Inhibition of Cardiac Hypertrophy Effects in D-Galactose-Induced Senescent Hearts byAlpinate Oxyphyllae FructusTreatment

Abstract

Aging is a complex physiological phenomenon accelerated by ROS accumulation, with multisystem decline and increasing vulnerability to degenerative diseases and death. Cardiac hypertrophy is a key pathophysiological component that accompanies the aging process. Alpinate Oxyphyllae Fructus (Alpinia oxyphylla MIQ, AOF) is a traditional Chinese medicine, which provides cardioprotective activity against aging, hypertension, and cerebrovascular disorders. In this study, we found the protective effect of AOF against cardiac hypertrophy in D-galactose-induced aging rat model. The results showed that treating rats with D-galactose resulted in pathological hypertrophy as evident from the morphology change, increased left ventricular weight/whole heart weight, and expression of hypertrophy-related markers (MYH7 and BNP). Both concentric and eccentric cardiac hypertrophy signaling proteins were upregulated in aging rat model. However, these pathological changes were significantly improved in AOF treated group (AM and AH) in a dose-dependent manner. AOF negatively modulated D-galactose-induced cardiac hypertrophy signaling mechanism to attenuate ventricular hypertrophy. These enhanced cardioprotective activities following oral administration of AOF reflect the potential use of AOF for antiaging treatments.

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.…”

“…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].…”

“…In support of this finding, decreased levels of endogenous antioxidant enzymes such as SOD [7,8], glutathione peroxidase [7], and reduced glutathione levels [14] were demonstrated in D-galactose-treated rats and mice. In addition, increased DHE fluorescence staining, decreased endogenous hydrogen sulphide production, endogenous hydrogen sulphide producing enzyme cystathionine c-lyase (CSE), and nitric oxide (NO) [7], and decreased haem oxygenase-1 (HO-1) [8] were also found in D-galactose-induced cardiac ageing models.…”

Aging induced by D-galactose aggravates cardiac dysfunction via exacerbating mitochondrial dysfunction in obese insulin-resistant rats

“…Currently, an aging condition induced by chronic D-galactose exposure has been shown to have similar phenotypes to one described in naturally aging rodents (Aydin et al 2012;Cebe et al 2014;Yanar et al 2011). There is an accumulation of evidence to demonstrate that administration of D-galactose in rodents can increase senescence markers in cardiac tissues (Cebe et al 2014;Chang et al 2017;Liu et al 2012;Lu et al 2010;Wu et al 2017;Yu et al 2015), increase oxidative stress, and decrease antioxidant proteins (Cebe et al 2014;Chang et al 2017;Wu et al 2017). In addition, recent studies have shown that D-galactose increased cardiac inflammatory and apoptosis markers (Ali et al 2015;Chang et al 2016;Gao et al 2015;Guo et al 2017;Liang et al 2017;Qian et al 2008;Sun et al 2014;Yu et al 2015).…”

“…The samples were then stored at 37°C overnight. Blue precipitation in the cytoplasm was observed in the senescent cells at × 200 magnification (Chang et al 2017). The number of SA-β-gal-positive cells was counted in four random fields with ImageJ software.…”