l-Theanine attenuates isoprenaline-induced heart failure in rats through modulation of the JNK/c-Jun/Beclin 1/Bcl2 pathway.

Heart failure (HF) is characterized by impaired cardiac function, cardiac hypertrophy, and elevated cardiomyocyte injury biomarkers. Dysregulation of autophagic pathways has been recently implicated in the pathogenesis of HF. The present study aimed to investigate the possible cardioprotective effects of l-theanine in an isoprenaline-induced HF rat model and to study its potential impact on the autophagic process in HF. Forty-two male Wistar rats were randomly allocated into four groups: a normal control group, an HF group (Isoprenaline, 170 mg/kg/day, SC, for 4 days), an HF + l-theanine group (Isoprenaline + l-theanine, 400 mg/kg/day, p.o., for 32 days) and an l-theanine control group. The HF group demonstrated significant deterioration in echocardiographic parameters, accompanied by significant cardiac injury, as evidenced by increased serum LDH and BNP and reduced cardiac troponin I levels. These changes were associated with dysregulated autophagy, as indicated by elevated Beclin-1, LC3-I, LC3-II, and ATG5 expression, along with increased levels of JNK and c-Jun and decreased Bcl-2 levels. Additionally, increased NF-κB levels and altered total antioxidant capacity indicate enhanced inflammatory responses and oxidative stress. Compared with HF, l-theanine administration effectively improved isoprenaline-induced cardiac dysfunction in rats by improving echocardiographic parameters (EF, FS and LVIDs), ameliorating alterations in cardiac injury markers, and attenuating histopathological damage. l-Theanine significantly decreased autophagy as demonstrated by reduced Beclin-1, LC3-I, LC3-II, and ATG5 levels. Additionally, l-theanine downregulated p-JNK/c-Jun signaling, reduced NF-κB levels, increased Bcl-2 expression, and increased total antioxidant capacity. This study revealed that the modulation of the JNK/c-Jun/Beclin-1/Bcl-2 pathway by l-theanine ameliorates isoprenaline-induced HF via the regulation of autophagic and inflammatory pathways.