Improving the inhibition of β-amyloid aggregation by withanolide and withanoside derivatives

Withania somnifera (L.) Dunal, a Potential Source of Phytochemicals for Treating Neurodegenerative Diseases: A Systematic Review

“…However, when W. somnifera extract or withanolide A was added to the β -amyloid treated cultures at concentrations of 0.15 µg/mL and 1.25 µg/mL–20 µg/mL, respectively, the cytotoxic effects of β -amyloid were neutralized and the cells were comparable to plain and Ashwagandha treated controls, suggesting the chemopreventive or protective effects of Ashwagandha and withanolide A against β -amyloid induced toxicity [ 54 , 55 ]. Recently, the same effects have been reported by Dubey et al (2021) [ 28 ] with withanolide A, withanolide B, withanoside IV, and withanoside V, which have significant therapeutic potential against amyloid β aggregation-induced cell toxicity, as the number of live cells was increased when these compounds were added (with half the concentration of the IC 50 value) after the addition of A β . The cell culture assays also indicate that the ability of the derivatives to reduce the cytotoxic effects of amyloid β fibrillation could be mediated by free radicals and oxidative stress [ 28 ].…”

“…These compounds are polyoxygenated; hence, it is thought that plants able to elaborate them possess an enzyme system capable of oxidizing all the carbon atoms in a steroid nucleus [ 9 ]. Although structurally similar, withanolide A differs from withanolide B through the presence of an additional hydroxyl group on the C-20 atom, and both can inhibit amyloid beta aggregation, known to cause Alzheimer’s disease [ 27 , 28 ]. 4 β ,27-dihydroxy-1-oxo-5 β , 6 β -epoxywitha-2-24-dienolide, also known as withaferin A, was first isolated from the W. somnifera leaves of a South Asian variety at a concentration of 0.13–0.31% dry weight.…”

“…Although structurally similar, withanoside IV differs from withanoside V in the presence of an extra hydroxyl group on the C-27 atom. Withanoside IV and withanoside V were seen to reduce the formation of the amyloid β-peptide fibril responsible for Alzheimer’s disease [ 27 , 28 ], while withanosides IV and VI induced dendritic formation [ 33 ]. A bioassay-guided purification of the methanolic extract of W. somnifera fruits yielded withanosides IV, V, and VI.…”

Discovery of New 1,3,4-Oxadiazoles with Dual Activity Targeting the Cholinergic Pathway as Effective Anti-Alzheimer Agents

“…Several recent studies reported that β-amyloid plaques are one of the major neuropathological features of AD. , Thus, reducing β-amyloid is envisaged as a promising strategy for possible management of the AD effect. , Therefore, the effect of 5e on reducing β-amyloid 1–42 levels was assessed and compared to that of rivastigmine. As shown in Figure , 5e succeeded in normalizing Aβ 1–42 levels and conversely rivastigmine-treated rats could not reach normal levels of Aβ 1‑42 , indicating the more efficient effect of 5e compared to that of rivastigmine.…”

Engineering of Saccharomyces cerevisiae for 24-Methylene-Cholesterol Production

“…Subsequently, some marine organisms—such as mussels and brown seaweeds—were also reported to contain 24-methylene-cholesterol [ 5 ]. Recent studies have demonstrated that 24-methylene-cholesterol has moderate antioxidant activity [ 6 ]. Importantly, it is a necessary precursor of withanolide and physalins, which have been proven to have the properties of fighting against cancers, inhibiting neurodegenerative diseases, and triggering apoptosis [ 7 , 8 , 9 , 10 ].…”