Trigonelline CAS NO.535-83-1

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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.

Chemical Properties of Trigonelline

Cas No.	535-83-1
PubChem ID	5570	Appearance	Powder
Formula	C7H7NO2	M.Wt	137.14
Type of Compound	Alkaloids	Storage	Desiccate at -20°C
Solubility	Soluble in Chloroform,Dichloromethane,Ethyl Acetate,DMSO,Acetone,etc.
Chemical Name	1-methylpyridin-1-ium-3-carboxylate
SMILES	C[N+]1=CC=CC(=C1)C(=O)[O-]
Standard InChIKey	WWNNZCOKKKDOPX-UHFFFAOYSA-N
Standard InChI	InChI=1S/C7H7NO2/c1-8-4-2-3-6(5-8)7(9)10/h2-5H,1H3
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 Trigonelline

The seeds of Trigonella foenum-graecum L.

Biological Activity of Trigonelline

Description	Trigonelline (1-methylpyridinium-3-carboxylate), an alkaloid present in coffee and fenugreek seed, exhibits phytoestrogenic, anti-adipogenesis, and anticancer activities, it also can reduce early glucose and insulin responses. Trigonelline has inhibition of the Nrf2 transcription factor and PPAR-γ.
Targets	PPAR | GLUT | Nrf2 | ROS | FAS | GLUT
In vitro	Inhibition of the Nrf2 transcription factor by the alkaloid trigonelline renders pancreatic cancer cells more susceptible to apoptosis through decreased proteasomal gene expression and proteasome activity.[Pubmed: 23108405 ] Oncogene. 2013 Oct;32(40):4825-35. Evidence accumulates that the transcription factor nuclear factor E2-related factor 2 (Nrf2) has an essential role in cancer development and chemoresistance, thus pointing to its potential as an anticancer target and undermining its suitability in chemoprevention. Through the induction of cytoprotective and proteasomal genes, Nrf2 confers apoptosis protection in tumor cells, and inhibiting Nrf2 would therefore be an efficient strategy in anticancer therapy. METHODS AND RESULTS: In the present study, pancreatic carcinoma cell lines (Panc1, Colo357 and MiaPaca2) and H6c7 pancreatic duct cells were analyzed for the Nrf2-inhibitory effect of the coffee alkaloid Trigonelline (trig), as well as for its impact on Nrf2-dependent proteasome activity and resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and anticancer drug-induced apoptosis. Chemoresistant Panc1 and Colo357 cells exhibit high constitutive Nrf2 activity, whereas chemosensitive MiaPaca2 and H6c7 cells display little basal but strong tert-butylhydroquinone (tBHQ)-inducible Nrf2 activity and drug resistance. Trig efficiently decreased basal and tBHQ-induced Nrf2 activity in all cell lines, an effect relying on a reduced nuclear accumulation of the Nrf2 protein. Along with Nrf2 inhibition, trig blocked the Nrf2-dependent expression of proteasomal genes (for example, s5a/psmd4 and α5/psma5) and reduced proteasome activity in all cell lines tested. These blocking effects were absent after treatment with Nrf2 siRNA, a condition in which proteasomal gene expression and proteasome activity were already decreased, whereas siRNA against the related transcription factor Nrf1 did not affect proteasome activity and the inhibitory effect of trig. Depending on both Nrf2 and proteasomal gene