N-Oxysophocarpine

Details:

Chemical Properties of Oxysophocarpine

Cas No.	26904-64-3
PubChem ID	161544	Appearance	White-pale yellow powder
Formula	C15H22N2O2	M.Wt	262.4
Type of Compound	Alkaloids	Storage	Desiccate at -20°C
Synonyms	Sophocarpidine; Sophocarpine N-oxide
Solubility	Soluble in chloroform and water
SMILES	C1CC2CN3C(CC=CC3=O)C4C2[N+](C1)(CCC4)[O-]
Standard InChIKey	QMGGMESMCJCABO-LHDUFFHYSA-N
Standard InChI	InChI=1S/C15H22N2O2/c18-14-7-1-6-13-12-5-3-9-17(19)8-2-4-11(15(12)17)10-16(13)14/h1,7,11-13,15H,2-6,8-10H2/t11-,12+,13+,15-,17?/m0/s1
General tips	For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging	1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment.
Shipping Condition	Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Source of Oxysophocarpine

The root of Styphnolobium japonicum (L.) Schott.

Biological Activity of Oxysophocarpine

Description	Oxysophocarpine shows anti-inflammatory, neuroprotective, anticonvulsant, and anti-nociceptive effects, it also attenuates inflammatory pain by suppressing the levels of phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, prostaglandin E2, tumor necrosis factor α, interleukin-1 beta and interleukin-6.
Targets	ERK | COX | PGE | TNF-α | IL Receptor | Caspase | GABA Receptor | Bcl-2/Bax | P450 (e.g. CYP17)
In vitro	Neuroprotective effects of oxysophocarpine on neonatal rat primary cultured hippocampal neurons injured by oxygen-glucose deprivation and reperfusion.[Pubmed: 24601951] Pharm Biol. 2014 Aug;52(8):1052-9. Oxysophocarpine (OSC), a quinolizidine alkaloid extracted from leguminous plants of the genus Robinia, is traditionally used for various diseases including neuronal disorders. This study investigated the protective effects of Oxysophocarpine on neonatal rat primary-cultured hippocampal neurons were injured by oxygen-glucose deprivation and reperfusion (OGD/RP). METHODS AND RESULTS: Cultured hippocampal neurons were exposed to OGD for 2 h followed by a 24 h RP. Oxysophocarpine (1, 2, and 5 μmol/L) and nimodipine (Nim) (12 μmol/L) were added to the culture after OGD but before RP. The cultures of the control group were not exposed to OGD/RP. MTT and LDH assay were used to evaluate the protective effects of Oxysophocarpine. The IC50 of OSC was found to be 100 μmol/L. Treatment with Oxysophocarpine (1, 2, and 5 μmol/L) attenuated neuronal damage (p < 0.001), with evidence of increased cell viability (p < 0.001) and decreased cell morphologic impairment. Furthermore, Oxysophocarpine increased MMP (p < 0.001), but it inhibited [Ca(2+)]i (p < 0.001) elevation in a dose-dependent manner at OGD/RP. Oxysophocarpine (5 μmol/L) also decreased the expression of caspase-3 (p < 0.05) and caspase-12 (p < 0.05). CONCLUSIONS: The results suggested that Oxysophocarpine has significant neuroprotective effects that can be attributed to inhibiting endoplasmic reticulum (ER) stress-induced apoptosis.
In vivo	Oxysophocarpine Ameliorates Carrageenan-induced Inflammatory Pain via Inhibiting Expressions of Prostaglandin E2 and Cytokines in Mice.[Pubmed: 26132856] Planta Med. 2015 Jul;81(10):791-7. Oxysophocarpine is an alkaloid extracted from Sophora alopecuroides. METHODS AND RESULTS: Mouse ear swelling tests and carrageenan-induced paw edema tests were used to investigate the effects of Oxysophocarpine on inflammatory pain in mice. Morphological changes on inflamed paw sections were measured by hematoxylin-eosin staining. Oxysophocarpine also significantly reduced the paw edema volume and improved mechanical allodynia threshold value on carrageenan-induced inflammatory pain, as well as relieved paw tissues inflammatory damage and reduced the numbers of neutrophils in mice. Oxysophocarpine significantly suppressed over-expression of cyclooxygenase-2, tumor necrosis factor α, interleukin-1 beta, interleukin-6 and prostaglandin E2, and inhibited the over-phosphorylation of extracellular signal-regulated kinase 1/2. CONCLUSIONS: Based on these findings we propose that Oxysophocarpine attenuates inflammatory pain by suppressing the levels of phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, prostaglandin E2, tumor necrosis factor α, interleukin-1 beta and interleukin-6. Oxysophocarpine induces anti-nociception and increases the expression of GABAAα1 receptors in mice.[Pubmed: 23563643] Mol Med Rep. 2013 Jun;7(6):1819-25. Oxysophocarpine (OSC) is an alkaloid extracted from Siphocampylus verticillatus. The aim of this study was to investigate the anti-nociceptive effects of Oxysophocarpine through systemic and intracerebroventricular administration in mice. Moreover, to evaluate its effectiveness and mechanism of action, this study investigated whether Oxysophocarpine altered the expression of γ-aminobutyric acid type A α1 (GABAAα1) receptors in the central nervous system. METHODS AND RESULTS: Thermal and chemical behavioral models of nociception were used to assess the anti?nociceptive action of Oxysophocarpine.Oxysophocarpine was administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.). Results showed that Oxysophocarpine (80 mg/kg, i.p.) significantly increased the tail withdrawal threshold with a peak effect of 25.46% maximal possible effect (MPE) at 60 min (P﹤0.01). Additionally, Oxysophocarpine (80 mg/kg) increased the positive staining of GABAAα1 receptors in cells. CONCLUSIONS: In conclusion, Oxysophocarpine administration is suggested to have anti-nociceptive effects on the central and peripheral nervous systems. The involvement of GABAA receptors in the anti-nociceptive activity of Oxysophocarpine is currently being investigated.

