The protective effects of protocatechualdehyde (PCA) on hearts of mice with diabetic cardiomyopathy (DCM) and its possible molecular mechanism were investigated. After the successful construction of DCM mouse models, PCA intervention was made. The heart-to-body mass ratio of mice and the cardiac function were determined. The expression levels of pro-inflammatory factors, troponin I, lactate dehydrogenase (LDH), and creatine kinase (CK) in the myocardial tissues were also determined. Hematoxylin and eosin (HE) staining and Masson staining methods were used to observe the morphological changes of the myocardial tissues. The expressions of nod-like receptor protein 3 (NLRP3) in the myocardial tissue and myocardial cells were detected, and the effects of PCA on the survival rate of myocardial cells were evaluated. The results showed that the heart-to-body mass ratio, ejection fraction, and fractional shortening increase by 5.42 mg/g, 54.91%, and 28.07%, respectively, after PCA intervention. At the same time, serum LDH, CK, and troponin I concentrations decrease to 538.51 U/L, 885.93 U/L, and 221.87 pg/mL, respectively. The levels of tumor necrosis factor-α, interleukin1β, and interleukin-6 also decreased (P<0.05). PCA also inhibited myocardial cytotoxicity and activation of NLRP3 inflammasome induced by high glucose concentrations. PCA can protect the myocardium of DCM mice. Inhibition of the activation of NLRP3 inflammasome may be the way to cardiac improvement.
[4] EGBERT B, PAULINA W, MICHAEL P, et al. Targeting cardiac hypertrophy: toward a causal heart failure therapy [J]. Journal of Cardiovascular Pharmacology, 2014, 64(4): 293-305.
[5] GE Z D, LIAN Q Q, MAO X W, et al. Current status and challenges of Nrf 2 as a potential therapeutic target for diabetic cardiomyopathy [J]. International Heart Journal, 2019, 60(3): 512-520.
[6] THOMAS H M, REBECCA R, DAVID K, et al. Implications of underlying mechanisms for the recognition and management of diabetic cardiomyopathy [J]. Journal of the American College of Cardiology, 2018, 71(3): 339-351.
[8] SHI M, HUANG F F, DENG C P, et al. Bioactivities, biosynthesis and biotechnological production of phenolic
acids in Salvia miltiorrhiza [J]. Critical Reviews in Food Science and Nutrition, 2019, 59(6): 953-964.
[10] KYOUNG J K, MI A K, JEE H J. Antitumor and antioxidant activity of protocatechualdehyde produced from streptomyces lincolnensis m-20 [J]. Archives of Pharmacal Research, 2008, 31(12): 1572-1577.
[11] YANG J K, LI J C, TAN R Z, et al. Protocatechualdehyde attenuates obstructive nephropathy through inhibiting lncRNA9884 induced inflammation [J]. Phytotherapy Research, 2021, 35(3): 1521-1533.
[12] WEI G, GUAN Y, YIN Y, et al. Anti-inflammatory effect of protocatechuic aldehyde on myocardial ischemia/reperfusion injury in vivo and in vitro [J]. Inflammation, 2013, 36(3): 592-602.
[13] TONG M M, ZHAI P Y, TOSHIRO S, et al. Mitophagy is essential for maintaining cardiac function during high fat diet-induced diabetic cardiomyopathy [J]. Circulation Research, 2019, 124(9): 1360-1371.
[14] YANG F, QIN Y, WANG Y Q, et al. Metformin inhibits the Nlrp3 inflammasome via Ampk/Mtor-dependent effects in diabetic cardiomyopathy [J]. International Journal of Biological Sciences, 2019, 15(5): 1010-1019.
[15] CHANG Y T, CHUNG M C, WU M J, et al. Evaluation of the therapeutic effects of protocatechuic aldehyde in diabetic nephropathy [J]. Toxins, 2021, 13(8): 560-572.
[16] WAN Y J, WANG Y H, GUO Q, et al. Protocatechualdehyde protects oxygen-glucose deprivation/reoxygenation-induced myocardial injury via inhibiting perk/atf α/ire 1α pathway [J]. European Journal of Pharmacology, 2021, 891: 173-723.
[17] FAN D, YANG Z, LIU F Y, et al. Sesamin protects against cardiac remodeling via Sirt3/Ros pathway [J]. Cellular Physiology and Biochemistry, 2017, 44(6): 2212-2227.
[21] RISHI B, MELISSA K S, JEFFREY S C, et al. IL-1β (interleukin-1β) and Tnf-α (tumor necrosis factor-α) impact abdomina aortic aneurysm formation by differential effects on macrophage polarization [J]. Arteriosclerosis Thrombosis and Vascular Biology, 2018, 38(2): 457-463.
[22] WAN Y J, GUO Q, LIU D, et al. Protocatechualdehyde reduces myocardial fibrosis by directly targeting conformational dynamics of collagen [J]. European Journal of Pharmacology, 2019, 855: 183-191.
[23] EDWARD J O, WILLIAM R R, GARY D G, et al. Targeting the Nlrp3 inflammasome in inflammatory diseases [J]. Nature Reviews Drug Discovery, 2018, 17(8): 588-606.
[24] HE Y, HIDEKI H, GABRIEL N. Mechanism and regulation of Nlrp3 inflammasome activation [J]. Trends in Biochemical Sciences, 2016, 41(12): 1012-1021.
[25] MORITZ H, LUKE A J O. NLRP3 at the interface of metabolism and inflammation [J]. Immunological Reviews, 2015, 265(1): 53-62.