expression, the sensitivity of all cell lines to anticancer drugs and TRAIL-induced apoptosis was enhanced by trig. Moreover, greater antitumor responses toward anticancer drug treatment were observed in tumor-bearing mice when receiving trig. CONCLUSIONS: In conclusion, representing an efficient Nrf2 inhibitor capable of blocking Nrf2-dependent proteasome activity and thereby apoptosis protection in pancreatic cancer cells, trig might be beneficial in improving anticancer therapy.
In vivo	Unfavorable effect of trigonelline, an alkaloid present in coffee and fenugreek, on bone mechanical properties in estrogen-deficient rats.[Pubmed: 24867387] Mol Nutr Food Res. 2014 Jul;58(7):1457-64. Trigonelline (1-methylpyridinium-3-carboxylate), an alkaloid present in coffee and fenugreek seed, has been reported to exhibit phytoestrogenic activity. The aim of the present study was to investigate the effects of Trigonelline on bone mechanical properties of rats with normal estrogen level and estrogen deficiency (developing osteoporosis). METHODS AND RESULTS: The experiments were performed on 3-month-old nonovariectomized and ovariectomized (estrogen-deficient) Wistar rats, divided into control rats and rats receiving Trigonelline (50 mg/kg p.o. daily) for 4 weeks. The ovariectomy was performed 7-8 days before the start of Trigonelline administration. Serum bone turnover markers and bone mineralization, as well as mechanical properties of the tibial metaphysis, femoral diaphysis, and femoral neck were examined. Estrogen deficiency caused worsening of bone mineralization and mechanical properties of the tibial metaphysis, as well as increases in bone turnover markers. Administration of Trigonelline did not affect the investigated parameters in nonovariectomized rats, but it worsened the mineralization and mechanical properties of cancellous bone in ovariectomized rats. CONCLUSIONS: Unfavorable effects of Trigonelline on the skeletal system depended on the estrogen status. They were observed only in cancellous bone of estrogen-deficient rats. Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance.[Pubmed: 19324944 ] Diabetes Care. 2009 Jun;32(6):1023-5. Coffee consumption has been associated with lower risk of type 2 diabetes. We evaluated the acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and Trigonelline on glucose tolerance. METHODS AND RESULTS: We conducted a randomized crossover trial of the effects of 12 g decaffeinated coffee, 1 g chlorogenic acid, 500 mg Trigonelline, and placebo (1 g mannitol) on glucose and insulin concentrations during a 2-h oral glucose tolerance test (OGTT) in 15 overweight men. Chlorogenic acid and Trigonelline ingestion significantly reduced glucose (-0.7 mmol/l, P = 0.007, and -0.5 mmol/l, P = 0.024, respectively) and insulin (-73 pmol/l, P = 0.038, and -117 pmol/l, P = 0.007) concentrations 15 min following an OGTT compared with placebo. None of the treatments affected insulin or glucose area under the curve values during the OGTT compared with placebo. CONCLUSIONS: Chlorogenic acid and Trigonelline reduced early glucose and insulin responses during an OGTT.

