Mangiferin ameliorates cardiac fibrosis in D-galactose-induced aging rats by inhibiting TGF-β/p38/MK2 signaling pathway

Abstract

Aging is the process spontaneously occurred in living organisms. Cardiac fibrosis is a pathophysiological process of cardiac aging. Mangiferin is a well-known C-glucoside xanthone in mango leaves with lots of beneficial properties. In this study, rat model of cardiac fibrosis was induced by injected with 150 mg/kg/d D-galactose for 8 weeks. The age-related cardiac decline was estimated by detecting the relative weight of heart, the serum levels of cardiac injury indicators and the expression of hypertrophic biomakers. Cardiac oxidative stress and local inflammation were measured by detecting the levels of malondialdehyde, enzymatic antioxidant status and proinflammatory cytokines. Cardiac fibrosis was evaluated by observing collagen deposition via masson and sirius red staining, as well as by examining the expression of extracellular matrix proteins via Western blot analysis. The cardiac activity of profibrotic TGF-β1/p38/MK2 signaling pathway was assessed by measuring the expression of TGF-β1 and the phosphorylation levels of p38 and MK2. It was observed that mangiferin ameliorated D-galactose-induced cardiac aging, attenuated cardiac oxidative stress, inflammation and fibrosis, as well as inhibited the activation of TGF-β1/p38/MK2 signaling pathway. These results showed that mangiferin could ameliorate cardiac fibrosis in D-galactose-induced aging rats possibly via inhibiting TGF-β/p38/MK2 signaling pathway.

Antioxidant Effect of Soymilk Fermented by Lactobacillus plantarum HFY01 on D-Galactose-Induced Premature Aging Mouse Model

“…D-galactose, which is an aging agent, has been widely used in the construction of cell and animal models of premature aging, but its mechanism is not fully understood. Excessive intake of D-galactose can lead to cellular metabolism disorders, enzyme activity changes, and increased peroxides, leading to oxidative damage to the structure and function of biological macromolecules, which then leads to systemic inflammatory responses and various complications (7,8).…”

D‐galactose‐induced cardiac ageing: A review of model establishment and potential interventions

“…Intraperitoneal injection of D-galactose at a dose of 150 mg/kg/day in Wistar rats for eight weeks, or subcutaneous injection of D-galactose at a dose of 500 mg/kg/day in mice for four weeks increased the cardiac index and led to cardiac fibrosis. [28][29][30] This difference may be related to the dose and duration of D-galactose treatment. In conclusion, taking rats as an example, intraperitoneal injection of a higher dose of D-galactose and for a prolonged period leads to a decrease in the cardiac index.…”

“…13,[32][33][34][35][36] Moreover, studies have shown that heavier Wistar rats require higher amounts of D-galactose at the same administration time. 10,12,28,30,37 Evidence suggests that D-galactose treatment increases oxidants levels and decreases antioxidants levels (Table 2). ROS can attack proteins, lipids and DNA, altering their structures and functions.…”

“…43,44 Studies have shown that p-NF-κB, NF-κB, P65 (a member of the NF-κB family of proteins), IL-1α, IL-1β, and IL-6 increase, and IkB decreases with D-galactose administration. 12,28,32,36,37…”

“…D-galactose administration of 120-500 mg/ kg/day for 4-8 weeks has been reported to cause an increase in the whole heart weight (WHW), left ventricular weight (LVW), and LV wall thickening, an increase in hypertrophic makers such as ANP, BNP, β-MHC, and MYH7 and a decrease in MYH6. 13,28,33,36 Chang et al 13 found that the concentric hypertrophy-related MAPKs such As summarized in Table 5, D-galactose administration increases cardiac fibrosis and collagen deposition. 5,9,28,30,33,36,60 After activation, excessive collagen secreted by cardiac fibroblasts is deposited in the extracellular matrix, resulting in myocardial fibrosis.…”