Trigonelline

137.13600

137.04800

208-620-5

3NQ9N60I00

714350

DTXSID2026230

Prisms, aqueous, from alcohol + water

29339900

44.01000

-1.12540

Solid

1.2528 (rough estimate)

234-236 °C

251.96°C (rough estimate)

1.554

In water, 1.0X10+6 mg/L at 25 deg C (est) /miscible/

3.18X10-3 mm Hg at 25 deg C (est)

Henry's Law constant = 3.03X10-15 atm-cu m/mol at 25 °C (est)

126.37 Ų [M+H]+ [CCS Type: DT, Method: stepped-field]|139.87 Ų [M+Na]+ [CCS Type: DT, Method: stepped-field]|124 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|135.9 Ų [M+Na]+ [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|122.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Crystals from ethanol, mp 230-233 °C. Salty taste. Very soluble in water; soluble in alcohol. Practically insoluble in ether, chloroform /Trigonelline monohydrate/|Crystals from 90% alcohol, mp 258-259 °C. Very soluble in water, slightly in alcohol. Practically insoluble in ether, benzene. /Trigonelline hydrochloride/|Hydroxyl radical reaction rate constant = 1.08X-11 cu cm/molec-sec at 25 °C (est)

24/25

P264, P280, P302+P352, P305+P351+P338, P321, P332+P313, P337+P313, P362

H315

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

|Warning|H315 (50%): Causes skin irritation [Warning Skin corrosion/irritation]|P264, P280, P302+P352, P305+P351+P338, P321, P332+P313, P337+P313, and P362|Aggregated GHS information provided by 3 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

IDENTIFICATION AND USE: Trigonelline is a solid. Trigonelline, an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee. It is used in biochemical research. HUMAN EXPOSURE AND TOXICITY: Trigonelline promotes functional neurite outgrowth in human neuroblastoma SK-N-SH cells. ANIMAL STUDIES: Trigonelline showed significant central nervous system (CNS) stimulant activities in rats. Trigonelline differentially affected the skeletal system of rats with streptozotocin-induced metabolic disorders, intensifying the osteoporotic changes in streptozotocin-treated rats and favorably affecting bones in the non-hyperglycemic (nicotinamide/streptozotocin-treated) rats. The results indicate that, in certain conditions, trigonelline may damage bone. In rats, 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. Unfavorable effects of trigonelline on the skeletal system depended on the estrogen status. They were observed only in cancellous bone of estrogen-deficient rats. The results of bacteria mutation assays (Salmonella typhimurium strains TA98, YG1024 and YG1029) showed that trigonelline, alone or in combination with most of the single amino acids and mixtures of amino acids, yielded potent mutagenic activity. However, in another study it was found not mutagenic in the Salmonella plate incorporation assay and mouse lymphoma L5178Y TK +/- assay.

The effects of both coffee components and coffee extract on the electrical responses of GABA(A) receptors expressed in Xenopus oocytes were studied by injecting cRNAs of the alpha(1) and beta(1) subunits of the bovine receptors. The aqueous extract of coffee dose-dependently inhibited the GABA-elicited responses, whereas the lipophilic extract of coffee by diethyl ether slightly potentiated it at low doses (0.1-0.4 uL/mL) but showed inhibition at high doses (0.5-0.8 uL/mL). Theophylline inhibited the response in a noncompetitive mechanism (K(i) = 0.55 mM), whereas theobromine and trigonelline hydrochloride inhibited it in a competitive manner, K(i) = 3.8 and 13 mM, respectively... /Trigonelline hydrochloride/

LD50 Rat oral 5 g/kg /from table/|LD50 Rat sc 5 g/kg /from table/

Trigonelline is a base formed in the seeds of many plants, including coffee beans(1). The compound has been detected in seeds of Trigonella foenumgraecum, L., Leguminosae, in seeds of Strophanthus spp., Apocynaceae and of Cannibis sativa L., Moraceae, in seeds of many other plants. Trigonelline is also found in sea urchin, Arabacia pustullosa, and in jellyfish, Velella spirans(2).

