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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... The antioxidant effects of coffee come from caffeine, cafestol, trigonelline, chlorogenic acid (CGA), melanoidins, quinine, and other phenols such as hydroxycinnamic acid [193,61]. Roasting the coffee seeds partially degrades trigonelline to nicotinic acid and pyridines, which also have antioxidant effects [64]. ...
... Trigonelline is a naturally occurring pyridine alkaloid that is a major constituent of the herb Mirabilis jalapa L. and is also isolated from coffee beans and fenugreek. The compound has antidiabetic and neuroprotective effects in addition to its antiinflammatory, antioxidant, and anti-aging effects [64,196]. It exerts hypoglycemic, hypolipidemic and antioxidant effects, inhibits intestinal glucose uptake, increases glucose tolerance and insulin resistance, and stimulates β-cell regeneration [64]. ...
... The compound has antidiabetic and neuroprotective effects in addition to its antiinflammatory, antioxidant, and anti-aging effects [64,196]. It exerts hypoglycemic, hypolipidemic and antioxidant effects, inhibits intestinal glucose uptake, increases glucose tolerance and insulin resistance, and stimulates β-cell regeneration [64]. In human mesangial cells exposed to high glucose, trigonelline reduces cell injury by regulating the Wnt/β-catenin signaling pathway [62], given that this pathway is involved in diabetic neuropathy [65]. ...
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Healthy diet is vital to cellular health. The human body succumbs to numerous diseases which afflict severe economic and psychological burdens on the patient and family. Oxidative stress is a possible crucial regulator of various pathologies, including type 2 diabetes and neurodegenerative diseases. It generates reactive oxygen species (ROS) that trigger the dysregulation of essential cellular functions, ultimately affecting cellular health and homeostasis. However, lower levels of ROS can be advantageous and are implicated in a variety of signaling pathways. Due to this dichotomy, the terms oxidative “eustress,” which refers to a good oxidative event, and “distress,” which can be hazardous, have developed. ROS affects multiple signaling pathways, leading to compromised insulin secretion, insulin resistance, and β-cell dysfunction in diabetes. ROS is also associated with increased mitochondrial dysfunction and neuroinflammation, aggravating neurodegenerative conditions in the body, particularly with age. Treatment includes drugs/therapies often associated with dependence, side effects including non-selectivity, and possible toxicity, particularly in the long run. It is imperative to explore alternative medicines as an adjunct therapy, utilizing natural remedies/resources to avoid all the possible harms. Antioxidants are vital components of our body that fight disease by reducing oxidative stress or nullifying the excess toxic free radicals produced under various pathological conditions. In this review, we focus on the antioxidant effects of components of dietary foods such as tea, coffee, wine, oils, and honey and the role and mechanism of action of these antioxidants in alleviating type 2 diabetes and neurodegenerative disorders. We aim to provide information about possible alternatives to drug treatments used alone or combined to reduce drug intake and encourage the consumption of natural ingredients at doses adequate to promote health and combat pathologies while reducing unwanted risks and side effects.
... Among the above, compounds numbered 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 are previously documented for antimicrobial properties (Holloway, 1982;Janiak and Milewski, 2001;Kannabiran, 2016;Nagata et al., 2006;Okoro et al., 2019;Sharifi-Rad et al., 2020;Torres et al., 2021;Turcios and Papenbrock, 2019;Zhou et al., 2012). Compounds 11, 12, and 13 are reported for antioxidant activities (Huang et al., 2017;Strong, 1996;Zeb, 2021), while compounds 5 and 10 are both antimicrobial and antioxidant (Nagata et al., 2006;Sharifi-Rad et al., 2020). ...
... Among the above, compounds numbered 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 are previously documented for antimicrobial properties (Holloway, 1982;Janiak and Milewski, 2001;Kannabiran, 2016;Nagata et al., 2006;Okoro et al., 2019;Sharifi-Rad et al., 2020;Torres et al., 2021;Turcios and Papenbrock, 2019;Zhou et al., 2012). Compounds 11, 12, and 13 are reported for antioxidant activities (Huang et al., 2017;Strong, 1996;Zeb, 2021), while compounds 5 and 10 are both antimicrobial and antioxidant (Nagata et al., 2006;Sharifi-Rad et al., 2020). Certain compounds numbered 14, 15, 16, 19, and 21 are related to antiinflammatory and anticancer activities (Abubakar et al., 2018;Cronstein, 1994;Prasher and Sharma, 2021;Tedesco and Haragsim, 2012;Ting et al., 2019). ...
