Transthyretin Anti-Amyloidogenic and Fibril Disrupting Activities of Bacopa monnieri (L.) Wettst (Brahmi) Extract

Abstract

The homotetrameric plasma protein transthyretin (TTR), is responsible for a series of debilitating and often fatal disorders in humans known as transthyretin amyloidosis. Currently, there is no cure for TTR amyloidosis and treatment options are rare. Thus, the identification and development of effective and safe therapeutic agents remain a research imperative. The objective of this study was to determine the effectiveness of Bacopa monnieri extract (BME) in the modulation of TTR amyloidogenesis and disruption of preformed fibrils. Using aggregation assays and transmission electron microscopy, it was found that BME abrogated the formation of human TTR aggregates and mature fibrils but did not dis-aggregate pre-formed fibrils. Through acid-mediated and urea-mediated denaturation assays, it was revealed that BME mitigated the dissociation of folded human TTR and L55P TTR into monomers. ANS binding and glutaraldehyde cross-linking assays showed that BME binds at the thyroxine-binding site and possibly enhanced the quaternary structural stability of native TTR. Together, our results suggest that BME bioactives prevented the formation of TTR fibrils by attenuating the disassembly of tetramers into monomers. These findings open up the possibility of further exploration of BME as a potential resource of valuable anti-TTR amyloidosis therapeutic ingredients.

Antiproliferative Activities of the Lipophilic Fraction of Eucalyptus camaldulensis against MCF-7 Breast Cancer Cells, UPLC-ESI-QTOF-MS Metabolite Profile, and Antioxidative Functions

“…The total flavonoid content was evaluated using the aluminum chloride colorimetric assay. 61 Briefly, various concentrations of Lipo-Eucam solution or quercetin (30 μL) were added into 2 mL Eppendorf tubes followed by 160 μL of methanol. Then, 30 μL of freshly prepared 10% aluminum chloride in methanol was added to the solutions and mixed.…”

Impact of Fermentation on the Phytochemical Content and Biological Properties of Moringa oleifera Lam. Shoot Teas

“…The total phenolic content of the MOS tea extracts was determined as previously described. [56] Succinctly, tea samples and gallic acid (used as standard) were solubilized in distilled water. The sample solutions (100 μL) were then injected into a 2-mL Eppendorf tubes.…”

“…The total flavonoid content of the samples was determined based on aluminium chloride colorimetric assay. [56] Briefly, the MOS tea extract samples were diluted with 50 % methanol while quercetin (standard) was diluted in methanol. The sample and standard solutions (30 μL) were introduced into 2-mL Eppendorf tubes.…”

Natural Products for Neurocognitive Disorders

“…It seems that Bacopa monnieri extracts are able to reduce the formation of transthyretin fibrils (TTR) by attenuating their disassembly from the tetrameric form to the monomeric form. This suggests bacopa has a role in preventing transthyretin amyloidosis, a very debilitating and often fatal disease in humans (27). The anti-inflammatory properties of bacopa have been beneficial in the treatment of many neurological diseases of the central nervous system.…”