2. Academic Validation
  3. 5-Hydroxymethylfurfural and Isoverbascoside Alleviate Oxidative Damage INS-1 and MIN6 β-Cells by Activating Autophagy and Inhibiting Apoptosis

5-Hydroxymethylfurfural and Isoverbascoside Alleviate Oxidative Damage INS-1 and MIN6 β-Cells by Activating Autophagy and Inhibiting Apoptosis

  • Metabolites. 2026 Jan 6;16(1):48. doi: 10.3390/metabo16010048.
Xianglong Meng 1 2 3 4,  Yuting Li 1 2 3 4,  Xiang Han 1 2 3 4,  Ziang Li 1 2 3 4,  Zhulin Bu 1 2 3 4,  Yuhui Wu 1 2 3 4,  Xiaofen Li 1 2 3 4,  Shuosheng Zhang 1 2 3 4,  Yuting Dai 5
Affiliations

Affiliations

  • 1 College of Traditional Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong 030619, China.
  • 2 Shanxi Key Laboratory of Tradition Herbal Medicines Processing, Jinzhong 030619, China.
  • 3 Traditional Chinese Medicine Processing Techniques Hertiage Base (Shanxi University of Chinese Medicine), National Adminstration of Traditional Chinese Medicine, Jinzhong 030619, China.
  • 4 Key Research Laboratory of Processing and Innovation in Chinese Medicinal Materials, Shanxi University of Chinese Medicine, Jinzhong 030619, China.
  • 5 First Clinical College, Shanxi University of Chinese Medicine, Jinzhong 030619, China.
PMID: 41590656 DOI: 10.3390/metabo16010048
Abstract

Background/Objectives: In type 2 diabetes (T2DM), dysregulated glucose and lipid metabolism impair cellular energy sensing and inhibit Autophagy, leading to the accumulation of dysfunctional cellular components, increased inflammation and oxidative stress, and activation of the intrinsic apoptotic pathway. Prepared Rehmannia glutinosa is an anti-diabetic traditional Chinese medicine whose active monomers, including 5-Hydroxymethylfurfural (5-HMF) and isoverbascoside, exhibit potential antioxidant and anti-apoptotic effects. However, their role in β-cell protection remains unexplored. This study aims to investigate the protective mechanisms of 5-HMF and isoverbascoside against H2O2-induced oxidative damage in pancreatic β-cells. Methods: INS-1 and MIN6 β-cells were treated with 5-HMF and isoverbascoside (20 μM, 40μM) for 24 h under H2O2-induced oxidative stress. Multiple techniques were employed, including transcriptomics, proteomics, machine learning, Western blot analysis, and molecular docking. Flow cytometry and Hoechst 33342 staining were used to assess Apoptosis, while Autophagy was evaluated via LC3 fluorescence intensity and Beclin-1 expression. Chloroquine (CQ), an Autophagy inhibitor, was applied to further examine autophagy's role. Conclusions: 5-HMF and isoverbascoside enhance autophagic activity in pancreatic β-cells, attenuate oxidative stress-induced Apoptosis, and improve cell survival and proliferation. These findings underscore their potential as protective agents in T2DM by modulating the autophagy-apoptosis balance.

Keywords

5-Hydroxymethylfurfural; T2DM; apoptosis; autophagy; isoverbascoside; pancreatic β cell.

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