| In vitro: |
| Biol. Pharm. Bull., 2010, 33(5):917-21. | | Aldose reductase inhibitory compounds from Glycyrrhiza uralensis.[Pubmed: 20460778] |
METHODS AND RESULTS:
We evaluated the inhibitory effects of components from the root of Glycyrrhiza uralensis (G. uralensis) on aldose reductase (AR) and sorbitol formation in rat lenses with high levels of glucose as part of our ongoing search of natural sources for therapeutic and preventive agents for diabetic complications. In order to identify the bioactive components of G. uralensis, 5 prenylated flavonoids (Semilicoisoflavone B, 7-O-methylluteone, dehydroglyasperin C, dehydroglyasperin D, and isoangustone A), three flavonoids (liquiritigenin, isoliquiritigenin, and licochalcone A), and two triterpenoids (glycyrrhizin and glycyrrhetinic acid) were isolated; their chemical structures were then elucidated on the basis of spectroscopic evidence and comparison with published data. The anti-diabetic complication activities of 10 G. uralensis-derived components were investigated via inhibitory assays using rat lens AR (rAR) and human recombinant AR (rhAR). From the 10 isolated compounds, Semilicoisoflavone B showed the most potent inhibition, with the IC(50) values of rAR and rhAR at 1.8 and 10.6microM, respectively.
CONCLUSIONS:
In the kinetic analyses using Lineweaver.Burk plots of 1/velocity and 1/concentration of substrate, Semilicoisoflavone B showed noncompetitive inhibition against rhAR. The results clearly indicated that the presence of a gamma,gamma-dimethylchromene ring is partly responsible for the AR inhibitory activity of isoprenoid-type flavonoids. Further, Semilicoisoflavone B inhibited sorbitol formation of rat lens incubated with a high concentration of glucose, indicating that this compound may be effective for preventing osmotic stress in hyperglycemia. |
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| In vivo: |
| Mol Nutr Food Res . 2018 Mar;62(6):e1700633. | | Glycyrrhiza uralensis and Semilicoisoflavone B Reduce Aβ Secretion by Increasing PPARγ Expression and Inhibiting STAT3 Phosphorylation to Inhibit BACE1 Expression[Pubmed: 29143445] | | Abstract
Scope: Glycyrrhiza uralensis extract (GUE) has been reported to improve amyloid beta (Aβ)-induced cognitive deficits in mice. However, the mechanisms underlying this effect and the components involved have not been previously explored. Extracellular Aβ plaques are one of the major pathological hallmarks of Alzheimer's disease (AD). Therefore, decreasing Aβ levels is one strategy for preventing the etiology of AD. This study aims to test the effect of GUE and Semilicoisoflavone B (SB) on Aβ secretion and investigates the mechanism underlying this effect.
Methods and results: GUE and its bio-activated compound SB reduce Aβ secretion. We find that this effect contribute to the downregulation of the β-secretase-1 (BACE1) protein and mRNA. In a subsequent mechanism study, we find that GUE and SB regulate BACE1 transcription factors by inducing the expression of peroxisome proliferator activated receptor γ (PPARγ) and inhibiting the phosphorylation of signal transducer and activator of transcription 3. In addition, the effect of GUE and SB on BACE1 expression and Aβ secretion are attenuated by treatment with PPARγ-siRNA or its antagonist, GW9662.
Conclusion: These findings indicate that GUE and SB may function as PPARγ agonists, thereby inhibiting BACE1 expression and ultimately reducing the secretion of Aβ.
Keywords: Alzheimer's disease; BACE1; PPARγ; amyloid beta; Semilicoisoflavone B. |
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