Novel Curcumin C66 That Protects Diabetes-Induced Aortic Damage Was Associated with Suppressing JNK2 and Upregulating...

Area of Science:

• Cardiovascular Research
• Diabetes Complications
• Molecular Mechanisms

Background:

• Diabetes-related cardiovascular diseases are a major global health concern.
• Previous research indicated a protective effect of curcumin analogue C66 on aortic changes in diabetes.
• The precise mechanisms underlying C66's protective action require elucidation.

Purpose of the Study:

• To investigate the underlying protective mechanisms of curcumin analogue C66 in diabetes-induced aortic pathology.
• To assess the role of JNK2 inhibition and Nrf2 activation in C66's therapeutic effects.

Main Methods:

• Diabetes was induced in wild-type (WT) and JNK2 knockout (JNK2-/-) mice using streptozotocin.
• Mice were treated with vehicle or C66 for three months.
• Aortic oxidative stress, apoptosis, inflammation, fibrosis, and Nrf2 expression were evaluated using immunohistochemistry and real-time PCR.

Main Results:

• Both C66 treatment and JNK2 deletion reversed diabetes-induced aortic oxidative stress, apoptosis, inflammation, and fibrosis.
• Nrf2 expression and function were upregulated by both C66 and JNK2 deletion.
• C66 demonstrated no additional benefit in JNK2 knockout diabetic mice, indicating JNK2 inhibition as a key pathway.

Conclusions:

• Curcumin analogue C66 protects against diabetes-induced aortic pathological changes primarily through JNK2 inhibition.
• The protective effects are associated with the upregulation of Nrf2 expression and function.
• Targeting the JNK2/Nrf2 pathway presents a potential therapeutic strategy for diabetic cardiovascular complications.