Leonurine Protects Bone Mesenchymal Stem Cells from Oxidative Stress by Activating Mitophagy through PI3K/Akt/mTOR Pathway

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 11; p. 1724
• Main Authors: Zhao, Bingkun, Peng, Qian, Wang, Dan, Zhou, Rong, Wang, Raorao, Zhu, Yizhun, Qi, Shengcai
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.05.2022; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Alkaloids; Animals; Antioxidants; Apoptosis; Bioinformatics; Bone growth; Bone marrow; Bone resorption; Cell culture; Cell differentiation; Chemical properties; Chinese medicine; Control; Cyclooxygenase-2; Development and progression; Fractures; Gallic Acid - analogs & derivatives; Homeostasis; Humans; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; leonurine; Medical research; Medicine, Experimental; Membrane potential; Membranes; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Metabolism; Mineralization; Mitochondria; Mitochondrial DNA; Mitophagy; mRNA; NOX4 protein; Osteogenesis; Osteoporosis; Osteoporosis - metabolism; Oxidative Stress; Phosphatase; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Protocol; PTEN-induced putative kinase; Rats; Risk factors; Stem cell transplantation; Stem cells; TOR protein; TOR Serine-Threonine Kinases - metabolism; China; New York; St Louis Missouri; United Kingdom > UK; United States > US; Japan; osteoporosis; mitophagy; leonurine
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11111724

Osteoporosis bears an imbalance between bone formation and resorption, which is strongly related to oxidative stress. The function of leonurine on bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress is still unclear. Therefore, this study was aimed at identifying the protective effect of leonurine on H O stimulated rat BMSCs. We found that leonurine can alleviate cell apoptosis and promote the differentiation ability of rat BMSCs induced by oxidative stress at an appropriate concentration at 10 μM. Meanwhile, the intracellular ROS level and the level of the COX2 and NOX4 mRNA decreased after leonurine treatment in vitro. The ATP level and mitochondrial membrane potential were upregulated after leonurine treatment. The protein level of PINK1 and Parkin showed the same trend. The mitophage in rat BMSCs blocked by 3-MA was partially rescued by leonurine. Bioinformatics analysis and leonurine-protein coupling provides a strong direct combination between leonurine and the PI3K protein at the position of Asp841, Glu880, Val882. In conclusion, leonurine protects the proliferation and differentiation of BMSCs from oxidative stress by activating mitophagy, which depends on the PI3K/Akt/mTOR pathway. The results showed that leonurine may have potential usage in osteoporosis and bone defect repair in osteoporosis patients.