Anti-Apoptotic and Pro-Survival Effect of Alpinate Oxyphyllae Fructus (AOF) in a d-Galactose-Induced Aging Heart

Abstract

Aging, a natural biological/physiological phenomenon, is accelerated by reactive oxygen species (ROS) accumulation and identified by a progressive decrease in physiological function. Several studies have shown a positive relationship between aging and chronic heart failure (HF). Cardiac apoptosis was found in age-related diseases. We used a traditional Chinese medicine, Alpinate Oxyphyllae Fructus (AOF), to evaluate its effect on cardiac anti-apoptosis and pro-survival. Male eight-week-old Sprague–Dawley (SD) rats were segregated into five groups: normal control group (NC), d-Galactose-Induced aging group (Aging), and AOF of 50 (AL (AOF low)), 100 (AM (AOF medium)), 150 (AH (AOF high)) mg/kg/day. After eight weeks, hearts were measured by an Hematoxylin–Eosin (H&E) stain, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-assays and Western blotting. The experimental results show that the cardiomyocyte apoptotic pathway protein expression increased in the d-Galactose-Induced aging groups, with dose-dependent inhibition in the AOF treatment group (AL, AM, and AH). Moreover, the expression of the pro-survival p-Akt (protein kinase B (Akt)), Bcl-2 (B-cell lymphoma 2), anti-apoptotic protein (Bcl-xL) protein decreased significantly in the d-Galactose-induced aging group, with increased performance in the AOF treatment group with levels of p-IGFIR and p-PI3K (Phosphatidylinositol-3′ kinase (PI3K)) to increase by dosage and compensatory performance. On the other hand, the protein of the Sirtuin 1 (SIRT1) pathway expression decreased in the aging groups and showed improvement in the AOF treatment group. Our results suggest that AOF strongly works against ROS-induced aging heart problems.

Effects of d‐galactose‐induced ageing on the heart and its potential interventions

“…In that study, Kunming mice at the age of 4–6 weeks old were used. Compared to this, the initial age of the rats and mice in other studies was 8–20 weeks old . Therefore, the differing findings could be explained by the fact that the starting age of experimental animals is the key determinant to create an effective d ‐galactose‐induced ageing model.…”

“…The mechanisms of how d ‐galactose induced an ageing heart can be identified, according to this review, include those resulting in increased oxidative stress and reduced levels of antioxidants , increased apoptosis , an alteration in calcium homeostasis and impaired cardiac morphology . These mechanisms, separately or severally, lead ultimately to cardiac dysfunction . These pathways may be targets for developing strategies for approaching the issues associated with anti‐ageing in the future.…”

“…All the experiments summarized in this review have been carried out in vivo or in vitro, and based on the evidence accumulated here, D-galactose treatment can successfully induce cardiac senescence models as indicated by increasing expression of senescence markers [3,[7][8][9]. The mechanisms of how D-galactose induced an ageing heart can be identified, according to this review, include those resulting in increased oxidative stress and reduced levels of antioxidants [3,7,8,14], increased apoptosis [21,22,25], an alteration in calcium homeostasis [9,21] and impaired cardiac morphology [3,8,15,22]. These mechanisms, separately or severally, lead ultimately to cardiac dysfunction [22].…”

“…Moreover, AGE-RAGE interactions in cardiac tissue can activate NF-jB nuclear translocation and increase inflammatory gene transcription, causing inflammation [12]. Currently, there is only one study that investigated cardiac function in D-galactose-induced aged rats, and the findings showed a decreased left ventricular ejection fraction and fraction shortening in D-galactose-induced aged rats when compared to control rats [22]. The dose that could induce cardiac dysfunction was 150 mg/kg/day by intraperitoneal injection for 8 weeks as displayed in Table 4.…”

Alpinate Oxyphyllae extracts enhance the longevity and homing of mesenchymal stem cells and augment their protection against senescence in H9c2 cells

“…Moreover, SIRT1 inhibits NF‐κB mediated transcriptional activations via direct interaction with the NF‐κB p65 subunit at lysine 310 (Yeung et al, ). Our previous study demonstrated that SIRT1 is markedly reduced in aging rat hearts; however, AOF treatment reverts the levels of SIRT1 and promotes PGC‐1α activation (Chang et al, ).…”