Protocol of Oxysophocarpine

Kinase Assay

Human microsomal cyttrochrome P450-mediated reduction of oxysophocarpine, an active and highly toxic constituent derived from Sophora flavescens species, and its intestinal absorption and metabolism in rat.[Pubmed: 26045316] Fitoterapia. 2015 Jun 2;105:26-36. Oxysophocarpine (OSC), an active and toxic quinolizidine alkaloid, is highly valued in Sophora flavescens Ait. and Subprostrate sophora Root. OSC is used to treat inflammation and hepatitis for thousands of years in China. METHODS AND RESULTS: This study aims to investigate the CYP450-mediated reduction responsible for metabolizing OSC and to evaluate the absorption and metabolism of OSC in rat in situ. Four metabolites were identified, with sophocarpine (SC) as the major metabolite. SC formation was rapid in human and rat liver microsomes (HLMs and RLMs, respectively). The reduction rates in the liver are two fold higher than in the intestine, both in humans and rats. In HLMs, inhibitors of CYP2C9, 3A4/5, 2D6, and 2B6 had strong inhibitory effects on SC formation. Meanwhile, inhibitors of CYP3A and CYP2D6 had significant inhibition on SC formation in RLMs. Human recombinant CYP3A4/5, 2B6, 2D6, and 2C9 contributed significantly to SC production. The permeability in rat intestine and the excretion rates of metabolites were highest in the duodenum (p<0.05), and the absorbed amount of OSC in duodenum and jejunum was concentration-dependent. The metabolism could be significantly decreased by CYP3A inhibitor ketoconazole. CONCLUSIONS: In conclusion, the liver was the main organ responsible for OSC metabolism. First-pass metabolism via CYP3A4/5, 2B6, 2D6, and 2C9 may be the main reason for the poor OSC bioavailability.