... Certain compounds numbered 14, 15, 16, 19, and 21 are related to antiinflammatory and anticancer activities (Abubakar et al., 2018;Cronstein, 1994;Prasher and Sharma, 2021;Tedesco and Haragsim, 2012;Ting et al., 2019). Compounds with multiple pharmacological activities include 8-hydroxyquinoline (1) (Torres et al., 2021), trigonelline (2) (Zhou et al., 2012), and psoralidin (5) (Sharifi-Rad et al., 2020). Apart from the above, Compound 3-(3, 4, 5-trimethoxyphenyl) propanoic acid (17) is antileishmanial (Ferreira et al., 2010), while artemisinin (18) produced from this endophytic fungi is a sesquiterpene lactone consist of peroxide bridge responsible for their antimalarial properties (Klayman, 1985). ...
... Diosgenin, a steroidal saponin, is an important starting material for the preparation of several steroidal drugs in the pharmaceutical industry and has shown high potential in the treatment of various types of disorders such as cancer, hypercholesterolemia, inflammation, and several types of infections 10 . The pharmacological activities of trigonelline, an alkaloid, include hypoglycaemic, hypolipidemic, neuroprotective, antimigraine, sedative, memory-improving, antibacterial, antiviral, and anti-tumour activities 11 . 4-hydroxyisoleucine (4-HIL), a modified amino acid is another bioactive compound abundant in fenugreek seeds. ...
... involved in synthesis of secondary metabolites belonging to alkaloids, saponins, volatiles and flavonoids, present in T. foenum-graecum were identified using strategy adapted from Joshi et al. 38 . The pathway information and related functional annotation was extracted from multiple sources such as PlantCyc MetaCyc, KEGG and literature 11,30,[39][40][41][42] . The pathway images were adapted from PlantCyc or literature. ...
... While identifying candidate genes involved in biosynthesis of secondary metabolites, it is vital to select appropriate start points for the rigorous sequence search and subsequent validation. We rely on multiple sources such as PlantCyc, MetaCyc, KEGG pathway and metabolites cited in literature 11,[39][40][41][42] to create such a knowledge base of start points. It further helps in identification of FIRs which resolves selection of true candidate genes along with the co-clustering of proteins from fenugreek transcripts with the selected start points. ...
Article
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Fenugreek (Trigonella foenum-graecum L.) is a self-pollinated leguminous crop belonging to the Fabaceae family. It is a multipurpose crop used as herb, spice, vegetable and forage. It is a traditional medicinal plant in India attributed with several nutritional and medicinal properties including antidiabetic and anticancer. We have performed a combined transcriptome assembly from RNA sequencing data derived from leaf, stem and root tissues. Around 209,831 transcripts were deciphered from the assembly of 92% completeness and an N50 of 1382 bases. Whilst secondary metabolites of medicinal value, such as trigonelline, diosgenin, 4-hydroxyisoleucine and quercetin, are distributed in several tissues, we report transcripts that bear sequence signatures of enzymes involved in the biosynthesis of such metabolites and are highly expressed in leaves, stem and roots. One of the antidiabetic alkaloid, trigonelline and its biosynthesising enzyme, is highly abundant in leaves. These findings are of value to nutritional and the pharmaceutical industry.
... Trigonella foenum-graecum [61] 2.3. Phenolic Acids ...
... Phenolic acids are described as phenolic compounds having one carboxylic acid group, and they are one of the main classes of plant phenolic compounds. Unlike flavonoids, free phenolic acids, such as benzoic, phenylacetic and cinnamic acids, have good Trigonella foenum-graecum [61] Antibiotics 2022, 11, 469 6 of 24 ...
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Despite culturing the fastest-growing animal in animal husbandry, fish farmers are often adversely economically affected by pathogenic disease outbreaks across the world. Although there are available solutions such as the application of antibiotics to mitigate this phenomenon, the excessive and injudicious use of antibiotics has brought with it major concerns to the community at large, mainly due to the rapid development of resistant bacteria. At present, the use of natural compounds such as phytocompounds that can be an alternative to antibiotics is being explored to address the issue of antimicrobial resistance (AMR). These phytocompounds are bioactive agents that can be found in many species of plants and hold much potential. In this review, we will discuss phytocompounds extracted from plants that have been evidenced to contain antimicrobial, antifungal, antiviral and antiparasitic activities. Further, it has also been found that compounds such as terpenes, phenolics, saponins and alkaloids can be beneficial to the aquaculture industry when applied. This review will focus mainly on compounds that have been identified between 2000 and 2021. It is hoped this review will shed light on promising phytocompounds that can potentially and effectively mitigate AMR.
... Feniletilamin memiliki mekanisme kerja dan efek fisiologis yang mirip dengan tiramin, tetapi efeknya jauh lebih rendah (Silalahi, 1994), sedangkan trigonellin merupakan hormon tumbuhan (Tramontano, 1986) yang diklaim memiliki efek hipoglikemik, hipolipidemik, neuroprotektif, antimigrain dan antitumor (Zhou, 2012). ...
... Literature studies report that trigonelline can be used as an antidiabetic, antibacterial, antiviral, sedative, anti-migraine, and antitumour agent [88,89]. ...
