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.
BackgroundThe Indigenous knowledge of plants is scientifically and culturally very significant. This paper elucidates the empirical findings of an ethnobotanical survey of Banda Daud Shah, District Karak, Pakistan.MethodsData collection was carried out from October 2011 to September 2012. Total twelve survey trips were made, three in each season. About 100 respondents were interviewed; most of them were aged people between 60–70 years. Interviews were conducted using structured questionnaire composed of variety of questions regarding ethnomedicinal uses of plants of the study area. Direct matrix ranking (DMR), informant citations and market survey of multipurpose plants were also carried out.ResultsThe local community was using 58 plant species belonging to 52 genera and 34 families for different purposes. A total of 25 plant species were herbs followed by 18 shrubs. Leaf (45%) was the most commonly used plant part followed by the whole plants (23%). In total, 40 plant species were medicinally used to treat variety of diseases, of which highest number of species being used for gastro-intestinal problems (19 spp.), expectorant (3 spp.) and antipyretic (3 spp.). Beside medicinal values, 25 species were used for fuel and 18 for fodder purposes. Informant consensus showed that gastrointestinal and respiratory infections were ranked highest (FIC = 0.75) among all ailments. According to DMR output, Dalbergia sisso ranked first due to high multipurpose uses among all species and was found most threatened with higher market value.ConclusionThe investigated area is rural in nature and the inhabitants are highly dependent on the native plants for their health care needs and other requirements like fuel wood and fodder due to financial constraints and unavailability of resources. Medicinal plants for high ranked diseases may be phtyochemicaly and pharmacologically investigated to prove their efficacy. The local medicinal flora is facing overexploitation, overgrazing and improper way of collection. Proper conservation strategies such as controlled grazing, reforestation and rangeland management among many others may be adopted to promote the sustainable use of medicinal plants.
Alzheimer's disease (AD) is a devastating and progressive neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau proteins in the brain. The deposition of Aβ aggregates triggers synaptic dysfunction, hyperphosphorylation of tau, and neurodegeneration, which lead to cognitive disorders. Here, we investigated the neuroprotective effect of fisetin in the Aβ mouse model of AD. Single intracerebroventricular injections of Aβ (3 μl/5 min/mouse) markedly induced memory/synaptic deficits, neuroinflammation, and neurodegeneration. Intraperitoneal injections of fisetin at a dose of 20 mg/kg/day for 2 weeks starting 24 h after Aβ injection significantly decreased the Aβ-induced accumulation of Aβ, BACE-1 expression, and hyperphosphorylation of tau protein at serine 413. Fisetin treatment also markedly reversed Aβ-induced synaptic dysfunction by increasing the levels of both presynaptic (SYN and SNAP-25) and postsynaptic proteins (PSD-95, SNAP-23, p-GluR1 (Ser 845), p-CREB (Ser 133) and p-CAMKII (Thr 286) and ultimately improved mouse memory, as observed in the Morris water maze test. Fisetin significantly activated p-PI3K, p-Akt (Ser 473), and p-GSK3β (Ser 9) expression in Aβ-treated mice. Moreover, fisetin prevented neuroinflammation by suppressing various activated neuroinflammatory mediators and gliosis; it also suppressed the apoptotic neurodegeneration triggered by Aβ injections in the mouse hippocampus. Fluorojade-B and immunohistochemical staining for caspase-3 revealed that fisetin prevented neurodegeneration in Aβ-treated mice. Our results suggest that fisetin has a potent neuroprotective effect against Aβ-induced neurotoxicity. These results demonstrate that polyphenolic flavonoids such as fisetin could be a beneficial, effective and safe neuroprotective agent for preventing neurological disorders such as AD.
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