Animal Research

The Anticonvulsant and Neuroprotective Effects of Oxysophocarpine on Pilocarpine-Induced Convulsions in Adult Male Mice.[Pubmed: 27481234] Cell Mol Neurobiol. 2017 Mar;37(2):339-349. Epilepsy is one of the prevalent and major neurological disorders, and approximately one-third of the individuals with epilepsy experience seizures that do not respond well to available medications. METHODS AND RESULTS: We investigated whether Oxysophocarpine (OSC) had anticonvulsant and neuroprotective property in the pilocarpine (PILO)-treated mice. Thirty minutes prior to the PILO injection, the mice were administrated with OSC (20, 40, and 80 mg/kg) once. Seizures and electroencephalography (EEG) were observed, and then the mice were killed for Nissl and Fluoro-jade B (FJB) staining. The oxidative stress was measured at 24 h after convulsion. Western blot analysis was used to examine the expressions of the Bax, Bcl-2, and Caspase-3. In this study, we found that pretreatment with OSC (40, 80 mg/kg) significantly delayed the onset of the first convulsion and status epilepticus (SE) and reduced the incidence of SE and mortality. Analysis of EEG recordings revealed that OSC (40, 80 mg/kg) significantly reduced epileptiform discharges. Furthermore, Nissl and FJB staining showed that OSC (40, 80 mg/kg) attenuated the neuronal cell loss and degeneration in hippocampus. In addition, OSC (40, 80 mg/kg) attenuated the changes in the levels of Malondialdehyde (MDA) and strengthened glutathione peroxidase and catalase activity in the hippocampus. Western blot analysis showed that OSC (40, 80 mg/kg) significantly decreased the expressions of Bax, Caspase-3 and increased the expression of Bcl-2. CONCLUSIONS: Collectively, the findings of this study indicated that OSC exerted anticonvulsant and neuroprotective effects on PILO-treated mice. The beneficial effects should encourage further studies to investigate OSC as an adjuvant in epilepsy, both to prevent seizures and to protect neurons in brain.

Preparing Stock Solutions of Oxysophocarpine

	1 mg	5 mg	10 mg	20 mg	25 mg
1 mM	3.811 mL	19.0549 mL	38.1098 mL	76.2195 mL	95.2744 mL
5 mM	0.7622 mL	3.811 mL	7.622 mL	15.2439 mL	19.0549 mL
10 mM	0.3811 mL	1.9055 mL	3.811 mL	7.622 mL	9.5274 mL
50 mM	0.0762 mL	0.3811 mL	0.7622 mL	1.5244 mL	1.9055 mL
100 mM	0.0381 mL	0.1905 mL	0.3811 mL	0.7622 mL	0.9527 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

 

References on Oxysophocarpine

Oxysophocarpine induces anti-nociception and increases the expression of GABAAalpha1 receptors in mice.[Pubmed:23563643]

Mol Med Rep. 2013 Jun;7(6):1819-25.

Oxysophocarpine (OSC) is an alkaloid extracted from Siphocampylus verticillatus. The aim of this study was to investigate the anti-nociceptive effects of OSC through systemic and intracerebroventricular administration in mice. Moreover, to evaluate its effectiveness and mechanism of action, this study investigated whether OSC altered the expression of gamma-aminobutyric acid type A alpha1 (GABAAalpha1) receptors in the central nervous system. Thermal and chemical behavioral models of nociception were used to assess the antinociceptive action of OSC. The warm water tail-flick test, the hotplate test, acetic acid-induced abdominal constriction and formalininduced pain were used in mice. OSC was administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.). Results showed that OSC (80 mg/kg, i.p.) significantly increased the tail withdrawal threshold with a peak effect of 25.46% maximal possible effect (MPE) at 60 min (P0.01). Additionally, OSC (80 mg/kg) increased the positive staining of GABAAalpha1 receptors in cells. In conclusion, OSC administration is suggested to have anti-nociceptive effects on the central and peripheral nervous systems. The involvement of GABAA receptors in the anti-nociceptive activity of OSC is currently being investigated.

