ArticleLiterature Review

Trigonelline: A Plant Alkaloid with Therapeutic Potential for Diabetes and Central Nervous System Disease

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Abstract

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 β 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.

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... Betaine has anti-inflammatory functions in several human diseases such as obesity, diabetes, cancer, and Alzheimer's disease [84]. Trigonelline has therapeutic activities in diabetes, diabetic complications, and central nervous system disease [85]. Triethanolamine has been reported to possess antibacterial and antifungal activities [86]. ...
... Methyl dihydrojasmonate has been reported to have an anticancer effect [89]. Some metabolites found in the coffee fermentation process, such as choline, betaine, trigonelline, Methyl dihydrojasmonate, 3 ′ -deoxy-Adenosine, cryptochlorogenic acid, and, L-Cyclo(leucylprolyl), are essential for neurodevelopment and reduce the risks of cardiovascular disease and diabetes, while also possessing antibacterial and antitumor activities [85,88,89,[92][93][94]. Theobromine is found in cocoa at high levels and was also present in our coffee fermentation. ...
... Methyl dihydrojasmonate has been reported to have an anticancer effect [89]. Some metabolites found in the coffee fermentation process, such as choline, betaine, trigonelline, Methyl dihydrojasmonate, 3′-deoxy-Adenosine, cryptochlorogenic acid, and, L-Cyclo(leucylprolyl), are essential for neurodevelopment and reduce the risks of cardiovascular disease and diabetes, while also possessing antibacterial and antitumor activities [85,88,89,[92][93][94]. Theobromine is found in cocoa at high levels and was also present in our coffee fermentation. ...
Article
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... calcium, potassium, amino acids (4-hydroxyisoleucine, lysine, arginine, and L-tryptophan), soluble dietary fiber, gum and saponins (diosgenin, yamogenin, tigogenin, gitogenin, sarsapogenin, yuccagenin, and smilagenin) [60][61][62]. Trigonelline is the major alkaloid of fenugreek and 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 [63]. It acts by affecting β-cell regeneration, insulin secretion, activities of enzymes related to glucose metabolism, reactive oxygen species, axonal extension, and neuron excitability [63,64]. ...
... Trigonelline is the major alkaloid of fenugreek and 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 [63]. It acts by affecting β-cell regeneration, insulin secretion, activities of enzymes related to glucose metabolism, reactive oxygen species, axonal extension, and neuron excitability [63,64]. Trigonelline is transformed into niacin when the seed is grilled. ...
... Trigonelline is transformed into niacin when the seed is grilled. Sotolon is a powerful aromatic component responsible for the distinctive maple syrup smell of fenugreek [63]. Polyphenols and germacrene-D are the most abundant components in fenugreek that could improve hyperlipidemia and the cardiovascular system [65][66][67]. ...
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... Besides the antioxidant activity, the presence of furostanol saponins with a predominance of trigoneoside Xa/b I-II, trigoneoside IVa, protodioscin, and trigoneoside XIIa/b in the extracts of fenugreek seeds could attribute antidiabetic potential in accordance with the patent of (Goel, 2010) where furostanol-rich saponin extract exhibited a significant antidiabetic action in a rat model as well as in a clinical trial. The alkaloid trigonelline has also been related to the antidiabetic, antimigraine, sedative, memory-improving, antiviral, antibacterial, and anti-tumor activities of fenugreek (Zhou, Chan, & Zhou, 2012). A recent work (Alsuliam et al., 2022) portrayed in a diabetic rats model, fenugreek seeds aqueous extracts and galactomannan-rich fraction at 500 mg/kg/each reduced islet of R.H. Mekky et al. ...
... Apigenin and related glycosides Antioxidant, anti-inflammatory (Materska, 2015;Mekky et al., 2019;Singh et al., 2022) Quercetin, kaempferol and related glycosides Antidiabetic, alleviative diabetic complications, anti-inflammatory, antioxidant (Abouzed et al., 2018;Mekky et al., 2015) Phenolic acids Antidiabetic, alleviative diabetic complications, anti-inflammatory, antioxidant (Abouzed et al., 2018;Tej et al., 2024) Furostanol saponins Antidiabetic, alleviative diabetic complications (Goel, 2010;Singh et al., 2022) Glutathione Antioxidant, anti-inflammatory (Herzog et al., 2019) Trigonelline Antidiabetic, alleviative diabetic complications, anti-inflammatory, antioxidant (Yao et al., 2020;Zhou et al., 2012) Citric acid and pyruvic acid Antioxidant, anti-inflammatory (Quiroga et al., 2019;Wang et al., 2007) ...
... This finding supports previous studies showing that orchids such as Dendrobium crumenatum, Brasolia cattleya, Sobralia powellii and Elleanthus oliganthus contain phenolic compounds and flavonoid glycosides with strong antibacterial activity against S. aureus bacteria [29,30]. From Table 2, flavone compounds found in the aerial part extract of G. speciosum, which have been reported for their antibacterial activity, include orientin [31] and vitexin [32] Additionally, another compound present in the extract known for its antibacterial activity is the alkaloid trigonelline [33]. ...
... Trigonelline has medical activity, including antioxidant activity, antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baumannii, Enterococcus faecalis, Bacillus subtilis, Candida albicans, and Candida parapsilosis, and antiviral activity against herpes simplex virus (type 1). Moreover, trigonelline was reported to have anticarcinogenic activity in P-388 lymphocytic leukemia in mice [33]. ...
Article
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Grammatophyllum speciosum Blume, a plant of significant pharmacological and cultural importance in its native regions, has been the subject of traditional medicinal use. This study, however, delves deeper into the unique attributes of G. speciosum aerial part and root extracts, particularly their phytochemical content, antioxidant potential, antibacterial activity, and anticancer properties against human skin cancer cells. The results unveiled a promising aspect-higher flavonoid and phenolic compound levels in the aerial part compared to the root extracts. Both aerial part and root extracts demonstrated significant antioxidant activities, as evidenced by their ability to scavenge DPPH radicals and reduce ferric ions in the FRAP assay. Moreover, the ethanolic extract derived from G. speciosum aerial parts showed promising antibacterial activity against both gram-positive and gram-negative bacteria, hinting at its potential therapeutic efficacy. Notably, this extract also demonstrates a capacity to impede the viability of human skin cancer cells (A375). Collectively, these results demonstrated the potential applications of the G. speciosum aerial part extracts. Further investigation is imperative to elucidate the intricate molecular mechanisms underpinning these diverse effects, thereby contributing to a deeper understanding of the pharmacological potential of G. speciosum and its prospective applications in medicine and beyond.
... Trigonelline demonstrated anti-diabetic action by enhancing the insulin signaling pathway and reducing oxidative and endoplasmic reticulum stress in type 2 diabetic rats. These effects affected the insulin release, pancreatic islet β-cell regeneration and the activity of enzymes that break down glucose (Zhou et al. 2012) [142] . ...
... Trigonelline demonstrated anti-diabetic action by enhancing the insulin signaling pathway and reducing oxidative and endoplasmic reticulum stress in type 2 diabetic rats. These effects affected the insulin release, pancreatic islet β-cell regeneration and the activity of enzymes that break down glucose (Zhou et al. 2012) [142] . ...
... Betaine has anti-in ammatory functions in several human diseases such as obesity, diabetes, cancer, and Alzheimer's disease (76). Trigonelline has therapeutic activities in diabetes, diabetic complications and central nervous system disease (77). Triethanolamine has been reported to possess antibacterial and antifungal activities (78). ...
... Methyl dihydrojasmonate has been reported to have an anticancer effect (81). Some metabolites found in the coffee fermentation process, such as choline, betaine, trigonelline, Methyl dihydrojasmonate, 3'-deoxy-Adenosine, cryptochlorogenic acid, L,L-Cyclo(leucylprolyl), are essential for neurodevelopment and reduce the risks of cardiovascular disease and diabetes, while also possessing antibacterial and antitumor activities (77,80,81,(84)(85)(86). Theobromine is found in cocoa at high levels and was also present in our coffee fermentation. ...
Preprint
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Coffee is a critical agricultural commodity and is used to produce premium beverages enjoyed by people worldwide. The microbiome of coffee beans has proven to be an essential tool that improves the flavor profile of coffee by creating aromatic flavor compounds through natural fermentation. Study of the microbial diversity of coffee beans has contributed to methods for rapid fermentation, as well as creating better quality of the final product. This study investigated the natural microbial consortium during wet process fermentation of coffee onsite in Thailand. Our study found 64 genera of bacteria and 59 genera of yeast/ fungi present during the fermentation process. A correlation between microbial diversity and biochemical characteristics including flavor, aroma and metabolic attributes was investigated.
... Trigonelline is another plant alkaloid that is chemically known as N-methylnicotinic acid and is derived from Trigonella foenum-graecum. It is known to have medicinal actions to treat hypoglycemia and hypolipidemia [161]. The effects of this alkaloid on transcriptional activity have been significant. ...
... Alkaloids are a diverse group of secondary plant metabolites that have been shown to treat a variety of ailments, including hypolipidemia and hypoglycemic and diabetic conditions [161]. It also has a significant impact on the antiinflammatory process by boosting the body's defenses against the infection. ...
... Trigonelline (TRIG), chemically known as N-methylnicotinic acid (C7H7 NO2), is a major alkaloid component commonly derived from fenugreek (Trigonella foenum-graecum) 61 . This polar hydrophilic alkaloid can also be extracted from Allium sepapea, Coffea sp, Pissum sativum, Glycine max and Lycopersicon esculentum. ...
