SCIENCE  |  SUPPLEMENTS

Trigonelline

Trigonelline is a naturally occurring alkaloid found in plants, particularly in fenugreek seeds and coffee beans. It’s known for its bitter taste and has been studied for various potential health benefits, including antioxidant properties and possible effects on glucose metabolism. Trigonelline is also noted for its role in contributing to the aroma and flavor profile of coffee.

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PUBLICATIONS

  1. Trigonelline is an NAD(+) precursor that improves muscle function during ageing and is reduced in human sarcopenia.
          • Nat Metab. 2024 Mar;6(3):433-447.
          • Design: Study on trigonelline’s effect on muscle health across multiple species.
          • Summary: Trigonelline enhances NAD+ levels, improves muscle strength, mitochondrial function, and lifespan in models, suggesting a therapeutic potential for age-related muscle decline. It incorporates into the NAD+ pool and increases NAD+ levels in Caenorhabditis elegans, mice, and human myotubes.
  2. Trigonelline mitigates bleomycin-induced pulmonary inflammation and fibrosis: Insight into NLRP3 inflammasome and SPHK1/S1P/Hippo signaling modulation.
          • Life Sci. 2024 Jan 1;336:122272.
          • Design: Study on rats to evaluate trigonelline’s effect on pulmonary fibrosis induced by bleomycin.
          • Summary: Trigonelline reduces inflammation and fibrosis through multiple signaling pathways and shows potential when combined with pirfenidone. It targets NF-κB/NLRP3/IL-1β signaling and activates autophagy, reducing apoptosis and senescence in alveolar epithelial cells.
  3. Neuroprotective effects of trigonelline in kainic acid-induced epilepsy: Behavioral, biochemical, and functional insights.
          • Saudi Pharm J. 2023 Dec;31(12):101843.
          • Design: Study on rats to assess trigonelline’s anti-epileptic effects in kainic acid-induced epilepsy.
          • Summary: Trigonelline improved behavior, reduced oxidative stress and inflammation, and showed potential as an anti-epileptic agent. It significantly lowered intrasynaptosomal calcium levels and LDH activity, ameliorating memory impairment and anxiety in epilepsy models.
  4. Trigonelline inhibits tubular epithelial-mesenchymal transformation in diabetic kidney disease via targeting Smad7.
          • Biomed Pharmacother. 2023 Dec;168:115747.
          • Design: Study on diabetic mice to evaluate trigonelline’s effect on kidney disease.
          • Summary: Trigonelline reduced renal damage and fibrosis by targeting Smad7, indicating its potential as a treatment for diabetic kidney disease. It also exhibited protective effects on proximal tubule epithelial cells, mitigating tubular EMT and renal fibrosis.
  5. Trigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathway.
          • Diabetol Metab Syndr. 2022 Feb 9;14(1):28.
          • Design: Cellular study on human mesangial cells treated with high glucose.
          • Summary: Trigonelline inhibited cell proliferation and ECM expression via the Wnt signaling pathway, highlighting its protective role in diabetic nephropathy. It suppressed levels of fibronectin and collagen IV in HG-stimulated HMCs and efficiently inhibited Wnt/β-catenin signaling activation.
  6. Trigonelline Extends the Lifespan of C. Elegans and Delays the Progression of Age-Related Diseases by Activating AMPK, DAF-16, and HSF-1.
          • Oxid Med Cell Longev. 2021 Sep 25;2021:7656834.
          • Design: Study on Caenorhabditis elegans to evaluate trigonelline’s anti-aging effects.
          • Summary: Trigonelline increased lifespan and stress resistance by activating key signaling pathways, showing potential for developing anti-aging therapies. It also delayed the development of neurodegenerative diseases like AD, PD, and HD in C. elegans models.
  7. Trigonelline induces browning in 3T3-L1 white adipocytes.
          • Phytother Res. 2021 Feb;35(2):1113-1124.
          • Design: Study on 3T3-L1 white adipocytes to investigate trigonelline’s anti-obesity potential.
          • Summary: Trigonelline induced browning and improved lipid metabolism, suggesting its potential as an anti-obesity compound. It enhanced expressions of brown-fat and beige-specific genes, and improved lipid catabolism.
  8. Efficacy of a novel extract of fenugreek seeds in alleviating vasomotor symptoms and depression in perimenopausal women: A randomized, double-blinded, placebo-controlled study.
          • J Food Biochem. 2020 Dec;44(12):e13507.
          • Design: 42-day randomized, double-blind, placebo-controlled study on fenugreek extract (250 mg × 2/day) in perimenopausal women.
          • Summary: Fenugreek extract significantly reduced vasomotor symptoms and depression, and improved hormonal balance without adverse effects. It showed significant improvement in somatic, psychological, and urogenital scores, especially for hot flashes and night sweats.
  9. Trigonelline Demonstrated Ameliorative Effects in Dexamethasone Induced Osteoporotic Rats.
          • Drug Res (Stuttg). 2020 Jun;70(6):257-264.
          • Design: Study on Wistar rats to evaluate trigonelline’s effects on dexamethasone-induced osteoporosis.
          • Summary: Trigonelline improved bone mineral density and restored bone physiology, indicating its potential as a treatment for osteoporosis. It also showed estrogenic activity, enhancing BMD and preventing bone resorption.
  10. Trigonelline protects hippocampal neurons from oxygen-glucose deprivation-induced injury through activating the PI3K/Akt pathway.
          • Chem Biol Interact. 2020 Feb 1;317:108946.
          • Design: Study on hippocampal neurons to evaluate trigonelline’s protective effects.
          • Summary: Trigonelline reduced oxidative stress and inflammation, and activated the PI3K/Akt pathway, showing potential for protecting against cerebral ischemia/reperfusion injury. It also decreased ROS generation and increased antioxidant enzyme levels in hippocampal neurons.
  11. Trigonelline reduced diabetic nephropathy and insulin resistance in type 2 diabetic rats through peroxisome proliferator-activated receptor-γ.
          • Exp Ther Med. 2019 Aug;18(2):1331-1337.
          • Design: Study on type 2 diabetic rats fed high-fat diet and treated with trigonelline (35 mg/kg).
          • Summary: Trigonelline reduced renal dysfunction, inflammation, oxidative stress, and improved insulin sensitivity through PPAR-γ activation. It also decreased blood glucose levels and markers of renal damage in diabetic rats.
  12. Trigonelline protects hippocampus against intracerebral Aβ(1-40) as a model of Alzheimer’s disease in the rat: insights into underlying mechanisms.
          • Metab Brain Dis. 2019 Feb;34(1):191-201.
          • Design: Study on rats to evaluate trigonelline’s protective effects in an Alzheimer’s disease model.
          • Summary: Trigonelline improved cognitive performance, reduced oxidative stress, and inflammation, and protected against neuronal loss in Alzheimer’s disease model. It ameliorated hippocampal oxidative damage and inflammatory markers, showing potential for AD treatment.
  13. Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance.
          • Diabetes Care. 2009 Jun;32(6):1023-5.
          • Design: Randomized crossover trial with 15 overweight men evaluating effects of coffee components on glucose tolerance.
          • Summary: Chlorogenic acid and trigonelline reduced early glucose and insulin responses during an OGTT, suggesting potential benefits for glucose metabolism. However, none of the treatments significantly affected insulin or glucose AUC values during the OGTT compared with placebo.
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