Anti-Alzheimer’s Studies on β-Sitosterol Isolated from Polygonum hydropiper L.

Abstract

The family Polygonaceae is known for its traditional use in the management of various neurological disorders including Alzheimer’s disease (AD). In search of new anti-AD drugs, β-sitosterol isolated from Polygonum hydropiper was subjected to in vitro, in vivo, behavioral and molecular docking studies to confirm its possibility as a potential anti-Alzheimer’s agent. The in vitro AChE, BChE inhibitory potentials of β-sitosterol were investigated following Ellman’s assay. The antioxidant activity was tested using DPPH, ABTS and H2O2 assays. Behavioral studies were performed on a sub-strain of transgenic mice using shallow water maze (SWM), Y-maze and balance beam tests. β-sitosterol was tested for in vivo inhibitory potentials against cholinesterase’s and free radicals in the frontal cortex (FC) and hippocampus (HC). The molecular docking study was performed to predict the binding mode of β-sitosterol in the active sites of AChE and BChE as inhibitor. Considerable in vitro and in vivo cholinesterase inhibitory effects were observed in the β-sitosterol treated groups. β-sitosterol exhibited an IC50 value of 55 and 50 μg/ml against AChE and BChE respectively. Whereas, the activity of these enzymes were significantly low in FC and HC homogenates of transgenic animals. Molecular docking studies also support the binding of β-sitosterol with the target enzyme and further support the in vitro and in vivo results. In the antioxidant assays, the IC50 values were observed as 140, 120, and 280 μg/ml in the DPPH, ABTS and H2O2 assays respectively. The free radicals load in the brain tissues was significantly declined in the β-sitosterol treated animals as compared to the transgenic-saline treated groups. In the memory assessment and coordination tasks including SWM, Y-maze and balance beam tests, β-sitosterol treated transgenic animals showed gradual improvement in working memory, spontaneous alternation behavior and motor coordination. These results conclude that β-sitosterol is a potential compound for the management of memory deficit disorders like AD.

Inhibitory effect of ethyl acetate fraction ofSolanum macrocarponL. leaves on cholinergic, monoaminergic, and purinergic enzyme activities

“…are among the major health problems affecting the lives of individuals, particularly the elderly ones globally (Ali et al, ). Ayaz, Junaid et al () reported that Alzheimer’s disease is the most common neurological disorder, characterized with gradual memory loss, cognitive dysfunctions, behavioral turbulence, etc., with more than 33.9 million people suffering from this disorder worldwide with a projection of three folds increase by the next 40 years. In spite of the presence of known medicine used in the treatment of these diseases, (especially Alzheimer’s disease) their related complications (e.g., erectile dysfunction, hypertension, etc.)…”

Aqueous–ethanol extracts of some South African seaweeds inhibit beta‐amyloid aggregation, cholinesterases, and beta‐secretase activities in vitro

“…Alpha‐tocopherol is a potent antioxidant and compounds with strong antioxidant properties and are able to attenuate neurodegeneration and retard the progression of AD (Kumar & Khanum, ). Furthermore, stigmasterol and beta‐sitosterol have also been reported to exhibit neuroprotective effects (Ayaz et al, ; Haque & Moon, ). The observed total phenol and flavonoid contents of the extracts suggests the presence of some phenolic compounds in the seaweeds.…”

“…Some of the compounds identified in the extracts may contribute to their cholinesterase inhibitory activities. Docking studies conducted by Ayaz et al () revealed that beta‐sitosterol effectively binds to the asparagine 285 and glycine 71 residues of AChE and BChE via hydrogen bonds, respectively, hence reducing the activity of the enzyme. Similarly, beta‐amyrone also exhibited moderate anti‐acetylcholinesterase activity (Mollataghi et al, ).…”

“…According to the IC 50 values in Table 2, the Fe 2+ chelating activity of the seaweed extracts followed the trend GCL > ECK>ULT and GLD. stigmasterol and beta-sitosterol have also been reported to exhibit neuroprotective effects (Ayaz et al, 2017;Haque & Moon, 2018).…”

Anticholinesterase, antioxidant potentials, and molecular docking studies of isolated bioactive compounds from Grewia optiva

“…In old age people (above 60 years), their frequencies are high. [8] Acetylcholine (ACh) and Butyrylcholine (BCh) are important neurotransmitters that are involved in acquisition and storage of memories, and in the transmission of impulses across the synapse. Usually in the neurodegenerative processes the level of neurotransmitters: ACh and BCh exhausted.…”