Trigonelline

Trigonelline As a result, the trigonelline content in roasted seeds (coffee beans) was lower than the content in the raw coffee seeds described above. From: Coffee in Health and Disease Prevention, 2015 Add to MendeleySet alert About this page Chapters and Articles Plant Biochemistry Hiroshi Ashihara, in Coffee in Health and Disease Prevention, 2015 3.7 Summary Points • Trigonelline accumulates to 1–3% dry weight in seeds of C. arabica and C. canephora. • Trigonelline is synthesized by the methylation of nicotinic acid. • S-adenosyl-l-methionine acts as a methyl group donor for trigonelline synthesis. • Nicotinic acid, a substrate of trigonelline synthase, is supplied from the pyridine nucleotide cycle. • Active trigonelline synthesis is found in young tissues of leaves and fruits. • Higher concentrations of trigonelline accumulate in mature coffee seeds than in pericarp. • Trigonelline synthesis is more active in pericarp than in seeds. • Trigonelline has several biological activities; it and nicotinic acid produced from trigonelline during the roasting process are useful in human nutrition. • Trigonelline-rich coffee beans produced by biotechnology may be useful as a functional food. Chemical Changes in the Components of Coffee Beans during Roasting Feifei Wei, Masaru Tanokura, in Coffee in Health and Disease Prevention, 2015 10.6 Changes of Trigonelline Trigonelline is a pyridine derivative known to contribute indirectly to the formation of desirable flavor products, including furans, pyrazine, alkyl-pyridines, and pyrroles, during coffee roasting. The importance of trigonelline, not only as a precursor of flavor and aroma compounds but also as a beneficial nutritional factor, has been well documented in previous studies.21,22 Reports on the thermal degradation of trigonelline have revealed nicotinic acid and nicotinamide, as well as their O- and N-methyl derivatives, as reaction products when trigonelline is heated in a sealed tube.22 In fact, studies confirmed that N-methylpyridinium and nicotinic acid are the major nonvolatile products of trigonelline pyrolysis by both mass spectrometry as well as NMR spectroscopy.4,23 The time courses of trigonelline, N-methylpyridinium, and nicotinic acid were observed by NMR spectroscopy. As shown in Figure 10.7,8 trigonelline, which is present at high levels in green coffee beans, decreased continuously during the roasting process. N-methylpyridinium and nicotinic acid, two thermal decomposition products of trigonelline, increased continuously during the roasting, with the N-methylpyridinium as the major thermal product. The decrease in the N-methylpyridinium level after roasting for 7 min was probably attributable to further decomposition and/or interaction with other thermolytic products. Nicotinic acid, which is an important vitamin as well as the second major thermal degradation product of trigonelline, was positively correlated with the roasting degree. Trigonelline and its thermolytic products undoubtedly have direct and indirect effects on other physicochemical properties of a cup of coffee, such as flavor and aroma. Sign in to download full-size image FIGURE 10.7. Nuclear magnetic resonance signal intensity changes of trigonelline, N-methylpyridinium, and nicotinic acid in the extracts of coffee beans during the coffee bean roasting process are shown. The integral value of the signal due to caffeine was set to a constant of 100.8 Read more Organic Compounds in Green Coffee Beans Feifei Wei, Masaru Tanokura, in Coffee in Health and Disease Prevention, 2015 17.4 Trigonelline Trigonelline (Figure 17.3(A)) is found in green coffee beans, and its content depends on the coffee species and origins. The amount of trigonelline in arabica is higher than that in robusta green coffee beans, and thus it can be used as a marker compound to distinguish the coffee bean species.4 During coffee bean maturity, the contents of trigonelline change very little with coffee seed development.7 During the roasting process of coffee beans, trigonelline changes into N-methylpyridinium (Figure 17.3(B)) and nicotinic acid (Figure 17.3(C)) as its major products, which makes it a useful index of the degree of roasting.8,9 Sign in to download full-size image FIGURE 17.3. Chemical structures of (A) trigonelline, (B) N-methylpyridinium, and (C) nicotinic acid. The importance of trigonelline in coffee is connected to nutritional aspects. It has been revealed in recent studies that the