Asiaticoside ameliorates β-amyloid-induced learning and memory deficits in rats by inhibiting mitochondrial apoptosis and reducing inflammatory factors

Abstract

Abstract. The present study aimed to investigate the effects of asiaticoside (AS) on the pathology and associated mechanisms of β-amyloid (Aβ)-induced Alzheimer's disease (AD) in rats. An AD rat model was established by lateral intracerebroventricular injection of Aβ 1-42 oligomers. Learning and memory function were evaluated by Morris water maze (MWM) test. In addition, hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), immunohistochemistry, ELISA and western blot analysis were performed to evaluate the disease pathogenesis. The results indicated that AS exerted protective effects in rats treated with Aβ oligomers, in a dose-dependent manner, as evidenced by the improved learning and memory function in the MWM test. In addition, H&E staining of hippocampal tissue showed that the histological structure was damaged in the model group, which was restored by AS treatment. Aβ deposition was dramatically increased in the model group, and the pathological changes were reversed by AS treatment. TEM revealed that the subcellular structure was injured by Aβ oligomers, however, the structure was ameliorated by AS treatment. Furthermore, AS was found to reduce the elevated levels of pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, in the brains of Aβ-treated rats. In addition, AS treatment resulted in a significant decrease in the expression of caspases-3, whereas the expression of B-cell lymphoma-2 was significantly increased, in these Aβ-treated rats. According to the findings of the observed study, AS has a marked protective effect on Aβ-induced AD pathology, and the underlying mechanism may be associated with the alleviation of the mitochondrial injuries, the anti-inflammatory activities, and the influence on the expression levels of apoptosis-associated proteins.

Asiaticoside Attenuates Cell Growth Inhibition and Apoptosis Induced by Aβ1-42 via Inhibiting the TLR4/NF-κB Signaling Pathway in Human Brain Microvascular Endothelial Cells

“…Asiaticoside (AS), a naturally triterpenoid saponin, isolated and extracted from Indian medicinal herb Centella asiatica (L.) Urban, displays broad bioactivities including neuroprotection, antidepressant, anti-oxidant, anti-inflammation, protection of DNA damage, and regulation of apoptotic factors in cortical neurons in vitro cell culture and in vivo animal models ( Luo et al, 2015 ; Sun et al, 2015 ; Hou et al, 2016 ; Zhang Z. et al, 2017 ). The neuroprotective effects of AS have been widely reported including repairing spinal cord injury ( Luo et al, 2015 ) and protecting neuronal damage induced by ischemia hypoxia ( Sun et al, 2015 ).…”

“…The neuroprotective effects of AS have been widely reported including repairing spinal cord injury ( Luo et al, 2015 ) and protecting neuronal damage induced by ischemia hypoxia ( Sun et al, 2015 ). AS was able to alleviate learning and memory impairment induced by Aβ in a rat model of AD ( Zhang Z. et al, 2017 ). Additional studies revealed that AS was capable of inhibiting several apoptotic-related signal pathways including p38-MAPK, PI3K/Akt/NF-κB, and hypoxia-induced transforming growth factor β1 (TGF-β1)/Smad2/3 ( Luo et al, 2015 ; Wang X.B.…”

Antinociceptive Activity of Asiaticoside in Mouse Models of Induced Nociception

“…The sugar moieties are split by the enzymes in the stomach to produce aglycone triterpenoids that are readily absorbed and, hence, enables asiaticoside to perform many biological activities [19]. It is known that asiaticoside has gastric ulcer healing [20], antioxidant and anti-inflammatory [17], antidepressant [21], neuroprotective [22], learning, memory-inducing [23], and antitumor [24] properties. In addition, asiaticoside is able to stimulate collagen synthesis and enhance the wound healing process [25].…”

Differences in Neuritogenic Activity and Signaling Activation of Madecassoside, Asiaticoside, and Their Aglycones in Neuro-2a cells

“…Several recent studies have demonstrated pharmacological effects of C. asiatica triterpenoids, particularly AA and AS, in various rodent models including those related to memory and learning assessment, where bioactive compound needs to reach brain tissue [18,39,40]. As a preliminary estimation of potency to relate our results to in vivo neurological responses, the apparently bioactive doses of AA or AS from memory and learning behavioral studies using similar animal species, oral administration of test compound, and purified test compounds from commercial source were compared.…”

“…As a preliminary estimation of potency to relate our results to in vivo neurological responses, the apparently bioactive doses of AA or AS from memory and learning behavioral studies using similar animal species, oral administration of test compound, and purified test compounds from commercial source were compared. The effective doses of AA and AS were shown to be 30 mg/kg/d and between 5 and 45 mg/kg/d, respectively, indicating that AS could be slightly more potent (about two-fold) when the molecular weights of both compounds are accounted [39,40]. Based on bioavailability data from two independent reports, the bioavailability of AA (16.25 %, 20 mg/kg administered orally) appeared approximately ten times higher than that of AS (1.86 %, 38 mg/kg administered orally), implying a much higher potency of AS than AA if bioactivities are only originated from intact molecules [41,42].…”