Human microsomal cyttrochrome P450-mediated reduction of oxysophocarpine, an active and highly toxic constituent derived from Sophora flavescens species, and its intestinal absorption and metabolism in rat.[Pubmed:26045316]

Fitoterapia. 2015 Sep;105:26-36.

Oxysophocarpine (OSC), an active and toxic quinolizidine alkaloid, is highly valued in Sophora flavescens Ait. and Subprostrate sophora Root. OSC is used to treat inflammation and hepatitis for thousands of years in China. This study aims to investigate the CYP450-mediated reduction responsible for metabolizing OSC and to evaluate the absorption and metabolism of OSC in rat in situ. Four metabolites were identified, with sophocarpine (SC) as the major metabolite. SC formation was rapid in human and rat liver microsomes (HLMs and RLMs, respectively). The reduction rates in the liver are two fold higher than in the intestine, both in humans and rats. In HLMs, inhibitors of CYP2C9, 3A4/5, 2D6, and 2B6 had strong inhibitory effects on SC formation. Meanwhile, inhibitors of CYP3A and CYP2D6 had significant inhibition on SC formation in RLMs. Human recombinant CYP3A4/5, 2B6, 2D6, and 2C9 contributed significantly to SC production. The permeability in rat intestine and the excretion rates of metabolites were highest in the duodenum (p<0.05), and the absorbed amount of OSC in duodenum and jejunum was concentration-dependent. The metabolism could be significantly decreased by CYP3A inhibitor ketoconazole. In conclusion, the liver was the main organ responsible for OSC metabolism. First-pass metabolism via CYP3A4/5, 2B6, 2D6, and 2C9 may be the main reason for the poor OSC bioavailability.

Oxysophocarpine Ameliorates Carrageenan-induced Inflammatory Pain via Inhibiting Expressions of Prostaglandin E2 and Cytokines in Mice.[Pubmed:26132856]

Planta Med. 2015 Jul;81(10):791-7.

Oxysophocarpine is an alkaloid extracted from Sophora alopecuroides. We investigated the analgesic effect of Oxysophocarpine on carrageenan-induced inflammatory pain in mice, in order to explore its possible mechanisms. Mouse ear swelling tests and carrageenan-induced paw edema tests were used to investigate the effects of Oxysophocarpine on inflammatory pain in mice. Morphological changes on inflamed paw sections were measured by hematoxylin-eosin staining. The mRNA and protein expression of extracellular signal-regulated kinase, phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and prostaglandin E2 were investigated by real-time quantitative polymerase chain reaction, immunohistochemistry, western-blot and enzyme-linked immunosorbent assay. In our results, Oxysophocarpine shows a significant anti-inflammatory effect in the mouse ear swelling test. Oxysophocarpine also significantly reduced the paw edema volume and improved mechanical allodynia threshold value on carrageenan-induced inflammatory pain, as well as relieved paw tissues inflammatory damage and reduced the numbers of neutrophils in mice. Oxysophocarpine significantly suppressed over-expression of cyclooxygenase-2, tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and prostaglandin E2, and inhibited the over-phosphorylation of extracellular signal-regulated kinase 1/2. Based on these findings we propose that Oxysophocarpine attenuates inflammatory pain by suppressing the levels of phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, prostaglandin E2, tumor necrosis factor alpha, interleukin-1 beta and interleukin-6.

The Anticonvulsant and Neuroprotective Effects of Oxysophocarpine on Pilocarpine-Induced Convulsions in Adult Male Mice.[Pubmed:27481234]

Cell Mol Neurobiol. 2017 Mar;37(2):339-349.

