Absorption, Distribution and Excretion
Following oral ingestion, serum isoflavone concentrations increase in a dose-dependent manner. Isoflavones are metabolized by gut microflora, where they need to undergo deglycosylation in order to be absorbed in the intestine. After oral ingestion, glycosylated isoflavones are rapidly deglycosylated, absorbed and metabolized in intestinal enterocytes and liver, entering the systemic circulation predominantly as conjugates with limited bioavailability. In humans, the mean time to reach peak plasma concentrations (Tmax) for conjugated and unconjugated genistein and daidzein are approximately 5-6 and 6-8 hours, respectively.
Renal excretion is the predominant route of elimination for dietary isoflavones, where approximately 10-60% of total administered dose is excreted in urine. Glucuronide conjugates account for the majority (70-90%) of the isoflavone content in urine, followed by sulphate conjugates (10-25%) and aglycone forms (1-10%). Fecal excretion is minimal, which accounts for 1-4% of the dietary isoflavone ingested.
Isoflavones are readily distributed to all tissues, and they are known to cross the placental barrier and blood brain barrier. They are also distributed to the extra-vascular compartments. In a human study, the volume of distribution of daidzein and genistein were 336.25 L and 258.76 L, respectively.
In a human study, the clearance rate for daidzein and genistein were 30.09 L/h and 21.85 L/h, respectively.

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Metabolism / Metabolites
The conversion of glycosylated isoflavones to de glycosylated isoflavones begins in the oral cavity, wherein oral microflora and oral epithelium exhibit β-glucosidase activity. Further conversion is mediated by intestinal lactase phlorizin hydrolase on the luminal side of the intestinal brush border to form aglycones that diffuses into the enterocytes. The glycosylated isoflavones may also be converted to aglycone in the large intestines by the resident intestinal microflora. Isoflavone aglycones that enter the intestinal cell via passive diffusion are rapidly conjugated into sulfate or glucuronide conjugates. Under the anaerobic, reductive conditions of the colon, genistein undergoes reduction to form dihydrogenistein and further to 5-hydroxyequol, while daidzein is reduced to dihydrodaidzein and equol. Microbial cleavage of the Ring-C of isoflavones produces deoxybenzoin metabolites (DOBs), which retains similar biological activity as unchanged isoflavones and are passively absorbed. There is a large interindividual variation in isoflavone metabolism, leading to circulating concentrations of isoflavone metabolites and parent isoflavones varying up to hundreds-fold. About 25% of the non-Asian and 50% of the Asian population host the intestinal bacteria that convert the daidzein into the isoflavonoid equol, which is a beneficial isoflavonoid.

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Biological Half-Life
The half-life of isoflavones is between 4 and 8 h. Daidzein has a longer intestinal half-life than genistein due to more rapid degradation of genistein. Individual half-life of daidzein and genistein in a human pharmacokinetic study were 7.75 h and 7.77 h, respectively.

Protein Binding
No pharmacokinetic data available.

[1]. Effects of soy protein and isoflavone on hepatic fatty acid synthesis and oxidation and mRNA expression of uncoupling proteins and peroxisome proliferator-activated receptor gamma in adipose tissues of rats. J Nutr Biochem. 2008;19(10.

[2]. Isoflavone.

Pharmacodynamics
Isolated soy protein with isoflavones was shown to decrease LDL cholesterol levels in randomized trials assessed by the American Heart Association. In a study of postmenopausal women, daily dietary intake of 101 mg of aglycone isoflavones (indicating [DB01645] and [DB13182]) was associated with lowered LDL cholesterol and apolipoprotein B levels by 8% and reduced systolic and diastolic blood pressure by 6.8% in hypertensive women. In a meta-analysis of randomized controlled trials of menopausal women, soy isoflavones attenuated bone loss of the spine and decreased the levels of deoxypyridinoline, a bone resorption marker, while increasing serum bone-specific alkaline phosphatase, a bone formation marker. The findings from studies investigating the effects of soy consumption on menopausal symptoms, breast cancer, and prostate cancer remain somewhat controversial and inconclusive. Consumption of soy isoflavones may decrease the markers of cancer development and progression in prostate cells, including prostate-specific antigen (PSA), testosterone, and androgen receptor in patients with prostate cancer but not in normal subjects. Although epidemiologic data in Asian women demonstrate that high soy food intake is associated with protection against breast cancer, soy foods have little effect on intermediary markers of breast cancer risk and postmenopausal soy intake may not reduce the risk of developing breast cancer. However, preliminary studies show that soy food intake reduces tumor recurrence in breast cancer patients. Soy isoflavones reported to interfere with thyroid peroxidase, which are involved in the production of thyroid hormones.

C15H10O2

222.2387

222.068

C, 81.07; H, 4.54; O, 14.40

574-12-9

72304

Light brown to brown solid powder

1.2±0.1 g/cm3

367.0±42.0 °C at 760 mmHg

150ºC

171.1±21.4 °C

0.0±0.8 mmHg at 25°C

1.635

3.58

0

2

1

17

326

0

O1C([H])=C(C2C([H])=C([H])C([H])=C([H])C=2[H])C(C2=C([H])C([H])=C([H])C([H])=C12)=O

GOMNOOKGLZYEJT-UHFFFAOYSA-N

InChI=1S/C15H10O2/c16-15-12-8-4-5-9-14(12)17-10-13(15)11-6-2-1-3-7-11/h1-10H

3-phenylchromen-4-one

3 Phenylchromone; 3-Phenylchromone; Isoflavone; NSC 135405; NSC-135405; NSC135405

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~449.96 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (11.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)