Red Ginseng Inhibits Tau Aggregation and Promotes Tau Dissociation In Vitro

Abstract

<jats:p>Tau, a microtubule-associated protein expressed in mature neurons, interacts with tubulin to promote the assembly and stabilization of microtubules. However, abnormally hyperphosphorylated tau dissociates from microtubules and self-aggregates. Tau aggregates, including paired helical filaments and neurofibrillary tangles, promote neuronal dysfunction and death and are the defining neuropathological feature of tauopathies. Therefore, suppressing tau aggregation or stimulating the dissociation of tau aggregates has been proposed as an effective strategy for treating neurodegenerative diseases associated with tau pathology such as Alzheimer’s disease (AD) and frontotemporal dementia. Interestingly, ginsenosides extracted from <jats:italic>Panax ginseng</jats:italic> reduced the hippocampal and cortical expression of phosphorylated tau in a rat model of AD. However, no studies have been conducted into the effect of red ginseng (RG) and its components on tau pathology. Here, we evaluated the effect of Korean red ginseng extract (KRGE) and its components on the aggregation and disassociation of tau. Using the thioflavin T assay, we monitored the change in fluorescence produced by the aggregation or disassociation of tau K18, an aggregation-prone fragment of tau<jats:sub>441</jats:sub> containing the microtubule-binding domain. Our analysis revealed that KRGE not only inhibited tau aggregation but also promoted the dissociation of tau aggregates. In addition, the KRGE fractions, such as saponin, nonsaponin, and nonsaponin fraction with rich polysaccharide, also inhibited tau aggregation and promoted the dissociation of tau aggregates. Our observations suggest that RG could be a potential therapeutic agent for the treatment of neurodegenerative diseases associated with tauopathy.</jats:p>

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

“…Mitochondrial function can also be regulated by melatonin [ 396 ], methylene blue [ 397 ], carotenoids [ 398 ], red gingseng [ 399 ], and oxaloacetate [ 400 ]. Most of these supplements have multiple effects, e.g., inhibition of tau aggregation may be involved in the effects of methylene blue [ 337 , 401 ], red gingseng [ 402 ], crocin [ 403 ], cinnamaldehyde and epicatechin [ 404 ], purpurin [ 405 ], and folate [ 406 ], and inhibition of Aβ toxicity may be involved in the effects of resveratrol [ 407 ], huperzine A (cholinesterase inhibitor and NMDA receptor antagonist) [ 408 , 409 ] and carvacrol (anti-acetylcholinesterase, antioxidant, and neuroprotective properties) [ 410 , 411 ].…”

Tau-targeting therapy in Alzheimer’s disease: critical advances and future opportunities

“…J-147, an oral curcumin derivative, has been demonstrated to easily cross BBB and enhance memory in aged AD mice [118] . In addition, purpurin [119] , ginseng [120] , and many other natural compounds are also being investigated, which will offer great potential for the treatment of AD.…”

Neuroprotective Natural Products for Alzheimer’s Disease

“…Another in vitro study has revealed that α-cyperone from rhizomes of Cyperus rotundus (Cyperaceae) exerts a significant effect on reducing the rate of tubulin polymerization and the concentration of polymerized tubulin, which may represent a beneficial neuroprotective strategy for AD [ 155 ]. Other well-known examples of natural products capable of inhibiting tau protein aggregation are curcumin, which inhibits amyloidogenic protein aggregation including Aβ and tau [ 156 ], resveratrol, which inhibits the aggregation of the repeat domain of tau along with many other neuroprotective mechanisms [ 157 ], purpurin, which inhibits tau fibrillization and breaks down the pre-formed fibrils [ 158 ], folic acid, which inhibits tau aggregation via stabilizing its native state [ 159 ], and the root extract of red ginseng [ 160 ].…”