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Diabetic nephropathy is one of the most severe microangiopathies of diabetes taking heavy toll on human lives. Diabetic nephropathy is characterized by the accumulation of extracelluar matrix protein leading to irreversible decline in renal function and end stage renal disease. Incomplete knowledge about molecular mechanism underlying nephropathy limit the use of modern medicines to treat this clinical entity. Moreover, current standard of therapy for diabetic nephropathy mainly focus on reduction in hyperglycemia and hypertension. These therapies have limited effect on delaying nephropathy progression. A pressing need for novel therapies initiated studies targeting various molecular pathways involved in nephropathic changes. Herbal medicines with beneficial phytochemicals are reported to delay the progression of nephropathic changes in diabetes in various experimental studies. This review try to summarize various phytoconstituents proved to be effective in management of diabetic nephropathy. The goal is to identify promising phytoconstituents that can be translated into beneficial therapeutic options. Keywords: Diabetic complications, Medicinal plants, Phytoconstituents, Oxidative stress.
... Trigonelline (TRG) is an alkaloid with various biological activities, such as antidiabetic, liver protection and anti-tumor (Hirakawa, Okauchi, Miura, & Yagasaki, 2005). It is rich in coffee beans, horseradish, pumpkin seeds and various leguminous plant seeds (Zhou, Chan, & Zhou, 2012). However, research on TRG is still limited to a few plants, and its content in other plants has not been thoroughly studied. ...
... Similarly, trigonelline has demonstrated antidiabetic properties by improving insulin sensitivity and reducing blood glucose levels. It may also protect pancreatic β-cells from glucotoxicity (Zhou et al., 2012;Hamden et al., 2013). This compound's capability of coping with diabetes through the inhibition of antidiabetic enzymes has been rectified in the in silico study. ...
Article
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In this study, the antidiabetic activities of Lepionurus sylvestris Blume extract (LSB) in rats was investigated. The in vitro antidiabetic properties of LSB was evaluated using α-amylase, α-glucosidase and DPP-IV inhibitory assays, while the antioxidant assay was analysed using DPPH, ABTS and FRAP assays. Type 2 diabetes was with high-fructose/streptozotocin, and the diabetic animals were treated with LSB for 5 weeks. At the end of the experiment, the effects of LSB were evaluated via insulin level, lipid profile and hepatorenal function biomarkers. The level of oxido-inflammatory parameters, histopathology and insulin immunohistochemical staining in the pancreas was evaluated. Diabetic rats manifested significant increases in the blood glucose level, food/water intake, lipid profiles, hepatorenal function biomarkers, as well as a marked decreases in the body weight and serum insulin levels. Histopathological and insulin immunohistochemical examination also revealed decreased pancreatic beta cells and insulin positive cells, respectively. These alterations were associated with significant increases in malondialdehyde, TNF-α and IL-1β, in addition to significant declines in GSH, SOD and CAT activities. LSB significantly reduced blood glucose level, glucose intolerance, serum lipids, restored altered hepatorenal and pancreatic functions in the treated diabetic rats. Further, LSB showed antioxidant and anti-inflammatory activities by reducing malondialdehyde, TNF-α, IL-1β, and increasing antioxidant enzymes activities in the pancreatic tissues. A total of 77 secondary metabolites were tentatively identified in the UPLC-Q-TOF-MS analysis of LSB. Overall, these findings provides insight into the potentials of LSB as an antidiabetic agent which may be associated to the plethora bioactive compounds in the plant.
... Nam is methylated by NNMT (Fig. 2). Although methyl-nicotinic acid (trigonelline) is a known catabolite found in plants 164,165 , NA is not a substrate of NNMT and production of methylnicotinic acid in mammalian cells has not been observed. Thus, NNMT appears to be specific for the removal of excess Nam 166 . ...
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Nicotinamide adenine dinucleotide, in its oxidized (NAD+) and reduced (NADH) forms, is a reduction-oxidation (redox) co-factor and substrate for signalling enzymes that have essential roles in metabolism. The recognition that NAD+ levels fall in response to stress and can be readily replenished through supplementation has fostered great interest in the potential benefits of increasing or restoring NAD+ levels in humans to prevent or delay diseases and degenerative processes. However, much about the biology of NAD+ and related molecules remains poorly understood. In this Review, we discuss the current knowledge of NAD+ metabolism, including limitations of, assumptions about and unappreciated factors that might influence the success or contribute to risks of NAD+ supplementation. We highlight several ongoing controversies in the field, and discuss the role of the microbiome in modulating the availability of NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), the presence of multiple cellular compartments that have distinct pools of NAD+ and NADH, and non-canonical NAD+ and NADH degradation pathways. We conclude that a substantial investment in understanding the fundamental biology of NAD+, its detection and its metabolites in specific cells and cellular compartments is needed to support current translational efforts to safely boost NAD+ levels in humans.
... It was reported that trigonelline could be partially transformed into nicotinic acid during the roasting process, form into vitamins and be involved in human metabolism 122 . Besides, the pharmacological activities of trigonelline have been explored in central nervous system disease, especially its neuroprotective effects 123,124 . The biochemical reactions of trigonelline in humans need to be further explored. ...
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Many studies have reported metabolomic analysis of different bio-specimens from Parkinson’s disease (PD) patients. However, inconsistencies in reported metabolite concentration changes make it difficult to draw conclusions as to the role of metabolism in the occurrence or development of Parkinson’s disease. We reviewed the literature on metabolomic analysis of PD patients. From 74 studies that passed quality control metrics, 928 metabolites were identified with significant changes in PD patients, but only 190 were replicated with the same changes in more than one study. Of these metabolites, 60 exclusively increased, such as 3-methoxytyrosine and glycine, 54 exclusively decreased, such as pantothenic acid and caffeine, and 76 inconsistently changed in concentration in PD versus control subjects, such as ornithine and tyrosine. A genome-scale metabolic model of PD and corresponding metabolic map linking most of the replicated metabolites enabled a better understanding of the dysfunctional pathways of PD and the prediction of additional potential metabolic markers from pathways with consistent metabolite changes to target in future studies.
... According to previous studies, LD 50 of TRG was determined to be 5000 mg/kg, a concentration much higher than the dose used in this research, which does not imply toxicity for the mice analyzed 25,48 . The non-toxicity of this compound in the dose used in this study is a strong point in its application in future clinical studies. ...
Article
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Glutamatergic neurotransmission and oxidative stress are involved in the pathophysiology of seizures. Some anticonvulsants exert their effects through modulation of these pathways. Trigonelline (TRG) has been shown to possess various pharmacological effects like neuroprotection. Therefore, this study was performed to determine TRG’s anticonvulsant effects, focusing on its potential effects on N-methyl-D-aspartate (NMDA) receptors, a type of glutamate receptor, and oxidative stress state in the prefrontal cortex (PFC) in PTZ-induced seizure in mice. Seventy-two male mice were randomly divided into nine groups. The groups included mice that received normal saline, TRG at doses of 10, 50, and 100 mg/kg, diazepam, NMDA (an agonist), ketamine (an antagonist), the effective dose of TRG with NMDA, as well as sub-effective dose of TRG with ketamine, respectively. All agents were administrated intraperitoneally 60 min before induction of seizures by PTZ. Latency to seizure, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels in serum and PFC were measured. Furthermore, the gene expression of NR2A and NR2B, subunits of NMDA receptors, was measured in the PFC. TRG administration increased the latency to seizure onset and enhanced TAC while reducing MDA levels in both the PFC and serum. TRG also decreased the gene expression of NR2B in the PFC. Unexpectedly, the findings revealed that the concurrent administration of ketamine amplified, whereas NMDA mitigated, the impact of TRG on latency to seizure. Furthermore, NMDA diminished the positive effects of TRG on antioxidant capacity and oxidative stress, while ketamine amplified these beneficial effects, indicating a complex interaction between TRG and NMDA receptor modulation. In the gene expression of NMDA receptors, results showed that ketamine significantly decreased the gene expression of NR2B when co-administrated with a sub-effective dose of TRG. It was found that, at least partially, the anticonvulsant effect of TRG in PTZ-induced seizures in male mice was mediated by the attenuation of glutamatergic neurotransmission as well as the reduction of oxidative stress.
... Moreover, its tender green leaves and pods are esteemed as edible vegetables for human consumption [2]. Fenugreek seeds contain bioactive compounds such as alkaloids, flavonoids, steroids and saponins along with various secondary metabolites known for their therapeutic benefits, including alkaloidal trigonelline [3][4][5]. Trigonelline is recognized not only for its potential role as an osmoregulator and osmoprotectant under conditions of salt, drought, and oxidative stresses but also as an inducer of Nod genes during the interaction between Rhizobium and leguminous plants [6,7]. ...
Article
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Background The combination of compost and biochar (CB) plays an important role in soil restoration and mitigation strategies against drought stress in plants. In the current study, the impact of CB was determined on the characteristics of saline calcareous soil and the productivity of fenugreek (Trigonella foenum-graecum L.) plants. The field trials examined CB rates (CB0, CB10 and CB20 corresponding to 0, 10, and 20 t ha‒1, respectively) under deficit irrigation [DI0%, DI20%, and DI40% receiving 100, 80, and 60% crop evapotranspiration (ETc), respectively] conditions on growth, seed yield (SY), quality, and water productivity (WP) of fenugreek grown in saline calcareous soils. Results In general, DI negatively affected the morpho-physio-biochemical responses in plants cultivated in saline calcareous soils. However, amendments of CB10 or CB20 improved soil structure under DI conditions. This was evidenced by the decreased pH, electrical conductivity of soil extract (ECe), and bulk density but increased organic matter, macronutrient (N, P, and K) availability, water retention, and total porosity; thus, maintaining better water and nutritional status. These soil modifications improved chlorophyll, tissue water contents, cell membrane stability, photosystem II photochemical efficiency, photosynthetic performance, and nutritional homeostasis of drought-stressed plants. This was also supported by increased osmolytes, non-enzymatic, and enzymatic activities under DI conditions. Regardless of DI regimes, SY was significantly (P ≤ 0.05) improved by 40.0 and 102.5% when plants were treated with CB10 and CB20, respectively, as similarly observed for seed alkaloids (87.0, and 39.1%), trigonelline content (43.8, and 16.7%) and WP (40.9, and 104.5%) over unamended control plants. Conclusions Overall, the application of organic amendments of CB can be a promising sustainable solution for improving saline calcareous soil properties, mitigating the negative effects of DI stress, and enhancing crop productivity in arid and semi-arid agro-climates.