administration of trigonelline allows diabetic rats to avoid diabetes-related organ damage and live longer, which can make it a potentially strong candidate for industrial application as a pharmacological agent for the treatment of hyperglycemia, hyperlipidemia, and liver/kidney dysfunctions.10 In addition, the urinary concentrations of trigonelline and its thermal product N-methylpyridinium of coffee drinkers are higher than those of noncoffee drinkers, which indicates that trigonelline and N-methylpyridinium may have potential as dietary biomarkers that could be used as analytical probes to control compliance in human intervention studies on coffee.11 Fenugreek Ramesh C. Garg, in Nutraceuticals, 2016 The Alkaloid—Trigonelline Trigonelline is a plant hormone that has diverse regulatory functions with respect to plant cell cycle regulation, nodulation, and oxidative stress, and in helping survival and growth of the plant. It is found in significant quantity in many plants like coffee beans and fenugreek seed. Because it was first isolated from the fenugreek seeds (Trigonella foenum-graecum), the name assigned to it has been “trigonelline.” The chemical formula for trigonelline is C7H7NO2. It is a methylation product of niacin (vitamin B3), and thus is also known as “methylated niacin.” At higher temperatures, trigonelline breaks down to niacin. In addition to trigonelline, fenugreek seeds contain other alkaloids such as gentianine and carpaine. Trigonelline is present in several other plants such as coffee beans, garden peas, hemp seed, and oats. Plants containing trigonelline at levels more than 1,000 ppm include coffee and fenugreek (Tice, 1997). Coffee consumption has been reported to lower the risk of colon cancer (Lee et al., 2007), type 2 diabetes (Campos and Baylin, 2007), and Alzheimer’s disease (AD) (Barranco Quintana et al., 2007; Arendash and Cao, 2010; Prasanthi et al., 2010). Trigonelline has been claimed to have other therapeutic benefits, such as the anticarcinogenic effect (Tice, 1997) and the hypocholesterolemic effect (Abdel-Mawla and Osman, 2011). Caution may be needed for usage in females because phytoesterogenic activity has also been reported for trigonelline (Allred et al., 2009). Coffee and the Liver J. Arauz, ... P. Muriel, in Liver Pathophysiology, 2017 Trigonelline Trigonelline is present in green coffee at 1% dry weight, with slightly higher values found in Arabica coffees than in Robustas (Ky et al., 2001). During the roasting process trigonelline is partially degraded to nicotinic acid (NA) and several pyridine derivatives. Trigonelline has been shown to possess hypoglycemic, neuroprotective, antiinvasive, estrogenic, and antibacterial activities. The transcription factor Nrf2 plays a key role in cancer development and chemoresistance as its overexpression confers stability to cells and it is thought to be an adaptive cell reaction to chemical and oxidative insults. This makes Nrf2 activation a potential target in anticancer therapy (Singh et al., 2010) as it leads to protection against DNA damage and a reduction in tumorigenesis (Osbum and Kensler, 2008) but Nrf2 activation is also a means by which cancer cells resist chemotherapy. Trigonelline is an effective inhibitor of Nrf2 and in the process it has been reported to increase the sensitivity of chemoresistant pancreatic, colon cell lines to anticancer drugs (Arlt et al., 2013). As noted earlier, trigonelline impacts on the adhesive properties of Streptococcus mutans, the major causative agent of dental caries in humans, by reducing the ability of the bacterium to adsorb onto saliva-coated hydroxyapatite beads. Besides, trigonelline is a potential antimicrobial agent against the highly invasive pathogen Salmonella enterica and depicts gastroprotective effects (Antonisamy et al., 2016). Summarizing, trigonelline is a pyridine alkaloid, found in substantial amounts in coffee, with therapeutic potential as a hypoglycemic and neuroprotective agent and it also has anticarcinogenic effects. However, at this juncture its use as an anticarcinogenic agent is controversial (Almeida et al., 2006). Development & Modification of Bioactivity S. Oestreich-Janzen, in Comprehensive Natural Products II, 2010 3.25.3.5.2 Trigonelline Trigonelline, the N-methylpyridinium-3-carboxylate, is, after caffeine, the second most important alkaloid of coffee, with about 1% of the green bean. During leaf development, it is synthesized in the leaves and in the fruits’ pericarp and accumulated in the seeds. The direct precursors are nicotinic acid and nicotine amide, deriving from the pyridine nucleotide cycle.145 Sign in to download full-size image Trigonelline is rapidly degraded during roasting, strongly depending on temperature and roasting time, with about 60–90% being lost.146 The products are nicotinic acid via demethylation and methyl-pvridines and pyridines via decarboxylation, with reactive intermediates and further recombination products including pyrrols. Trigonelline products have an impact on the overall aromatic perception of roast coffee and beverage. Niacin (nicotinic acid), the degradation product of Trigonellin, serves for vitamin supply in human nutrition; it is an accepted vitamin in European legislation.147 Physiologically important are the recently identified N-methylpyridinium (NMPY) ions;148 they act in vivo, as identified through an activity guided screening procedure in the coffee brew,149 as key components to turn on the endogeneous antioxidant defense system through induction of the phase II biotransformation enzymes.149 Sign in to download full-size image COFFEE | Analysis of Coffee Products L.C. Trugo, in Encyclopedia of Food Sciences and Nutrition (Second Edition), 2003 Trigonelline and Niacin Trigonelline is a pyridine derivative present in several species of fruits and seeds, including coffee. It is present in both Arabica and Robusta coffees in the average amount of 1%. It is extensively degraded during coffee roasting and when dark roasting conditions are used, only about 0.1–0.2% remains in the roasted coffee (Table 2). Due to the high solubility in water, trigonelline is readily extracted from instant coffees, appearing in the range 0.9–1.7%. The final concentration in instant coffee depends on the extraction conditions used as well as on the original material and on the roasting degree. Many volatiles are formed by trigonelline degradation, such as pyrrols and pyridines which will contribute to the aroma fraction of the coffee. Nicotinic acid is another important product formed by demethylation of trigonelline. Nicotinic acid or niacin is a vitamin which is absent in green coffee and in fact is produced during coffee roasting, being present in both roasted and instant coffees, in the range 10–26 and 20–50 mg%, respectively. Because niacin is produced during coffee processing, the vitamin is highly bioavailable in the coffee beverage, in contrast with natural sources where it is present in the bound form. Table 2. Loss of trigonelline during coffee roasting and the correspondent increase in niacin Type of coffee Type of roasting Trigonelline g% (dry basis) Niacin mg% (dry basis) Arabica Light 0.9 4.9 Medium 0.7 10.2 Dark 0.4 14.2 Very dark 0.2 15.0 Robusta Light 0.7 9.9 Medium 0.6 15.0 Dark 0.3 23.4 Very dark 0.1 27.0 From Trugo, LC (1984) PhD thesis. University of Reading, UK. The analysis of trigonelline in coffee products may be carried out by isolating it from coffee extract using a celite column followed by measurement by ultraviolet (UV) spectrophotometry, by paper chromatography followed by elution and UV measurement of the spot, or by HPLC. This last technique has been shown to produce more reliable results and is presently widely used. A simple reverse-phase method using a C18 column, water with a small amount of methanol as solvent, and monitoring at 265–272 nm has been quite adequate for routine analysis. Clarification of coffee extracts may be achieved by solid-phase extraction or precipitation of proteins and pigments by means of lead acetate solution or other adsorbent material except Carrez solutions, since trigonelline is strongly adsorbed by zinc ferrocyanide. Nicotinic acid may be determined by microbiological, colorimetric (with cyanogen bromide and p-aminoacetophenone), or chromatographic methods. However, HPLC has frequently been the technique of choice. In this case better results have been achieved using reverse-phase procedures with a C18 column, and a buffered ion-paired mobile phase to attenuate the nicotinic acid polarity and increase its retention in the column and detection at 254 nm. As for trigonelline analysis, some clarification procedure of the coffee extract must be used. Read more Antidiabetic Effects of Trigonelline Orie Yoshinari, Kiharu Igarashi, in Coffee in Health and Disease Prevention, 2015 85.6 Summary Points • The antidiabetic effects of trigonelline on nonobese and obese models of T2DM are