| Animal Research: |
| Nat Prod Bioprospect. 2017 Apr;7(2):207-214. | | Otophylloside B Protects Against Aβ Toxicity in Caenorhabditis elegans Models of Alzheimer's Disease.[Pubmed: 28194725 ] | Alzheimer's disease (AD) is a major public health concern worldwide and the few drugs currently available only treat the symptoms. Hence, there is a strong need to find more effective anti-AD agents. Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy, and Otophylloside B (Ot B), isolated from C. otophyllum, is the essential active component.
METHODS AND RESULTS:
Having previously identified anti-aging effects of Ot B, we evaluated Ot B for AD prevention in C. elegans models of AD and found that Ot B extended lifespan, increased heat stress-resistance, delayed body paralysis, and increased the chemotaxis response.
CONCLUSIONS:
Collectively, these results indicated that Ot B protects against Aβ toxicity. Further mechanistic studies revealed that Ot B decreased Aβ deposition by decreasing the expression of Aβ at the mRNA level.
Genetic analyses showed that Ot B mediated its effects by increasing the activity of heat shock transcription factor (HSF) by upregulating the expression of hsf-1 and its target genes, hsp-12.6, hsp-16.2 and hsp-70. Ot B also increased the expression of sod-3 by partially activating DAF-16, while SKN-1 was not essential in Ot B-mediated protection against Aβ toxicity. | | Nat Prod Bioprospect. 2015 Aug;5(4):177-183. | | The Lifespan-Promoting Effect of Otophylloside B in Caenorhabditis elegans.[Pubmed: 26112394] | Aging is the major risk factor for many human diseases and degeneration. Thus, clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted. In traditional Chinese medicine (TCM), some were claimed to slow down aging. Qingyangshen (Cynanchum otophyllum schneid) is such a TCM.
METHODS AND RESULTS:
Here, we assayed the longevity effect of compound Otophylloside B (Ot B), a C-21 steroidal glycoside isolated from Qingyangshen, in Caenorhabditis elegans, which is a popular model for aging research.
CONCLUSIONS:
Our results showed that Ot B could modestly extend the lifespan of C. elegans, delay the age-related decline of body movement and improve the stress resistance. Further investigating the molecular mechanism of lifespan extension effect revealed that Ot B could activate the FOXO transcription factor DAF-16. Ot B could not further extend the lifespan of long-lived mutant of insulin/IGF-1-like receptor (daf-2). In addition, Ot B also requires SIR-2.1 and CLK-1 which is an enzyme in ubiquinone synthesis, for lifespan extension. |
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| Structure Identification: |
| J Nat Prod. 2015 Jul 24;78(7):1548-55. | | Bioactive C21 Steroidal Glycosides from the Roots of Cynanchum otophyllum That Suppress the Seizure-like Locomotor Activity of Zebrafish Caused by Pentylenetetrazole.[Pubmed: 26135914] | Six new C21 steroidal glycosides, cynotophyllosides A-F (1-6), together with 16 known compounds, were isolated from the roots of Cynanchum otophyllum.
METHODS AND RESULTS:
The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. The three major components, otophylloside F (15), Otophylloside B (17), and rostratamine 3-O-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (18), suppressed the seizure-like locomotor activity caused by pentylenetetrazole in zebrafish.
CONCLUSIONS:
Preliminary structure-activity relation studies revealed that a pregnene skeleton with a C-12 ester group (ikemaoyl > cinnamoyl > hydroxy > p-hydroxybenzoyl) and a C-3 sugar chain consisting of three 2,6-dideoxysaccharide units is essential for this suppressive activity. |
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