... These stresses could be associated with the aging as well as over-drying of the seed. Moreover, all the evidenced metabolites are known in the literature to show antioxidant, anti-inflammatory, and positive properties for the immune system, in addition to conferring more resilience to environmental stresses, further confirming that the optimal harvest time for this cultivar to be at 40 days [2,58,[63][64][65][66][67][68][69]. ...
Article
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The yellow pea (Pisum sativum L. ‘Eso’, sin. Lathyrus oleracaeus Lam.(YP)) is an annual herbaceous plant that belongs to the Fabaceae family. Peas, along with other legumes, are an excellent source of proteins and essential amino acids; the yellow variety is known for maintaining a good protein profile even if subjected to industrial processing. However, the presence of antinutrients, such as phytates and oligosaccharides, limits its consumption as a fresh legume to its use as a source of isolated proteins or for animal feed. The aim of the study is to evaluate the changes in the entire phytochemical profile of YP seeds as a function of the harvest time. YPs harvested at about 40, 50, 60, and 70 days from sowing were examined by high-resolution NMR spectroscopy employing 1H-NMR, 1H-1H TOCSY, and 1H-13C HSQC. In total, 40 molecular species were identified and quantified; it was observed that there was a monotonous decrease in amino acids, carbohydrates, and secondary metabolites as a function of time. Antinutrient levels increased, but only in later sampling times. This study identified the optimal harvest time for yellow peas “Eso” in the fortieth day from sowing, adding new information about the best nutritional outcome for humans.
... The transcriptional activities have been significantly impacted by this alkaloid. Before trigonelline could be used therapeutically to treat diabetes and its repercussions on illnesses of the central nervous system, further study was required, especially to understand the mechanism of action (Zhou et al., 2012). ...
Chapter
Secondary metabolites produced by plants are particular to their species or genus and do not contribute to the basic processes of growth, development, and reproduction. These compounds play a key role as feed deterrents against herbivores, protectants from microbial infection, abiotic stresses, UV-protectants, pollinators attractants, antioxidants, and signalling molecules. Based on their chemical structures and production routes, secondary metabolites may be further classified across several classes. Alkaloids, terpenes, and phenolic chemicals make up the largest and most common group. The importance of secondary metabolites found in plants for human nutrition has grown to be an important interesting research area. Secondary metabolites are used by people as medicine to cure illnesses and infections, flavourings, and pesticides in the recent past. Therefore, an overview of plants is provided in this chapter including secondary metabolites and how these compounds are relevant to human health.
... This modification may help regulate tears and shield meibomian gland ducts from inflammation and meibum stagnation [109]. When MGD patients received the omega-3 dietary supplement, their HRQoL significantly improved, lid margin inflammation decreased, and the ocular surface's homeostasis was restored [110]. Very long-chain omega-3 fatty acids are another name for EPA and DHA. ...
Article
Comprehensive and effective care techniques have become essential due to the global epidemic dimensions of metabolic disorders, including diabetes, obesity, and cardiovascular ailments. Recent research highlights the potential of dietary supplements, herbal extracts, and phytochemicals in treating metabolic diseases. This abstract conveys the current state of the science in this field by highlighting these findings' underlying mechanisms and potential therapeutic applications. Plant-based diets contain naturally occurring bioactive molecules termed phytochemicals, which have shown promise in treating various metabolic illnesses. Examples include curcumin, flavonoids, and polyphenols' insulin-sensitizing, antioxidant, and antiinflammatory properties. Herbal extracts, derived from ancient medicinal herbs, have been used by people for years to treat a wide range of ailments. Recent studies have shown the efficacy of these strategies in improving lipid profiles, glucose metabolism, and overall cardiovascular health. Omega-3 fatty acids, vitamins, and minerals are just a few of the numerous nutritional supplements that are critical to metabolic health. These vitamins improve insulin sensitivity, regulate blood sugar, and decrease inflammation. Probiotics and prebiotics also affect the gut flora, which significantly affects metabolic function. These natural medicines' ability to treat metabolic diseases either by themselves or in combination with conventional medical interventions. However, when using it therapeutically, one must consider the differences in doses, individual responses, and bioavailability. The article concludes that phytochemicals, plant extracts, and food supplements offer a promising avenue for the management of metabolic illnesses. Comprehensive research, including clinical studies, is needed to ascertain their safety and efficacy characteristics. When added to treatment strategies, these natural therapies could be helpful supplements that improve overall health and the quality of life among individuals with metabolic diseases. Naringenin, a citrus flavonoid, can potentially prevent kidney injury in hyperuricemia by reducing uric acid, inflammation, apoptosis, DNA damage, and activating antioxidants. Further research and professional consultation are essential. Factors contributing to metabolic diseases, current approaches to management nutritional approaches for managing obesityassociated metabolic impairments in the liver and small intestine, and nutritional approaches for managing obesity-associated metabolic dysregulation are also explained briefly.
... The three most abundant metabolites in hemp seeds from the Bama region, cannflavin A, B, and C, as flavonoids, have been shown to have various health benefits, such as those mentioned above [26,27]. Trigonelline has been shown to have various biological activities, including anticancer and antidiabetic activities; it has also been shown to improve memory [28][29][30]. Citric acid is a food additive that is harmless to humans; it has various uses in the food industry and exhibits antibacterial and antiviral activities [31]. Vitexin shows various biological activities, including antioxidant, anticancer, and anti-inflammatory activities [32,33]. ...
Article
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Hemp seeds are consumed in “Bama longevity villages” in China and are believed to contribute to the locals’ longevity. However, the molecular breeding of hemp seeds is limited due to our lack of understanding of molecular regulation and metabolite accumulation at different maturity stages. Here, we conducted metabolomic and transcriptomic analyses of hemp seeds from the Bama region at four maturity stages (S1 to S4). In total, 1231 metabolites of 11 classes were detected in hemp seeds from S1–S4, including 233 flavonoids, 214 phenolic acids, 159 lipids, 118 amino acids and derivatives, 100 alkaloids, 100 organic acids, 71 nucleotides and derivatives, 43 lignans and coumarins, 14 terpenoids, 13 tannins, and 166 others. The metabolomic analysis of hemp seeds (from the Bama region) revealed a higher number of flavonoid metabolites compared with seven other varieties from other regions in China. Hemp seeds are rich in metabolites like cannflavin, trigonelline, citric acid, vitexin, choline alfoscerate, and choline, which may potentially contribute to the longevity of the Bama people. Through transcriptomic and metabolomic analyses, a gradual decrease in the overall expression pattern of genes and metabolite accumulation was observed during seed maturation. Weighted gene co-expression network analysis revealed that two genes (ncbi_115696993 and ncbi_115706674) are involved in regulating main metabolites, while transcription factor association analysis revealed that three transcription factor genes (MYB, NAC, and GRAS) are also involved in regulating the metabolites. The expression pattern of these five candidate genes was further verified by qPCR. Our study provides valuable insights into the metabolic substances during seed maturation and identifies candidate genes that could be utilized for future genetic engineering to enhance the endogenous biosynthesis of health-promoting metabolites in hemp seeds, potentially leading to improved nutritional and medicinal properties.
... TRG has a sedative role [73]. TRG-enriched green coffee bean powders could function as a sleep aid and pain relief (Tan, W. (University of South Carolina, Columbia, MO, USA); Cui, T. (University of Missouri, Columbia, MO, USA). ...
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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. Further validations are required to define its specific targeting molecules, dissect the underlying mechanistic networks, and corroborate its efficacy in clinical trials.
... Un número significativo de personas asocian su consumo de café a factores determinados: la realización de actividades específicas, la disminución de sueño, un mayor nivel de concentración, la estimulación e incluso los efectos antioxidantes (Bonilla, 2017). Asimismo, relacionan sus efectos a uno de sus componentes: la cafeína; cabe resaltar, sin embargo, que, además del café, existen diversas sustancias que, debido a su composición química, son utilizadas para tratar enfermedades del sistema nervioso central y poseen propiedades neuroprotectoras, antimigrañosas, sedantes y mejoradoras de la memoria (Zhou et al., 2012). ...
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El consumo de café se ha asociado a múltiples efectos positivos sobre el cuerpo humano: aumento de memoria a corto plazo, estímulos al sistema nervioso central y beneficios en las funciones intelectuales. A su vez, no obstante, se ha relacionado con cuadros y enfermedades degenerativas. Al respecto, el presente artículo tuvo como objetivo identificar los efectos del consumo de café en los habitantes de la ciudad de Neiva. Para lo cual se desarrolló una investigación con un enfoque cuantitativo, y de corte transversal, cuyos datos se recolectaron a partir de 138 personas encuestadas. Los resultados evidencian una prevalencia entre el consumo de café y variaciones en el estado de ánimo y situaciones comportamentales. Asimismo, se resalta una mayor probabilidad de presentar cuadros depresivos, posteriores al consumo, para las personas que tienen una ingesta ocasional de café. Por último, se recomienda la realización de estudios relacionados con los parámetros de influencia del género en torno a los efectos del consumo de café.