introduced. Furthermore, the effect of nicotinic acid, which is similar in its structure to trigonelline is discussed. • Dietary trigonelline improved diabetes on nonobese T2DM rats, but the effect was not observed in the rats fed nicotinic. • Trigonelline inhibited internal oxide generation on nonobese T2DM rats. • Trigonelline had influence on diabetes-related genes on nonobese T2DM rats’ liver. • On the other hand, both trigonelline and nicotinic acid improved diabetes on obese T2DM mice. Espresso Machine and Coffee Composition Sauro Vittori, ... Gianni Sagratini, in Coffee in Health and Disease Prevention, 2015 28.3.3 Other Bioactive Compounds Caffeine, trigonelline, and nicotinic acid are three important bioactive components in coffee. On this, we recently started an investigation on the effect of water temperature and water pressure on EC extraction. Experiments are carried out using an Aurelia Competizione EC machine, analyzing both robusta and arabica samples. Preliminary results showed that an increase of temperature from 88 to 92 °C leads to an increase in the content of caffeine in the cup. On the contrary, a temperature of 98 °C displayed a reduction in the levels of caffeine for all the three pressures examined. Using arabica and robusta blends, similar trends are evident. At a constant temperature, the increase of pressure plays a slightly depressor role, particularly evident at 11 bar with robusta. On the contrary, minimal influence of pressure on the extraction efficiency of caffeine at constant temperature is observed with arabica (Figure 28.3). Sign in to download full-size image FIGURE 28.3. Preliminary data on mg of caffeine, trigonelline, and nicotinic acid obtained in (A) robusta and (B) arabica espresso coffee samples, by setting the espresso coffee machine at different water temperatures and pressures. (Unpublished results.) With the two blends, the increase of temperature from 88 to 92 °C led to an initial increase in the extraction of trigonelline that is reduced by switching to 98 °C. Keeping temperature constant, the increase of pressure decreases the extraction of trigonelline for robusta; for arabica, change of pressure does not affect the quantity of trigonelline, with a small variation at each temperature (Figure 28.3). For nicotinic acid, preliminary data show an increase of the extracted amount from 88 to 92 °C and a low amount working at 98 °C for robusta (Figure 28.3). Moreover, the most efficient extraction condition using arabica seems to be 9 bar/98 °C and 9 bar/92 °C. Afterward, the extracted amount of those compounds in EC, prepared with the Aurelia machine set at 9 bar and 92 °C, were compared with those prepared with the Leva machine, using either robusta or arabica blends. Again, preliminary data show that in EC prepared from robusta using the “Leva” EC machine, the content of these compounds is lower than for the Aurelia. These data are in agreement with those seen using the Aurelia EC machine, in which there is a low extraction efficiency at low pressures and high temperatures (98 °C, 7 bar), conditions in which the Leva machine operates. On the contrary, in EC prepared from arabica using the Leva EC machine, the contents of these compounds are higher than those for the Aurelia. Making a parallelism between the two EC machines, the obtained results confirmed a good extraction efficiency of caffeine at high temperature and low pressure. Read more Coffee, Granulocyte Colony-Stimulating Factor (G-CSF), and Neurodegenerative Diseases Chuanhai Cao, ... Qing Xu, in Coffee in Health and Disease Prevention, 2015 48.2.3.1 Coffee Effects in AD Pharmacokinetic profiles find that trigonelline, caffeine and its metabolites, as well as late-appearing dihydroferulic acid, feruloylglycine, and dihydroferulic acid sulfate formed from chlorogenic acid by the intestinal microflora accumulate in the plasma, some of which have been reported to show antioxidant effects in vivo, antioxidant-response-element activating potential, and neuroprotective properties, respectively, and might account for the AD risk-reducing effects reported for habitual lifetime consumption of coffee.33 The effect may be mediated by caffeine, other mechanisms such as antioxidant capacity and increased insulin sensitivity, or a combination.17 Caffeine synergizes with another coffee component to increase plasma G-CSF: linkage to cognitive benefits in Alzheimer’s mice synergizes with other molecules.32 Related terms: Amino Acid