Article
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The medicinal potential of hop (Humulus lupulus L.) is widely cited in ancient literature and is also allowed in several official pharmacopoeias for the treatment of a variety of ailments, mainly related to anxiety states. This is due to the plethora of phytoconstituents (e.g., bitter acids, polyphenols, prenyl flavonoids) present in the female inflorescences, commonly known as cones or strobili, endowed with anti-inflammatory, antioxidant, antimicrobial, and phytoestrogen activities. Hop has recently attracted the interest of the scientific community due to the presence of xanthohumol, whose strong anti-cancer activity against various types of cancer cells has been well documented, and for the presence of 8-prenyl naringenin, the most potent known phytoestrogen. Studies in the literature have also shown that hop compounds can hinder numerous signalling pathways, including ERK1/2 phosphorylation, regulation of AP-1 activity, PI3K-Akt, and nuclear factor NF-κB, which are the main targets of the antiproliferative action of bitter acids and prenylflavonoids. In light of these considerations, the aim of this review was to provide an up-to-date overview of the main biologically active compounds found in hops, as well as their in vitro and in vivo applications for human health and disease prevention. To this end, a quantitative literature analysis approach was used, using VOSviewer software to extract and process Scopus bibliometric data. In addition, data on the pharmacokinetics of bioactive hop compounds and clinical studies in the literature were analysed. To make the information more complete, studies on the beneficial properties of the other two species belonging to the genus Humulus, H. japonicus and H. yunnanensis, were also reviewed for the first time.
... Trigonelline is a pyridine alkaloid ( Figure 10). It differs from nicotinic acid, better known as vitamin B3, only by an additional methyl group at the nitrogen atom [46]. It is soluble in water [47], implying that it is also detectable in beverages made from coffee cherries. ...
Article
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Coffee bean harvesting incurs various by-products known for their long traditional use. However, they often still end up being a waste instead of being used to their full potential. On the European market, coffee cherry (cascara) products are not yet common, and a novel food approval for beverages made from coffee cherry pulp was issued only recently. In this article, exposure and risk assessment of various products such as juice, jam, jelly, puree, and flour made from coffee cherry pulp and husk are reviewed. Since caffeine in particular, as a bioactive ingredient, is considered a limiting factor, safe intake will be derived for different age groups, showing that even adolescents could consume limited quantities without adverse health effects. Moreover, the composition can be influenced by harvesting methods and processing steps. Most interestingly, dried and powdered coffee cherry can substitute the flour in bakery products by up to 15% without losing baking properties and sensory qualities. In particular, this use as a partial flour substitute is a possible approach to counteract rising grain prices, transport costs, and disrupted supply chains, which are caused by the Russia–Ukraine war and changing climatic conditions. Thus, the supply of affordable staple foods could be partially ensured for the inhabitants of countries that depend on imported wheat and cultivate coffee locally by harvesting both beans and by-products.
... At the end of experiments, Trigonelline (C 7 H 8 NO 2 ), which is a quaternary ammonium alkaloid was isolated (Al-Khateeb 2019; Yuyama and Suzuki 1985). Trigonelline is endowed with anti-cancer, antiseptic, anti-chlolesteromic and antiglycaemic properties (Abe and Kaneda, 1975;Al-Khateeb;Anthoni et al., 1991;Beckstrom and Duke 1997;Helal et al., 2013;Mathur and Kamal, 2012;Shani et al., 1974;Sheikhlar, 2013;Subramanian and Prasath, 2014;Yoshinari et al., 2009;Zhou et al., 2012; White1983). ...
Experiment Findings
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The genus Diospyros belonging to the family Ebenaceae is compound of plants wherein one finds natural products of great pharmacological interest. Plants from this genus grow in geographical areas with tropical or moderately warm climate such as the region of Katanga in the Democratic Republic of Congo (DRC). These are commonly used for therapeutic purposes in by traditional healers in Africa, Asia and South America. This research was interested in natural products from the plant species Diospyros mweroensis and succeeded isolating from the stem bark's extracts a quaternary ammonium alkaloid (Trigonelline) endowed with anti-cancer, antiseptic, anti-chlolesteromic and anti-glycaemic properties. The experiments included solvent extraction, isolation of natural products using column chromatography, purification by the high-performance liquid chromatography (HPLC) on reverse phase silica (RP-C18) and spectroscopic analyses (NMR-1H, UV-visible and MS). These enabled identifying Trigonelline-C 7 H 8 NO 2 among the isolated natural products.
... Trigonelline is a metabolite that contributes to the stabilization of glucose and lipid levels in the blood, besides having neuroprotective and antibacterial effects. 19 Malic acid is among the most important organic acids in wine production and plays a major role in providing microbial stability and in malolactic fermentation, a process that reduces the acidity of grapes; moreover, it gives an ...