... Moreover, CS extract has other and different alkaloids than spent coffee extract such as trigonelline, theobromine, and theophylline. Trigonelline, which is present in CS extract in a concentration of 23.7 μg/g, is a pyridine alkaloid compound and a methylation product of vitamin B3 (niacin) (Zhou et al., 2012). This alkaloid has been shown to provide evidence of therapeutic effects, such as the enhancement of distinct neuron function and memory in mice with ...
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In a world where a greener approach is increasingly necessary, it is mandatory to reduce waste production and reuse residues from the company's supply chain. Spent Coffee grounds (SCG) and Coffee Silverskin (CS) are two important by-products of coffee production, being sources of important dietary fibers and bioactive compounds, which is why some authors have proposed their reuse in the nutraceutical, food and cosmetic industries. However, their nutrients chemical content has been insufficiently studied. Therefore, the aim of the present review was to investigate the main components, such as carbohydrates, dietary fibers, lipids, and bioactive compounds of SCG and CS. In addition, the most common extraction methods to obtain these aforementioned nutrients were evaluated.
... It has been evaluated against neurodegenerative diseases for its neuroprotective activity, and it also possesses antimigraine, sedative, memory-enhancing, and hypolipidemic activities. Moreover, it may reduce auditory neuropathy and platelet aggregation [74]. ...
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The metabolite fingerprinting of four Italian commercial bean seed cultivars, i.e., Phaseolus Cannellino (PCANN), Controne (PCON), Vellutina (PVEL), and Occhio Nero (PON), were investigated by Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate data analysis. The hydroalcoholic and organic extract analysis disclosed more than 32 metabolites from various classes, i.e., carbohydrates, amino acids, organic acids, nucleosides, alkaloids, and fatty acids. PVEL, PCON, and PCANN varieties displayed similar chemical profiles, albeit with somewhat different quantitative results. The PON metabolite composition was slightly different from the others; it lacked GABA and pipecolic acid, featured a higher percentage of malic acid than the other samples, and showed quantitative variations of several metabolites. The lipophilic extracts from all four cultivars demonstrated the presence of omega-3 and omega-6 unsaturated fatty acids. After the determination of the total phenolic, flavonoids, and condensed tannins content, in vitro antioxidant activity was then assessed using the DPPH scavenging activity, the ABTS scavenging assay, and ferric-reducing antioxidant power (FRAP). Compared to non-dark seeds (PCON, PCANN), brown seeds (PVEL, PON) featured a higher antioxidant capacity. Lastly, only PON extract showed in vitro antifungal activity against the sclerotia growth of S. rolfsii, by inhibiting halo growth by 75%.
... Trigonelline (Fig. 1, panel A) is an alkaloid with chemical formula C 7 H 8 ClNO 2 (see Materials and Methods section), is highly water soluble, and it is the most substantial element that contributes to undue bitterness in coffee. It has been reported to have hypoglycemic, hypolipidemic, sedative, antimigraine, antibacterial, antiviral, and anti-tumor effects, and to improve memory retention and inhibit platelet aggregation [12]. played by the carboxylate group with respect to solute-solvent interactions. ...
... Our study suggests parallel observations, in diabetic mice increased blood glucose level could be due to above mentioned reasons. In TRG and TNP group, blood glucose level was significantly lowered than the normal level; these findings suggest that trigonelline has antihyperglycemic effect which lowers the blood glucose level (Al-Habori M, Raman, 1998; Zhou et al., 2012). In T2DM, insulin signalling was severely disrupted and glucose uptake and glycogen storage was depleted because of insulin resistance (Bogardus et al., 1984). ...
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Disturbed insulin signalling and glucose metabolism are the key features of type 2 diabetes mellitus (T2DM) Various phytomedicines have proved their anti hyperglycemic effects. This study has been done to evaluate the therapeutic potential of trigonelline nanoparticle in diabetic complication in mice model. 4 mice groups were used for this study, control, diabetic control, treated I and treated II. Treated I was treated with trigonelline and treated II treated with trigonelline nanoparticles (TNP) for 20 days and serum insulin concentration and blood glucose level were measured as well as glucokinase (GLK), glucose 6 phosphatase (G6Pase) and glucose 6 phosphate dehydrogenase (G6PD) activity were analysed by enzymatic assay. Treated II-showed improved glucose metabolic pathways and insulin sensitivity. Serum insulin concentration, blood glucose level and GLK activity was to be found significantly increased in this group and also G6PD, G6Pase activity were significantly decreased. Recovery of glucose metabolism and insulin sensitivity is due to nanoformulation of TNP indicating its increased bioavailability and therapeutic potential, these findings are useful for future studies related to diabetic complications such as insulin signalling and insulin resistance (IR).
... Trigonelline is the active plant alkaloid chemically known as N-methylnicotinic acid (C7H7NO2) which was first isolated from the fenugreek seed. Number of previous studies with good results showed that trigonelline have antidiabetic [32], antioxidative, antiviral, antibacterial, antimigraine, antihyperlipidimic properties and also beneficial in prevention and treatment of central nervous system diseases [33] [34]. It is reported that trigonelline suppresses oxidative stress in kidney in STZ induced neonatal diabetic rats [35]. ...
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In medical sciences nanotechnology helps us to produce nano-scale medication or medicine. Various studies showed that nanoparticles are smoothly enters through cell membranes in organisms and get interacted quickly with biological systems because of its number of advantages such as targeted drug delivery, bioavailability, less immunogenicity and also overcomes traditional therapy problems like less bioavailability and adverse effects. In present investigation we synthesized Trigonelline nanoparticles (TNPs) successfully. Trigonelline is the active plant alkaloid chemically known as N-methylnicotinic acid (C7H7NO2) which was first isolated from the fenugreek seed. Diabetic Mellitus is a metabolic disease associated with impaired uptake and metabolism of glucose. Hyperglycemic condition in diabetic case leads oxidative stress in body and finally results in damage to the various biomolecules in the body such as lipid protein and nucleic acid. The present investigation was aims to study the antioxidative effect of TNPs on Streptozotocin induced diabetic mice (Mus musculus). Mice were divided into three groups viz, a) Control group (Group I) b) Diabetic group (Group II) c) Recovery group (Group III). Diabetic mice treated with TNPs 100 mg/kg body weight intraperitoneally. The activity of antioxidative enzymes i.e. Superoxide dismutase (SOD), Catalase (CAT), Glutathion peroxidase (GPx) and lipid peroxidation in the liver and pancreas was recorded at the end of experiment. There was decrease in antioxidative enzymes and increase in lipid peroxidation in pancreas of diabetic mice as compare to control (Group I). After the treatment of TNPs significant increase in levels of antioxidative enzymes and significant decrease in lipid peroxidation in liver and pancreas of recovery group (Group III) was observed. The study suggest that nano-scaling of trigonelline reduces oxidative stress improves antioxidative status of diabetic mice.
... Proteins such as globulin, lecithin, and albumin are abundant in fenugreek endosperm (43.8 g/100 g) (Mathur and Choudhry, 2009;Naidu et al, 2011). It contains a high percentage (20-30%) of free amino acids, especially histidine and 4-hydroxyisoleucine, which may increase insulin activity (Işıklı and Karababa, 2005). The proteins found in fenugreek are sufficiently stable and unaffected by booking (Srinivasan, 2006). ...
... 9 Trigonelline a bioactive compound of Trigonella foenum-graecum have anti-diabetic, antioxidant, anti-inflammatory, antibacterial and antiviral, antispasmodic and analgesic effects. 10 Lipids metabolic profiles are the main component of cell membranes and they involved in signal transduction, energy storage and cell signaling. In our study, we analyzed lipid metabolic profiles in alcohol exposed rats. ...
... Trigonelline, a primary compound found in Trigonella foenum-graecum L, is a hydrophilic pyridine present in various plant species, such as Nelumbo nucifera, Lupinus albus, and Coffea arabica. Various researchers reported Trigonelline's antioxidant, antitumor, antibacterial, and other pharmacological properties [11,12]. Studies have reported that Trigonelline exhibits anticancer effects against lymphocytic leukemia in mice [13]. ...
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Breast cancer, a highly prevalent and fatal cancer that affects the female population worldwide, stands as a significant health challenge. Despite the abundance of chemotherapy drugs, the adverse side effects associated with them have initiated an investigation into natural plant-based compounds. Trigonelline, an alkaloid found in Trigonella foenum-graecum, was previously reported for its anticancer properties by the researchers. In this present study, we have identified the molecular targets of Trigonelline in breast cancer and predicted its drug-like properties and toxicity. By analyzing breast cancer targets from databases including TTD, TCGA, Gene cards, and Trigonelline targets obtained from CTD, we identified 14 specific targets of Trigonelline in the context of breast cancer. The protein–protein interaction (PPI) network of the 14 Trigonelline targets provided insights into the complex relationships between different genes and targets. Heatmap analysis demonstrated the expression patterns of these 14 genes at the protein and RNA levels in breast cancer cells and breast tissues. Notably, four genes, namely EGF, BAX, EGFR, and MTOR, were enriched in the breast cancer pathway. At the same time, PARP1, DDIT3, BAX, and TNF were associated with the apoptosis pathway according to KEGG pathway enrichment analyses. Molecular docking studies between Trigonelline and target proteins from the Protein Data Bank (PDB) revealed favorable binding affinity. Furthermore, mutation analysis of target genes within a dataset of 1918 samples from cBioPortal revealed the absence of mutations. Remarkably, Trigonelline also exhibited binding affinity towards two mutant proteins, and based on these findings, we predicted that Trigonelline could be utilized to target breast cancer genes and their mutants through network pharmacology. Additionally, this was supported by molecular dynamic simulation studies. As our study is preliminary, further validation through in vitro and in vivo studies is essential to confirm the efficacy of Trigonelline in breast cancer treatment. Graphical abstract
... It has also been shown that both compounds can improve insulin sensitivity and stimulate glucose transport in skeletal muscle through adenosine monophosphate-activated protein kinase (AMPK) activation. Both caffeine, chlorogenic acid, and trigonelline can also reduce oxidative stress through their antioxidant capabilities (Lu et al., 2020;Sanlier et al., 2019;Zhou et al., 2012). Moreover, the major diterpenes in coffee, cafestol, and kahweol may also increase glucose uptake in muscle via activation of AMPK, which in turn may indirectly stimulate glycolysis via activation of the enzyme phosphofructokinase-2 (Ren et al., 2019). ...