Antioxidant Nicotinamide Niacin Therapeutic Procedure Antiinfective Agent Chlorogenic Acid Metabolite Aroma Methanol View all Topics Recommended publications Phytomedicine Phytomedicine Journal Biomedicine & Pharmacotherapy Biomedicine & Pharmacotherapy Journal The American Journal of Clinical Nutrition The American Journal of Clinical Nutrition Journal The Journal of Nutritional Biochemistry The Journal of Nutritional Biochemistry Journal Featured Authors Subramanian, Sorimuthu Pillai University of Madras, Chennai, India Citations5,774h-index42Publications32 Lu, Fu'er Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China Citations2,794h-index27Publications14 Ilavenil, Soundharrajan Rural Development Administration, Jeonju, South Korea Citations1,679h-index25Publications29 Science Newsfrom research organizations Trigonelline derived from coffee improves cognitive functions in mice Date: September 22, 2023 Source: University of Tsukuba Summary: Trigonelline is derived from coffee; researchers have found that it improves spatial learning and memory in senescence-accelerated mice. The study also suggested that this effect results from inhibiting neuroinflammation and restoring neurotransmitter levels in the brain. Share: FULL STORY The search for functional natural compounds that can improve age-related cognitive decline has recently emerged as an important research focus to promote healthy aging. Trigonelline (TG), a plant alkaloid found in coffee, as well as in fenugreek seed and radish, was anticipated to possess cognitive enhancement properties. In this study, researchers led by the University of Tsukuba investigated the effects of TG on memory and spatial learning (acquiring, retaining, structuring, and applying information related to the surrounding physical environment) from both a cognitive and molecular biology perspective in an integrated manner using a senescence-accelerated mouse prone 8 (SAMP8) model. Following oral administration of TG to SAMP8 mice for 30 days, the Morris water maze test indicated a significant improvement in spatial learning and memory performance compared with SAMP8 mice that did not receive TG. Next, the researchers performed whole-genome transcriptomic analysis of the hippocampus to explore the underlying molecular mechanisms. They found that signaling pathways related to nervous system development, mitochondrial function, ATP synthesis, inflammation, autophagy, and neurotransmitter release were significantly modulated in the TG group. Furthermore, the research team found that TG suppressed neuroinflammation by negatively regulating signaling factor Traf6-mediated activation of the transcription factor NF-κB. Additionally, quantitative protein analysis confirmed that the levels of inflammatory cytokines TNF-α and IL-6 were significantly decreased and the levels of neurotransmitters dopamine, noradrenaline, and serotonin were significantly increased in the hippocampus. These findings suggest the efficacy of TG in preventing and improving age-related spatial learning memory impairment. This work was supported by DyDo DRINCO and Japan Science and Technology Agency (JST grant number JPMJPF2017) RELATED TOPICS Mind & Brain Intelligence Dementia Memory Educational Psychology Numeracy Neuroscience Schizophrenia K-12 Education RELATED TERMS Computational neuroscience Memory bias Neuroscience Brain damage Memory Cognition Mnemonic Memory-prediction framework Story Source: Materials provided by University of Tsukuba. Note: Content may be edited for style and length. Journal Reference: Sharmin Aktar, Farhana Ferdousi, Shinji Kondo, Tamami Kagawa, Hiroko Isoda. Transcriptomics and biochemical evidence of trigonelline ameliorating learning and memory decline in the senescence-accelerated mouse prone 8 (SAMP8) model by suppressing proinflammatory cytokines and elevating neurotransmitter release. GeroScience, 2023; DOI: 10.1007/s11357-023-00919-x Cite This Page: MLA APA Chicago University of Tsukuba. "Trigonelline derived from coffee improves cognitive functions in mice." ScienceDaily. ScienceDaily, 22 September 2023. . Explore Morefrom ScienceDaily RELATED STORIES Older Organs Accelerate Aging in Transplant Recipients Dec. 5, 2023 — A study found that in preclinical models, transplanting older organs can trigger senescence in younger recipients. They observed that young and middle-aged mice that received heart transplants from ... Astrocyte Networks in the Mouse Brain Control Spatial Learning and Memory Mar. 8, 2022 — Astrocytes form large networks of interconnected cells in the central nervous system. 