We investigated the protective effect and mechanisms of apigenin against cognitive impairments in a scopolamine-injected mouse model. Our results showed that intraperitoneal (i.p.) injection of scopolamine leads to learning and memory dysfunction, whereas the administration of apigenin (synthetic compound, 100 and 200 mg/kg/day) improved cognitive ability, which was confirmed by behavioral tests such as the T-maze test, novel objective recognition test, and Morris water maze test in mice. In addition, scopolamine-induced lipid peroxidation in the brain was attenuated by administration of apigenin. To further evaluate the protective mechanisms of apigenin on cognitive and memory function, Western blot analysis was carried out. Administration of apigenin decreased the B-cell lymphoma 2-associated X/B-cell lymphoma 2 (Bax/Bcl-2) ratio and suppressed caspase-3 and poly ADP ribose polymerase cleavage. Furthermore, apigenin down-regulated the β-site amyloid precursor protein-cleaving enzyme, along with presenilin 1 (PS1) and PS2 protein levels. Apigenin-administered mice showed lower protein levels of a receptor for advanced glycation end-products, whereas insulin-degrading enzyme, brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) expression were promoted by treatment with apigenin. Therefore, this study demonstrated that apigenin is an active substance that can improve cognitive and memory functions by regulating apoptosis, amyloidogenesis, and BDNF/TrkB signaling pathways.

In the present study, we investigated the cognitive improvement effects and its mechanisms of krill oil (KO) in Aβ_25–35-induced Alzheimer’s disease (AD) mouse model. The Aβ_25–35-injected AD mouse showed memory and cognitive impairment in the behavior tests. However, the administration of KO improved novel object recognition ability and passive avoidance ability compared with Aβ_25–35-injected control mice in behavior tests. In addition, KO-administered mice showed shorter latency to find the hidden platform in a Morris water maze test, indicating that KO improved learning and memory abilities. To evaluate the cognitive improvement mechanisms of KO, we measured the oxidative stress-related biomarkers and apoptosis-related protein expressions in the brain. The administration of KO inhibited oxidative stress-related biomarkers such as reactive oxygen species, malondialdehyde, and nitric oxide compared with AD control mice induced by Aβ_25–35. In addition, KO-administered mice showed down-regulation of Bax/Bcl-2 ratio in the brain. Therefore, this study indicated that KO-administered mice improved cognitive function against Aβ_25–35 by attenuations of neuronal oxidative stress and neuronal apoptosis. It suggests that KO might be a potential agent for prevention and treatment of AD.

Recently, adipose-derived stem cells (ADSCs) are considered to be ideal for application in cell therapy or tissue regeneration, mainly due to their wide availability and easy access. In this study, we examined the anti-inflammatory effects of membrane-free stem cell extract (MFSC-Ex) derived from ADSCs against lipopolysaccharide (LPS)/interferon-gamma (IFN-γ) on RAW 264.7 macrophage cells. Exposure of RAW macrophages to LPS and IFN-γ stimuli induced high levels of nitric oxide (NO), cyclooxygenase-2 (COX-2), and prostaglandin E₂ (PGE₂) production. However, pretreatment with MFSC-Ex inhibited LPS/IFN-γ-induced these pro-inflammatory mediators. To clarify the molecular mechanisms underlying the anti-inflammatory property of MFSC-Ex, we analyzed nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) protein expressions by Western blotting. Our study showed that treatment of MFSC-Ex significantly down-regulated inducible nitric oxide synthase (iNOS) and COX-2 protein expressions. Furthermore, phosphorylation of extracellular signal-regulated kinase (ERK) and p38 was also blocked by treatment with MFSC-Ex, indicating that inhibitory effect of MFSC-Ex on MAPK signaling cascade may attribute to inactivation of NF-κB. From these findings, we suggest that MFSC-Ex exert anti-inflammatory activities, which suppressed LPS/IFN-γ-induced production of NO, COX-2 and PGE₂ by regulation of NF-κB and MAPK signaling pathway in RAW 264.7 macrophages. In conclusion, MFSC-Ex might provide a new therapeutic opportunity to treatment of inflammatory-related diseases.

Accumulation of amyloid beta (Aβ) is a major pathological hallmark of Alzheimer’s disease (AD). In this study, we evaluated the protective effect of membrane-free stem cell extract (MFSCE), which is a component of adipose-tissue-derived stem cells, on cognitive impairment in Aβ_25–35-injected AD mice. The ICR mice were i.c.v. injected with Aβ_25–35 and then treated with MFSCE for 14 days (i.p.). The Aβ_25–35-injected mice showed deficits in spatial and object perception abilities, whereas treatment with MFSCE inhibited Aβ_25–35-induced learning and memory impairment in the T-maze, novel object recognition, and Morris water maze tests. Moreover, Aβ_25–35-induced lipid peroxidation and nitric oxide overproduction were attenuated by treatment with MFSCE. These antioxidant effects of MFSCE were related to the inhibition of the apoptotic signaling pathway. In particular, the combination treatment of MFSCE and pyridoxal 5′-phosphate (PLP) showed greater suppression of Bax and cleaved caspase-3 protein expression compared to the MFSCE- or PLP-only treatment. Furthermore, the MFSCE and PLP combination significantly downregulated the amyloidogenic-pathway-related protein expressions, such as amyloid precursor protein, presenilin 1, and presenilin 2. Therefore, the MFSCE and PLP combination may synergistically prevent Aβ_25–35-induced neuronal apoptosis and amyloidogenesis, which contributes to cognitive improvement and has potential therapeutic implications for AD patients.

Deposition of amyloid-beta (Aβ) in the aging brain has been often observed and is thought to be a pathological feature of Alzheimer’s disease. The use of natural products for disease prevention and treatment is gaining attention worldwide. Carthamus tinctorius L. seed and Taraxacum coreanum have been used as traditional medicines in Asian countries, where they have been reported to exert anti-inflammatory and anti-oxidative effects. It has been demonstrated that the combination of C. tinctorius L. seed and T. coreanum has an effect on cognitive enhancement, indicating a ratio of 5:5 synergistically enhancing learning and memory abilities in comparison with a single treatment. Here, we aimed to investigate the protective effect of C. tinctorius L. seed and T. coreanum mixture (CT) at different concentrations on cognition in Aβ_25-35-infused mice. CT-administered mice showed significant cognitive improvement in the T-maze, novel object recognition, and Morris water maze tests. Moreover, amyloidogenesis-related proteins, such as β-secretase and γ-secretase, were detected and their protein levels decreased after treatment with CT. Our study shows that CT attenuates cognitive dysfunction by improving learning and memory capability and regulating Aβ-related proteins in Aβ_25-35-injected mice. These findings suggest that CT might be a candidate for functional food on cognitive improvement.