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Diabetes mellitus (DM) is a chronic metabolic disorder and a major global problem. Coffee contains several bioactive compounds, such as caffeine, chlorogenic acid, trigonelline, cafestol, and kahweol, associated with a reduced risk of type 2 DM. This study aimed to assess the relationship between coffee consumption habits and blood glucose levels of farmers in Jenggawah Village, Jenggawah Subdistrict, Jember Regency. We used a cross-sectional study design. The sample of this study was 137 farmers who were taken by purposive sampling. Assessment of coffee consumption habits was conducted using a questionnaire. At the same time, data on random blood glucose levels were obtained from medical records of the Bakti Sosial Akbar dan Pengobatan Gratis Agromedis activities in Jenggawah Village in June 2022. Statistical analysis was performed using the Kruskall-Wallis test, and multivariate analysis using linear regression. The results showed that there was no statistically significant difference in random blood glucose levels between groups based on the variable type of coffee consumed (p=0.212), the level of coffee consumption (p=0.211), and the amount of sugar added to the coffee (p=0.086). However, the linear regression test results showed that the amount of added sugar in coffee had the greatest relationship with blood glucose levels compared to other independent variables (p=0.031). In conclusion, there was no relationship between coffee consumption habits and random blood glucose levels of farmers in Jenggawah Village. Further research is needed to confirm these findings.
... It has been claimed that trigonelline has beneficial effects including antioxidant, neuroprotective, memory-improving, hypoglycemic, and hypolipidemic effects. 1 Apart from having beneficial systemic effects, it has been claimed that topical use of emulsion formulation containing hydroalcoholic extract can improve the appearance and mechanical properties of skin, hydrating the skin, and increase the resistance of the skin to photoaging. 2 Tyrosinase, the main enzyme that contributed to the synthesis of melanin, is a copper-containing oxidase that catalyzes the first two subsequent reactions of melanogenesis including the hydroxylation reaction of l-tyrosine to l-dopa (monophenolase activity) and the oxidation of l-dopa to o-dopaquinone (diphenolase activity). [3][4][5] o-dopaquinone and its derivatives finally polymerize to eumelanin and pheomelanin in a series of reactions. ...
... However, higher fold increase was noted under T1 conditions followed by T3 and T2 conditions. Zhou et al. (2012) previously reported trigonelline as a therapeutic alkaloid majorly found in Trigonella herbs. The same study also discussed about hypoglycaemic, hypolipidemic, neuroprotective, antimigraine, sedative, memory-improving, antibacterial, antiviral, and anti-tumour activities of Trigonelline. ...
Chapter
Diabetes Mellitus (DM) receives significant attention from most scientists due to being a major global public health threat. Diabetes is considered one of the leading causes of death due to its micro and macrovascular complications. This insidious killer is estimated to reach a staggering number of 578 million (700 million by 2045) cases by 2030. In this book, utilizing the disciplines of clinical sciences, various contemporary topics related to diabetes are extensively discussed. These include the classification of diabetes, underlying causes, epidemiology, pathogenesis, impact on sexual functions, association with cancer, clinical manifestations, diagnostic methods, complications, and treatment options. Furthermore, intriguing and current subjects such as ""antidiabetic phytotherapy"" and ""the relationship between oral health and diabetes"" are also covered. By doing so, readers will acquire comprehensive and detailed knowledge about the clinical management of diabetes. Thus, this book not only serves those who seek to understand the scientific aspects of diabetes but also proves to be a valuable resource for healthcare professionals, researchers, and students in a clinical setting. We believe that this book will contribute to understanding the complexity of diabetes and provide beneficial solutions while shedding light on future studies.
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Background: One of the most popular chemotherapy medications is doxorubicin (DOX), however it can have non-negligible damage. When the underlying mechanisms of damage are investigated, the most prominent pathways are oxidative stress, inflammation and apoptosis. Aim: We investigated the NF-κB/MAPK inflammatory pathway and cellular apoptosis to determine the efficacy of trigonelline alkaloid (TRIG) in preventing DOX-induced lung injury. Methodology: The study consisted of C, TRIG, DOX and TRIG+DOX groups. TRIG and TRIG+DOX groups received 50 mg/kg TRIG for 7 days. On day 8, DOX and TRIG+DOX groups received a single dose of 15 mg/kg DOX. Results: Our results showed that apoptosis markers and inflammation were higher in the DOX group. In contrast, TRIG pretreatment partially suppressed apoptosis and decreased inflammation by blocking the activation of the MAPK/NF-κB pathway, lowering IL-6 levels, and protecting the lung from apoptotic cell death. Conclusion: Assessing TRIG's effectiveness in lung tissue injury, this study may be a crucial first step.
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Oxidative stress, driven by reactive oxygen, nitrogen, and sulphur species (ROS, RNS, RSS), poses a significant threat to cellular integrity and human health. Generated during mitochondrial respiration, inflammation, UV exposure and pollution, these species damage cells and contribute to pathologies like cardiovascular issues, neurodegeneration, cancer, and metabolic syndromes. Lifestyle factors exert a substantial influence on oxidative stress levels, with mitochondria emerging as pivotal players in ROS generation and cellular equilibrium. Phytochemicals, abundant in plants, such as carotenoids, ascorbic acid, tocopherols and polyphenols, offer diverse antioxidant mechanisms. They scavenge free radicals, chelate metal ions, and modulate cellular signalling pathways to mitigate oxidative damage. Furthermore, plants thriving in high-altitude regions are adapted to extreme conditions, and synthesize secondary metabolites, like flavonoids and phenolic compounds in bulk quantities, which act to form a robust antioxidant defence against oxidative stress, including UV radiation and temperature fluctuations. These plants are promising sources for drug development, offering innovative strategies by which to manage oxidative stress-related ailments and enhance human health. Understanding and harnessing the antioxidant potential of phytochemicals from high-altitude plants represent crucial steps in combating oxidative stress-induced disorders and promoting overall wellbeing. This study offers a comprehensive summary of the production and physio-pathological aspects of lifestyle-induced oxidative stress disorders and explores the potential of phytochemicals as promising antioxidants. Additionally, it presents an appraisal of high-altitude medicinal plants as significant sources of antioxidants, highlighting their potential for drug development and the creation of innovative antioxidant therapeutic approaches.
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Fenugreek seed extract (FSE) is known to possess antidiabetic properties. The current study evaluated the comparative potency of 4 different components of FSE (Trigonelline, 4-Hydroxyisoleucine, Diosgenin, and Galactomannan) in amelioration of diabetes-induced hyperglycaemia; metabolic and stress disorders. FSE and the four bioactives were fed to normal and alloxan-induced type-1 diabetic rats for four weeks. Changes in pancreatic hormones, lipid profile, antioxidant enzymes, and expression of Glucose transporter-2 (GLUT-2) and Glucagon-like peptide-1 receptor (GLP-1R) were evaluated. Key findings revealed the highest levels of serum insulin and GLP-1; islet cell regeneration, increased Dipeptidyl peptidase-IV enzyme inhibition, significant recovery of GLUT-2 and GLP-1R expression, and maximum levels of low-density lipoprotein receptors (LDLR) in trigonelline fed diabetic rats. The same bioactive also caused the maximum increase in various antioxidant enzymes with decreased serum malondialdehyde (MDA) levels in diabetic rats. The 4-Hydroxyisoleucine showed antidiabetic properties either equal to or less significantly as compared to trigonelline. Diosgenin on the other hand caused maximum stimulation only in lipid metabolism whereas galactomannan couldn’t produce significant changes in any parameters over the other 3 components. The results indicated trigonelline is the most desirable component of FSE and may be used as a phytotherapeutic agent for the holistic management of type-1 diabetes.
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Non-alcoholic fatty liver disease (NAFLD), with a global prevalence of 25%, continues to escalate, creating noteworthy concerns towards the global health burden. NAFLD causes triglycerides and free fatty acids to build-up in the liver. The excessive fat build-up causes inflammation and damages the healthy hepatocytes leading to non-alcoholic steatohepatitis (NASH). Dietary habits, obesity, insulin resistance, type 2 diabetes, and dyslipidemia influence NAFLD progression. The disease burden is complicated due to the paucity of therapeutic interventions. Obeticholic acid is the only approved therapeutic agent for NAFLD. With more scientific enterprise being directed towards understanding of underlying mechanisms of NAFLD, novel targets like lipid synthase, farnesoid X receptor signalling, peroxisome proliferator-activated receptors associated with inflammatory signalling and hepatocellular injury have played a crucial role in progression of NAFLD to NASH. Phytocompounds have shown promising results in modulating hepatic lipid metabolism and de novo lipogenesis suggesting their possible role in managing NAFLD. This review discusses the ameliorative role of different classes of phytochemicals with molecular mechanisms in different cell lines and established animal models. These compounds may lead to the development of novel therapeutic strategies for NAFLD progression to NASH. This review also deliberates on phytomolecules undergoing clinical trials for effective management of NAFLD.
