TRG Nature®

Trigonelline (TRG)

Health Benefits Delivered by Nature

“Trigonelline (TRG) is a natural polar hydrophilic alkaloid that is found in many plants such as green coffee beans and fenugreek seeds. TRG potentially acts on multiple molecular targets, including nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor γ, glycogen synthase kinase, tyrosinase, nerve growth factor, estrogen receptor, amyloid-β peptide, and several neurotransmitter receptors. In this review, we systematically summarize the pharmacological activities, medicinal properties, and mechanistic actions of TRG as a potential therapeutic agent. Mechanistically, TRG can facilitate the maintenance and restoration of the metabolic homeostasis of glucose and lipids. It can counteract inflammatory constituents at multiple levels by hampering pro-inflammatory factor release, alleviating inflammatory propagation, and attenuating tissue injury. It concurrently modulates oxidative stress by the blockage of the detrimental Nrf2 pathway when autophagy is impaired. Therefore, it exerts diverse therapeutic effects on a variety of pathological conditions associated with chronic metabolic diseases and age-related disorders. It shows multidimensional effects, including neuroprotection from neurodegenerative disorders and diabetic peripheral neuropathy, neuromodulation, mitigation of cardiovascular disorders, skin diseases, diabetic mellitus, liver and kidney injuries, and anti-pathogen and anti-tumor activities.”(3)

Health effects include:(3)

  • modulation of glucose and lipid homeostasis,
  • recovery from neurological impairments such as neurodegenerative disorders, ischemia-induced brain damage, depression, cognitive decline, and diabetic peripheral neuropathy, mitigation of DM and its complications,
  • protection of cardiovascular system, liver, lungs, kidney, gastric system, and skin, and
  • inhibition of tumor cell proliferation and migration.

Introduction

Trigonelline (1-methylpyridin-1-ium-3-carboxylate, C7H7NO2, TRG) was first isolated from the seeds of fenugreek (Trigonella foenum-graecum L.).(1) It is a solid, crystallizable pyridine alkaloid, with a molecular weight of 137.14 g/mol and an octanol-water partition coefficient of -2.53. (1) It is a small, highly hydrophilic, and thermolabile phytochemical naturally occurring in numerous plants as a secondary metabolite.(1)

TRG, as the most abundant alkaloid, is found with the highest content in coffee beans, which makes coffee the most important commercial source of TRG.(1,2) TRG contents in coffee vary from 0.2 to 63 g/kg depending on many factors, including country of origin, coffee species and cultivar, part of the coffee plant, age of the plant part, applied industrial production processes, used preparation methods, water content of the sample, pH condition of the sample media, and analytical method used.(1) TRG content in green coffee beans ranges 2.3-34.2 g TRG/kg green coffee beans, and 3.1-7.5 g/kg in roasted coffee.(1)

Health Effects

TRG shows various beneficial roles in many pathological conditions, including modulation of glucose and lipid homeostasis, recovery from neurological impairments such as neurodegenerative disorders, ischemia-induced brain damage, depression, cognitive decline, and diabetic peripheral neuropathy, mitigation of DM and its complications, protection of cardiovascular system, liver, lungs, kidney, gastric system, and skin, and inhibition of tumor cell proliferation and migration.(3)

Mechanism

TRG can potentially bind to PPARγ, NGF, and several neurotransmitter receptors, restoring glucose and lipid homeostasis, promoting neuronal survival, and modulating neuronal activity. TRG can act as a phytoestrogen to stimulate ER. TRG can potentially bind to GSK, MPO, and Aβ, executing inhibitory effects. TRG can interfere Nrf2 nuclear translocation, prevent EMT, and suppress tyrosinase activity.(3)

Safety

TRG ingested as a component of coffee appears to be safe for human health, based on the safe traditional use of these products.(1) No evidence of adverse effects following acute exposure to TRG was identified.(1) In addition, the lack of abortifacient activity or teratogenicity in animals confirms the safety of TRG during pregnancy.(4)

Reference

  1. Konstantinidis N, Franke H, Schwarz S, Lachenmeier DW. Risk Assessment of Trigonelline in Coffee and Coffee By-Products. Molecules. 2023 Apr 14;28(8):3460. doi: 10.3390/molecules28083460. PMID: 37110693; PMCID: PMC10146819.
  2. Taguchi H, Sakaguchi M, Shimabayashi Y. Trigonelline Content in Coffee Beans and the Thermal Conversion of Trigonelline into Nicotinic Acid during the Roasting of Coffee Beans, Agricultural and Biological Chemistry, 1985, 49:12, 3467-3471, DOI: 10.1080/00021369.1985.10867295
  3. Nguyen V, Taine EG, Meng D, Cui T, Tan W. Pharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline. International Journal of Molecular Sciences. 2024; 25(6):3385. https://doi.org/10.3390/ijms25063385.
  4. Kandhare AD, Thakurdesai PA, Wangikar P, Bodhankar SL. A systematic literature review of fenugreek seed toxicity by using ToxRTool: evidence from preclinical and clinical studies. Heliyon. 2019 Apr 24;5(4):e01536. doi: 10.1016/j.heliyon.2019.e01536. PMID: 31049444; PMCID: PMC6482331.