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Under healthy physiological conditions, living organisms possess a variety of antioxidant mechanisms to scavenge overproduced reactive oxygen species (ROS). However, under pathological circumstances, endogenous antioxidant systems may not be adequate to eliminate the excessive amount of oxidants, and thus, a continuous exogenous antioxidant income is required. In this regard, sumac (Rhus coriaria) extract is a good candidate for therapeutic applications, because of its high content of antioxidant polyphenolic compounds. In this work, sumac extract-loaded nanosheets (sumac-nanosheet) have been exploited for loading and controlled release of sumac extract, envisioning topical drug delivery applications. Sumac extract has been obtained through the solvent extraction method, and polymeric nanosheets have been thereafter prepared through the spin coating-assisted layer-by-layer deposition of polycapro-lactone (PCL), sumac extract, and poly(D,L-lactic acid) (PDLLA). The collected data show a rich content of the sumac extract in terms of polyphenolic compounds, as well as its strong antioxidant properties. Moreover, for the first time in the literature, we demonstrated the possibility of efficiently loading such extract in polymeric nanosheets and the suitability of this nanoplatform as a reactive oxygen species scavenger in human dermal fibroblasts treated with a pro-oxidant insult.
... 39 The antidiabetic mechanisms of trigonelline have been summarized as improving β cell regeneration and insulin secretion as well as regulating key enzymes related to reactive oxygen species and glucose metabolism. 40 In this study, both types of anthocyanins (particularly, L-NAAB, H-NAAB, and H-AAPP) significantly increased trigonelline levels at week 4, which is suggestive of the protection activity of these anthocyanin extracts in diabetes by modulating key enzymes related to energy metabolism. 41 The concentrations of urinary hippurate, dimethylamine, and trimethylamine are associated with the activities and composition of microbes in the gut, 42 and changes in these metabolites indicate altered gut microbiota. ...
Article
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The effect of nonacylated and acylated anthocyanins on urinary metabolites in diabetic rats was investigated. Nonacylated anthocyanins extract from bilberries (NAAB) or acylated anthocyanins extract from purple potatoes (AAPP) was given to Zucker diabetic fatty (ZDF) rats for 8 weeks at daily doses of 25 and 50 mg/kg body weight. 1H NMR metabolomics was applied to study alterations in urinary metabolites from three time points (weeks 1, 4, and 8). Both types of anthocyanins modulated the metabolites associated with the tricarboxylic acid cycle, gut microbiota metabolism, and renal function at weeks 1 and 4, such as 2-oxoglutarate, fumarate, alanine, trigonelline, and hippurate. In addition, only a high dose of AAPP decreased monosaccharides, formate, lactate, and glucose levels at week 4, suggesting improvement in energy production in mitochondria, glucose homeostasis, and oxidative stress. This study suggested different impacts of AAPP and NAAB on the metabolic profile of urine in diabetes.
... Animal experimentation was done as reported previously [14,15,19] ...
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Background DNA is the main target for UV-B-irradiation-induced skin photodamage and accounts for 90 % of all the non-melanoma skin cancers. Purpose In this study, we explored the mechanistic basis of photoprotective effect of Trigonelline, a naturally occurring alkaloid from the Trigonella foenum-graecum, against UV-B-induced oxidative DNA Damage Response using Primary Human Dermal Fibroblasts (HDFs) and BALB/C mice as models of skin photodamage. Methods Primary HDFs were subjected to UV-B exposure (10 mJ/cm²) with or without TG for 24 h. Effect of UV-B exposure and TG treatment was evaluated by analyzing the cell survival, cellular morphology, oxidative stress & DNA damage response markers by performing biochemical studies, florescent microscopy & protein expression studies. In in-vivo study, TG pre-treated BALB/c mice were -irradiated with 180 mJ/cm² of UV-B dose thrice a week on alternative days for four months, followed by topical application of different concentrations of TG. The photodamage caused by UV-B exposure and its ameleoriation by topical treatment of TG was studied by physical and morphological appearance and analyzing the oxidative stress & DNA damage response markers from skin. Results We found that TG significantly alleviates UV-B–induced cell death effects in HDFs. TG protects HDF cells and BALB/c mice from UV-B-induced DNA damage by regulating the expression profile of key protein markers of DNA damage which include P53, ATM, ATR, ϒH2AX, Chk1 and Chk2. We found that TG offers geno-protection to UV-B–irradiated HDFs by alleviating CPD induction, reducing the number of TUNEL positive cells and by decreasing the expression levels of DNA damage marker protein ϒH2AX in immunocytochemistry. Further, we found that TG prevents the UVB induced oxidative stress by activating the PI3K-AKT-Nrf2 signalling pathway. On employing PI3K inhibitor, LY294002, we found the expression of ϒH2AX and p-P53 is significantly increased compared to UV-B treated only, indicating that TG mediates the geno-protection against UV-B irradiation via PI3K-AKT-Nrf2 signalling pathway. Conclusion Current study presents for the first time the photo-protective role of TG against UV-B–induced oxidative DNA damage and provides its mechanistic insights also and provide strong evidence for TG to be carried forward as a potential remedial and cosmeceutical agent against UV-B–induced skin photodamage disorders.