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Background Human demand for meat and dairy products will increase as a result of economic development and population growth, and the farming of ruminants, such as cattle and sheep, will also increase. Methane (CH 4 ) emission from the enteric fermentation of ruminant livestock is a major source of greenhouse gas emissions and a significant contributor to global warming. Meanwhile, growth performance is often limited and animals are more vulnerable to diseases in high-density, intensive farming, greatly reducing livestock productivity, so developing ways to reduce CH 4 emissions and improve ruminant productivity has become a research hotspot. Studies have reported that fenugreek ( Trigonella foenum-graecum L.) as feed additives have the potential to reduce ruminant methane and improve the productivity. However, systematic reviews of such studies are lacking. Methodology In this review, databases of Google Scholar, Web of Science, PubMed, Scopus and Science Direct were used for the literature search. The initial keywords search was fenugreek or Trigonella foenum-graecum L. For more focused search, we added terms such as methane, rumen fermentation, growth, milk production and antioxidants. All were done for ruminants. The literature that conforms to the theme of this article is selected, summarized, and finally completed this article. Results By regulating the rumen microbiome (suppressing protozoans, methanogenic bacteria, and fungi), fenugreek can lower CH 4 emissions according to many in vitro anaerobic fermentation experiments. Fenugreek secondary metabolites (saponins and tannins) are responsible for this impact, but it is still unclear exactly how they work. Therefore, more long-term in vivo experiments are needed to verify its efficacy. Fenugreek is also rich in alkaloids, amino acids, flavonoids, saponins and phenolic acids. These compounds have been shown to have beneficial effects on ruminant growth, lactation, and total antioxidant capacity. Therefore, fenugreek has a great opportunity to develop into a new green feed additive. Conclusions This review provides a summary of the effect of fenugreek and its bioactive compounds on rumen fermentation, CH 4 emissions and production performance by ruminants. In addition, based on the available data, the possible biochemical pathway of fenugreek to reduce CH 4 emissions in ruminants was described. Overall, the livestock feed industry has the opportunity to develop natural, environmentally-friendly feed additives based on fenugreek.
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Background The continuous evolution of drug-resistant influenza viruses highlights the necessity for repurposing naturally-derived and safe phytochemicals with anti-influenza activity as novel broad-spectrum anti-influenza medications. Methods In this study, nitrogenous alkaloids were tested for their viral inhibitory activity against influenza A/H1N1 and A/H5N1 viruses. The cytotoxicity of tested alkaloids on MDCK showed a high safety range (CC50 > 200 µg/ml), permitting the screening for their anti-influenza potential. Results Herein, atropine sulphate, pilocarpine hydrochloride and colchicine displayed anti-H5N1 activities with IC50 values of 2.300, 0.210 and 0.111 µg/ml, respectively. Validation of the IC50 values was further depicted by testing the three highly effective alkaloids, based on their potent IC50 values against seasonal influenza A/H1N1 virus, showing comparable IC50 values of 0.204, 0.637 and 0.326 µg/ml, respectively. Further investigation suggests that colchicine could suppress viral infection by primarily interfering with IAV replication and inhibiting viral adsorption, while atropine sulphate and pilocarpine hydrochloride could directly affect the virus in a cell-free virucidal effect. Interestingly, the in silico molecular docking studies suggest the abilities of atropine, pilocarpine, and colchicine to bind correctly inside the active sites of the neuraminidases of both influenza A/H1N1 and A/H5N1 viruses. The three alkaloids exhibited good binding energies as well as excellent binding modes that were similar to the co-crystallized ligands. On the other hand, consistent with in vitro results, only colchicine could bind correctly against the M2-proton channel of influenza A viruses (IAVs). This might explicate the in vitro antiviral activity of colchicine at the replication stage of the virus replication cycle. Conclusion This study highlighted the anti-influenza efficacy of biologically active alkaloids including colchicine. Therefore, these alkaloids should be further characterized in vivo (preclinical and clinical studies) to be developed as anti-IAV agents.
Chapter
Humans are subjected to an array of external and internal stimuli during their lives, which injure genetic material and generate somatic mutations that lead to accumulating genomic stress. Several human pathologies like chronic degenerative diseases, including hepatic, neurodegenerative, and cardiovascular disorders; diabetes; arthritis; cancer; chronic inflammation; and aging, are associated with genotoxic stress. In the past few decades, a great deal of research has been done to find substances that can shield humans from DNA damage and its impact. Natural substances continue to show a beneficial impact on genome integrity. Scientists have identified and reviewed unique bioactive plant-derived compounds, such as flavonoids, phenolic compounds, and carotenoids, that can mitigate the impact of genotoxic stress; however, the genoprotective potential of alkaloids is not being reviewed so far. Herbs high in alkaloidal content have a plethora of pharmacological traits, which are utilized as drugs, and are significant to the pharmaceutical sector. This chapter summarizes the literature on the genoprotective/antigenotoxic action of alkaloids acting against endogenously and exogenously produced genetic damage. The current knowledge regarding the function of alkaloids to guard the genome can be exploited to create dietary plans and natural health products that are beneficial in the sequel of chemotherapeutic-associated toxicities.
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Trigonelline is synthesized from nicotinic acid in many plant species. This compound accumulates in seeds of leguminous plants and Coffea sp. The present article reviews the distribution of nicotinic acid conjugates and biosynthetic pathways of trigonelline, including the pyridine nucleotide cycle and de novo synthesis. The function of trigonelline in plants is also discussed.
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Fenugreek (Trigonella foenum-graecum L.), wild or cultivated, is widely distributed throughout the world and belongs to the Fabacecae family. It is an old medicinal plant and has been commonly used as a traditional food and medicine. Fenugreek is known to have hypoglycemic, and hypocholesterolaemic, effects. Recent research has identified fenugreek as a valuable medicinal plant with potential for multipurpose uses and also as a source for preparing raw materials of pharmaceutical industry, especially steroidal hormones. A significant increase in quantity and quality yields through the suitable management of cultivation, breeding and biotechnology practices could make an immediate and important contribution to farm and pharmaceutical industry income. To achieve these goals with regard to sustainable production, we reviewed a summary of biology, cultivation and biotechnology of fenugreek in this paper.
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The main objective of the presented study was the development of a simple analytical tool for exploring the influence of naturally occurring compounds on the aggregation of amyloid-β peptide (Aβ(40)) in order to find potential anti-neurodegenerative drugs. The gold discs used for surface plasmon resonance (SPR) measurements were modified with thioaliphatic acid. The surface functionalized with carboxylic groups was used for covalent attaching of Aβ(40) probe by creation of amide bonds in the presence of EDC/NHS. The modified SPR gold discs were used for exploring the Aβ(40) aggregation process in the presence of selected alkaloids: arecoline hydrobromide, pseudopelletierine hydrochloride, trigonelline hydrochloride and α-lobeline hydrochloride. The obtained results were discussed with other parameters which govern the phenomenon studied such as lipophilicity/hydrophilicy and Aβ(40)-alkaloid association constants.
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Coffee consumption is associated with a lower risk of type 2 diabetes. We tested the hypothesis that this is mediated by incretin hormones by measuring the acute effects of decaffeinated coffee and coffee components on GLP-1 and GIP concentrations. A randomized cross-over trial of the effects of 12 g decaffeinated coffee, 1 g chlorogenic acid, 500 mg trigonelline, and placebo on total and intact GLP-1 and GIP concentrations during an oral glucose tolerance test took place in fifteen overweight men. No treatment significantly affected the overall GLP-1 or GIP secretion pattern following an OGTT relative to placebo. Decaffeinated coffee slightly increased total GLP-1 concentration 30 minutes after ingestion (before the OGTT) relative to placebo (2.7 pmol/L, p = 0.03), but this change did not correspond with changes in glucose or insulin secretion. These findings do not support the hypothesis that coffee acutely improves glucose tolerance through effects on the secretion of incretin hormones. Chronic effects of coffee and its major components still need to be investigated.
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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.
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Coffee consumption has been associated with lower risk of type 2 diabetes. We evaluated the acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance. We conducted a randomized crossover trial of the effects of 12 g decaffeinated coffee, 1 g chlorogenic acid, 500 mg trigonelline, and placebo (1 g mannitol) on glucose and insulin concentrations during a 2-h oral glucose tolerance test (OGTT) in 15 overweight men. Chlorogenic acid and trigonelline ingestion significantly reduced glucose (-0.7 mmol/l, P = 0.007, and -0.5 mmol/l, P = 0.024, respectively) and insulin (-73 pmol/l, P = 0.038, and -117 pmol/l, P = 0.007) concentrations 15 min following an OGTT compared with placebo. None of the treatments affected insulin or glucose area under the curve values during the OGTT compared with placebo. Chlorogenic acid and trigonelline reduced early glucose and insulin responses during an OGTT.
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Fenugreek seeds (Trigonella foenum graecum), a commonly used condiment in Indian homes, were evaluated for hypoglycaemic property. In a metabolic study, 15 non-insulin dependent diabetic patients were given randomly, in a cross over design, diets with or without 100 g of defatted fenugreek seed powder, each for 10 days. Incorporation of fenugreek produced a significant fall in fasting blood glucose levels and an improvement in glucose tolerance test. Insulin responses were significantly reduced. There was a 64% reduction in 24 hr urinary glucose excretion with significant alterations in serum lipid profile. Serum total cholesterol, LDL and VLDL cholesterol and triglyceride levels decreased without any alteration in HDL cholesterol fraction with fenugreek diet.Incorporation of fenugreek seeds for 20 days in the diets of 5 diabetic patients resulted in similar changes of higher magnitude in all the above parameters.
