Trigonelline hydrochloride
[CAS# 6138-41-6]

Identification

• Classification: Natural product >> Alkaloid
• Name: Trigonelline hydrochloride
• Synonyms: 1-Methylpyridinium-3-carboxylate hydrochloride; N-Methylnicotinic acid betaine hydrochloride
• Molecular Formula: C₇H₇NO₂.HCl
• Molecular Weight: 173.60
• CAS Registry Number: 6138-41-6
• EC Number: 228-119-5
• SMILES: C[N+]1=CC=CC(=C1)C(=O)O.[Cl-]

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

Trigonelline hydrochloride is a quaternary ammonium salt derivative of nicotinic acid (niacin), in which a methyl group substitutes the nitrogen atom of the pyridine ring to form N-methylnicotinic acid. The compound occurs naturally as trigonelline in many plants, particularly in fenugreek (Trigonella foenum-graecum), coffee beans, and legumes. The hydrochloride form enhances its stability and solubility in water, facilitating its use in biochemical and pharmaceutical applications.

The discovery of trigonelline dates back to the early 19th century, when it was first isolated from fenugreek seeds. Subsequent studies confirmed its presence in other botanical sources, especially in roasted coffee, where it is a prominent alkaloid. The compound's concentration in coffee can vary depending on species, processing, and roasting conditions. During roasting, trigonelline undergoes thermal degradation and contributes to the formation of aroma compounds and niacin, increasing the nutritional value of brewed coffee.

Trigonelline hydrochloride has garnered interest due to its multifaceted applications in scientific research and potential health benefits. Its chemical structure, featuring a permanently charged nitrogen atom, renders it biologically active and capable of interacting with various cellular targets. It has been investigated for its potential roles in neuroprotection, glucose metabolism, and lipid regulation. Animal models and in vitro experiments have suggested that trigonelline may exhibit antidiabetic, antihyperlipidemic, and antioxidant properties, though these effects are not yet fully understood or established in clinical settings.

In addition to its physiological effects, trigonelline hydrochloride has been explored in analytical and pharmaceutical chemistry. Its presence in biological fluids, such as urine, has been used as a biomarker for coffee consumption. Analytical methods including liquid chromatography and mass spectrometry have been developed for its accurate quantification in complex matrices. In drug development, trigonelline derivatives have been examined as potential lead compounds for modifying pharmacological profiles of existing drugs.

Further applications of trigonelline hydrochloride include its use in cosmetics and functional foods. Its antioxidant and skin-protective properties make it a candidate for anti-aging formulations. In agriculture, trigonelline has been studied for its influence on plant physiology and growth regulation. In microbial systems, it has shown antimicrobial activity, particularly against certain bacterial strains, although the mechanism of action remains to be clarified.

As a naturally occurring metabolite and a promising bioactive compound, trigonelline hydrochloride continues to attract attention from researchers across multiple disciplines. Ongoing studies aim to elucidate its pharmacokinetics, molecular targets, and therapeutic potentials. However, comprehensive human clinical trials are necessary to validate any health claims or develop standardized therapeutic applications.

References

2024. Pharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline. International Journal of Molecular Sciences, 25(6).
DOI: 10.3390/ijms25063385

2024. Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia. Nature Metabolism, 6(3).
DOI: 10.1038/s42255-024-00997-x

1946. CONVERSION OF TRIGONELLINE TO NICOTINIC ACID. The Journal of biological chemistry, 166(2).
DOI: 10.1016/s0021-9258(17)35196-7