Neuroprotective Effect of <i>Rhodiola crenulata</i> in D-Galactose-Induced Aging Model

Abstract

The medicinal plant <i>Rhodiola crenulata</i> grows at high altitudes in the Arctic and mountainous regions and is commonly used in phytotherapy in Eastern European and Asian countries. In the present study, we investigated the anti-apoptotic effect of <i>Rhodiola crenulata</i> and its neuroprotective mechanism of action in a rat model of D-galactose-induced aging. Two groups of twelve-week-old male Wistar rats received a daily injection of D-galactose (150<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math>mg/kg/day, i.p.) and orally administered <i>Rhodiola crenulata</i> (0, 248<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math>mg/kg/day) for eight weeks, while a control group received a saline injection (1<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mspace></mml:mspace></mml:math>ml/kg/day, i.p.). We examined apoptosis in the cortex and hippocampus of three groups of rats based on a terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling (TUNEL) positive assay. The expression levels of apoptotic and anti-apoptotic proteins in excised brains were analyzed by Western blotting. Our findings indicated that D-galactose caused marked neuronal apoptosis via activation of both extrinsic-dependent and mitochondrial-dependent apoptotic pathways. When compared to the control group, the protein levels of Fas receptor, Fas ligand, Fas-associated death domain (FADD), and activated caspase-8 (Fas-dependent apoptotic pathways), as well as those of t-Bid, Bax, cytochrome <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>c</mml:mi></mml:math>, activated caspase-9, and activated caspase-3 (mitochondrial-dependent apoptotic pathways), were significantly increased in the D-galactose treated group. In addition, D-galactose impaired the phosphorylation of PI3K/Akt, an important survival signaling event in neurons. <i>Rhodiola crenulata</i>, however, protected against all these neurotoxicities in aging brains. The present study suggests that neuronal survival promoted by <i>Rhodiola crenulata</i> may be a potentially effective method to enhance the resistance of neurons to age-related disorders.