5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, a microbiota metabolite of flavan-3-ols, activates SIRT1-mediated autophagy to attenuate H₂O₂-induced inhibition of osteoblast differentiation in MC3T3-E1 cells

• Published in: Free radical biology & medicine Vol. 208; pp. 309 - 318
• Main Authors: Chen, Fengyan, Zhang, Xuanrui, Chen, Shanshan, Wu, Yulin, Wei, Qinzhi, Chu, Xinwei, Zhang, Zheqing
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2023
• Subjects: 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone; H₂O; MC3T3-E1 cells; Osteoblast differentiation; SIRT1; 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone; H₂O; SIRT1; MC3T3-E1 cells; Osteoblast differentiation
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2023.08.018

Phenolic compounds are promising agents for the prevention of osteoporosis. 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone (DHPV) is the major microbiota metabolite of the flavan-3-ols phenolic compound. Herein, we aimed to investigate the potential mechanisms underlying the effects of DHPV on an osteoblast cell model with H2O2-induced oxidative injury. The MC3T3-E1 cell cultured with H2O2 was used as an oxidative injury model after pretreating with DHPV. Pretreatment with DHPV significantly attenuated cell viability decline, enhanced the activity of alkaline phosphatase and mineralization capacity in MC3T3-E1 cells. Reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels as well as increased in mitochondrial membrane potential and superoxide dismutase (SOD) activities indicated that DHPV affected both the oxidative and antioxidative processes in the cells. DHPV administration increased the LC3-II/I ratio and Beclin-1 protein levels, thereby promoting autophagy, which perhaps contributes to ROS elimination. However, the inhibition of Sirtuin 1 (SIRT1) by SIRT1 small interfering RNA reduced the protective effect of DHPV or SRT1720, as revealed by the increased ROS and MDA levels and decreased SOD, LC3-II/I ratio and Beclin-1 levels. DHPV may promote autophagy and reduce oxidative stress through the SIRT1-mediated pathway, thereby protecting MC3T3-E1 cells from H2O2-induced oxidative damage. [Display omitted] •DHPV improved autophagy and inhibited oxidative stress in H2O2-treated MC3T3-E1 cells.•DHPV promoted osteoblast differentiation of H2O2-induced MC3T3-E1 cells via stimulating SIRT1-mediated autophagy pathway.•DHPV hold promise as a novel protective agent for osteoporosis.