Protocol of Trigonelline

Kinase Assay	Trigonelline attenuates the adipocyte differentiation and lipid accumulation in 3T3-L1 cells.[Pubmed: 24369814] Phytomedicine. 2014 Apr 15;21(5):758-65. Trigonelline is a natural alkaloid mainly found in Trigonella Foenum Graecum (fenugreek) Fabaceae and other edible plants with a variety of medicinal applications. Therefore, we investigated the molecular mechanism of Trigonelline (TG) on the inhibition of adipocyte differentiation and lipid accumulation in 3T3-L1 cells. Trigonelline suppressed lipid droplet accumulation in a concentration (75 and 100 μM) dependent manner. Treatment of adipocyte with of TG down regulates the peroxisome proliferator-activated receptor (PPARγ) and CCAAT element binding protein (C/EBP-α) mRNA expression, which leads to further down regulation of other gene such as adiponectin, adipogenin, leptin, resistin and adipocyte fatty acid binding protein (aP2) as compared with respective control cells on 5th and 10th day of differentiation. Further, addition of triognelline along with troglitazone to the adipocyte attenuated the troglitazone effects on PPARγ mediated differentiation and lipid accumulation in 3T3-L1 cells. Trigonelline might compete against troglitazone for its binding to the PPARγ. In addition, adipocyte treated with Trigonelline and isoproterenol separately. Isoproterenol, a lipolytic agent which inhibits the fatty acid synthase and GLUT-4 transporter expression via cAMP mediated pathway, we found that similar magnitude response of fatty acid synthase and GLUT-4 transporter expression in Trigonelline treated adipocyte. CONCLUSIONS: These results suggest that the Trigonelline inhibits the adipogenesis by its influences on the expression PPARγ, which leads to subsequent down regulation of PPAR-γ mediated pathway during adipogenesis. Our findings provide key approach to the mechanism underlying the anti-adipogenic activity of Trigonelline.
Cell Research	Anti-invasive activity of niacin and trigonelline against cancer cells.[Pubmed: 15785001] Biosci Biotechnol Biochem. 2005 Mar;69(3):653-8. METHODS AND RESULTS: The effects of niacin, namely, nicotinic acid and nicotinamide, and Trigonelline on the proliferation and invasion of cancer cells were studied using a rat ascites hepatoma cell line of AH109A in culture. Niacin and Trigonelline inhibited the invasion of hepatoma cells at concentrations of 2.5-40 microM without affecting proliferation. Hepatoma cells previously cultured with a reactive oxygen species (ROS)-generating system showed increased invasive activity. Niacin and Trigonelline suppressed this ROS-potentiated invasive capacity through simultaneous treatment of AH109A cells with the ROS-generating system. CONCLUSIONS: The present study indicates for the first time the anti-invasive activities of niacin and Trigonelline against cancer cells.
Structure Identification	J Nanosci Nanotechnol. 2014 Aug;14(8):5633-7. Antitumor activity of trigonelline-incorporated chitosan nanoparticles.[Pubmed: 25935980] METHODS AND RESULTS: In this study, Trigonelline, a niacin-related compound was incorporated into chitosan nanoparticles through ion-complex formation between anionic carboxylic acid group of Trigonelline and cationic amine group of chitosan. Morphology of Trigonelline-incorporated chitosan nanoparticles have spherical shape with less than 500 nm in size and thier size distribution showed quite unimodel phase. Even though Trigonelline and Trigonelline-incorporated chitosan nanoparticles were not significantly affected to the proliferation of tumor cells, invasion of tumor cells was effectively inhibited by Trigonelline-incorporated chitosan nanoparticles. CONCLUSIONS: We suggested that Trigonelline-incorporated chitosan nanoparticles are promising candidate for inhibition of tumor cell invasion.

Preparing Stock Solutions of Trigonelline

	1 mg	5 mg	10 mg	20 mg	25 mg
1 mM	7.2918 mL	36.4591 mL	72.9182 mL	145.8364 mL	182.2955 mL
5 mM	1.4584 mL	7.2918 mL	14.5836 mL	29.1673 mL	36.4591 mL
10 mM	0.7292 mL	3.6459 mL	7.2918 mL	14.5836 mL	18.2295 mL
50 mM	0.1458 mL	0.7292 mL	1.4584 mL	2.9167 mL	3.6459 mL
100 mM	0.0729 mL	0.3646 mL	0.7292 mL	1.4584 mL	1.823 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 Trigonelline

Anti-invasive activity of niacin and trigonelline against cancer cells.[Pubmed:15785001]

Biosci Biotechnol Biochem. 2005 Mar;69(3):653-8.

The effects of niacin, namely, nicotinic acid and nicotinamide, and Trigonelline on the proliferation and invasion of cancer cells were studied using a rat ascites hepatoma cell line of AH109A in culture. Niacin and Trigonelline inhibited the invasion of hepatoma cells at concentrations of 2.5-40 microM without affecting proliferation. Hepatoma cells previously cultured with a reactive oxygen species (ROS)-generating system showed increased invasive activity. Niacin and Trigonelline suppressed this ROS-potentiated invasive capacity through simultaneous treatment of AH109A cells with the ROS-generating system. The present study indicates for the first time the anti-invasive activities of niacin and Trigonelline against cancer cells.

