Metabolism / Metabolites
Paraoxygenase 1 (PON1) is a key enzyme in organophosphate metabolism. PON1 can inactivate certain organophosphates through hydrolysis. PON1 hydrolyzes active metabolites from various organophosphate pesticides and nerve agents (such as soman, sarin, and VX). The polymorphism of PON1 leads to differences in its enzyme activity and catalytic efficiency, suggesting that different individuals may be more susceptible to the toxic effects of organophosphate exposure.

Toxicity Summary
Chelidonine is a cholinesterase, or acetylcholinesterase (AChE) inhibitor. Cholinesterase inhibitors (or "anticholinesterases") inhibit the activity of acetylcholinesterase. Because acetylcholinesterase plays a vital physiological role, chemicals that interfere with its activity are potent neurotoxins; even low doses can cause excessive salivation and lacrimation, followed by muscle spasms and ultimately death. Neurotoxins and substances in many pesticides have been shown to exert their effects by binding to serine residues at the active site of acetylcholinesterase, thus completely inhibiting the enzyme's activity. Acetylcholinesterase breaks down the neurotransmitter acetylcholine, which is released at the neuromuscular junction, causing muscle or organ relaxation. Inhibition of acetylcholinesterase results in the accumulation and sustained action of acetylcholine, leading to continuous nerve impulse transmission and an inability to stop muscle contractions. The most common acetylcholinesterase inhibitors are phosphorus-containing compounds designed to bind to the enzyme's active site. Its structural requirements include a phosphorus atom with two lipophilic groups, a leaving group (e.g., a halide or thiocyanate), and a terminal oxygen atom. Chelidonine exhibits inhibitory activity against acetylcholinesterase and butyrylcholinesterase. (Wikipedia) Generally, some alkaloid extracts from Chelidonium majus, such as those containing protoberberine and benzo[c]phenanthridine alkaloids (e.g., chelidonine), can intercalate into DNA, thereby inhibiting the biosynthesis of DNA and RNA polymerases, topoisomerases, telomerases, and even ribosomal proteins, or binding to tubulin/microtubules, thus acting as a spindle toxin. Chelidonine can overcome multidrug resistance (MDR) in different cancer cell lines by interacting with ABC transporters, CYP3A4, and GST to induce apoptosis and exert cytotoxic effects. It can induce apoptosis in MDR cells, accompanied by activation of caspase-3, -8, -6/9 and exposure of phosphatidylserine (PS). (A15442) Chelidonine is known to cause mitotic arrest and interact weakly with tubulin. Chelidonine has been shown to have a weak inhibitory effect on cell growth in two normal cell lines (monkey kidney cells and Hs27 cells), two transformed cell lines (Vero cells and Graham 293 cells), and two malignant cell lines (WHCO5 cells and HeLa cells). (A15443)

Chelidonine (-)- has been reported to be found in scaly sea anemones, celandine, and other organisms with available data.

C20H19NO5

353.37

353.126

88200-01-5

4312-31-6 (hydrochloride) ; 63937-19-9 (sulfate)

978315

Typically exists as solids at room temperature

2.269

1

6

0

26

560

3

CN1CC2=C(C=CC3=C2OCO3)C4C1C5=CC6=C(C=C5CC4O)OCO6

GHKISGDRQRSCII-ZMYBRWDISA-N

InChI=1S/C20H19NO5/c1-21-7-13-11(2-3-15-20(13)26-9-23-15)18-14(22)4-10-5-16-17(25-8-24-16)6-12(10)19(18)21/h2-3,5-6,14,18-19,22H,4,7-9H2,1H3/t14-,18-,19+/m1/s1

(1R,12R,13S)-24-methyl-5,7,18,20-tetraoxa-24-azahexacyclo[11.11.0.02,10.04,8.014,22.017,21]tetracosa-2,4(8),9,14(22),15,17(21)-hexaen-12-ol

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)

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.)