Identification of novel autophagic Radix Polygalae fraction by cell membrane chromatography and UHPLC-(Q)TOF-MS for degradation of neurodegenerative disease proteins

Abstract

With its traditional use in relieving insomnia and anxiety, our previous study has identified onjisaponin B from Radix Polygalae (RP), as a novel autophagic enhancer with potential neuroprotective effects. In current study, we have further identified a novel active fraction from RP, contains 17 major triterpenoid saponins including the onjisaponin B, by the combinational use of cell membrane chromatography (CMC) and ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry {UHPLC-(Q)TOF-MS}. By exhibiting more potent autophagic effect in cells, the active fraction enhances the clearance of mutant huntingtin, and reduces protein level and aggregation of α-synuclein in a higher extent when compared with onjisaponin B. Here, we have reported for the first time the new application of cell-based CMC and UHPLC-(Q)TOF-MS analysis in identifying new autophagy inducers with neuroprotective effects from Chinese medicinal herb. This result has provided novel insights into the possible pharmacological actions of the active components present in the newly identified active fraction of RP, which may help to improve the efficacy of the traditional way of prescribing RP, and also provide new standard for the quality control of decoction of RP or its medicinal products in the future.

Characterization of anti-leukemia components from Indigo naturalis using comprehensive two-dimensional K562/cell membrane chromatography and in silico target identification

“…Traditionally, the components in TCM formulae were separated and identified by phytochemical methods, and evaluated by pharmacological assays for their molecular targets and mechanism, but the processes were incomprehensive, time-consuming and also inefficient 8 . In recent years, cell membrane chromatography (CMC) has been extensively used for active component screening and identification based on the interactions between membrane receptors and active ingredients 9 10 11 . It combines the advantages of both biomaterials and classic chromatography and realizes online and high-throughput screening of potential active ingredients from complicated biological samples 12 .…”

New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy

“…RP was reported to inhibit the phosphatidylinositol 3-kinase (PI3K)/Akt or activate the N-methyl-D-aspartate (NMDA) signaling pathways [394,395]. The active ingredients of RP such as onjisaponin B and other identified saponins, were proved to accelerate the clearance of neurodegenerative disease proteins such as huntingtin and α-synuclein, reduce aggregation and toxicity of mutant proteins through the induction of autophagy [170,396]. Therefore, RP may play its traditional sedative effect through degradation of unwanted proteins or organelles by autophagy.…”

Polyphenols Derived from Lychee Seed Suppress Aβ (1-42)-Induced Neuroinflammation

“…Traditional Chinese medicines (TCMs) have a long usage history in the prevention and treatment of diverse diseases. There are many Chinese medical herbs and formulas—such as Radix polygalae , Radix ginseng , Ginkgo biloba , Salvia miltiorrhiza , Ginseng , Dangguishaoyao San, Tiaoxin Fang, and Zhiling Tang—that have been proven to modulate neurodegenerative disease [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”