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Rhodiola rosea extract and isolated compounds and their use in the treatment of neurodegenerative diseases

A neurodegenerative disease and compound technology, applied to Rhodiola rosea extracts and isolated compounds and their application fields in the treatment of neurodegenerative diseases, can solve the problems of reduced therapeutic effect, side effects and the like

Active Publication Date: 2019-07-12
THE HONG KONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Over the years, many dopamine receptor agonists have been studied for the treatment of PD; however, after a period of treatment, the therapeutic effect decreases
And this medication, in some patients, also has side effects, such as gastrointestinal disorders and psychological cognitive problems (eg, confusion, hallucinations, psychosis, etc.)

Method used

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  • Rhodiola rosea extract and isolated compounds and their use in the treatment of neurodegenerative diseases
  • Rhodiola rosea extract and isolated compounds and their use in the treatment of neurodegenerative diseases
  • Rhodiola rosea extract and isolated compounds and their use in the treatment of neurodegenerative diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0235] Example 1 - Rhodiola rosea extract inhibits aggregation of α-synuclein protein

[0236] A total extract (TE) of Rhodiola rosea (RR) was prepared. This extract (0.07 μg) was incubated with recombinant-α-synuclein in TBS for 7 days at 37°C. After incubation, samples were filtered using Bio-Dot SF microfiltration devices (Bio Rad) according to the manufacturer's instructions. After filtration, the amount of retained α-synuclein was determined by Western blot analysis.

[0237] As shown in Figure 1, in the untreated control samples, the amount of aggregated forms of the α-synuclein protein was significantly increased at day 7 compared to day 0. Similar amounts of aggregated forms of the α-synuclein protein were found in samples treated with DMSO for 7 days when compared to untreated controls. Samples treated with Congo red, a known inhibitor against α-synuclein aggregation, were used as positive controls. Incubation of α-synuclein protein with 1 μg to 100 μg of RR’s TE ...

Embodiment 2

[0238] Example 2 - Aqueous and ethanol components of Rhodiola rosea extract inhibit aggregation of alpha-synuclein protein

[0239] Preparation of total extract (TE) and fractions of Rhodiola rosea (RR). Recombinant-α-synuclein in TBS was then incubated with the extract (μg / ml) for 7 days at 37°C. After incubation, samples were filtered with Bio-Dot SF microfiltration devices (Bio Rad) according to the manufacturer's instructions. After filtration, the amount of retained α-synuclein was determined by Western blot analysis.

[0240] RR total extract (RRTE) and RR fractions (RRPE (Rhodiola rosea petroleum ether fraction), RREA (Rhodiola rosea ethyl acetate fraction), RRBU (Rhodiola rosea butanol fraction) and RRWA (Rhodiola rosea water fraction)) was incubated with recombinant α-synuclein for 7 days. Filter cut-off assays were performed as described in Example 1. Untreated samples served as negative controls, and Congo red-treated samples served as positive controls.

[024...

Embodiment 3

[0242] Example 3 - Inhibition of α-Synuclein Protein Aggregation

[0243] Compounds RR-C20 (salidroside) and RR-C36 (rosevin) were isolated from RRWA. Then, recombinant α-synuclein in TBS was incubated with compounds RR-C20 and RR-36 for 7 days at 37°C, respectively. After incubation, samples were filtered with Bio-Dot SF microfiltration devices (Bio Rad) according to the manufacturer's instructions. After filtration, the amount of retained α-synuclein was determined by Western blot analysis.

[0244] As shown in Figure 3A, after 7 days of incubation, α-synuclein aggregates increased, and Congo red inhibited the increase in α-synuclein aggregation. RR-C36 (Rosevir) isolated from RRBU or RRWA inhibits α-synuclein aggregation in a dose-dependent manner.

[0245] Figure 3B shows that RR-C36 (rosavir) inhibits the aggregation of α-synuclein in vitro in a dose-dependent manner. The IC50 of RR-C36 anti-aggregation was -0.36 μΜ as determined by PRISM GraphPad (version 5.03).

[...

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Abstract

This invention relates to extract, fractions and isolated compound of Rhodiola rosea, and uses thereof for treating neuropathological and neurodegenerative diseases. The extracts and compounds of the present invention inhibit the aggregation of alpha-synuclein. In one embodiment, Rhodiola rosea extracts and compounds of the present invention can be used to treat synucleinopathies including PD, dementia with Lewy bodies, pure autonomic failure, multiple system atrophy, and Alzheimer's disease.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Provisional Application Serial No. 61 / 573,022, filed August 8, 2011, which is hereby incorporated by reference in its entirety. Background technique [0003] Parkinson's disease (PD) is a disabling, progressive neurodegenerative disorder. Clinical manifestations of PD include resting tremor, rigidity, bradykinesia and postural instability with cognitive and affective impairment. The main pathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta and the presence of intracytoplasmic inclusion bodies called Lewy bodies. [0004] The etiology and pathogenesis of PD have not been fully elucidated. Both environmental and genetic factors can lead to the formation of PD (Broussolle & Thobois, 2002). Most PD patients are sporadic, however some PD patients with familial inheritance of susceptibility genes have also been identified. Three mis...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/7034A61K31/7028A61K36/41A61K125/00A61P43/00A61P25/28A61P25/16A61P25/08
CPCA61K31/7028A61K31/7034A61K36/41A61K2236/39A61P25/08A61P25/16A61P25/28A61P43/00
Inventor 叶玉如叶翠芬浮光苗官可祈伍儒邦
Owner THE HONG KONG UNIV OF SCI & TECH
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