Institute of Traditional Medicine, National Yang Ming Chiao Tung University, 155 Li-Nung St., Sec. 2, Shipai, Beitou, Taipei 112, Taiwan.
Institute of Traditional Medicine, National Yang Ming Chiao Tung University, 155 Li-Nung St., Sec. 2, Shipai, Beitou, Taipei 112, Taiwan; Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
Int J Biol Macromol. 2024 Nov;279(Pt 4):135548. doi: 10.1016/j.ijbiomac.2024.135548. Epub 2024 Sep 11.
Antrodia cinnamomea-derived sulfated polysaccharides (Ac-SPSs) have health benefits, but their yield is low. This study explores a strategy to increase Ac-SPS yield and elucidates the biofunctions of Ac-SPS. For this, A. cinnamomea mycelia were treated with zinc sulfate (ZnSO) administered at 1, 10, and 100 μM. Firstly, functional assay indicated that ZnSO increases the Ac-SPS yield by 20 %-30 % compared with the control treatment. ZnSO engenders a population of middle-molecular-weight (~200 kDa) Ac-SPSs. Ac-SPS (ASZ-10) from A. cinnamomea treated with 10 μM ZnSO exhibits the best anti-proliferation ability against lung cancer A549 cells. Co-treatment of ASZ-10 does not inhibit lipopolysaccharide-induced inflammation but does induce M1-related markers of macrophage RAW264.7 cells. Secondly, immunomodulatory properties showed that ASZ-10 increases the expression of CD80 and CD86 in M-CSF-stimulated bone-marrow-derived macrophages. ASZ-10 induces M1 polarization through up-regulation of the AKT/mTOR pathway as confirmed by AKT and mTOR inhibitors eliminating ASZ-10-induced M1-like markers of macrophages. Through systemic chemical and functional analysis, this study shows that trace amounts (10 μM) of ZnSO increase Ac-SPS yield and it reveals that ASZ-10 exhibits anti-cancer activity and acts as a stimulator for M1 macrophages by stimulation of AKT and mTOR.
樟芝来源的硫酸化多糖（Ac-SPSs）具有健康益处，但产量较低。本研究探讨了一种提高 Ac-SPS 产量的策略，并阐明了 Ac-SPS 的生物功能。为此，用 1、10 和 100 μM 的硫酸锌（ZnSO）处理樟芝菌丝体。首先，功能测定表明，与对照处理相比，ZnSO 使 Ac-SPS 产量增加 20%-30%。ZnSO 产生了一种中等分子量（~200 kDa）的 Ac-SPS 群体。用 10 μM ZnSO 处理的樟芝来源的 Ac-SPS（ASZ-10）对肺癌 A549 细胞表现出最佳的抗增殖能力。ASZ-10 与脂多糖共同处理不会抑制炎症，但会诱导 RAW264.7 巨噬细胞的 M1 相关标志物。其次，免疫调节特性表明，ASZ-10 增加了 M-CSF 刺激的骨髓来源巨噬细胞中 CD80 和 CD86 的表达。ASZ-10 通过上调 AKT/mTOR 通路诱导 M1 极化，这一点通过 AKT 和 mTOR 抑制剂消除巨噬细胞中 ASZ-10 诱导的 M1 样标志物得到证实。通过系统的化学和功能分析，本研究表明痕量（10 μM）的 ZnSO 可提高 Ac-SPS 的产量，并揭示 ASZ-10 通过刺激 AKT 和 mTOR 表现出抗癌活性，并作为 M1 巨噬细胞的刺激物。
