Alzheimer’s disease (AD) is a neurodegenerative disease that causes a gradual loss of normal motor and cognitive function. The complex AD pathophysiology involves various factors such as oxidative stress, neuroinflammation, amyloid-beta (Aβ) aggregation, disturbed neurotransmission, and apoptosis. The available drugs suffer from a range of side effects and are not able to cover different aspects of the disease. Therefore, finding a safer therapeutic approach that can affect multiple targets at a time is highly desirable. In the present study, the underlying neuroprotective mechanism of an important culinary spice, Syzygium aromaticum (Clove) extract, and major bioactive compounds were studied in hydrogen peroxide-induced oxidative stress in human neuroblastoma SH-SY5Y cell lines as a model. The extracts were subjected to GC-MS to identify important bioactive components. The extracts and key bio-actives reduced reactive oxygen species (ROS), restored mitochondrial membrane potential (MMP), and provided neuroprotection from H2O2-induced oxidative stress in cell-based assays due to the antioxidant action. They also reduced lipid peroxidation significantly and restored GSH content. Clove extracts have also displayed anti-acetylcholinesterase (AChE) activity, anti-glycation potential, and Aβ aggregation/fibrilization inhibition. The multitarget neuroprotective approach displayed by Clove makes it a potential candidate for AD drug development.
A form of dementia distinct from healthy cognitive aging, Alzheimer’s disease (AD) is a complex multi-stage disease that currently afflicts over 50 million people worldwide. Unfortunately, previous therapeutic strategies developed from murine models emulating different aspects of AD pathogenesis were limited. Consequently, researchers are now developing models that express several aspects of pathogenesis that better reflect the clinical situation in humans. As such, this review seeks to provide insight regarding current applications of mammalian models in AD research by addressing recent developments and characterizations of prominent transgenic models and their contributions to pathogenesis as well as discuss the advantages, limitations, and application of emerging models that better capture genetic heterogeneity and mixed pathologies observed in the clinical situation.
Neurodegeneration diseases (NDs) are a group of complex diseases primarily characterized by progressive loss of neurons affecting mental function and movement. Oxidative stress is one of the factors contributing to the pathogenesis of NDs, including Alzheimer’s disease (AD). These reactive species disturb mitochondrial function and accelerate other undesirable conditions including tau phosphorylation, inflammation, and cell death. Therefore, preventing oxidative stress is one of the imperative methods in the treatment of NDs. To accomplish this, we prepared hexane and ethyl acetate extracts of Anethum graveolens (dill) and identified the major phyto-components (apiol, carvone, and dihydrocarvone) by GC-MS. The extracts and major bioactives were assessed for neuroprotective potential and mechanism in hydrogen peroxide-induced oxidative stress in the SH-SY5Y neuroblastoma cell model and other biochemical assays. The dill (extracts and bioactives) provided statistically significant neuroprotection from 0.1 to 30 µg/mL by mitigating ROS levels, restoring mitochondrial membrane potential, reducing lipid peroxidation, and reviving the glutathione ratio. They moderately inhibited acetylcholine esterase (IC50 dill extracts 400–500 µg/mL; carvone 275.7 µg/mL; apiole 388.3 µg/mL), displayed mild anti-Aβ1–42 fibrilization (DHC 26.6%) and good anti-oligomerization activity (>40% by dill-EA, carvone, and apiole). Such multifactorial neuroprotective displayed by dill and bioactives would help develop a safe, low-cost, and small-molecule drug for NDs.
A form of dementia distinct from healthy cognitive aging, Alzheimer's disease (AD) is a complex multi-stage disease that currently afflicts over 50 million people worldwide. Unfortunately, previous therapeutic strategies developed from murine models emulating different aspects of AD pathogenesis have failed. Consequently, researchers are now developing models that express several aspects of pathogenesis that better reflect the clinical situation in humans. As such, this review seeks to provide insight regarding current applications of mammalian models in AD research by addressing recent developments and characterizations of prominent transgenic models and their contributions to pathogenesis as well as discuss the advantages, limitations, and application of emerging models (hAβ-KI) that better capture genetic heterogeneity and mixed pathologies observed in the clinical situation.
Background: Anethum graveolans commonly known as Dill is an herb from celery family displaying anti‐oxidant benefits. The present study focused on the potential of Anethum graveolans as a multifunctional curative remedy for AD treatment.Method: Hexane (H) and ethyl acetate (EA) extracts of Dill were prepared and subjected to GC‐MS for identification of important bioactive components. H2O2 was used to induce oxidative stress in SH‐SY5Y cells and evaluation was done based on neuroprotection, reduced reactive oxygen species, and restoration of mitochondrial membrane potential (MMP). Additionally, anti‐Aβ fibrilization/ oligomerization activities were also analyzed along with anti‐acetylcholinesterase activity.Result: Based on GC‐MS results, 3 major components were identified apiole, carvone and dihydrocarvone (DHC). The extracts and pure compounds were assessed for their neuroprotective potential in which dose‐dependent increase in neuroprotection was observed in both extracts, apiole and carvone. Dill‐H displayed a dose‐dependent decrease in ROS levels which was more prominent than Dill‐EA extract. Pure compounds also exerted a decrease in ROS level with increasing concentration. Dill extracts (H/EA) exhibited dose‐dependent increase in mitochondrial membrane potential along with Carvone and DHC. Apiole showed less restoration of MMP compared to other pure compounds. For anti‐Aβ fibrilization activity, Dill‐EA, Carvone and Apiole show ≈40% inhibition followed by DHC (35%) and Dill‐H (30%). In MDS, maximum oligomerization inhibition was observed in DHC (26%) and apiole (14%). Dill extracts and compounds exhibit anti‐AChE activity and inhibited the enzyme through competitive inhibition except for DHC.Conclusion: We focused our research on small molecules from food to prevent AD. There is a need for a drug that is easily accessible, cost‐effective and has no/fewer side effects. In our study, Dill extracts and its identified bioactive compounds exhibited a multitargeted neuroprotection in the SH‐SY5Y cells making it a promising candidate for AD drug development.