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Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Trigonelline is the major component of Mirabilis jalapa L., which has been used to treat diabetes in China. The present study was designed to evaluate the beneficial effects of trigonelline against hyperglycemia, hyperlipidemia, β cell damage and antioxidant of pancreas in diabetic rats. Diabetic rats were induced by intraperitoneal injection 35 mg/kg streptozotocin and a high-carbohydrate/high-fat diet. Rats were divided into four groups: normal control, diabetic control, trigonelline-treated diabetic, and glibenclamide-treated diabetic. After 4-week treatment, blood glucose, serum insulin, total cholesterol (TC), and triglyceride (TG) levels, insulin content in pancreas, and oxidative stress parameters in pancreatic homogenate were assayed. Pancreas was examined by hematoxylin/eosin staining. Trigonelline significantly decreased blood glucose, TC, and TG levels of diabetic rats. Pancreas-to-body weight ratio, insulin level, insulin sensitivity index, insulin content in pancreas, malonaldehyde and nitric oxide contents, and superoxide dismutase, catalase, glutathione and inducible nitric oxide synthase activities were altered in diabetic rats, and were near control levels treated with trigonelline. These findings suggest that trigonelline has beneficial effect for diabetes through decreasing blood glucose and lipid levels, increasing insulin sensitivity index and insulin content, up-regulating antioxidant enzyme activity and decreasing lipid peroxidation.
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From the results of an ethnomedicinal investigation of plants from Uganda with antimalarial activity, Citropsis articulata was selected because of the antiplasmodial effect of an ethyl acetate extract of its root bark. Thus, from the cyclohexane, ethyl acetate, and methanol extracts, two new heterocyclic compounds, omubioside (1) and katimborine (2), were isolated in addition to five known coumarins (rutarin (3), seselin (4), suberosin (5), demethylsuberosin (6), and haploperoside (7)), two known alkaloids (5-hydroxynoracronycine (8) and 1,5-dihydroxy-2,3-dimethoxy-10-methyl-9-acridone (9)), trigonelline (10), and the limonoid 7α-obacunyl acetate (11). The best growth inhibitors of Plasmodium falciparum were alkaloids 8 and 9, with IC50 values of 0.9 and 3.0 μg/mL.
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Coffee shows distinct antimicrobial activity against several bacterial genera. The present study investigated molecular mechanisms and active ingredients mediating the antimicrobial effect of coffee. Depending on concentration, roasted, but not raw coffee brew inhibited the growth of Escherichia coli and Listeria innocua. Several coffee ingredients with known antibacterial properties were tested for their contribution to the observed effect. In natural concentration, caffeine, ferulic acid and a mixture of all test compounds showed very weak, but significant activity, whereas trigonelline, 5-(hydroxymethyl)furfural, chlorogenic acid, nicotinic acid, caffeic acid, and methylglyoxal were not active. Antimicrobial activity, however, was completely abolished by addition of catalase indicating that H(2)O(2) is a major antimicrobial coffee component. In accordance with this assumption, bacterial counts during 16 h of incubation were inversely related to the H(2)O(2) concentration in the incubation solution. Pure H(2)O(2) showed slightly weaker activity. The H(2)O(2) dependent antimicrobial activity of coffee could be mimicked by a reaction mixture of d-ribose and l-lysine (30 min 120 °C) indicating that H(2)O(2) is generated in the coffee brew by Maillard reaction products. Identification of H(2)O(2) as major antimicrobial coffee component is important to evaluate the application of coffee or coffee extracts as natural preservatives.
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We report the characterization of a new insulinotropic compound, 4-hydroxyisoleucine. This amino acid has been extracted and purified from fenugreek seeds, which are known in traditional medicine for their antidiabetic properties. 4-Hydroxyisoleucine increases glucose-induced insulin release, in the concentration range of 100 micromol/l to 1 mmol/l, through a direct effect on isolated islets of Langerhans from both rats and humans. The stimulating effect of 4-hydroxyisoleucine was strictly glucose dependent; indeed, ineffective at low (3 mmol/l) or basal (5 mmol/l) glucose concentrations, the amino acid potentiated the insulin secretion induced by supranormal (6.6-16.7 mmol/l) concentrations of glucose. In addition, in the isolated perfused rat pancreas, we could show 1) that the pattern of insulin secretion induced by 4-hydroxyisoleucine was biphasic, 2) that this effect occurred in the absence of any change in pancreatic alpha- and delta-cell activity, and 3) that the more glucose concentration was increased, the more insulin response was amplified. Moreover, 4-hydroxyisoleucine did not interact with other agonists of insulin secretion (leucine, arginine, tolbutamide, glyceraldehyde). Therefore, we conclude that 4-hydroxyisoleucine insulinotropic activity might, at least in part, account for fenugreek seeds' antidiabetic properties. This secretagogue may be considered as a novel drug with potential interest for the treatment of NIDDM.
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We have previously reported on study results showing that certain types of coffee have the activity to enhance fibrinolysis. This report covers the activity of 10 types of hot water extracts of coffee on human tissue-type plasminogen activator producing cells. Particularly strong activity (29-35 times the control amount) was observed for Blue Mountain, Yunnan and Kilimanjaro beans. It was found that the hot water extracts have anti-thrombin activity, and that coffee components have anti-platelet aggregation activity, although weak. It was revealed that there is no activity affecting tissue-type plasminogen activator producing cells in the coffee components chlorogenic acid, caffeine, quinic acid, trigonelline hydrochloride, 5-(hydroxymethyl)-2-furfuryl and caffeic acid. It was also revealed that there is activity in fractions with a molecular weight of 10,000 or less. This could also be inferred from the fact that oral administration of such fractions of coffee to human subjects resulted in a shortening of their plasma ELT (p<0.05).
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Some natural products consisting of the alkaloids yohimbine and vincamine (indole-type), scopolamine and atropine (tropane-type), colchicine (tropolone-type), allantoin (imidazolidine-type), trigonelline (pyridine-type) as well as octopamine, synephrine, and capsaicin (exocyclic amine-type); the flavonoid derivatives quercetin, apigenin, genistein, naringin, silymarin, and silibinin; and the phenolic acids namely gallic acid, caffeic acid, chlorogenic acid, and quinic acid, were tested for their in vitro antiviral, antibacterial, and antifungal activities and cytotoxicity. Antiviral activity of the compounds was tested against DNA virus herpes simplex type 1 and RNA virus parainfluenza (type-3). Cytotoxicity of the compounds was determined using Madin-Darby bovine kidney and Vero cell lines, and their cytopathogenic effects were expressed as maximum non-toxic concentration. Antibacterial activity was assayed against following bacteria and their isolated strains: Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, and Bacillus subtilis, although they were screened by microdilution method against two fungi: Candida albicans and Candida parapsilosis. Atropine and gallic acid showed potent antiviral effect at the therapeutic range of 0.8-0.05 µg ml(-1), whilst all of the compounds exerted robust antibacterial effect. Antiviral and antimicrobial effects of the compounds tested herein may constitute a preliminary step for further relevant studies to identify the mechanism of action.
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Oxidative cellular stress initiates Nrf2 translocation into the nucleus, thus inducing antioxidant response element (ARE)-mediated expression of Phase II enzymes involved in detoxification and antioxidant defence. We investigated whether coffee extracts (CEs) of different proveniences and selected constituents have an impact on the Nrf2/ARE pathway in human colon carcinoma cells (HT29). Assessed as increased nuclear Nrf2 protein, Nrf2 nuclear translocation was modulated by different CEs as observed by Western blot analysis. In addition to the known Nrf2 activator 5-O-caffeoylquinic acid (CGA), pyridinium derivatives like the N-methylpyridinium ion (NMP) were identified as potent activators of Nrf2 nuclear translocation and ARE-dependent gene expression of selected antioxidative Phase II enzymes in HT29. Thereby, the substitution pattern at the pyridinium core structure determined the impact on Nrf2-signalling. In contrast, trigonelline was found to interfere with Nrf2 activation, effectively suppressing the NMP-mediated induction of Nrf2/ARE-dependent gene expression. In conclusion, several coffee constituents, partly already present in the raw material as well as those generated during the roasting process, contribute to the Nrf2-translocating properties of consumer-relevant coffee. A fine tuning in the degradation/formation of activating and deactivating constituents of the Nrf2/ARE pathway during the roasting process appears to be critical for the chemopreventive properties of the final coffee product.
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Epidemiological studies suggest that coffee can reduce the risk of degenerative diseases such as diabetes type 2, cardiovascular disease and cancer. These beneficial effects have partly been attributed to the antioxidant activity of coffee. We determined composition and antioxidant potential of differentially roasted coffee extracts and investigated the impact of selected original constituents and roast products. Parameters studied were direct antioxidant activity (trolox equivalent antioxidant capacity/oxygen radical absorbing capacity), cellular reactive oxygen species (ROS) level, DNA damage and protein expression of NAD(P)H: quinone oxidoreductase, γ-glutamylcysteine ligase and glutathione reductase in HT-29/Caco-2 cells at 24-h incubation. All extracts showed distinct direct antioxidant activity: medium roasts>light roast AB1 (caffeoylquinic acid (CQA)-rich Arabica Brazil extract); dark roast AB2 (N-methylpyridinium (NMP)-rich Arabica Brazil extract), and diminished t-butylhydroperoxide-induced ROS level in HT-29 cells (AB2>medium roasts>AB1). NAD(P)H:quinone oxidoreductase 1 expression and γ-glutamylcysteine ligase expression were distinctly induced by AB1 and 5-CQA, but not by AB2 and NMP. 5-CQA and caffeic acid exhibited highest trolox equivalent antioxidant capacity/oxygen radical absorbing capacity values (5-CQA: 1.3/3.5 mM and caffeic acid: 1.3/3.9 mM trolox); ROS level was distinctly diminished by 5-CQA (≥3 μM), catechol (30 μM) and trigonelline (≥30 μM), whereas menadione-induced DNA damage in Caco-2 cells was reduced by NMP compounds (1-30 μM). The results emphasize that both original constituents and roast products contribute to the cellular antioxidant effectiveness of coffee.
