Jatrorrhizine hydroxide is an alkaloid extracted from Coptis chinensis and has neuro-protection, antibacterial, antiplasmodial and antioxidant activities. Jatrorrhizine hydroxide is a potent, orally bioactive inhibitor of acetylcholinesterase (AChE) (IC50=872 nM), with 115-fold selectivity for BuChE. Jatrorrhizine hydroxide reduces the uptake of serotonin (5-HT) and norepinephrine (NE) by inhibiting the activity of the uptake-2 transporter.

Physicochemical Properties

Molecular Formula	C20H20NO4
Molecular Weight	338.377
Exact Mass	355.141
CAS #	483-43-2
Related CAS #	Jatrorrhizine chloride;6681-15-8;Jatrorrhizine;3621-38-3
PubChem CID	12304700
Appearance	Brown to black solid powder
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Heavy Atom Count	26
Complexity	461
Defined Atom Stereocenter Count	0
SMILES	C12C([H])C3C([H])C([H])C(OC([H])([H])[H])C(OC([H])([H])[H])C3C([H])N1C(C(C1C2C([H])C(OC([H])([H])[H])C(O[H])C1[H])([H])[H])([H])[H]
InChi Key	FLLCSIZPVWDZQO-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H19NO4.H2O/c1-23-18-5-4-12-8-16-14-10-19(24-2)17(22)9-13(14)6-7-21(16)11-15(12)20(18)25-3;/h4-5,8-11H,6-7H2,1-3H3;1H2
Chemical Name	2,9,10-trimethoxy-5,6-dihydroisoquinolino[2,1-b]isoquinolin-7-ium-3-ol;hydroxide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	IC50: 872 nM (AChE)[1]
ln Vitro	Jatrorrhizine exhibits antiplasmodial and antiamoebic properties, with IC50 values of 3.15 and 82.7 µM, respectively, against Plasmodium falciparum and E. histolytica[1]. Neurotransmitters known as monoamines can be transported in the brain via the hOCT2 (organic cation transporter 2), hOCT3, and PMAT (plasma membrane monoamine transporter)[3]. When it comes to 5-HT and NE uptake in hOCT2-, hOCT3-, and PMAT-transfected cells, jatrorrhizine exhibits the same inhibitory effectiveness. With a PMAT-mediated MPP+ uptake IC50 value of 1.05 μM, jatrorrhizine severely inhibits it. It also decreases 5-HT and NE uptake mediated by hOCT2, hOCT3, and hPMAT, with IC50 values of 1-10 μM for PMAT and 0.1-1 μM for OCT2 and OCT3[3]. Two separate processes determine the clearance of neurotransmitters produced into the synaptic cleft. The serotonin transporter, or "SERT," has a high affinity but a limited ability to take up [3H]5-HT. Uptake-1, the typical target of currently used antidepressants, is made up of this protein. An essential supplemental regulatory mechanism for the clearance of monoamines is the uptake-2 transporter.Low affinity but great capacity to absorb [3H]5-HT into brain slices characterizes what is believed to be the "NET." 5-HT and NE absorption in synaptosomes was markedly reduced by jatrorrhizine at 25 μM and 50 μM[3].
ln Vivo	In the tail suspension test (TST), jatrorrhizine (intraperitoneal injection; 5, 10, 20 mg/kg) can dramatically shorten the period of immobility in comparison to the vehicle control group[2].
Animal Protocol	Animal/Disease Models: Male ICR albino mice[2] Doses: 5, 10, 20 mg/kg Route of Administration: intraperitoneal (ip)injection; 5, 10, 20 mg/kg Experimental Results: diminished immobility period in tail suspension test.
References	[1]. Jatrorrhizine reduces 5-HT and NE uptake via inhibition of uptake-2 transporters and produces antidepressant-like action in mice. Xenobiotica. 2019 Oct;49(10):1237-1243. [2]. Synthesis and Biological Evaluation of Novel Jatrorrhizine Derivatives with Amino Groups Linked at the 3-Position as Inhibitors of Acetylcholinesterase. Research Article Volume 2017. [3]. In vitro antiplasmodial, antiamoebic, and cytotoxic activities of some monomeric isoquinoline alkaloids. J Nat Prod. 2000 Dec;63(12):1638-40.

Solubility Data

Solubility (In Vitro)

H2O : 5 mg/mL (14.07 mM) DMSO : 3.33 mg/mL (9.37 mM)

Solubility (In Vivo)

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. Injection Formulations (e.g. IP/IV/IM/SC) 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). 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) Oral Formulations 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). 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 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.9553 mL	14.7763 mL	29.5526 mL
	5 mM	0.5911 mL	2.9553 mL	5.9105 mL
	10 mM	0.2955 mL	1.4776 mL	2.9553 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.