Table 1.

Antioxidant strategies in the management of DCM.

Sl. No.	Agents	Mechanisms	References
1	Coenzyme Q10	It elicits protection for cardiomyocyte function by augmenting antioxidant properties. It reduces cardiac inflammation, fibrosis, and hypertrophy induced by T1DM and T2DM.	[138,139]
2	Catalase	Upregulation of catalase causes improvement in the cardiac morphology, mitochondrial, and myofibrillar characters and cardiomyocyte contractility with a significant reduction in the levels of ROS. It has been found to ameliorate diabetes-induced autophagy by increasing NF-κB activity.	[61,140]
3	Thioredoxin	Thioredoxin 2 acts like a mitochondrial antioxidant that offers protection against oxidative stress. Overexpression of thioredoxin 2 has been reported to reduce high glucose-induced mitochondrial oxidative damage along with decreasing expression of ANP and BNP. Loss of thioredoxin 2 has been found to induce cardiomyocyte hypertrophy.	[141,142]
4	Edaravone	Edaravone inhibits fibrosis and cardiac apoptosis by activating Nrf2, NADP quinone oxidoreductase and heme oxygenase. Increased activity of sirtuin 1 and PGC-1α by edaravone has been reported. Additionally, it reduces apoptosis by increasing Bcl-2 expression and reducing Bax and caspase-3 expressions in cardiomyocytes.	[143,144]
5	Quercetin	Quercetin prevents cardiac remodeling by promoting Nrf-2 and inhibiting NF-κB signaling. It inhibits the RAAS pathway, decreases expression of TGF-β1, and subsequently reduces deposition of the ECM. Additionally, it modulates the sirtuin 3/PARP-1 pathway and inhibits cardiac hypertrophy.	[145,146]
6	Taxifolin	Taxifolin exerts an antifibrotic effect by inhibiting TGF-β/SMAD signaling. It has been found to improve diastolic dysfunction, ameliorate myocardium structure abnormality, and enhance endogenous antioxidant enzyme activities. It also reduces angiotensin II levels in the myocardium and inhibits NADPH oxidase activity. It has been found to prevent myocyte apoptosis by inhibiting caspase-3 and caspase-9 activation and restoring mitochondrial membrane potential.	[147,148]
7	Luteolin	Luteolin protects against DCM by inhibiting NF-κB and activating the Nrf2-mediated antioxidant responses. It inhibits TGF-β1, NOX4, and NOX2.	[149,150]
8	Kaempferol	Kaempferol inhibits NF-κB and endorses Nrf-2 activation. It prevents diabetes-induced cardiac fibrosis and apoptosis.	[151,152]
9	Szeto–Schiller peptide (SS31)	SS31 is a positively charged free radical scavenger that accumulates in the mitochondria and prevents diastolic dysfunction, myocardial fibrosis, and subsequent cardiac hypertrophy. SS31 has been reported to mitigate oxidative stress, autophagy, and ER stress.	[153,154]
10	Isorhamnetin	Isorhamnetin reduces cardiac fibrosis and hypertrophy. It improves insulin signaling and restores the arrangement of myofibrils. It upregulated Akt-2, microRNA (miR)-1, and miR-3163 expression in skeletal muscle and adipose tissue.	[155,156]
11	Sulphoraphane	Sulforaphane prevents DCM via the upregulation of Nrf2 and metallothionein. It also prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation.	[157,158]