||Daidzin is a potent, selective aldehyde dehydrogenase 2 (ALDH2,IC50 = 80 nM) inhibitor, which has antiallergic anti-oxidant, anti-carcinogenic, antithrombotic,and anti-atherosclerotic activities, It has preventive effect on bone loss in ovariectomized rats appears to be due to suppression of bone turnover. A mixture of daidzin and glycitin has anti-obese and anti-diabetic effects.|
|Biosci Biotechnol Biochem. 2015 Jan;79(1):117-23. |
|Anti-obese and anti-diabetic effects of a mixture of daidzin and glycitin on C57BL/6J mice fed with a high-fat diet.[Pubmed: 25209298]|
METHODS AND RESULTS:
We investigated the effects of a mixture of Daidzin and glycitin, which are the glycoside-form isoflavones of daidzein and glycitein, respectively, on body weight, lipid levels, diabetic markers, and metabolism in a high-fat diet (HF) fed C57BL/6J mice for 92 days. The mice were divided into basic diet group (CON), HF group, and HF companied with the isoflavone mixture group (HFISO). Results showed that mice in HFISO had a significantly lower body weight and adipose tissue compared to HF group. Blood glucose, serum HbA1c, and serum insulin also showed lower levels in HFISO group. In addition, higher hepatic GSH level and lower serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) level were found in HFISO group mice.
This suggests that the regulation of oxidative stress by Daidzin and glycitin was closely related to the suppression of adipose tissue and the progression of diabetes.
|J Hepatol. 2014 Dec 24. pii: S0168-8278(14)00943-X. |
|Pharmacological activation of aldehyde dehydrogenase 2 by Alda-1 reverses alcohol-induced hepatic steatosis and cell death in mice.[Pubmed: 25543082]|
|Effective therapies for alcoholic liver disease are currently unavailable. The present study tested the efficacy of Alda-1, a specific aldehyde dehydrogenase 2 (ALDH2) activator, in treating alcoholic liver disease.
METHODS AND RESULTS:
Male C57BL/6J mice were exposed to alcohol for a time-course study on aldehyde metabolism. The specificity and efficacy of Alda-1 on activating hepatic ALDH2 and aldehyde clearance were determined by acute treatments. Then, mice were fed alcohol for 8 weeks with Alda-1 administration for the last 10 days to test the therapeutic potential of Alda-1. Lastly, H4IIEC3 cells were treated with ethanol, acetaldehyde, or 4-hydroxynonenal to define the link between aldehydes and hepatotoxicity.
Alcohol feeding for 8 weeks induced hepatic ALDH2 dysfunction and aldehyde accumulation. One dose of Alda-1 administration elevated hepatic ALDH activity, which was blocked by the specific ALDH2 inhibitor, Daidzin. Alda-1 accelerated acetaldehyde clearance after acute alcohol intoxication. Alda-1 treatment in the 8-week alcohol feeding model reversed liver damage along with reduction of hepatic aldehydes. Alda-1 re-activated transcription factors, upregulated fatty acid oxidation enzymes, and reversed steatosis. Alcohol-induced endoplasmic reticulum stress and apoptotic cell death were also attenuated by Alda-1. Acetaldehyde or 4-hydroxynonenal treatment to H4IIEC3 cells inactivated transcription factors and induced endoplasmic reticulum stress and apoptosis, while ethanol per se showed limited effects.
Pharmacological activation of ALDH2 by Alda-1 reversed alcoholic steatosis and apoptosis through accelerating aldehyde clearance. This study indicates that ALDH2 is a promising molecular target and Alda-1 has therapeutic potential for treating alcoholic liver disease.
|Biol Pharm Bull. 2002 Oct;25(10):1328-32. |
|Antithrombotic and antiallergic activities of daidzein, a metabolite of puerarin and daidzin produced by human intestinal microflora.[Pubmed: 12392089]|
|To evaluate the antithrombotic activities of puerarin and Daidzin from the rhizome of Pueraria lobata, in vitro and ex vivo inhibitory activities of these compounds and their metabolite, daidzein, were measured. These compounds inhibited ADP- and collagen-induced platelet aggregation. Daidzein was the most potent. However, when puerarin and Daidzin were intraperitoneally administered, their antiaggregation activities were weaker than when these compounds were administered orally.
When in vivo antithrombotic activities of these compounds against collagen and epinephrine were measured, these compounds showed significant protection from death due to pulmonary thrombosis in mice.
METHODS AND RESULTS:
To evaluate the antiallergic activity of puerarin, Daidzin, and daidzein, their inhibitory effects on the release of beta-hexosaminidase from RBL 2H3 cells and on the passive cutaneous anaphylaxis (PCA) reaction in mice were examined. Daidzein exhibited potent inhibitory activity on the beta-hexosaminidase release induced by DNP-BSA and potently inhibited the PCA reaction in rats. Daidzein administered intraperitoneally showed the strongest inhibitory activity and significantly inhibited the PCA reaction at doses of 25 and 50mg/kg with inhibitory activity of 37 and 73%, respectively. The inhibitory activity of intraperitoneally administered daidzein was stronger than those of intraperitoneally and orally administered puerarin and Daidzin.
Therefore we believe that puerarin and Daidzin in the rhizome of Pueraria lobata are prodrugs, which have antiallergic and antithrombotic activities, produced by intestinal microflora.