Lu Mei-Kuang, Cheng Jing-Jy, Lai Wen-Lin, Lin Yen-Ju, Huang Nai-Kuei
National Research Institute of Chinese Medicine, 155-1 Li-Nung Street, Sec. 2, Shipai, Peitou, Taipei 112, Taiwan.
J Agric Food Chem. 2008 Feb 13;56(3):865-74. doi: 10.1021/jf072828b. Epub 2008 Jan 11.
Antrodia cinnamomea (formerly A. camphorata) has recently and commercially been used in the formulation of nutraceuticals and functional foods in Taiwan. Because of its diverse properties, the neuroprotective effect was investigated using a fermented A. cinnamomea extract in this study. Serum deprivation-induced apoptosis in neuronal-like pheochromocytoma (PC12) cells was used as a cell stress model, and it was found that A. cinnamomea was effective in preventing serum-deprived apoptosis according to results of an MTT assay and Hoechst staining. Serum deprivation resulted in decreased phosphorylation of extracellular signal-regulated kinase (ERK) and increased phosphorylations of c-Jun NH2-terminal kinase (JNK) and p38, of the family of mitogen-activated protein kinases (MAPKs); however, A. cinnamomea reversed these phenomena, supporting the antagonistic effects between ERK and JNK-p38 in regulating cell survival. The previously identified active component of A. cinnamomea, adenosine (ADO), also exerted the same effects as A. cinnamomea in preventing apoptosis and regulating phosphorylations of MAPKs. Although an inhibitor of the ERK upstream activator blocked A. cinnamomea-induced ERK phosphorylations, it failed to block the protection of A. cinnamomea and ADO. A protein kinase A (PKA) inhibitor blocked the protection by both A. cinnamomea and ADO. Both JNK and p38 inhibitors were effective in preventing the phosphorylations of JNK and p38 and serum deprivation-induced apoptosis. Collectively, A. cinnamomea prevented serum deprivation-induced PC12 cell apoptosis through a PKA-dependent pathway and by suppression of JNK and p38 activities.
樟芝（原称牛樟芝）最近在台湾已被商业化用于营养保健品和功能性食品的配方中。由于其具有多种特性，本研究使用发酵樟芝提取物对其神经保护作用进行了研究。血清剥夺诱导的神经元样嗜铬细胞瘤（PC12）细胞凋亡被用作细胞应激模型，根据MTT法和Hoechst染色结果发现，樟芝可有效预防血清剥夺诱导的细胞凋亡。血清剥夺导致细胞外信号调节激酶（ERK）磷酸化减少，而丝裂原活化蛋白激酶（MAPK）家族中的c-Jun氨基末端激酶（JNK）和p38磷酸化增加；然而，樟芝逆转了这些现象，支持了ERK与JNK-p38在调节细胞存活中的拮抗作用。先前鉴定出的樟芝活性成分腺苷（ADO）在预防细胞凋亡和调节MAPK磷酸化方面也具有与樟芝相同的作用。尽管ERK上游激活剂的抑制剂可阻断樟芝诱导的ERK磷酸化，但它未能阻断樟芝和ADO的保护作用。蛋白激酶A（PKA）抑制剂可阻断樟芝和ADO的保护作用。JNK和p38抑制剂均能有效预防JNK和p38的磷酸化以及血清剥夺诱导的细胞凋亡。总体而言，樟芝通过PKA依赖性途径并通过抑制JNK和p38活性来预防血清剥夺诱导的PC12细胞凋亡。