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Trigonelline (TRG) and nicotinic acid (NA), in which the former but not the latter improved the blood glucose level in the oral glucose tolerance test (OGTT) in Goto-Kakizaki (GK) rats were tested for anti-diabetic effects in mellitus models of KK-A(y) obese mice that had type 2 diabetes. Blood glucose level in OGTT carried out on day 22-23 was lowered after feeding in mice fed TRG and NA than that of the control mice not fed these compounds, indicating that both TRG and NA have sufficient activity to improve glucose tolerance in diabetes with obesity. The serum insulin levels at fasting showed significantly lower levels in mice fed TRG, and a lower tendency in mice fed NA, compared with the control mice. The triglyceride (TG) levels in the liver and adipose tissue in mice fed TRG and NA showed lower values or a lower tendency than those of the control mice, indicating that TRG and NA were also effective to improve the changes in lipid levels accompanied with diabetes. Higher values or a higher tendency of the glucokinase (GLK)/glucose-6-phosphatase (G6Pase) ratio in the liver and lower levels of the serum tumor necrosis factor (TNF)-alpha in the TRG- and NA-fed mice, compared to the control mice, suggested that the regulation of GLK and G6Pase, and TNF-alpha production by TRG and NA are closely related in suppressing the progression of diabetes in the KK-A(y) mice.
Article
Ethno pharmacological approach has provided several leads to identify potential new drugs from plant sources, including those for memory disorders. Acetylcholinesterase inhibitors (AChEI) give a symptomatic relief to some of the clinical manifestations of the disease. The main objective of this study is to standardize the extract of Trigonella foenum graecum L with trigonelline by HPTLC method and determine the in vitro AChE inhibitory activity of Trigonella foenum graecum L and its constituents using galanthamine as a reference. Different concentrations of hydro alcoholic extract of Trigonella foenum graecum and trigonelline were subjected to HPTLC analysis using the mobile phase n propanol, methanol and water (4:1:2, v/v). The R(f) of trigonelline was found to be 0.43, and the correlation coefficient of 0.99 was indicative of good linear dependence of peak area on concentration. The concentration of trigonelline was found to be 13mgg(-1)w/w in the hydro alcoholic extract of Trigonella foenum graecum. The AChE inhibitory activity of crude fenugreek seed extracts, fractions and trigonelline was evaluated using Ellman's method in 96-well micro plate's assay and TLC bioassay detection. The ethyl acetate fraction of the alcohol extract (IC50 53.00 +/- 17.33microg/ml), and total alkaloid fraction (IC50 9.23+/-6.08microg/ml) showed potential AChE inhibition. Trigonelline showed IC50 233+/-0.12microM. Galanthamine was used as standard and it showed inhibition of acetyl cholinesterase with an IC50 value of 1.27+/-0.21microM.
Article
Auditory neuropathy (AN) is a hearing disorder characterized by an abnormal auditory brainstem response (ABR). This study examined experimental AN model induced in mice following increased dosages of pyridoxine. Induced AN was examined for < or =10 weeks following the last pyridoxine treatment. To assess AN, we evaluated the ABR, auditory middle latency response (AMLR), otoacoustic emission (OAE), and histochemical morphology of the auditory nerve. Pyridoxine-treated mice exhibited an increase in the hearing threshold shift and delayed latency of both ABR and AMLR in proportion to pyridoxine dosage. Additionally, the extent of auditory nerve fiber loss increased in a dose-dependent manner following pyridoxine intoxication. Coffee or trigonelline treatment ameliorated the hearing threshold shift, delayed latency of the auditory evoked potential, and improved sensory fiber loss induced by pyridoxine intoxication. The present findings demonstrate that high-dose pyridoxine administration can be used to produce a new mouse model for AN, and coffee or trigonelline as a main active compound of coffee extract can potentially facilitate recovery from pyridoxine-induced auditory neuropathy.
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An extract with cholinergic activities was isolated from instant regular and decaffeinated coffees and purified. Intravenous injection of this cholinomimetic extract of coffee produced an abrupt depression in blood pressure and heart rate, changes that were distinct from those of known components of coffee, including caffeine, trigonelline, catechin, and chlorogenic acid. Pretreatment of the animals with naloxone, propranolol, isobutylmethylxanthine, hexamethonium bromide, and hemicholinium-3 chloride or bilateral vagotomy did not affect the cardiodepressive effects of the extract, whereas atropine completely abolished them. Direct injection of the cholinomimetic extract of coffee (20-100 micrograms) into the periaqueductal gray area of the midbrain did not produce any cardiovascular effect. However, the extract of coffee did cause relaxation of isolated rat and rabbit aortic ring preparations that were contracted under norepinephrine. The cholinomimetic extract did not inhibit purified acetylcholinesterase. This pharmacologic profile indicates that the cholinomimetic extract of coffee acts as a direct muscarinic agonist.
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During the development of a procedure for the determination of trigonel-line (Tg) in human urine (Yuyama and Suzuki, 1987), an organic acid with a similar ultra-violet spectrum was isolated. The compound was found to be N1-methyl-2-pyridone-5-carboxylic acid (Tg-2Py) (Lindenblad et al., 1956), which Holman et al. (1950) were unable to detect in normal human urine. In the present study, Tg-2Py was determined by HPTLC. The urinary excretion of Tg-2Py, Tg and N1-methylnicotinamide (MNA) were determined before and after the oral administration of nicotinic acid (NiA), Tg and Tg-2Py.
Article
Trigonelline, i.e., N-methylnicotinate, which has a zwitterionic structure similar to a substrate D-amino acid, is a useful active site probe for D-amino acid oxidase (DAO). The affinity of trigonelline for DAO in the deprotonated state at the enzyme bound FAD 3-imino group is higher than in the neutral state, contrary to in the case of benzoate, which is a competitive inhibitor and is in a monoanionic form. The time course of the absorbance change was monitored for the binding of DAO with trigonelline by means of a stopped-flow technique. The reaction, on monitoring at 507 nm, was found to be biphasic at pH 8.3, with fast and slow phases. The dissociation of the 3-imino proton of the enzyme bound FAD was observed in the same time course as the slow phase. These results suggest that the positive charge of trigonelline exists near the 3-imino group of the enzyme bound FAD and interacts repulsively with the proton of the 3-imino group. The absorption spectra of the DAO-trigonelline complex at various pHs also support this hypothesis. In the catalysis of DAO, a similar mechanism may be involved, that is, the positive charge of a D-amino acid may interact repulsively with the 3-imino proton of the enzyme bound FAD, and this interaction may be important for the catalysis.
Article
The effect of fenugreek (Trigonella foenumgraecum L.) and lupine (Lupinus termis Forssk.) seeds on the development of experimental diabetes in rats was investigated. Blood glucose and lipid levels of normal and streptozotocin diabetic rats were determined after treatment with supplemented diets containing either 20% fenugreek or lupine seeds. Animals were placed on the above diets for a period of ten weeks after diabetes induction or five weeks prior to streptozotocin injection, followed by six weeks of feeding with the same diets. In the first category of experiments, where a pretreatment period was not used, both supplemented diets did not improve the diabetic state, as judged by body weight loss, and blood glucose and lipid levels. On the other hand, diabetic animals pretreated with fenugreek diet showed a general improvement in their clinical status, as reflected by blood parameters and body weight gain: hyperglycemia was significantly reduced, free fatty acids, cholesterol and triglycerides were significantly reduced and returned to normal levels. It is therefore concluded that the antidiabetic effect of fenugreek is apparent after a pretreatment period with the supplemented diet. On the other hand, lupine diet did not improve the hyperglycemia nor the above-mentioned blood parameters, except for triglyceride levels which were reduced in both diabetic and control animals.
Article
The mutagenicity of 4 coffee flavor ingredients (chlorogenic acid, caffeic acid, pyrazine, and trigonelline) was evaluated in the Salmonella plate incorporation assay and mouse lymphoma L5178Y TK +/- assay. Two of the compounds, pyrazine and trigonelline, were negative in both assays. The other two compounds, caffeic acid and chlorogenic acid, were positive in the mouse lymphoma assay but negative in the Salmonella assay.
Article
The major alkaloids of T foenum graecum and Lupinus termis seeds were tested for hypoglycemic activity in normal and alloxan diabetic rats. This study was stimulated by popular folk belief referring to these seeds as 'antidiabetic' and by the fact that Yemenites and Bedouins add the seeds to their diabetic diet. Extracts from Trigonella seeds exert a mild hypoglycaemic effect, and so does their major alkaloid component, trigonelline. Another Trigonella component, nicotinic acid, displayed, like nicotinamide, a much more profound hypoglycaemic activity than did trigonelline, but their effect persisted for a short period only. Coumarin, another Trigonella component, caused the most severe degree of hypoglycemia, lasting for 24 hr in alloxan diabetic rats. The only alkaloids active in non diabetic rats were nicotinic acid as a short acting drug, and coumarin, exerting a prolonged effect. Some borderline hypoglycemic activity was noticed in normal rats with high doses of scopoletine. Lupinus seed extract produced a mild and transient hypoglycemia in diabetic rats, most probably due to 2 of its major alkaloids, sparteine and lupanine. No hypoglycaemic effect was noticed in non diabetic rats. Coumarin and sparteine were the only 2 major components of both types of seeds to exert anti diuretic activity. Labelled nicotinic acid injected I.V. into non diabetic rats was concentrated mainly in the kidney and liver, and to a lower extent in the pancreas, thus permitting the conclusion that nicotinic acid and coumarin, but not trigonelline, are the major hypoglycemic components of trigonella seeds. The acute and sub chronic toxicity of the major alkaloids of the 2 seeds were determined in rats.