... Conversely, high levels of caffeoylquinic acids, feruloylquinic acids and their oxidation products are associated with poor cup quality and off-flavor (Farah, 2012;Farah et al., 2006) and caffeine is associated with bitterness and astringency of the brew (Sualeh et al., 2020). Some of the biochemicals that contribute to flavor, e.g., chlorogenic acids (CGAs) and trigonelline, also have useful bioactive properties, such as antioxidant, α-glucosidase inhibitory and antimicrobial activities (Bhattacherjee et al., 2014;Bhattacherjee and Datta, 2015;Zhou et al., 2012), whereas other biochemicals, e.g., caffeine and diterpenes, may have harmful effects by affecting endothelial function and raising a fraction of blood lipids, respectively (Godos et al., 2014). On the other hand, consumption of caffeine could reduce the risk of Parkinson's disease development (Higdon and Frei, 2006). ...
Article
Hitherto, studies on shade and postharvest processing (PHP) effects on coffee quality across elevation ranges (ER) are limited. The effects of shade, PHP and their interaction on quality and caffeine, sucrose and chlorogenic acids (CGAs) contents of arabica coffee beans in lowland and midland were evaluated. The results showed that physical, total preliminary and total specialty qualities were higher for beans grown in midland than those grown in lowland, but CGAs (57.5 g kg⁻¹ dw) were higher for beans grown in lowland. Dry-processed midland coffee had higher physical and total preliminary qualities with lower 3,5diCQA (6.9 g kg⁻¹ dw) and FQA (4.4 g kg⁻¹ dw) than wet-processed lowland and midland coffees. Conversely, wet-processed lowland coffee had lower physical and total preliminary qualities with higher 3,5diCQA (8.7 g kg⁻¹ dw) and FQA (4.7 g kg⁻¹ dw) than dry-processed lowland and midland coffees. Coffee beans grown with shade in lowland had lower acidity than those grown without shade in lowland and midland. But, coffee beans grown without shade in lowland had lower caffeine (13.8 kg⁻¹ dw) than those grown with shade in lowland and midland. Physical and total preliminary qualities were negatively correlated with caffeine, 4-CQA, 3,5diCQA, FQA and total CGAs. This study is the first to show the relationship between ER and PHP in coffee quality and biochemical composition of green arabica coffee beans.
... High levels of caffeoylquinic acids, feruloylquinic acids and their oxidation products are, however, associated with poor cup quality and off-flavor (Farah, 2012;Farah et al., 2006) and caffeine is associated with bitterness and astringency of the brew (Sualeh et al., 2020). Some of the biochemicals that contribute to flavor, e.g., chlorogenic acids and trigonelline, have also useful bioactive properties, such as antioxidant, α-glucosidase inhibitory and antimicrobial activities (Bhattacherjee and Datta, 2015;Bhattacherjee et al., 2014;Zhou et al., 2012), whereas others, e.g., caffeine and diterpenes, may produce harmful effects by affecting endothelial function and raising a fraction of blood lipids, respectively (Godos et al., 2014). Consumptions of caffeine, on the other hand, could reduce a risk of Parkinson's disease development (Higdon and Frei, 2006) and rise energy availability, alertness and concentration, and learning capacity (Farah, 2012;Jiang et al., 2014). ...
Article
Coffee quality and biochemical composition are believed to vary with geographical origin. Seed weight, quality attributes, and contents of caffeine, sucrose and chlorogenic acids of green arabica coffee beans from five coffee regions (eastern or Harar, southern, southwestern, western and northwestern regions of Ethiopia) and 24 coffee localities across the five coffee regions were evaluated. Coffee samples varied with their growing region and locality in these bean features. Coffee samples from Harar and southern regions had much higher bean physical quality (BPQ), acidity and total preliminary quality (TPQ) than those from southwestern region, but lower caffeine content than those from the remaining regions. Samples from Harar had also higher 100 seed weight, and sucrose and total chlorogenic acids (TCGAs) contents than those of the other regions. Lem-Kaffa coffee from southwestern region had much lower BPQ, TPQ and TCGAs than most of the other locality coffees and significantly differed from any of the studied locality coffees in its 100 bean weight, quality and biochemical composition. This study generally highlights the variation of Ethiopian coffee with growing region and locality, and the presence of similarity between some locality coffees across the coffee regions in their bean weight, quality and biochemical composition.
... Toxicological studies showed that the lethal dose (LD 50 ) of trigonelline in rats was around 5000 mg/kg after oral and subcutaneous administration [77]. In mice, trigonelline was fed 50 mg/kg daily for 21 days, and there was no change in the weight of the liver, kidney, thymus, thyroid, or adrenal gland [82]. Furthermore, trigonelline has good absorption and bioavailability. ...
