2. Academic Validation
  3. Tubuloside B Alleviates Aβ25-35 Induced PC12 Cell Injury by Attenuating Pyroptosis, Apoptosis and Excessive Autophagy

Tubuloside B Alleviates Aβ25-35 Induced PC12 Cell Injury by Attenuating Pyroptosis, Apoptosis and Excessive Autophagy

  • Neurotox Res. 2026 Mar 19;44(2):12. doi: 10.1007/s12640-026-00791-5.
Hao Yang # 1 2,  Rao Fu # 1 3,  Yueyang Duan 1,  Yongjiao Hua 1,  Tianyu Wei 1 3,  Guiping Li 1,  Xinru Gu 4,  Ming Li 1 3,  Xiao Yu 1,  Liang Li 1,  Liang Cao 1,  Zhen-Zhong Wang 1,  Chenfeng Zhang 1,  Yaozhong Lv 5,  Mingli He 6,  Wei Xiao 7 8 9 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture (Jiangsu Kanion Pharmaceutical Co.,Ltd. & Nanjing University of Chinese Medicine), Nanjing, Jiangsu, 211112, PR China.
  • 2 Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 200120, PR China.
  • 3 Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu, 210023, PR China.
  • 4 Neurology Department, The First People Hospital of Lianyungang, Tongguan North Road, No. 182 Xinpu District, Lianyungang, Jiangsu, 222002, PR China.
  • 5 State Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture (Jiangsu Kanion Pharmaceutical Co.,Ltd. & Nanjing University of Chinese Medicine), Nanjing, Jiangsu, 211112, PR China. [email protected].
  • 6 Neurology Department, The First People Hospital of Lianyungang, Tongguan North Road, No. 182 Xinpu District, Lianyungang, Jiangsu, 222002, PR China. [email protected].
  • 7 State Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture (Jiangsu Kanion Pharmaceutical Co.,Ltd. & Nanjing University of Chinese Medicine), Nanjing, Jiangsu, 211112, PR China. [email protected].
  • 8 Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 200120, PR China. [email protected].
  • 9 Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu, 210023, PR China. [email protected].
  • 10 Neurology Department, The First People Hospital of Lianyungang, Tongguan North Road, No. 182 Xinpu District, Lianyungang, Jiangsu, 222002, PR China. [email protected].
  • # Contributed equally.
PMID: 41854817 DOI: 10.1007/s12640-026-00791-5
Abstract

Cistanche, a traditional Chinese medicine with reported neuroprotective effects, contains multiple bioactive constituents whose specific mechanisms of action remain incompletely defined. Here, we aimed to identify a key neuroprotective component and explore its potential mechanism against Aβ-induced neurotoxicity. Fourteen commercially available Cistanche-derived compounds were screened for neuroprotection in an Aβ25-35 (Aβ fragment 25–35)-injured PC12 cell model. The most active compound, Tubuloside B (TB), was further investigated using polymerase chain reaction (PCR) array, immunoblotting, flow cytometry, immunofluorescence, and mitochondrial function assays. TB exerted concentration-dependent protective effects in the Aβ25-35-injured PC12 model. Aβ25-35 exposure was associated with marked activation of pyroptotic signaling, characterized by Caspase-1 activation, GSDMD cleavage, and increased interleukin (IL)-1β/IL-18 levels. These alterations were substantially blunted in the presence of TB. Modulation of the absent in melanoma 2 (AIM2) inflammasome pathway was further supported by reduced AIM2 expression and diminished apoptosis-associated speck-like protein containing a CARD (ASC) speck formation. Mitochondrial perturbations induced by Aβ25-35, including excessive mitochondrial Reactive Oxygen Species (ROS) generation, membrane depolarization, and cytosolic mtDNA accumulation, were concurrently ameliorated by TB. In addition, markers of Apoptosis and dysregulated Autophagy were partially normalized following TB treatment. These findings suggest that TB may contribute to neuroprotection in an Aβ25-35-induced PC12 cell model, potentially involving modulation of mitochondrial dysfunction–associated inflammasome activation and downstream cell death pathways. Given the in vitro design and limited sample size, these results should be considered preliminary and warrant further validation in vivo.

Keywords

AIM2; Alzheimer's disease; Apoptosis; Autophagy; Pyroptosis.

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