pre-training (Pre), Post-training (Post) and after Detraining with (MP) and without MP (Con). The exercise test in the Pre, Post and the Detraining consisted of 15 min exercise at Δ40% followed by 1 h of recovery. At all time-points, the postexercise reduction in mean arterial pressure (MAP) was reduced in MP compared to Con (all p < 0.01). Four weeks of high-intensity exercise training resulted in a reduction in the magnitude of postexercise hypotension (i.e., the change in MAP from baseline was mitigated) across both trials (All p < 0.01) when compared to Pre and Detraining. Following Detraining, the reduction of MAP from baseline was reduced compared to Pre, but was not different from Post. We conclude that high-intensity exercise training combined with skeletal MP reduces the magnitude of postexercise hypotension, and this effect is partially retained for 4 weeks following the complete cessation of high-intensity exercise training.

Neuroprotective Strategies for Stroke by Natural Products: Advances and Perspectives.

Cerebral ischemic stroke is a disease with high prevalence and incidence. Its management focuses on rapid reperfusion with intravenous thrombolysis and endovascular thrombectomy. Both therapeutic strategies reduce disability, but the therapy time window is short, and the risk of bleeding is high. Natural products (NPs) have played a key role in drug discovery, especially for cancer and infectious diseases. However, they have made little progress in clinical translation and pose challenges to the treatment of stroke. Recently, with the investigation of precise mechanisms in cerebral ischemic stroke and the technological development of NP-based drug discovery, NPs are addressing these challenges and opening up new opportunities in cerebral stroke. Thus, in this review, we first summarize the structure and function of diverse NPs, including flavonoids, phenols, terpenes, lactones, quinones, alkaloids, and glycosides. Then we propose the comprehensive neuroprotective mechanism of NPs in cerebral ischemic stroke, which involves complex cascade processes of oxidative stress, mitochondrial damage, apoptosis or ferroptosis-related cell death, inflammatory response, and disruption of the blood-brain barrier (BBB). Overall, we stress the neuroprotective effect of NPs and their mechanism on cerebral ischemic stroke for a better understanding of the advances and perspective in NPs application that may provide a rationale for the development of innovative therapeutic regimens in ischemic stroke.

Astragalosides Supplementation Enhances Intrinsic Muscle Repair Capacity Following Eccentric Exercise-Induced Injury.

Astragalosides have been shown to enhance endurance exercise capacity in vivo and promote muscular hypertrophy in vitro. However, it remains unknown whether astragalosides supplementation can alter inflammatory response and enhance muscle recovery after damage in humans. We therefore aimed to evaluate the effect of astragalosides supplementation on muscle's intrinsic capacity to regenerate and repair itself after exercise-induced damage. Using a randomized double-blind placebo-controlled cross-over design, eleven male participants underwent 7 days of astragalosides supplementation (in total containing 4 mg of astragalosides per day) or a placebo control, following an eccentric exercise protocol. Serum blood samples and variables related to muscle function were collected prior to and immediately following the muscle damage protocol and also at 2 h, and 1, 2, 3, 5, and 7 days of the recovery period, to assess the pro-inflammatory cytokine response, the secretion of muscle regenerative factors, and muscular strength. Astragalosides supplementation reduced biomarkers of skeletal muscle damage (serum CK, LDH, and Mb), when compared to the placebo, at 1, 2, and 3 days following the muscle damage protocol. Astragalosides supplementation suppressed the secretion of IL-6 and TNF-α, whilst increasing the release of IGF-1 during the initial stages of muscle recovery. Furthermore, following astragaloside supplementation, muscular strength returned to baseline 2 days earlier than the placebo. Astragalosides supplementation shortens the duration of inflammation, enhances the regeneration process and restores muscle strength following eccentric exercise-induced injury.

Astragalus membranaceus Enhances Myotube Hypertrophy through PI3K-Mediated Akt/mTOR Signaling Phosphorylation.

