salvianolic-acid-a and Alzheimer-Disease

Both caffeic acid and 3,4-dihydroxyphenyllactic acid (danshensu) are synthesized through two distinct routs of the shikimic acid biosynthesis pathway. In many plants, especially the rosemary and sage family of Lamiaceae, these two compounds are joined through an ester linkage to form rosmarinic acid (RA). A further structural diversity of RA derivatives in some plants such as

Topics: Alkenes; Alzheimer Disease; Amyloid beta-Peptides; Animals; Cell Differentiation; Cinnamates; Dementia, Vascular; Depsides; Disease Models, Animal; Gene Expression Regulation; Humans; Lactates; Neural Stem Cells; Neurons; Neuroprotective Agents; Nootropic Agents; Polyphenols; Rosmarinic Acid; Stroke; tau Proteins

Oxidative stress may play an important role in neuronal degenerative diseases such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. These disorders make the elderly not being able to live normally and move freely. So it is necessary to find effective antioxidants to prevent or cure the aged persons from diseases related to neuronal degeneration. Schisanhenol (Sal) and salvianolic acid A (Sal A) are known antioxidants which were isolated from Chinese herbs respectively. SY-L is a totally synthetic new compound. The results showed that Sal, Sal A and SY-L significantly protect cerebral cells from the injuries induced by oxidative stress.

Topics: Alzheimer Disease; Animals; Caffeic Acids; Cyclooctanes; Drugs, Chinese Herbal; Free Radical Scavengers; Humans; Lactates; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Polycyclic Compounds

Danshen water extract (DWE), obtained from the Salvia miltiorrhiza Bunge (Family Lamiaceae) root, is usually employed in Chinese traditional medicine as treatment to cardiovascular ailments and cerebrovascular diseases. Intriguingly, the extract was also found to contain vast beneficial properties in Alzheimer's disease (AD) treatment.. Alzheimer's disease is the most significant type of neurodegenerative disorder plaguing societies globally. Its pathogenesis encompasses the hallmark aggregation of amyloid-beta (Aβ). Of all the Aβ oligomers formed in the brain, Aβ42 is the most toxic and aggressive. Despite this, the mechanism behind this disease remains elusive. In this study, DWE, and its major components, Salvianolic acid A (SalA) and Salvianolic acid B (SalB) were tested for their abilities to attenuate Aβ42's toxic effects.. The composition of DWE was determined via Ultra-Performance Liquid Chromatography (UPLC). DWE, SalA and SalB were first verified for their capability to diminish Aβ42 fibrillation using an in vitro activity assay. Since Aβ42 aggregation results in neuronal degeneration, the potential Aβ42 inhibitors were next evaluated on Aβ42-exposed PC12 neuronal cells. The Drosophila melanogaster AD model was then employed to determine the effects of DWE, SalA and SalB.. DWE, SalA and SalB were shown to be able to reduce fibrillation of Aβ42. When tested on PC12 neuronal cells, DWE, SalA and SalB ameliorated cells from cell death associated with Aβ42 exposure. Next, DWE and its components were tested on the Drosophila melanogaster AD model and their rescue effects were further characterized. The UPLC analysis showed that SalA and SalB were present in the brains and bodies of Drosophila after DWE feeding. When human Aβ42 was expressed, the AD Drosophila exhibited degenerated eye structures known as the rough eye phenotype (REP), reduced lifespan and deteriorated locomotor ability. Administration of DWE, SalA and SalB partially reverted the REP, increased the age of AD Drosophila and improved most of the mobility of AD Drosophila.. Collectively, DWE and its components may have therapeutic potential for AD patients and possibly other forms of brain diseases.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Benzofurans; Caffeic Acids; Cell Survival; Drosophila melanogaster; Female; Lactates; Neurons; PC12 Cells; Peptide Fragments; Phytotherapy; Plant Extracts; Rats; Salvia miltiorrhiza

The effects of Salvianolic acid A (Sal A) on the treatment of Alzheimer's disease (AD) were investigated. Sal A significantly inhibits amyloid beta [Formula: see text] self-aggregation and disaggregates pre-formed [Formula: see text] fibrils, reduces metal-induced [Formula: see text] aggregation through chelating metal ions, and blocks the formation of reactive oxygen species (ROS) in SH-SY5Y cells. Sal A protects cells against [Formula: see text]-induced toxicity. Furthermore, Sal A, possibly because of the effects of decreasing toxicity effects of [Formula: see text] species, alleviates [Formula: see text]-induced paralysis in transgenic Caenorhabditis elegans. Circular dichroism (CD) experiments and Molecular dynamic (MD) simulations demonstrate that Sal A inhibits [Formula: see text] self-aggregation through binding to the C-terminus of [Formula: see text], and therefore stabilizing the [Formula: see text]-helical conformations. Altogether, our data show that Sal A, as the multifunctional agent, is likely to be promising therapeutics for AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Caenorhabditis elegans; Caffeic Acids; Cell Line, Tumor; Circular Dichroism; Copper; Drug Evaluation, Preclinical; Humans; Iron; Iron Chelating Agents; Lactates; Molecular Dynamics Simulation; Oxidative Stress; Plant Extracts; Plaque, Amyloid; Reactive Oxygen Species; Salvia miltiorrhiza; Serum Amyloid A Protein; Zinc