Korean J Physiol Pharmacol.  2021 Mar;25(2):131-137. 10.4196/kjpp.2021.25.2.131.

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

• Cheng J
• Ren C
• Cheng R
• Li Y
• Liu P
• Wang W
• Liu L

• KMID: 2512956
• DOI: http://doi.org/10.4196/kjpp.2021.25.2.131

Abstract

Aging is the process spontaneously occurred in living organisms. Cardiac fibrosis is a pathophysiological process of cardiac aging. Mangiferin is a wellknown 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 Dgalactose 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.

Keyword

Aging; Heart fibrosis; Inflammation; Mangiferin; Oxidative stress

Figure

• 

  Fig. 1 Effects of mangiferin on serum levels (A) of CK and LDH, as well as on cardiac expression (B) of ANP, BNP, and β-MHC in D-gal-induced aging rats. The levels of serum CK and LDH were detected using commercial kits according to instructions (n = 8). The expression of cardiac ANP, BNP, and β-MHC was detected by Western blot analysis (n = 3). Values were presented as mean ± standard deviation. CK, creatine kinase; LDH, lactate dehydrogenase; ANP, natriuretic peptides A; β-MHC, β-myosin heavy chain; D-gal, D-galactose; Veh group, vehicle control group; Aging group, D-gal-induced aging group. *p < 0.05, **p < 0.01 compared to the Aging group. ##p < 0.01 compared to the Veh group.

• 

  Fig. 2 Effect of mangiferin on cardiac collagen deposition. (A) Histological analysis for the effects of mangiferin on D-gal-induced collagen deposition in rat heart sections stained by masson and sirius red. The proportion of masson- and sirius red-positive area in sections were measured using Image-Pro Plus 6.0. Images were captured at 200× magnification. Scale bar of 100 μm was marked. (B) The proportion of masson-positive area and sirius red in heart sections. Values (n = 8) were presented as mean ± standard deviation. D-gal, D-galactose; Veh group, vehicle control group; Aging group, D-gal-induced aging group. **p < 0.01 compared to the Aging group. ##p < 0.01 compared to the Veh group.

• 

  Fig. 3 Effects of mangiferin on cardiac oxidative stress (A) and inflammation (B) in D-gal-induced aging rats. The activities of enzymatic antioxidants SOD and CAT, as well as the level of lipid peroxidation marker MDA and proinflammatory cytokines IL-1β, IL-6 and TNF-α were measured in accordance with the instructions of commercial kits. Values (n = 8) were presented as mean ± standard deviation. D-gal, D-galactose; SOD, superoxide dismutase; CAT, catalase; MDA, malondialdehyde; IL, interleukin; TNF, tumor necrosis factor; Veh group, vehicle control group; Aging group, D-gal-induced aging group. **p < 0.01 compared to the Aging group. ##p < 0.01 compared to the Veh group.

• 

  Fig. 4 Analysis for cardiac expression of pro-fibrogenic proteins (TGF-β1, p-p38, p-MK2, p38, and MK2) and ECM proteins (Col-I, Col-III, and α-SMA) in D-gal-induced aging rats. Values (n = 3) were presented as mean ± standard deviation. D-gal, D-galactose; Veh group, vehicle control group; Aging group, D-gal-induced aging group. *p < 0.05, **p < 0.01 compared to the Aging group. #p < 0.05, ##p < 0.01 compared to the Veh group.

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