Epilepsy is one of the prevalent and major neurological disorders, and approximately one-third of the individuals with epilepsy experience seizures that do not respond well to available medications. We investigated whether Oxysophocarpine (OSC) had anticonvulsant and neuroprotective property in the pilocarpine (PILO)-treated mice. Thirty minutes prior to the PILO injection, the mice were administrated with OSC (20, 40, and 80 mg/kg) once. Seizures and electroencephalography (EEG) were observed, and then the mice were killed for Nissl and Fluoro-jade B (FJB) staining. The oxidative stress was measured at 24 h after convulsion. Western blot analysis was used to examine the expressions of the Bax, Bcl-2, and Caspase-3. In this study, we found that pretreatment with OSC (40, 80 mg/kg) significantly delayed the onset of the first convulsion and status epilepticus (SE) and reduced the incidence of SE and mortality. Analysis of EEG recordings revealed that OSC (40, 80 mg/kg) significantly reduced epileptiform discharges. Furthermore, Nissl and FJB staining showed that OSC (40, 80 mg/kg) attenuated the neuronal cell loss and degeneration in hippocampus. In addition, OSC (40, 80 mg/kg) attenuated the changes in the levels of Malondialdehyde (MDA) and strengthened glutathione peroxidase and catalase activity in the hippocampus. Western blot analysis showed that OSC (40, 80 mg/kg) significantly decreased the expressions of Bax, Caspase-3 and increased the expression of Bcl-2. Collectively, the findings of this study indicated that OSC exerted anticonvulsant and neuroprotective effects on PILO-treated mice. The beneficial effects should encourage further studies to investigate OSC as an adjuvant in epilepsy, both to prevent seizures and to protect neurons in brain.

Neuroprotective effects of oxysophocarpine on neonatal rat primary cultured hippocampal neurons injured by oxygen-glucose deprivation and reperfusion.[Pubmed:24601951]

Pharm Biol. 2014 Aug;52(8):1052-9.

CONTEXT: Oxysophocarpine (OSC), a quinolizidine alkaloid extracted from leguminous plants of the genus Robinia, is traditionally used for various diseases including neuronal disorders. OBJECTIVE: This study investigated the protective effects of OSC on neonatal rat primary-cultured hippocampal neurons were injured by oxygen-glucose deprivation and reperfusion (OGD/RP). MATERIALS AND METHODS: Cultured hippocampal neurons were exposed to OGD for 2 h followed by a 24 h RP. OSC (1, 2, and 5 mumol/L) and nimodipine (Nim) (12 mumol/L) were added to the culture after OGD but before RP. The cultures of the control group were not exposed to OGD/RP. MTT and LDH assay were used to evaluate the protective effects of OSC. The concentration of intracellular-free calcium [Ca(2+)]i and mitochondrial membrane potential (MMP) were determined to evaluate the degree of neuronal damage. Morphologic changes of neurons following OGD/RP were observed with a microscope. The expression of caspase-3 and caspase-12 mRNA was examined by real-time quantitative PCR. RESULTS: The IC50 of OSC was found to be 100 mumol/L. Treatment with OSC (1, 2, and 5 mumol/L) attenuated neuronal damage (p < 0.001), with evidence of increased cell viability (p < 0.001) and decreased cell morphologic impairment. Furthermore, OSC increased MMP (p < 0.001), but it inhibited [Ca(2+)]i (p < 0.001) elevation in a dose-dependent manner at OGD/RP. OSC (5 mumol/L) also decreased the expression of caspase-3 (p < 0.05) and caspase-12 (p < 0.05). DISCUSSION AND CONCLUSION: The results suggested that OSC has significant neuroprotective effects that can be attributed to inhibiting endoplasmic reticulum (ER) stress-induced apoptosis.

Description

Oxysophocarpine is an alkaloid extracted from Siphocampylus verticillatus. Oxysophocarpine has neuroprotective and anti-nociceptive effects on the central and peripheral nervous systems. Oxysophocarpine inhibits the growth and metastasis of oral squamous cell carcinoma (OSCC).

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