Unfavorable effect of trigonelline, an alkaloid present in coffee and fenugreek, on bone mechanical properties in estrogen-deficient rats.[Pubmed:24867387]

Mol Nutr Food Res. 2014 Jul;58(7):1457-64.

SCOPE: Trigonelline (1-methylpyridinium-3-carboxylate), an alkaloid present in coffee and fenugreek seed, has been reported to exhibit phytoestrogenic activity. The aim of the present study was to investigate the effects of Trigonelline on bone mechanical properties of rats with normal estrogen level and estrogen deficiency (developing osteoporosis). METHODS AND RESULTS: The experiments were performed on 3-month-old nonovariectomized and ovariectomized (estrogen-deficient) Wistar rats, divided into control rats and rats receiving Trigonelline (50 mg/kg p.o. daily) for 4 weeks. The ovariectomy was performed 7-8 days before the start of Trigonelline administration. Serum bone turnover markers and bone mineralization, as well as mechanical properties of the tibial metaphysis, femoral diaphysis, and femoral neck were examined. Estrogen deficiency caused worsening of bone mineralization and mechanical properties of the tibial metaphysis, as well as increases in bone turnover markers. Administration of Trigonelline did not affect the investigated parameters in nonovariectomized rats, but it worsened the mineralization and mechanical properties of cancellous bone in ovariectomized rats. CONCLUSION: Unfavorable effects of Trigonelline on the skeletal system depended on the estrogen status. They were observed only in cancellous bone of estrogen-deficient rats.

Antitumor activity of trigonelline-incorporated chitosan nanoparticles.[Pubmed:25935980]

J Nanosci Nanotechnol. 2014 Aug;14(8):5633-7.

In this study, Trigonelline, a niacin-related compound was incorporated into chitosan nanoparticles through ion-complex formation between anionic carboxylic acid group of Trigonelline and cationic amine group of chitosan. Morphology of Trigonelline-incorporated chitosan nanoparticles have spherical shape with less than 500 nm in size and thier size distribution showed quite unimodel phase. Even though Trigonelline and Trigonelline-incorporated chitosan nanoparticles were not significantly affected to the proliferation of tumor cells, invasion of tumor cells was effectively inhibited by Trigonelline-incorporated chitosan nanoparticles. We suggested that Trigonelline-incorporated chitosan nanoparticles are promising candidate for inhibition of tumor cell invasion.

Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance.[Pubmed:19324944]

Diabetes Care. 2009 Jun;32(6):1023-5.

OBJECTIVE: Coffee consumption has been associated with lower risk of type 2 diabetes. We evaluated the acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and Trigonelline on glucose tolerance. RESEARCH DESIGN AND METHODS: We conducted a randomized crossover trial of the effects of 12 g decaffeinated coffee, 1 g chlorogenic acid, 500 mg Trigonelline, and placebo (1 g mannitol) on glucose and insulin concentrations during a 2-h oral glucose tolerance test (OGTT) in 15 overweight men. RESULTS: Chlorogenic acid and Trigonelline ingestion significantly reduced glucose (-0.7 mmol/l, P = 0.007, and -0.5 mmol/l, P = 0.024, respectively) and insulin (-73 pmol/l, P = 0.038, and -117 pmol/l, P = 0.007) concentrations 15 min following an OGTT compared with placebo. None of the treatments affected insulin or glucose area under the curve values during the OGTT compared with placebo. CONCLUSIONS: Chlorogenic acid and Trigonelline reduced early glucose and insulin responses during an OGTT.

Inhibition of the Nrf2 transcription factor by the alkaloid trigonelline renders pancreatic cancer cells more susceptible to apoptosis through decreased proteasomal gene expression and proteasome activity.[Pubmed:23108405]

Oncogene. 2013 Oct;32(40):4825-35.