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Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and its prevalence is still growing rapidly. However, the efficient therapies for this kidney disease are still limited. The pathogenesis of DKD involves glucotoxicity, lipotoxicity, inflammation, oxidative stress, and renal fibrosis. Glucotoxicity and lipotoxicity can cause oxidative stress, which can lead to inflammation and aggravate renal fibrosis. In this review, we have focused on in vitro and in vivo experiments to investigate the mechanistic pathways by which natural compounds exert their effects against the progression of DKD. The accumulated and collected data revealed that some natural compounds could regulate inflammation, oxidative stress, renal fibrosis, and activate autophagy, thereby protecting the kidney. The main pathways targeted by these reviewed compounds include the Nrf2 signaling pathway, NF-κB signaling pathway, TGF-β signaling pathway, NLRP3 inflammasome, autophagy, glycolipid metabolism and ER stress. This review presented an updated overview of the potential benefits of these natural compounds for the prevention and treatment of DKD progression, aimed to provide new potential therapeutic lead compounds and references for the innovative drug development and clinical treatment of DKD.
... Eight healthy mice were given a mixture of distilled water/DMSO (2:1) by oral gavage as a vehicle daily for ten days and considered the normal control group. The remaining mice were divided into six groups (each = 8) as follows: MTX group: mice were injected i.p. with a single dose of 20 mg/kg MTX at the fifth day [91]. Methanolic extract + MTX group: mice received 100 mg/kg methanolic extract of M. alysson L. every day for ten days by oral gavage with single MTX dose at the fifth day [92]. ...
Article
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Despite the efficient anti-cancer capabilities of methotrexate (MTX), it may induce myelosuppression, liver dysfunction and testicular toxicity. The purpose of this investigation was to determine whether Marrubium alysson L. (M. alysson L.) methanolic extract and its polyphenol fraction could protect mouse testicles from MTX-induced damage. We also investigated the protective effects of three selected pure flavonoid components of M. alysson L. extract. Mice were divided into seven groups (n = 8): (1) normal control, (2) MTX, (3) Methanolic extract + MTX, (4) Polyphenolic fraction + MTX, (5) Kaempferol + MTX, (6) Quercetin + MTX, and (7) Rutin + MTX. Pre-treatment of mice with the methanolic extract, the polyphenolic fraction of M. alysson L. and the selected pure compounds ameliorated the testicular histopathological damage and induced a significant increase in the serum testosterone level and testicular antioxidant enzymes along with a remarkable decline in the malondialdehyde (MDA) level versus MTX alone. Significant down-regulation of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), p53 and miRNA-29a testicular expression was also observed in all the protected groups. Notably, the polyphenolic fraction of M. alysson L. displayed a more pronounced decline in the testicular levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and MDA, with higher testosterone levels relative to the methanolic extract. Further improvements in the Johnsen score, histopathological results and all biochemical assays were achieved by pre-treatment with the three selected pure compounds kaempferol, quercetin and rutin. In conclusion, M. alysson L. could protect against MTX-induced testicular injury by its antioxidant, anti-inflammatory, antiapoptotic activities and through the regulation of the miRNA-29a testicular expression. The present study also included chemical profiling of M. alysson L. extract, which was accomplished by LC-ESI-TOF-MS/MS analysis. Forty compounds were provisionally assigned, comprising twenty compounds discovered in the positive mode and seventeen detected in the negative mode.
... L-glutamic acid, the compound present in the second-highest amount in the extract, is a major excitatory transmitter in the central nervous system; moreover, it is a precursor of other neurotransmitters, in particular GABA (Garattini, 2000). Trigonelline, the third highest-amount present molecule, is a metabolite that contributes to decrease the level of glucose and lipids in the blood, besides owning neuroprotective and anti-bacterial effects (Zhou et al., 2012). In addition to the above-mentioned compounds, many other biologically active molecules, including amino acids, vitamins, and metabolites, were also identified in the extract, presenting interesting properties leading to antioxidant, antibiotic, and antiinflammatory effects. ...
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Reactive oxygen species (ROS) are a common hallmark of many degenerative diseases, developing in all those cases where a failure of physiological antioxidant mechanisms occurs (in particular, antioxidant enzymes and the glutathione system), or in case of exposure to an extremely high level of oxidants. In this regard, antioxidant natural extracts are promising compounds as preventive or therapeutic agents against ROS-dependent degenerations. In this study, a deep investigation of hazelnut (Corylus avellana) extract has been performed in terms of mass spectroscopy, evaluation of phenolic content, and antioxidant capacity. Then, nanostructured lipid carriers (NLCs) have been exploited for encapsulation of the hazelnut extracts in order to achieve prolonged bioactivity, increased stability, and targeting through a sustainable delivery approach. The hazelnut extract-loaded NLCs (NE_NLCs) have been deeply characterized for their stability, production yield, and encapsulation efficiency. Moreover, NE_NLCs showed optimal cytocompatibility on human dermal fibroblast (HDF) cells, as well as excellent antioxidant activity, upon pro-oxidant stimulus on HDF cells.
