L‐Theanine Alleviates Alcohol‐Induced Kidney Injury by Inhibiting the Sphingolipid Metabolism‐S1PR2‐JNK Pathway and Activating the PPARα‐Steroid Synthesis Pathway

ABSTRACT Alcohol exposure induces kidney oxidative stress and inflammatory responses. L‐theanine (LTA) can protect the kidneys through its antioxidant and immunomodulatory effects; however, its role and underlying mechanisms in alleviating alcoholic kidney injury remain unclear. In this study, LTA significantly ameliorated alcohol‐induced kidney tissue structural damage, excessive release of inflammatory factors, and oxidative stress imbalance, with the 400 mg kg −1 day −1 dose group showing the most effective intervention. LTA inhibited the sphingolipid metabolism‐S1PR2‐JNK signaling pathway, reduced sphingosine levels, downregulated the S1PR2 proinflammatory receptor, blocked S1PR2 signal transduction, and subsequently suppressed JNK phosphorylation and AP‐1 activity. Additionally, LTA activated the PPARα and steroid synthesis pathway, promoting the production of endogenous anti‐inflammatory steroids. These results indicate that LTA alleviates alcohol‐induced kidney injury by inhibiting the sphingolipid metabolism‐S1PR2‐JNK pathway and activating the PPARα and steroid synthesis pathways, providing a safe and effective nutritional intervention strategy for alcoholic kidney injury.