/EXPL THER/ Fenugreek seeds are known for their characteristic smell of soup seasoning and as an ingredient of Indian curry. Traditionally the seeds are used as macerate for the treatment of diabetes, cough, and flatulence, to increase breast milk secretion, and for anti-inflammatory and aphrodisiac effects. The use is limited by its unpleasant smell and bitter taste which can be modified by adding mint leaves to the macerate. Antidiabetic properties are attributed mainly to galactomannan, 4-hydroxyisoleucin (4-OH-Ile), diosgenin and trigonelline. These substances demonstrate direct antidiabetic properties in clinical studies by increasing insulin secretion (4-OH-Ile), decreasing insulin resistance and glucose resorption from the GIT (galactomannan) and improvement in B-cells regeneration (trigonelline). Besides this main effect, the herb improves blood lipid spectre (4-OH-Ile, diosgenin), and has reno-protective (4-OH-Ile, trigonelline), neuroprotective (trigonelline) and antioxidant (diosgenin, trigonelline) effects. Antidiabetic efficacy of trigonelline is comparable to glibenclamide treatment and more effective than sitagliptine therapy. Given the large body of evidence and promising results in comparison with standard pharmacotherapy, fenugreek active substances have a potential to become a source of new antidiabetic medication.Key words: fenugreek Trigonella foenum-graecum diabetes mellitus type 2 biological activity.|/EXPL THER/ There is evidence that Trigonella foenum-graecum L. (fenugreek), a traditional Chinese herb, and its components are beneficial in the prevention and treatment of diabetes and central nervous system disease. The pharmacological activities of trigonelline, a major alkaloid component of fenugreek, have been more thoroughly evaluated than fenugreek's other components, especially with regard to diabetes and central nervous system disease. Trigonelline has hypoglycemic, hypolipidemic, neuroprotective, antimigraine, sedative, memory-improving, antibacterial, antiviral, and anti-tumor activities, and it has been shown to reduce diabetic auditory neuropathy and platelet aggregation. It acts by affecting beta cell regeneration, insulin secretion, activities of enzymes related to glucose metabolism, reactive oxygen species, axonal extension, and neuron excitability. However, further study of trigonelline's pharmacological activities and exact mechanism is warranted, along with application of this knowledge to its clinical usage. This review aims to give readers a survey of the pharmacological effects of trigonelline, especially in diabetes, diabetic complications and central nervous system disease. In addition, because of its pharmacological value and low toxicity, the reported adverse effects of trigonelline in experimental animal models and humans are briefly reviewed, and the pharmacokinetics of trigonelline are also discussed.

... The concentration-time curves of trigonelline in rabbits after ... iv administration were shown to fit one-compartment and two-compartment open model, respectively. The main parameters after iv /administration/ of trigonelline were as follows: T1/2 alpha was 10.8 min, T1/2 beta was 44.0 min, K21 was 0.044 min-1, K10 was 0.026 min-1, K12 was 0.017 min-1, AUC was 931.0 mg.min/L . /It was concluded that/ trigonelline showed a middle rate of absorption and fast rate of elimination in rabbit...

... Trigonelline (N-methylnicotinic acid) /is a metabolite of nicotinamide/.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/ENDOCRINE MODULATION/ Drinking coffee has been associated with the development of several endocrine-related cancers. The interpretation of these data has often been limited to the role that caffeine plays. Trigonelline (Trig), a niacin-related compound, is a natural constituent of coffee accounting for approximately 1% dry matter in roasted beans. Studies exploring the effects of this bioactive compound on mammalian cells are limited. The initial purpose of our studies was to determine whether Trig alters the actions of estradiol (E(2)), using proliferation of estrogen-dependent human breast cancer (MCF-7) cells as a model system. When cells were cotreated with suboptimal doses of E(2) (10 pmol/L) and Trig (100 pmol/L), an additive enhancement of MCF-7 growth was observed. In the absence of E(2), Trig stimulated MCF-7 cell proliferation in a dose-responsive manner and significantly enhanced cell growth at concentrations as low as 100 pmol/L. Cotreatment of MCF-7 cells with Trig and ICI 182,780, an estrogen receptor (ER) antagonist, inhibited Trig-induced cell proliferation. Trig treatment also induced activation of estrogen response element reporter assays in MCF-7 cells and increased expression of ER target genes (pS2, progesterone receptor, and cyclin D1) similar to E(2). While our data demonstrate that Trig activates the ER, competitive binding assays showed that Trig does not compete E(2) off of the ER at any concentration. This suggests that Trig is activating the ER through a separate mechanism. Collectively, these data demonstrate that Trig even at low concentrations stimulates MCF-7 cell growth and that this effect is mediated through ER, clearly identifying Trig as a novel phytoestrogen.|/ALTERNATIVE and IN VITRO TESTS/ 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 a5/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.|/ALTERNATIVE and IN VITRO TESTS/ Extension of dendrites and axons in neurons may compensate and rescue damaged neuronal networks in the dementia brain. ... Among the extracts of raw and roasted coffee beans, a methanol fraction of the ethanol extract (1 ug/mL) of raw beans increased significantly the percentage of cells with neurites in human neuroblastoma SK-N-SH cells. Among subfractions of this methanol fraction was a basic fraction (5 ug/mL) which exhibited significant neurite outgrowth activity. Finally, trigonelline in the basic fraction was identified to be active as far neurite extension was concerned. Treatment with trigonelline (30 uM) increased the percentage of cells with neurites at 3 and 6 d after treatment. In addition, the number of neurites reacting positively to phosphorylated neurofilament-H was increased by treatment with 30 uM trigonelline for 6 d, suggesting enhancement of axonal extension. These results show that trigonelline promotes functional neurite outgrowth.

trigonelline

/Has/ phytotoxic and growth regulatory properties. ... Trigonelline, a betaine derivative of nicotinic acid, arrests cell division at the G2 phase after DNA transcription. ... It has some selectivity towards legumes, arresting cell division in root tips of several leguminous species, while having no measurable effect on wheat or common sunflower ...