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It is not intended to provide medical or other professional advice. Views expressed here do not necessarily reflect those of ScienceDaily, contributors or partners. Financial support for ScienceDaily comes from advertisements and referral programs. What foods are high in trigonelline? Common foods containing trigonelline include barley, cantaloupe, corn, onions, peas, soybeans, and tomatoes. Exposure also occurs from herbel remedies, drinking coffee, and from eating fish, mussels, or crustaceans containing trigonelline. About 5% of niacin consumed is converted to trigonelline. Trigonelline (CASRN - National Toxicology Program nih.gov https://ntp.niehs.nih.gov › exsumpdf › trigonelline_508 Search for: What foods are high in trigonelline? Does coffee have trigonelline? Trigonelline is a bioactive pyridine alkaloid that occurs naturally in high concentrations in coffee (up to 7.2 g/kg) and coffee by-products (up to 62.6 g/kg) such as coffee leaves, flowers, cherry husks or pulp, parchment, silver skin, and spent grounds.Apr 14, 2023 Original Article Trigonelline induces autophagy to protect mesangial cells in response to high glucose via activating the miR-5189-5p-AMPK pathway Author links open overlay panelChen Chen b, Jiulong Ma a, Chun Sheng Miao a, Huayu Zhang a, Ming Zhang a, Xia Cao b, Yan Shi a Show more Add to Mendeley Share Cite https://doi.org/10.1016/j.phymed.2021.153614 Get rights and content Abstract Background Diabetic nephropathy (DN) is a primary cause of end‐stage renal disease. Increasing evidence indicates that microRNAs (miRNAs) are involved in DN pathogenesis. Trigonelline (TRL) has been shown to lower blood sugar and cholesterol levels, promote nerve regeneration, and exert anti-cancer and sedative properties. Method The effect of TRL on human mesangial cell (HMC) growth was assessed using the MTT assay. Differentially expressed miRNAs were validated using real-time quantitative polymerase chain reaction (real-time PCR). Bioinformatics, cell transfection, and Western blot analyses were utilized to confirm the binding of miR-5189-5p to HIF1AN. The effects of miR-5189-5 expression on cell proliferation were also assessed. Western blot analysis was used to determine the activation of multiple signaling molecules including phosphorylated-(p)-AMPK, SIRT1, LC3B, p62, and Beclin-1 in the autophagy pathway. Results TRL improved proliferation, increased the expression of miR-5189-5p, reduced HIF1AN, and restored the inhibition of autophagy in HMCs induced by high glucose. MiR-5189-5p mimics inhibited HIF1AN expression, and the miR-5189-5p inhibitor increased HIF1AN expression. MiR-5189-5p mimics significantly improved the proliferation of HMCs induced by high glucose, reduced the relative protein expression of p-AMPK, SIRT1, LC3B, and Beclin-1, and significantly increased the relative protein expression of p62. Conclusion We showed that TRL up-regulated miR-5189-5p expression, activated the AMPK pathway, and activated autophagy in HMCs. Our study demonstrates that TRL could be a new treatment strategy to protect mesangial cells in response to high glucose. Graphic abstract Image, graphical abstract Download : Download high-res image (120KB) Download : Download full-size image Introduction Diabetic nephropathy (DN) is one of the most common complications of diabetes and the main cause of end-stage renal disease (ESRD). The main pathological features of DN include early glomerular mesangial hyperplasia, extracellular matrix accumulation, thickening of the basement membrane, late diffuse glomerulosclerosis, and interstitial fibrosis, eventually leading to renal failure (Brenneman et al., 2016). Changes in the function and morphology of mesangial cells are the main cause of DN and its pathological consequences (Lu et al., 2017; Chen et al., 2018). MicroRNA (miRNA) is a type of single-stranded non-coding RNA composed of 19-25 nucleotides. MiRNA can bind to the 3′-untranslated region (3′-UTR) of target genes and regulate gene expression by promoting mRNA degradation or blocking protein translation, thereby regulating physiological processes including cell proliferation, growth, differentiation, and apoptosis (Mohr and Mott, 2015). MiRNAs are differentially expressed in tissues and are involved in the development of various human pathologies, such as diabetes, kidney