... As for white sesame seeds, the top two up-regulated compounds were dimethylglycine and trigonelline (Supplementary Table S2). Both dimethylglycine and trigonelline have been reported to be associated with therapeutic potential for many diseases, especially for diabetes [34]. ...
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The present study was conducted to clarify the differences in the multi-element, volatile organic compound, fatty acid, and metabolite fingerprints between black and white sesame seeds. A total of 53 chemical elements, 32 volatile flavor compounds, 40 fatty acids, and 283 metabolites were identified and evaluated in the two groups of sesame seeds. Univariate and multivariate statistics indicated a distinct separation between the two groups of sesame seeds. A panel of 16 chemical elements, 3 volatile compounds, 8 individual fatty acids, and 54 metabolites with p value < 0.05 and variable importance in projection score > 1 were selected as the most important discriminants for the two types of sesame seeds. Overall, these data reveal the influence of genotype on the chemical composition of sesame seeds. Our findings also demonstrate that the hybrid model of instrumental analysis and chemometrics is feasible for the discrimination of black and white sesame seeds.
... Meanwhile, a few others belonging to the Nothapodytes genus have also reported containing various forms of camptothecin and its derivatives (Devanand P. Gayakwad et al., 2015). Trigonelline detected in the extract is a major plant alkaloid component that has been reported to possess hypoglycaemic, neuroprotective, antibacterial, antimigraine, antiviral activities (Zhou et al., 2012). Two sesquiterpene lactones, Costunolide (COS) and dehydro costus lactone (DEH) detected in the extract have recorded to possess activity against leukaemia and breast cancer . ...
Article
Nothapodytes foetida is an endemic medicinal plant belonging to the family Icacinaceae from the deciduous forests of the Western Ghats. The extract yield, nutritional and phytochemical composition, metabolite profiling of N. foetida leaf extract has been analysed, along with the assessment of its antioxidant, anti-inflammatory, anti-microbial and anti-cancer potentialities. The effect of different extracting solvents and techniques was optimized to obtain maximum extract yield, and ultrasonication-assisted extraction with aqueous methanol as the solvent was chosen. Appreciable amounts of total phenolics (67.59 mg GAE/g DW), total flavonoids (24.75 mg QCE/g DW), and total tannins (55.67 mg GAE/g DW) were detected. FT-IR spectroscopy also confirmed the presence of alcohols, phenols, alkanes, amino acids, carboxylic acids, nitro compounds and amines in the extract. Further, GC-MS analysis detected the presence of 33 volatile compounds that comprised of viminalol, α, β-amyrins, β, γ-sitosterol, 9-methoxy-camptothecin, lupeols, and various di and tri terpenes in significant quantities. ¹H NMR spectra revealed well-resolved signals for flavonoids, amino acids (trp, his, tyr, phe, ala, ile, gly, gln, thr, val) and organic acids. LC-MS analysis of the methanolic N. foetida extract depicted a higher polyphenolic content followed by the ethanolic and aqueous extracts. Additionally, the aqueous methanolic extract of N. foetida exhibited significant in-vitro antioxidant, anti-inflammatory, anti-microbial activity and anti-cancer activity. The overall results of this work ascertain the potency of N. foetida in nutraceutical and biomedical applications.
... Gershenzon (1984) indicated that plants respond to abiotic stresses by inducing various phytochemicals with health-promoting qualities in the human diet, including chlorogenic acid. Trigonelline has been shown to contain antibacterial, antiviral, and anti-tumor activities, and it has been shown to reduce diabetic auditory neuropathy and platelet aggregation (Mahady 2001;Zhou & Zhou, 2012). ...
... As shown in Fig. 4, Anti-diabetic drugs screened in metabolome of H. roretzi such as Pravastatin, Clofibrate, Gemfibrozil were used to manage and treat hyperlipemia or dyslipidemia (Sidhu and Sapra, 2021;Clofibrate, 2012;Quintanilla Rodriguez and Correa, 2021). Others, Daidzein, Hesperetin, L-arabinose, Trigonelline and Astaxanthin had been reported the effect on the improvement of dyslipidemia, hyperglycemia and other complications associated with diabetes mellitus (Das et al., 2018;Akiyama et al., 2009;Zhuge et al., 2021;Wang et al., 2012;Zhou et al., 2012). Besides, Metformin and Nateglinide, two first-line drugs treatment for type 2 diabetes (Foretz et al., 2014;Nateglinide, 2012), was also detected in H. roretzi tissue. ...
