Kim Min Ju, Zhang Ting, Kim Keun Nam, Bae Gun Won, Yoon Sun Myung, Yue Yu, Wu Xuangao, Park Sunmin
Department of R&D, Unimed Pharmaceuticals Inc., Seoul 05567, Republic of Korea.
Department of Bio-Convergence System, Obesity/Diabetes Center, Hoseo University, Asan 31499, Republic of Korea.
Biology (Basel). 2022 Nov 29;11(12):1739. doi: 10.3390/biology11121739.
Intense exercise is reported to induce physical and cognitive fatigue, but few studies have focused on treatments to alleviate fatigue. We hypothesized that the oral supplementation of enzymatic porcine placenta hydrolysate (EPPH) prepared using protease enzymes could alleviate exercise-induced fatigue in an animal model. The objectives of the study were to examine the hypothesis and the action mechanism of EPPH in relieving physical and cognitive fatigue. Fifty male Sprague−Dawley rats aged 8 weeks (body weight: 201 g) were classified into five groups, and rats in each group were given oral distilled water, EPPH (5 mg nitrogen/mL) at doses of 0.08, 0.16, or 0.31 mL/kg body weight (BW)/day, or glutathione (100 mg/kg BW/day) by a feeding needle for 5 weeks, which were named as the control, L-EPPH, M-EPPH, H-EPPH, or positive-control groups, respectively. Ten additional rats had no intense exercise with water administration and were designated as the no-exercise group. After 2 weeks, the rats were subjected to intense exercise and forced swimming trial for 30 min once per week for an additional 4 weeks. At 5 min after the intense exercise, lactate concentrations and lactate dehydrogenase (LDH) activity in the serum and the gastrocnemius muscle were higher in the control group, whereas M-EPPH and H-EPPH treatments suppressed the increase better than in the positive-control (p < 0.05). Intense exercise decreased glycogen content in the liver and gastrocnemius muscle, and M-EPPH and H-EPPH inhibited the decrement (p < 0.05). Moreover, lipid peroxide contents in the gastrocnemius muscle and liver were higher in the control group than in the M-EPPH, H-EPPH, positive-control, and no-exercise groups (p < 0.05). However, antioxidant enzyme activities such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were opposite to the lipid peroxide contents. Hypothalamic corticosterone and hippocampal mRNA expressions of tumor necrosis factor (TNF)-α and IL-1β were higher. However, hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression and protein contents were lower in the control group than in the positive-control group. M-EPPH, H-EPPH, and positive-control suppressed the changes via activating hippocampal cAMP response element-binding protein phosphorylation, and H-EPPH showed better activity than in the positive-control (p < 0.05). In conclusion, EPPH (0.16−0.31 mL/kg BW) intake reduced exercise-induced physical and cognitive fatigue in rats and could potentially be developed as a therapeutic agent for relieving fatigue in humans.
据报道，剧烈运动会导致身体和认知疲劳，但很少有研究关注缓解疲劳的治疗方法。我们假设，口服使用蛋白酶制备的酶解猪胎盘水解物（EPPH）可以缓解动物模型中的运动性疲劳。本研究的目的是检验这一假设以及EPPH缓解身体和认知疲劳的作用机制。将50只8周龄的雄性Sprague-Dawley大鼠（体重：201 g）分为五组，每组大鼠通过饲管分别口服蒸馏水、剂量为0.08、0.16或0.31 mL/kg体重（BW）/天的EPPH（5 mg氮/mL），或谷胱甘肽（100 mg/kg BW/天），持续5周，分别命名为对照组、低剂量EPPH组、中剂量EPPH组、高剂量EPPH组或阳性对照组。另外10只大鼠不进行剧烈运动，只给予水，被指定为非运动组。2周后，大鼠进行剧烈运动，并每周进行一次30分钟的强迫游泳试验，持续4周。在剧烈运动后5分钟，对照组血清和腓肠肌中的乳酸浓度和乳酸脱氢酶（LDH）活性较高，而中剂量EPPH组和高剂量EPPH组对这种升高的抑制作用优于阳性对照组（p < 0.05）。剧烈运动降低了肝脏和腓肠肌中的糖原含量，中剂量EPPH组和高剂量EPPH组抑制了这种降低（p < 0.05）。此外，对照组腓肠肌和肝脏中的脂质过氧化物含量高于中剂量EPPH组、高剂量EPPH组、阳性对照组和非运动组（p < 0.05）。然而，超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）等抗氧化酶活性与脂质过氧化物含量相反。下丘脑促肾上腺皮质激素和海马中肿瘤坏死因子（TNF）-α和白细胞介素-1β的mRNA表达较高。然而，对照组海马脑源性神经营养因子（BDNF）的mRNA表达和蛋白含量低于阳性对照组。中剂量EPPH组、高剂量EPPH组和阳性对照组通过激活海马cAMP反应元件结合蛋白磷酸化来抑制这些变化，高剂量EPPH组的活性优于阳性对照组（p < 0.05）。总之，摄入EPPH（0.16 - 0.31 mL/kg BW）可减轻大鼠运动引起的身体和认知疲劳，并有可能开发成为缓解人类疲劳的治疗药物。
