Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions

Abstract

The genus Cordyceps and its specific ingredient, cordycepin, have attracted much attention for multiple health benefits and expectations for lifespan extension. We analyzed whether Cordyceps militaris (CM), which contains large amounts of cordycepin, can extend the survival of Dahl salt-sensitive rats, whose survival was reduced to ∼3 months via a high-salt diet. The survival of these life-shortened rats was extended significantly when supplemented with CM, possibly due to a minimization of the effects of stroke. Next, we analyzed the effect of CM on hypertension-sensitive organs, the central nervous systems (CNS), heart, kidney and liver of these rats. We attempted to ascertain how the organs were improved by CM, and we paid particular attention to mitochondria and autophagy functions. The following results were from CM-treated rats in comparison with control rats. Microscopically, CNS neurons, cardiomyocytes, glomerular podocytes, renal epithelial cells, and hepatocytes all were improved. However, immunoblot and immunohistochemical analysis showed that the expressions of mitochondria-related proteins, ATP synthase β subunit, SIRT3 and SOD2, and autophagy-related proteins, LC3-II/LC3-I ratio and cathepsin D all were reduced significantly in the CNS neurons, but increased significantly in the cells of the other three organs, although p62 was decreased in its expression in all the organs tested. Activity of Akt and mTOR was enhanced but that of AMPK was reduced in the CNS, while such kinase activity was completely the opposite in the other organs. Together, the influence of CM may differ between mitochondria and autophagy functioned between the two organ groups, as mitochondria and autophagy seemed to be repressed and promoted, respectively, in the CNS, while both mitochondria and autophagy were activated in the others. This could possibly be related to the steady or improved cellular activity in both the organs, which might result in the life extension of these rats.

Sirt3 inhibits cerebral ischemia-reperfusion injury through normalizing Wnt/β-catenin pathway and blocking mitochondrial fission

“…In fact, ample evidence has shown the role of Sirt3 in mitochondrial homeostasis and ROS management. For example, Sirt3 is associated with mitochondrial cardiolipin expression (Chabi et al 2018), mPTP opening regulation (Nassir et al 2018), mitochondrial energy production (Wu et al 2018), autophagy activity (Takakura et al 2017), cellular oxidative stress (Lee et al 2018), and metabolic reprogramming (Lee et al 2017a). More importantly, the protective effects of Sirt3 on mitochondria have been verified in different disease models, including Alzheimer's disease (Lee et al 2018), gastric cancer (Lee et al 2017a), fatty liver disease (Liu et al 2017a), and heart failure (Du et al 2017).…”

Cell Clearing Systems as Targets of Polyphenols in Viral Infections: Potential Implications for COVID-19 Pathogenesis

“…This is recapitulated in salt-sensitive rats that are fed via a high-salt diet, where cordycepin-induced autophagy is associated with lifespan extension and protection of hypertension-sensitive organs, including the brain, heart, kidney, and liver [ 228 ]. Morphologically, neurons, cardiomyocytes, glomerular podocytes, renal epithelial cells, and hepatocytes are all improved in cordycepin-treated rats featuring reduced levels of AKT/mTOR, increased levels of AMPK, and decreased levels of p62 witnessing for autophagy flux progression, as compared to the untreated controls [ 228 ]. A cordycepin derivative, through AMPK activation, also alleviates atherosclerosis in High-Fat Diet-Fed ApoE-KO mice, by protecting the vascular endothelial cells from inflammatory and oxidative damage [ 229 ].…”

Polysaccharides Obtained from Cordyceps militaris Alleviate Hyperglycemia by Regulating Gut Microbiota in Mice Fed a High-Fat/Sucrose Diet

“…Our past research has found that in the process of liquid culture of C. militaris, different fermentation substrates not only affect the yields of biomass production (including extracellular polysaccharides, cordycepin, and mycelium production), but also affect the activity of suppressing oral cancer [6]. In addition to cancer suppression, C. militaris also has the potential to improve metabolic syndrome, including diabetes [7], hypertension blood pressure [8], and hyperlipidemia [9]. There are more than 1000 different microbial species (species) in the human gastrointestinal (GI) tract; these bacterial phases constitute a specific microenvironment in the gut.…”