Astragalus membranaceus (AM) is classified as a high-class traditional herbal medicine, which has strengthened vitality and multifunctional pharmacological activities, but limited empirical evidence is available to support its effects in muscular hypertrophy. It evokes skeletal muscle hypertrophy by increasing anabolic pathway, which is essential to prevent sarcopenia in elderly population. In this study, we examined the effects of AM on skeletal muscle hypertrophy by focusing on the molecular mechanism. We employed an in vitro model to investigate whether AM-treated skeletal muscle, as represented by myotube C2C12 cells, was hypertrophic, and to further investigate the efficacy of AM-activated phosphorylation of PI3K/Akt/mTOR signaling that must occur prior to myotube hypertrophy. The results showed that the myotubes formed larger multinucleated myotubes with increased diameter and thickness (1.16-fold relative to control group, p < 0.05). Administration of PI3K and mTOR inhibitors abolished AM-induced muscular hypertrophy. Moreover, AM-induced PI3K-mediated myotube hypertrophy was accompanied by the activation of Akt and mTOR signaling. We concluded that the AM is a nutritional activator to enhance muscular hypertrophy by increasing PI3K/Akt/mTOR signaling phosphorylation. As the AM is effective in myotube hypertrophy, AM and its derivatives may be promising candidates for ergogenic aid to prevent sarcopenia.

Monoamine oxidase A (MAO A) inhibitors decrease glioma progression.

Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-alone drugs or as combination therapy with low dose TMZ for drug-resistant gliomas. NMI can also be used as a non-invasive imaging tool. Thus has a dual function for both therapy and diagnosis.

Angelica Sinensis promotes myotube hypertrophy through the PI3K/Akt/mTOR pathway.

BACKGROUND: Angelica Sinensis (AS), a folk medicine, has long been used in ergogenic aids for athletes, but there is little scientific evidence supporting its effects. We investigated whether AS induces hypertrophy in myotubes through the phosphatidylinositol 3-kinase (PI3K)/Akt (also termed PKB)/mammalian target of the rapamycin (mTOR) pathway. METHODS: An in vitro experiment investigating the induction of hypertrophy in myotubes was conducted. To investigate whether AS promoted the hypertrophy of myotubes, an established in vitro model of myotube hypertrophy with and without AS was used and examined using microscopic images. The role of the PI3K/Akt/mTOR signaling pathway in AS-induced myotube hypertrophy was evaluated. Two inhibitors, wortmannin (an inhibitor of PI3K) and rapamycin (an inhibitor of mTOR), were used. RESULT: The results revealed that the myotube diameters in the AS-treated group were significantly larger than those in the untreated control group (P < 0.05). Wortmannin and rapamycin inhibited AS-induced hypertrophy. Furthermore, AS increased Akt and mTOR phosphorylation through the PI3K pathway and induced myotube hypertrophy. CONCLUSION: The results confirmed that AS induces hypertrophy in myotubes through the PI3K/Akt/mTOR pathway.

Angelica sinensis improves exercise performance and protects against physical fatigue in trained mice.

Angelica sinensis (AS) is a well-known medicinal herb and food material with antioxidative and multifunctional pharmacological activities. However, we lack evidence of the effect of AS on exercise performance and physical fatigue. We aimed to evaluate the potential beneficial effect of AS on ergogenic and anti-fatigue functions after physiological challenge. Male ICR strain mice were randomly assigned to four groups (n=10 per group) for treatment: (1) sedentary control and vehicle treatment (vehicle control); (2) exercise training with vehicle treatment (exercise control); (3) exercise training with AS treatment at 0.41 g/kg/day (Ex-AS1); and (4) 2.05 g/kg/day (Ex-AS5); both the vehicle and AS were orally administered for 6 weeks. Exercise performance and anti-fatigue function were evaluated by forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, and creatine kinase (CK) after a 15-min swimming exercise. Trend analysis revealed that AS treatments significantly increased endurance swimming time and blood glucose level, and decreased serum lactate, ammonia and CK levels. Liver and muscle glycogen contents were higher for Ex-AS1 and Ex-AS5 groups than the exercise control. Therefore, AS supplementation improved exercise performance and had anti-fatigue properties in mice and may be an effective ergogenic aid in exercise training.

Astragalus membranaceus improves exercise performance and ameliorates exercise-induced fatigue in trained mice.

