Wang Qiaona, Zhu Canhe, Song Zhaoran, Qiao Yunfa, Hu Yuefeng, Hu Liyun, Li Shengjie, Wang Renlei
School of Ecology and Applied Meteorology, Nanjing University of Information Science & Technology, Nanjing, 210044, People's Republic of China.
School of Food Science, Nanjing Xiaozhuang University, Nanjing, 211171, People's Republic of China.
BMC Complement Med Ther. 2025 Jun 9;25(1):208. doi: 10.1186/s12906-025-04956-1.
The objective of this investigation was to produce fermented solid-state products of Salvia miltiorrhiza Bunge (SMB) utilizing Shiraia bambusicola Henn. (FSSMB). Additionally, it was intended to further explore toxicity-reducing potential and antioxidant effects of FSSMB ethanol extract against HO-induced oxidative stress in rat pheochromocytoma cell line 12 (PC12).
PC12 cells were pre-treated with SMB or FSSMB ethanol extract for 24 h, followed by exposure to 1 mmol/L HO for 3 h to induce oxidative stress. Subsequently, the cell viability, reactive oxygen species (ROS) level, malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, p-p38/p38 and p-JNK/JNK proteins were assessed. Additionally, the content of antioxidant, including tanshinones (tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone) and salvianolic acids (danshensu, rosmarinic acid, lithospermic acid, and salvianolic acid B) were quantified by HPLC in SMB and FSSMB.
Here, we found that FSSMB exhibited lower cytotoxicity compared to SMB in PC12 cells, and FSSMB instead of SMB significantly increased cell viability in HO-induced PC12 cells. Notably, FSSMB exhibited superior antioxidant properties in HO-induced PC12 cells, as evidenced by reduced levels of ROS, MDA, and enhanced SOD activity compared to SMB. Mechanistically, FSSMB reversed HO-induced increase of phosphorylation of p38 and JNK protein in mitogen-activated protein kinase (MAPK) signaling pathway, thereby protecting PC12 cells from oxidative stress-induced injury. Furthermore, we found a significant increase of tanshinone IIA and cryptotanshinone content, accompanied by decreased levels of tanshinone I, dihydrotanshinone and salvianolic acids in FSSMB compared to SMB.
Our study explores a new biological transformation approach through solid-state fermentation (SSF) with Shiraia bambusicola Henn. on SMB. This study demonstrated that the SSF may reduce the cytotoxicity and enhance the antioxidant capacity of SMB in PC12 cells, thus paving the way for safer and more efficacious applications in the future. FSSMB may be an effective substitute for traditional Chinese medicine SMB for resistance to oxidative stress.
本研究旨在利用竹黄（Shiraia bambusicola Henn.）制备丹参（Salvia miltiorrhiza Bunge，SMB）的发酵固态产物（FSSMB）。此外，旨在进一步探讨FSSMB乙醇提取物对过氧化氢（HO）诱导的大鼠嗜铬细胞瘤细胞系12（PC12）氧化应激的减毒潜力和抗氧化作用。
PC12细胞用SMB或FSSMB乙醇提取物预处理24小时，然后暴露于1 mmol/L HO 3小时以诱导氧化应激。随后，评估细胞活力、活性氧（ROS）水平、丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性、磷酸化p38/p38和磷酸化JNK/JNK蛋白。此外，通过高效液相色谱法（HPLC）对SMB和FSSMB中抗氧化剂的含量进行定量，包括丹参酮（丹参酮I、丹参酮IIA、二氢丹参酮和隐丹参酮）和丹酚酸（丹参素、迷迭香酸、紫草酸和丹酚酸B）。
在此，我们发现与SMB相比，FSSMB在PC12细胞中表现出较低的细胞毒性；在HO诱导的PC12细胞中，FSSMB而非SMB显著提高了细胞活力。值得注意的是，在HO诱导的PC12细胞中FSSMB表现出优异的抗氧化性能，与SMB相比，ROS和MDA水平降低，SOD活性增强证明了这一点。机制上，FSSMB逆转了HO诱导的丝裂原活化蛋白激酶（MAPK）信号通路中p38和JNK蛋白磷酸化的增加，从而保护PC12细胞免受氧化应激诱导的损伤。此外，我们发现与SMB相比，FSSMB中丹参酮IIA和隐丹参酮含量显著增加，同时丹参酮I、二氢丹参酮和丹酚酸水平降低。
我们的研究探索了一种通过竹黄对SMB进行固态发酵（SSF）的新生物转化方法。本研究表明，SSF可能降低SMB在PC12细胞中的细胞毒性并增强其抗氧化能力从而为未来更安全、更有效的应用铺平道路。FSSMB可能是传统中药SMB抵抗氧化应激的有效替代品。
