Cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signaling

Abstract

Background: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to significant mortality. Cyclocarya paliurus is a tree, the leaves of which are often utilized to prevent and treat diabetes mellitus. Whether C. paliurus leaves can prevent or treat DCM, however, it remains to be formally assessed. The present study was therefore designed to assess the ability of C. paliurus to protect against DCM in db/db mice. Methods: Male wild-type (WT) and db/db mice were administered C. paliurus ethanol leaf extracts (ECL) or appropriate vehicle controls daily via gavage, and levels of blood glucose in treated animals were assessed on a weekly basis. After a 10-week treatment, the levels of cardiac troponin I (cTn-I), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), total triglycerides (TG), and total cholesterol (TC) in serum were measured. Activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in heart tissues were detected. Hematoxylin-eosin (HE) and Masson staining were conducted. The protein expression that related with oxidative stress and inflammatory reaction was evaluated by Western blotting. Results: Compared with WT mice, the TG, TC, and blood glucose levels in db/db mice increased significantly, which were reduced by ECL treatment. Compared with WT mice, the levels of LDH, CK-MB, AST, and cTn-I in serum and MDA in heart tissues of db/db mice increased significantly. Activities of SOD, GSH-Px, and CAT in heart tissues of db/db mice decreased significantly. The levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in heart tissues of db/db mice increased remarkably. However, ECL treatment improved the above pathological changes significantly. ECL alleviated pathological injury and fibrosis in heart tissues of mice. Western blotting showed that ECL increased Bcl-2 level and decreased Bax, cle-caspase-3, and clecaspase-9 expression. Furthermore, ECL inhibited NF-κB nuclear translocation and increased PI3K and p-Akt expressions. Popular scientific summary • Cyclocarya paliurus ethanol leaf extract (ECL) is able to protect against the development of diabetic cardiomyopathy in db/db mice. • The protective efficacy of ECL is associated with antioxidant, antiapoptotic, and anti-inflammatory mechanisms. • ECL is able to inhibit the activation and nuclear localization of NF-κB via promoting PI3K/Akt signaling in db/db mice.

Orange Juice Attenuates Circulating miR-150-5p, miR-25-3p, and miR-451a in Healthy Smokers: A Randomized Crossover Study

“…These enzymes are activated by either upstream tyrosine kinase receptors or G protein-coupled receptors and mediate multiple cellular processes (62). PI3K/Akt signaling is essential for regulation of inflammatory responses, at least in part via controlling intracellular NF-κB activity (63). Our data did not show NF-κB associated with orange juice intake.…”

“…Experimental studies on cancer, myocardial ischemia/reperfusion injury, and arthritis have already shown the effects of hesperidin in modulation of the PI3K-Akt pathway (62)(63)(64)(65). The PI3K/Akt signaling pathway regulates various cellular responses such as cell growth, proliferation, survival, metabolism, and inflammation.…”

Potential Role of Natural Plant Medicine Cyclocarya paliurus in the Treatment of Type 2 Diabetes Mellitus

“…Further mechanistic exploration revealed that C. paliurus extract reduced the expression of NF- κ B and myocarditis by activating the PI3K/Akt signaling pathway, improving antiapoptotic Bcl-2, and reducing prapoptotic cle-caspase-3, cle-caspase-9, and Bax, to reduce myocardial inflammation and injury in mouse models. Therefore, it is speculated that it may effectively reduce pathological damage and fibrosis of the heart tissue in diabetic patients [ 100 ].…”

Targeting interleukin‐β by plant‐derived natural products: Implications for the treatment of atherosclerotic cardiovascular disease

“…Its leaves (commonly known as "magical tea" and "sweet tea") have several biological activities such as antiinflammatory, antihyperlipidemic, antioxidant, antihypertensive, antihyperglycemic, and antiobesity effects (Kurihara et al, 2003;Wang et al, 2013;Xie & Xie, 2008;Yan, Jiang, & Xu, 2020). Male Given its various functions and lack of significant adverse effects, C. paliurus leaf extract may have therapeutic value in diabetic cardiomyopathy (Wang et al, 2020).…”