Luteolin alleviates diabetic cardiac injury related to inhibiting SHP2/STAT3 pathway

Diabetic cardiomyopathy, a heart disease resulting from diabetes mellitus, inflicts structural and functional damage to the heart. Recent studies have highlighted the potential role of luteolin, a flavonoid, in mitigating diabetic cardiovascular injuries. The Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) is implicated in exacerbating diabetes- and obesity-related complications. Interestingly, luteolin has been shown to inhibit protein tyrosine phosphatases, but it's unclear how SHP2 relates to luteolin's protective effects against diabetic heart disease. Here, we hypothesized that the inhibition of SHP2 signaling could play a role in luteolin's protective action against diabetic heart injury. Diabetes was induced in male Sprague-Dawley rats through a high-fat diet followed by a single intraperitoneal dose of streptozotocin (30 mg/kg). Five weeks post-diabetes induction, these rats were intraperitoneally injected with luteolin at varying doses (5, 10, 20 mg/kg) every other day for an additional 5 weeks. Then cardiac function was assessed, and hearts were isolated for further analysis. We found that luteolin notably improved cardiac function, inhibited cardiac hypertrophy and fibrosis, reduced levels of inflammatory factors and reactive oxygen species, and activated superoxide dismutase. Importantly, luteolin treatment also reduced the expression of SHP2 and phosphorylated signal transducer and activator of transcription 3 (STAT3) in a dose-dependent manner. These findings suggest that luteolin protects the diabetic heart against inflammation, oxidative stress, hypertrophy, and fibrosis, which may relate to down-regulating cardiac SHP2/STAT3 signaling.