Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils

Abstract

Compelling evidence indicates that α-synuclein (α-syn) aggregation plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. Identification of compounds that inhibit or reverse the aggregation process may thus represent a viable therapeutic strategy against PD and related disorders. Ginseng is a well-known medicinal plant that has been used in East Asia for more than two thousand years to treat several conditions. It is now understood that the pharmacological properties of ginseng can be attributed to its biologically active components, the ginsenosides, which in turn have been shown to have neuroprotective properties. We therefore sought to determine for the first time, the potential of the most frequently used and studied ginsenosides, namely Rg1, Rg3 and Rb1, as anti-amyloidogenic agents. The effect of Rg1, Rg3 and Rb1 on α-syn aggregation and toxicity was determined by an array of biophysical, biochemical and cell-culture-based techniques. Among the screened ginsenosides, only Rb1 was shown to be a potent inhibitor of α-syn fibrillation and toxicity. Additionally, Rb1 exhibited a strong ability to disaggregate preformed fibrils and to inhibit the seeded polymerization of α-syn. Interestingly, Rb1 was found to stabilize soluble non-toxic oligomers with no β-sheet content, that were susceptible to proteinase K digestion, and the binding of Rb1 to those oligomers may represent a potential mechanism of action. Thus, Rb1 could represent the starting point for designing new molecules that could be utilized as drugs for the treatment of PD and related disorders.

Estrogen receptor‐β of microglia underlies sexual differentiation of neuronal protection via ginsenosides in mice brain

“…Ginsenoside Rb1 exerts neuroprotective effects against CNS injury. However, the underlying neuronal mechanism remains unclear . ER‐β activation is one mechanism that protects microglia by downregulating NF‐κB signaling .…”

Antibodies against alpha‐synuclein: tools and therapies

“…; Ardah et al . , ; Wrasidlo et al . ), increasing the clearance of α‐syn via autophagy (Sarkar et al .…”

Natural product-based amyloid inhibitors

“…How diet-specific natural compounds may provide healthy effects are not well known. Nevertheless, information from these epidemiological sources as well as information reported by alternative and complementary medicine led to testable hypotheses and experimental efforts that successfully identified numerous natural compound amyloid inhibitors [22–25]. …”