Institute of Innovation and Applied Research in Chinses Medicine, Hunan University of Chinese Medicine, Changsha 410208, PR China; Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha 410013, PR China.
Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha 410013, PR China.
J Pharm Biomed Anal. 2023 Sep 20;234:115533. doi: 10.1016/j.jpba.2023.115533. Epub 2023 Jun 15.
Polygonatum cyrtonema Hua polysaccharide (PCP) is the main bioactive compound derived from the herb Polygonati Rhizoma, known for its anti-fatigue, antioxidant, immunomodulatory, and anti-inflammatory properties. However, its effectiveness on alleviating chemotherapy-induced muscle atrophy has been unclear. In this study, we utilized proteomic analysis to investigate the effects and mechanisms of PCP on gemcitabine plus cisplatin (GC) induced muscle atrophy in mice. Quality control analysis revealed that the functional PCP, rich in glucose, is a heterogeneous polysaccharide comprised of nine monosaccharides. PCP (64 mg/kg) significantly alleviated body muscle, organ weight loss, and muscle fiber atrophy in chemotherapy-induced cachectic mice. Moreover, PCP suppressed the decrease in serum immunoglobulin levels and the increase in pro-inflammatory factor interleukin-6 (IL-6). Proteomic analysis demonstrated that PCP contributed to the homeostasis of protein metabolism in gastrocnemius muscle. Diacylglycerol kinase (DGKζ) and cathepsin L (CTSL) were identified as primary PCP targets. Furthermore, the IL-6/STAT3/CTSL and DGKζ/FoxO/Atrogin1 signaling pathways were validated. Our findings suggest that PCP exerts an anti-atrophy effect on chemotherapy-induced muscle atrophy by regulating the autophagy-lysosome and ubiquitin-proteasome systems.
玉竹多糖（PCP）是从百合科植物玉竹中提取的主要生物活性化合物，具有抗疲劳、抗氧化、免疫调节和抗炎作用。然而，其缓解化疗引起的肌肉萎缩的效果尚不清楚。本研究采用蛋白质组学分析方法研究 PCP 对吉西他滨联合顺铂（GC）诱导的小鼠肌肉萎缩的作用及其机制。质量控制分析表明，功能 PCP 富含葡萄糖，是一种由九种单糖组成的不均一多糖。PCP（64mg/kg）可显著缓解化疗致恶病质小鼠的体重、器官重量减轻和肌纤维萎缩。此外，PCP 抑制了血清免疫球蛋白水平的降低和促炎因子白细胞介素 6（IL-6）的增加。蛋白质组学分析表明，PCP 有助于维持腓肠肌的蛋白质代谢平衡。二酰基甘油激酶（DGKζ）和组织蛋白酶 L（CTSL）被鉴定为 PCP 的主要靶标。此外，还验证了 IL-6/STAT3/CTSL 和 DGKζ/FoxO/Atrogin1 信号通路。我们的研究结果表明，PCP 通过调节自噬溶酶体和泛素-蛋白酶体系统对化疗引起的肌肉萎缩发挥抗萎缩作用。