Article
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Halocynthia roretzi has been cultured and utilized as a nutritious seafood in Southeastern Asia for many years because of its abundance active molecules. Here, we reported that feeding of H. roretzi tissues resulted in improving oral glucose tolerance in rats. To screen the active components, we identified 950 chemical compounds from H. roretzi metabolome. Furthermore, 11 molecules with the activity of regulating blood glucose and lipids were selected based on structural identity. Among them, two natural products, hesperetin and astaxanthin were selected for further quantitative detection. The results showed that concentrations of hesperetin and astaxanthin in the tissues of H. roretzi were calculated to be 13.7 ± 9.5 and 167.9 ± 48.4 µg/100 g, respectively. The high content of astaxanthin in H. roretzi indicates its potential roles and functions in anti-diabetes activity. Taken together, our results showed that H. roretzi could be used as a functional food supplement for regulating lipid/glucose metabolism.
... Trigonelline is an alkaloid that has many beneficial effects on insulin resistance, including reducing glucose uptake from the GI tract and enhancing pancreatic beta-cell recovery [45]. The solubility of trigonelline is considered to be good [46], but the absorption rate is moderate, and its improvement by nanoformulations is currently the target of research [47]. ...
Article
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Fenugreek is used as a spice and a traditional herbal medicine for a variety of purposes, given its antidiabetic and antioxidant effects. Self-emulsifying drug delivery systems (SEDDS) of herbal drugs are targets of extensive research aiming to increase bioavailability and stability. The study’s objective was to formulate SEDDS containing Trigonella foenum-graecum extract to improve the stability of herbal extract and to increase their permeability through a Caco-2 monolayer. A characterized fenugreek dry extract was used for the formulations, while the SEDDS properties were examined by particle size analysis and zeta potential measurements. Permeability assays were carried out on Caco-2 cell monolayers, the integrity of which was monitored by follow-up trans-epithelial electric resistance measurements (TEER). Cytocompatibility was tested by the MTT method, and an indirect dissolution test was performed, using DPPH antioxidant reagent. Two different SEDDS compositions were formulated from a standardized fenugreek dry extract at either the micro- or the nanoemulsion scale with sufficient stability, enhanced bioavailability of the compounds, and sustained release from HPMC capsules. Based on our results, a modern, non-toxic, cytocompatible fenugreek SEDDS formulation with high antioxidant capacity was developed in order to improve the permeability and bioavailability of all components.
... B. I. NCBI, 2021). Trigonelline is a plant alkanoid that may have a treatment potential for diabetes and diseases of the central nervous system (Zhou et al., 2012;Koupý et al., 2015). Caffeine as a world's most widely consumed psychoactive drug is quite known for its nerve stimulation of the methylxanthine class whereby its metabolism and the involved gene are elucidated in several literature (Zhou and Hyppönen, 2019;Barcelos et al., 2020;Thorn et al., 2012). ...
Article
Discovered in Ethiopia, coffee became a popular beverage in Asia, Europe, Latin America, Australia, Africa and the North America as a drink after water and the largest goods after petroleum. However, the coffee industry generates a huge biomass as its byproducts of which the spent coffee grounds (SCG) is concerning, especially in the production chain away from the farm. Therefore, the valorization and revalorization of the SCG has a huge impact on the socioeconomic and environmental sustainability of the industry, up to the realization of the circular bioeconomy. With the advancing biorefinery concept, even an almost complete recovery of the SCG is reported at an experimental level. Such kind of studies increased with time following the action of the Sustainable Development Goals by the United Nations Development Program promulgated in 2015. The current review highlights on the background, socioeconomic, environmental contexts of coffee production and the SCG valorization and revalorization studies. Refereeing to 154 screened articles published in over 30 years' time, the SCG revalorization efforts and its integrated biorefinery as a green management approach are uniquely addressed. Plenty of studies have reported the production of bio-products from the SCG, such as the derivation of adsorbents, biochar, bioethanol, biogas, biodiesel, bio-oil, compost, construction material aggregates, cosmetics, electricity and food ingredients. In conclusion, the recovery potential of the SCG is promising and can substantially contribute to a sustainable and green bioeconomy. Nevertheless, the recovery of bioactive materials through SCG fermentation is still lacking. Most studies are conducted on a lab scale, which needs to be piloted and commissioned. Furthermore, the link between climate change and variability vis-à-vis the sustainable management of the SCG remains unaddressed.
... In addition to the nitrogen storage form for the plant, trigonelline has also been suggested as a signal for a symbiotic relationship with leguminous bacteria (Boivin et al., 1990), nyctinasty (Ueda et al., 1995) and response to various stresses (salinity, ultraviolet, and oxidative stress) (Tramontano and Jouve, 1997). Extensive therapeutic effects for trigonelline have been reported in the human body, causing this metabolite to receive more attention (Ashihara et al., 2015;Zhou et al., 2012). In many plants, especially the Abbreviations: US, Ultrasound; NA, Nicotinic acid; CVG, Coefficient of the velocity of germination; FGP, Final germination percentage; GI, