The primary and considerable weakening event affecting elderly individuals is age-dependent cognitive decline and dementia. Alzheimer’s disease (AD) is the chief cause of progressive dementia, and it is characterized by irreparable loss of cognitive abilities, forming senile plaques having Amyloid Beta (Aβ) aggregates and neurofibrillary tangles with considerable amounts of tau in affected hippocampus and cortex regions of human brains. AD affects millions of people worldwide, and the count is showing an increasing trend. Therefore, it is crucial to understand the underlying mechanisms at molecular levels to generate novel insights into the pathogenesis of AD and other cognitive deficits. A growing body of evidence elicits the regulatory relationship between the mammalian target of rapamycin (mTOR) signaling pathway and AD. In addition, the role of autophagy, a systematic degradation, and recycling of cellular components like accumulated proteins and damaged organelles in AD, is also pivotal. The present review describes different mechanisms and signaling regulations highlighting the trilateral association of autophagy, the mTOR pathway, and AD with a description of inhibiting drugs/molecules of mTOR, a strategic target in AD. Downregulation of mTOR signaling triggers autophagy activation, degrading the misfolded proteins and preventing the further accumulation of misfolded proteins that inhibit the progression of AD. Other target mechanisms such as autophagosome maturation, and autophagy-lysosomal pathway, may initiate a faulty autophagy process resulting in senile plaques due to defective lysosomal acidification and alteration in lysosomal pH. Hence, the strong link between mTOR and autophagy can be explored further as a potential mechanism for AD therapy.
Objective: This study evaluates the anti-inflammatory activities of different solvent extracts of Moringa oleifera flowers using carrageenan-induced mice paw edema.Methods: Soxhlet extraction method was employed in this study to extract the crude phytochemicals. Phytochemical analysis testing of Moringa oleifera extracts was performed to identify the presence of various phytoconstituents based on the standard procedures. The anti-inflammatory activity was evaluated using acute inflammatory model carrageenan-induced paw edema. Three different flower extracts (petroleum ether, chloroform and methanol) of Moringa oleifera at the dose level of 500 mg/kg body weight. The anti-inflammatory activity on the different extracts of Moringa oleifera was determined through the α-carrageenan induced left hind paw oedema method in albino mice. 0.05 ml of 1% w/v carrageenan suspension was reconstituted with normal saline (0.9% NaCl) to give a homogenous solution which then be injected into the subplantar tissue of the left hind paw of each mice to induce acute inflammation.
Results:Treatment with three different solvent extracts showed significant (p<0.05) inhibition in carrageenan-induced paw edema. Petroleum ether and chloroform extracts were found to be less effective than methanolic extracts when compared to (Indomethacin) reference standard at the dose of 10 mg/kg body weight. The phytochemical results obtained indicates that anti-edematous action of Moringa oleifera flowers exhibited in this study is due to the presence of potent anti-inflammatory phytoconstituents (flavonoid, alkaloid, tannin) in impeding arachidonic acid metabolism and production of reactive free radicals. A significant (p<0.05) increase of left hind paw thickness after the drug injection was noticed in the negative control mice group as time persisted. It showed the highest paw thickness at the fifth hour with 4.72 mm±0.07. Whereas the indomethacin treated group showed the highest percent oedema inhibition amongst all experimental group with 38.60% at the fifth-hour postcarrageenan induction. It exhibited a significant inhibition of 29.02% against the oedema after the third hour of carrageenan injection.
Conclusion:The methanolic extract of Moringa oleifera flowers extract has anti-inflammatory activity. This activity was related to the dose and these results collaborate the potential traditional use of the plant in folk medicine.
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