Absorption, Distribution and Excretion
This study determined the pharmacokinetics of dietary capsanthin in four male volunteers who had virtually no capsanthin in their plasma at the start of the study. They consumed chili juice for one week, equivalent to 5.4 μmol capsanthin three times daily, for a total of 16.2 μmol daily. Plasma capsanthin concentrations plateaued between days 2 and 7 (0.10–0.12 μmol/L), becoming undetectable in plasma by day 16. After one week, the distribution of capsanthin in plasma lipoproteins was as follows: very low density lipoprotein, 13 ± 3%; low density lipoprotein, 44 ± 3%; high density lipoprotein, 43 ± 3%. In one study, the same group of men who consumed chili juice (equivalent to 34.2 μmol capsanthin) showed plasma capsanthin concentrations ranging from 0.10 to 0.29 μmol/L 8 hours after ingestion. In contrast, after a single intake of tomato soup (equivalent to 186.3 mmol of lycopene) by the same group of subjects, the increase in plasma concentration of the noncyclic carotenoid lycopene was minimal (0.02–0.06 mmol/L). The area under the plasma concentration-time curve for capsanthin over 0–74 hours was 4.68 ± 1.22 μmol·hr/L, and for lycopene over 0–72 hours it was 0.81 ± 0.17 μmol·hr/L. The half-lives of capsanthin and lycopene were 20.1 ± 1.3 hours and 222 ± 15 hours, respectively. The conclusion is that although capsanthin is transported more into plasma lipoproteins, its clearance rate is much faster than that of lycopene. This study evaluated the bioavailability of carotenoids (zeaxanthin, β-cryptoxanthin, β-carotene, capsanthin, and capsanthin rubigin) in capsicum oleoresin in humans. Nine volunteers, after an overnight fast, received a single intake of capsicum oleoresin containing 6.4 mg zeaxanthin, 4.2 mg β-cryptoxanthin, 6.2 mg β-carotene, 35.0 mg capsanthin, and 2.0 mg capsanthin. The carotenoid profile of whole blood chylomicron fractions was analyzed at different time points to assess carotenoid absorption. Among the major carotenoids in capsicum oleoresin, only zeaxanthin, β-cryptoxanthin, and β-carotene were detected. Although lutein in capsicum oleoresin exists primarily as monoesters or diesters, only free zeaxanthin and β-cryptoxanthin were detected. The bioavailability of capsanthin and capsanthin, the capsicum-specific carotenoids in capsicum oleoresin, was very low.

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Metabolism/Metabolites
A study reported that after rats were administered a mixture of Capsanthins by gavage, these substances were extensively metabolized through multiple metabolic pathways, including: 1) hydrolysis and deamination of the acid-amide bond to produce vanillin; 2) hydroxylation of the vanillin ring; 3) oxidation of the hydroxyl group on the ring; and 4) oxidation of the terminal carbon of the side chain. /Capsanthin/
Subsequent steps in the biosynthesis of carotenoids are catalyzed by cyclases, involving the formation of the α-ring, β-ring, and κ-ring. Analysis of the primary structure of lycopene β-cyclase showed that it shared 55% homology with the primary structure of antherin κ-cyclase. Recombinant lycopene β-cyclase only produced β-carotene, while recombinant antherin κ-cyclase catalyzed the conversion of lycopene to β-carotene and antherin to the κ-carotenoid Capsanthin. Since the formation of both the β-ring and κ-ring involves transient carotenoid carbocations, this suggests that the two cyclases may initiate and/or neutralize this carbocation through similar mechanisms. To investigate the molecular basis of this phenomenon, we used several amine derivatives protonated under physiological pH conditions. The results showed that β-cyclase and κ-cyclase exhibited similar inhibition patterns. Both cyclases were irreversibly inactivated by affinity or photoaffinity labeling with p-dimethylaminophenyldiazofluoroborate, N,N-dimethyl-2-phenylaziridine, and nicotine. Photoaffinity labeling with [H(3)]nicotine, followed by radioactive sequencing and site-directed mutagenesis, revealed that the cyclases possess two domains characterized by the presence of active aromatic and carboxyl amino acid residues. The researchers proposed that these residues represent “negatively charged sites” involved in the initial carotenoid carbocation coordination.

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Biological Half-Life
...In one study, subjects ingested a single serving of chili juice (equivalent to 34.2 μmol capsanthin). The calculated half-lives after this single intake were: capsanthin 20.1 ± 1.3 hours, lycopene 222 ± 15 hours. ……

Non-Human Toxicity Values
Oral LD50 in rats: 11.25 g/kg body weight/capsicum powder/

[1]. Red paprika (Capsicum annuum L.) and its main carotenoids, capsanthin and β-carotene, prevent hydrogen peroxide-induced inhibition of gap-junction intercellular communication. Chem Biol Interact. 2016 Jul 25;254:146-55.

[2]. Prevention of N-methylnitrosourea-induced colon carcinogenesis in rats by oxygenated carotenoid capsanthin and capsanthin-rich paprika juice. Proc Soc Exp Biol Med. 2000 Jun;224(2):116-22.

[3]. Purified canola lutein selectively inhibits specific isoforms of mammalian DNA polymerases and reduces inflammatory response. Lipids. 2010 Aug;45(8):713-21.

Capsanthin is a carotenoid and a plant metabolite. It has been reported that Capsanthin is found in chili peppers (Capsicum annuum), chicken (Gallus gallus), and lilies (Lilium lancifolium), and relevant data exists. See also: Red chili peppers (partial).

C40H56O3

584.8709

584.422

465-42-9

5281228

Brown to red liquid

1.0±0.1 g/cm3

726.6±60.0 °C at 760 mmHg

177-178ºC

407.2±29.4 °C

0.0±5.4 mmHg at 25°C

1.563

9.9

2

3

11

43

1310

3

O([H])[C@]1([H])C([H])([H])[C@](C(/C(/[H])=C(\[H])/C(=C(\[H])/C(/[H])=C(\[H])/C(=C(\[H])/C(/[H])=C(\[H])/C(/[H])=C(\C([H])([H])[H])/C(/[H])=C(\[H])/C(/[H])=C(\C([H])([H])[H])/C(/[H])=C(\[H])/C2=C(C([H])([H])[H])C([H])([H])[C@]([H])(C([H])([H])C2(C([H])([H])[H])C([H])([H])[H])O[H])/C([H])([H])[H])/C([H])([H])[H])=O)(C([H])([H])[H])C(C([H])([H])[H])(C([H])([H])[H])C1([H])[H]

VYIRVAXUEZSDNC-RDJLEWNRSA-N

InChI=1S/C40H56O3/c1-29(17-13-19-31(3)21-23-36-33(5)25-34(41)26-38(36,6)7)15-11-12-16-30(2)18-14-20-32(4)22-24-37(43)40(10)28-35(42)27-39(40,8)9/h11-24,34-35,41-42H,25-28H2,1-10H3/b12-11+,17-13+,18-14+,23-21+,24-22+,29-15+,30-16+,31-19+,32-20+/t34-,35+,40+/m1/s1

(2E,4E,6E,8E,10E,12E,14E,16E,18E)-19-[(4R)-4-hydroxy-2,6,6-trimethylcyclohexen-1-yl]-1-[(1R,4S)-4-hydroxy-1,2,2-trimethylcyclopentyl]-4,8,13,17-tetramethylnonadeca-2,4,6,8,10,12,14,16,18-nonaen-1-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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