Zhu Zixia, Li Cong, Gu Xiaofan, Wang Xiaoting, Zhang Gang, Fan Meng, Zhao Yun, Liu Xuan, Zhang Xiongwen
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, PR China.
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201003, China.
Toxicol Appl Pharmacol. 2024 Mar;484:116846. doi: 10.1016/j.taap.2024.116846. Epub 2024 Feb 6.
Cancer cachexia is a progressive wasting syndrome, which is mainly characterized by systemic inflammatory response, weight loss, muscle atrophy, and fat loss. Paeoniflorin (Pae) is a natural compound extracted from the dried root of Paeonia lactiflora Pallas, which is featured in anti-inflammatory, antioxidant, and immunoregulatory pharmacological activities. While, the effects of Pae on cancer cachexia had not been reported before. In the present study, the effects of Pae on muscle atrophy in cancer cachexia were observed both in vitro and in vivo using C2C12 myotube atrophy cell model and C26 tumor-bearing cancer cachexia mice model. In the in vitro study, Pae could alleviate myotubes atrophy induced by conditioned medium of C26 colon cancer cells or LLC Lewis lung cancer cells by decreasing the expression of Atrogin-1 and inhibited the decrease of MHC and MyoD. In the in vivo study, Pae ameliorated weight loss and improved the decrease in cross-sectional area of muscle fibers and the impairment of muscle function in C26 tumor-bearing mice. The inhibition of TLR4/NF-κB pathway and the activation of AKT/mTOR pathway was observed both in C2C12 myotubes and C26 tumor-bearing mice treated by Pae, which might be the main basis of its ameliorating effects on muscle atrophy. In addition, Pae could inhibit the release of IL-6 from C26 tumor cells, which might also contribute to its ameliorating effects on muscle atrophy. Overall, Pae might be a promising candidate for the therapy of cancer cachexia.
癌症恶病质是一种进行性消瘦综合征，主要特征为全身炎症反应、体重减轻、肌肉萎缩和脂肪减少。芍药苷（Pae）是从芍药干燥根中提取的一种天然化合物，具有抗炎、抗氧化和免疫调节药理活性。然而，此前尚未有Pae对癌症恶病质影响的报道。在本研究中，利用C2C12肌管萎缩细胞模型和C26荷瘤癌症恶病质小鼠模型，在体外和体内观察了Pae对癌症恶病质中肌肉萎缩的影响。在体外研究中，Pae可通过降低Atrogin-1的表达减轻C26结肠癌细胞或LLC刘易斯肺癌细胞条件培养基诱导的肌管萎缩，并抑制MHC和MyoD的降低。在体内研究中，Pae改善了C26荷瘤小鼠的体重减轻，改善了肌纤维横截面积的减少和肌肉功能的损伤。在Pae处理的C2C12肌管和C26荷瘤小鼠中均观察到TLR4/NF-κB通路的抑制和AKT/mTOR通路的激活，这可能是其改善肌肉萎缩作用的主要基础。此外，Pae可抑制C26肿瘤细胞释放IL-6，这也可能有助于其改善肌肉萎缩的作用。总体而言，Pae可能是治疗癌症恶病质的一个有前景的候选药物。