Astragalus membranaceus (AM) is a popular "Qi-tonifying" herb with a long history of use as a Traditional Chinese Medicine with multiple biological functions. However, evidence for the effects of AM on exercise performance and physical fatigue is limited. We evaluated the potential beneficial effects of AM on ergogenic and anti-fatigue functions following physiological challenge. Male ICR strain mice were randomly assigned to four groups (n = 10 per group) for treatment: (1) sedentary control and vehicle treatment (vehicle control); (2) exercise training with vehicle treatment (exercise control); and (3) exercise training with AM treatment at 0.615 g/kg/day (Ex-AM1) or (4) 3.075 g/kg/day (Ex-AM5). Both the vehicle and AM were orally administered for 6 weeks. Exercise performance and anti-fatigue function were evaluated by forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, and creatine kinase after 15-min swimming exercise. Exercise training combined with AM supplementation increased endurance exercise capacity and increased hepatic and muscle glycogen content. AM reduced exercise-induced accumulation of the byproducts blood lactate and ammonia with acute exercise challenge. Moreover, we found no deleterious effects from AM treatment. Therefore, AM supplementation improved exercise performance and had anti-fatigue effects in mice. It may be an effective ergogenic aid in exercise training.

Supplementation with soybean peptides, taurine, Pueraria isoflavone, and ginseng saponin complex improves endurance exercise capacity in humans.

The purpose of this study was to investigate the effects of a proprietary blend of soybean peptides, taurine, Pueraria isoflavone, and ginseng saponin complex (STPG capsule) on exercise performance in humans. Fourteen male volunteers were randomly assigned to two crossover treatments in which they consumed either four STPG capsules (STPG treatment) or placebo (P treatment) for 15 days before a 75% maximal oxygen uptake (VO(2max)) exhaustive cycling test. Blood samples and respiratory gas were collected prior to the exercise (Pre-Ex), at 10 (Ex-10), 15 (Ex-15), 20 (Ex-20), and 25 (Ex-25) minutes during exercise, and immediately after exercise (exhaustion) to assess the blood metabolites, cardiorespiratory responses, and energy substrate utilization. The result showed that exercise time to exhaustion of the 75% (VO(2max)) exhaustive cycling test of the STPG-treated subjects was significantly greater than with the P treatment (30.99 ± 2.01 vs. 28.05 ± 1.48 minutes). The plasma lactate concentrations at Ex-20 and Ex-25 in the STPG treatment were significantly lower with STPG treatment than with P treatment (10.5 ± 0.7 vs. 11.5 ± 0.8 and 10.7 ± 0.9 vs.12.3 ± 1.0 mmol/L, respectively). Nonesterified fatty acid levels at Ex-15, Ex-20, Ex-25, and exhaustion in the STPG group (0.27 ± 0.03, 0.32 ± 0.04, 0.32 ± 0.06, and 0.37 ± 0.05 mmol/L, respectively) were significantly higher than those in the P treatment (0.21 ± 0.03, 0.23 ± 0.03, 0.24 ± 0.03, and 0.25 ± 0.03 mmol/L, respectively). It was concluded that supplementation of four capsules (2 g) of STPG complex, consisting of soybean peptides, taurine, Pueraria isoflavone, and ginseng saponin, for 15 days was effective in promoting utilization of free fatty acids and improving exhaustive cycling test performance in humans.

Effect of purple sweet potato leaves consumption on exercise-induced oxidative stress and IL-6 and HSP72 levels.

The aim of this study was to evaluate the effects of purple sweet potato leaves (PSPL) consumption on oxidative stress markers in a healthy, nontrained, young male population after completing a running exercise protocol. A crossover design was applied, with 15 subjects participating in a two-step dietary intervention period. Each subject was given a high- (PSPL group) or low-polyphenol (control group) diet for 7 days with a 14-day washout period. After each dietary intervention period, all subjects performed 1 h of treadmill running at a speed corresponding to 70% of each subject's individual maximal oxygen uptake (Vo(2max)). Blood samples were taken before exercise and at 0, 1, and 3 h after exercise. Compared with the control group, PSPL consumption significantly increased plasma total polyphenols concentration and total antioxidant power (i.e., the ferric-reducing ability of plasma) in the PSPL group. The markers of oxidative damage, plasma TBARS and protein carbonyl, significantly decreased. Plasma IL-6 concentration also decreased. However, no significant difference was found in HSP72 levels between the two groups. These findings indicate that consuming a high-polyphenol diet for 7 days can modulate antioxidative status and decrease exercise-induced oxidative damage and pro-inflammatory cytokine secretion.