Evidence accumulates that the transcription factor nuclear factor E2-related factor 2 (Nrf2) has an essential role in cancer development and chemoresistance, thus pointing to its potential as an anticancer target and undermining its suitability in chemoprevention. Through the induction of cytoprotective and proteasomal genes, Nrf2 confers apoptosis protection in tumor cells, and inhibiting Nrf2 would therefore be an efficient strategy in anticancer therapy. In the present study, pancreatic carcinoma cell lines (Panc1, Colo357 and MiaPaca2) and H6c7 pancreatic duct cells were analyzed for the Nrf2-inhibitory effect of the coffee alkaloid Trigonelline (trig), as well as for its impact on Nrf2-dependent proteasome activity and resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and anticancer drug-induced apoptosis. Chemoresistant Panc1 and Colo357 cells exhibit high constitutive Nrf2 activity, whereas chemosensitive MiaPaca2 and H6c7 cells display little basal but strong tert-butylhydroquinone (tBHQ)-inducible Nrf2 activity and drug resistance. Trig efficiently decreased basal and tBHQ-induced Nrf2 activity in all cell lines, an effect relying on a reduced nuclear accumulation of the Nrf2 protein. Along with Nrf2 inhibition, trig blocked the Nrf2-dependent expression of proteasomal genes (for example, s5a/psmd4 and alpha5/psma5) and reduced proteasome activity in all cell lines tested. These blocking effects were absent after treatment with Nrf2 siRNA, a condition in which proteasomal gene expression and proteasome activity were already decreased, whereas siRNA against the related transcription factor Nrf1 did not affect proteasome activity and the inhibitory effect of trig. Depending on both Nrf2 and proteasomal gene expression, the sensitivity of all cell lines to anticancer drugs and TRAIL-induced apoptosis was enhanced by trig. Moreover, greater antitumor responses toward anticancer drug treatment were observed in tumor-bearing mice when receiving trig. In conclusion, representing an efficient Nrf2 inhibitor capable of blocking Nrf2-dependent proteasome activity and thereby apoptosis protection in pancreatic cancer cells, trig might be beneficial in improving anticancer therapy.

Trigonelline attenuates the adipocyte differentiation and lipid accumulation in 3T3-L1 cells.[Pubmed:24369814]

Phytomedicine. 2014 Apr 15;21(5):758-65.

Trigonelline is a natural alkaloid mainly found in Trigonella Foenum Graecum (fenugreek) Fabaceae and other edible plants with a variety of medicinal applications. Therefore, we investigated the molecular mechanism of Trigonelline (TG) on the inhibition of adipocyte differentiation and lipid accumulation in 3T3-L1 cells. Trigonelline suppressed lipid droplet accumulation in a concentration (75 and 100 muM) dependent manner. Treatment of adipocyte with of TG down regulates the peroxisome proliferator-activated receptor (PPARgamma) and CCAAT element binding protein (C/EBP-alpha) mRNA expression, which leads to further down regulation of other gene such as adiponectin, adipogenin, leptin, resistin and adipocyte fatty acid binding protein (aP2) as compared with respective control cells on 5th and 10th day of differentiation. Further, addition of triognelline along with troglitazone to the adipocyte attenuated the troglitazone effects on PPARgamma mediated differentiation and lipid accumulation in 3T3-L1 cells. Trigonelline might compete against troglitazone for its binding to the PPARgamma. In addition, adipocyte treated with Trigonelline and isoproterenol separately. Isoproterenol, a lipolytic agent which inhibits the fatty acid synthase and GLUT-4 transporter expression via cAMP mediated pathway, we found that similar magnitude response of fatty acid synthase and GLUT-4 transporter expression in Trigonelline treated adipocyte. These results suggest that the Trigonelline inhibits the adipogenesis by its influences on the expression PPARgamma, which leads to subsequent down regulation of PPAR-gamma mediated pathway during adipogenesis. Our findings provide key approach to the mechanism underlying the anti-adipogenic activity of Trigonelline.

Description

Trigonelline, an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee.

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