Patel Darpan I, Wallace Derek, Abuchowski Kira, Rivas Paul, Gallegos Amber, Musi Nicolas, Kumar Addanki Pratap
School of Nursing, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Barshop Institute for Aging, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Physiol Rep. 2019 Aug;7(16):e14217. doi: 10.14814/phy2.14217.
Muscle loss is a debilitating side effect to prostate cancer (PCa) experienced by nearly 60% of men. The purpose of this study was to test the hypothesis that Nexrutine , a bark extract from the Phellodendrum amurense, can protect against prostate cancer induced muscle loss in a similar manner as exercise, using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Forty-five, 8- to 10-week old TRAMP mice were randomized to either control, Nexrutine (600 mg/kg pelleted in chow) or exercise (voluntary wheel running). Mice were serially sacrificed at weeks 4, 8, 12, and 20, at which time either the left or right gastrocnemius muscle was harvested, weighted, and frozen. Proteolysis inducing factor (PIF), ubiquitin, and NF-κB concentrations were quantified using ELISA kits. Nexrutine and exercise were equally able to protect TRAMP mice against PCa-induced muscle loss (P = 0.04). Both interventions decreased intramuscular PIF concentrations at 20 weeks compared to control (P < 0.05). A treatment effect was also observed when all time points were combined with exercise significantly lowering PIF concentrations (P < 0.01). Exercise significantly lowered intramuscular ubiquitin concentrations in weeks 4, 8, and 20 compared to control mice (P < 0.001). A treatment effect was also observed with exercise significantly lowering ubiquitin compared to control mice (P < 0.001). No significant changes were observed for NF-κB. The results of this investigation demonstrate that PCa-induced muscle loss can be attenuated with the herbal supplement Nexrutine . This investigation provides preliminary evidence to support continued research into Nexrutine as a potential exercise analog in protecting against muscle loss.
肌肉流失是近60%的男性前列腺癌（PCa）患者所经历的一种使人衰弱的副作用。本研究的目的是检验以下假设：黄柏树皮提取物Nexrutine能够以与运动相似的方式预防前列腺癌诱发的肌肉流失，采用小鼠前列腺转基因腺癌（TRAMP）模型进行研究。将45只8至10周龄的TRAMP小鼠随机分为对照组、Nexrutine组（饲料中添加600 mg/kg Nexrutine）或运动组（自愿轮转跑步）。在第4、8、12和20周对小鼠进行连续处死，此时采集左侧或右侧腓肠肌，称重并冷冻。使用ELISA试剂盒对蛋白水解诱导因子（PIF）、泛素和NF-κB的浓度进行定量分析。Nexrutine和运动同样能够保护TRAMP小鼠免受PCa诱发的肌肉流失（P = 0.04）。与对照组相比，两种干预措施均使20周时肌肉内PIF浓度降低（P < 0.05）。当将所有时间点合并分析时，也观察到了治疗效果，运动显著降低了PIF浓度（P < 0.01）。与对照小鼠相比，运动在第4、8和20周显著降低了肌肉内泛素浓度（P < 0.001）。与对照小鼠相比，运动也显著降低了泛素水平，观察到了治疗效果（P < 0.001）。未观察到NF-κB有显著变化。本研究结果表明，草药补充剂Nexrutine可以减轻PCa诱发的肌肉流失。本研究提供了初步证据，支持继续研究Nexrutine作为预防肌肉流失的潜在运动类似物。