disease, tumors, and cardiovascular diseases (Wang et al., 2020; Dang et al., 2020; Xiao et al., 2018). Recent studies have shown that under diabetic conditions, miRNAs can promote fibrosis, regulate autophagy, and accumulate extracellular matrix proteins related to glomerular dysfunction in the kidney (Li et al., 2019). Autophagy occurs at a basal level in most cells to maintain cellular homeostasis, as well as to respond to cell stress and excessive nutrition caused by metabolic dysfunction (as typically observed in obesity or diabetes), which activates the mammalian rapamycin complex (MTORC1) and reduces AMP-activated kinase (AMPK) and Sirt1 activity to reduce autophagy (Parzych and Klionsky, 2014). The AMPK pathway can sense changes in cellular energy metabolism (Tamargo-Gomez and Marino, 2018). AMPK is widely expressed in all types of kidney cells (Kitada et al., 2017). In DN, AMPK activation is inhibited, and autophagy in glomerular mesangial cells is reduced. Activating the AMPK signaling pathway can improve high glucose-induced glomerular mesangial cell autophagy dysfunction (Cetrullo et al., 2015). Under high glucose conditions, phosphorylation of the AMPKα subunit in glomerular mesangial cells is inhibited, and AMPK activators can improve high glucose-induced cell damage. Trigonelline (TRL) is one of the main alkaloids in the fenugreek seed extract of legumes. Its pharmacological activity has been more thoroughly studied compared to the other components of fenugreek (Yinyan et al., 2019; Ghule et al., 2012). TRL has been shown to lower blood sugar and cholesterol levels, promote nerve regeneration, and exert anti-cancer and sedative properties, but its effect on the AMPK pathway and autophagy in glomerular mesangial cells in a state of high glucose remains unclear. In this study, we investigated the effects of TRL on mesangial cell proliferation, microRNA expression, AMPK pathway activation, and autophagy function in response to high glucose. We focused on the mechanism of action of one particular miRNA, miR-5189-5p, in human mesangial cells (HMCs). Section snippets Cell culture and transfection The HMC line was cultured in low glucose Dulbecco's modified Eagle medium (DMEM; Hyclone, USA) containing 10% fetal bovine serum (FBS; Hyclone, USA) and 1% penicillin-streptomycin (Procell, China). The culture dishes were placed in an incubator at 5% CO2 and 37 °C. The cells were passaged every 2 - 3 days and then divided into five groups: the control group (CON) was treated with normal glucose (NG) (5.6 mM); the high glucose group (HG) was treated with 30 mM glucose; and group 200, group 100, TRL suppresses excessive HMC proliferation We first tested the effect of TRL on HMC proliferation using optical density (OD) readings. The OD value was significantly increased in the HG group compared to the CON group (p < 0.01), and the OD value in the HG group significantly decreased in a dose-dependent manner after treatment with TRL [100 μM group (p < 0.05); 200 μM group, 400 μM group, and 800 μM groups (p < 0.01)]. The histogram presented in Fig. 1A F shows that as the TRL concentration increased, the inhibitory effect on Discussion DN is a major cause of ESRD, but specific treatment for DN has not yet been elucidated. Mesangial cells have the ability to contract, phagocytose, proliferate, and synthesize mesangial matrix and collagen (Fu et al., 2015, Kim and Park, 2017), and changes in their function and morphology are a primary factor underlying DN pathogenesis. Gaining a better understanding of the molecular mechanism underlying mesangial cell dysfunction could lead to more effective therapeutic strategies to treat DN ( Funding This work was supported by funding from the Jilin Province Science and Technology Department (No. 20190701045GH, No. 20190201086JC). Author contributions Chen Chen: Methodology, Formal analysis, Investigation, Writing-original-draft. Jiulong Ma: Resources, Chemical methodology. Chunsheng Miao: Resources, Writing-review & editing. Huayu Zhang: Resources, Visualization. Ming Zhang: Technical support. Xia Cao and Yan Shi: Resources, Conceptualization, Formal analysis, Supervision. Yan Shi contributed to the funding acquisition. All authors reviewed the manuscript. All data were generated in-house, and no paper mill was used. All authors agree to be Declaration of Competing Interest The authors declare no conflicts of interest in this work. 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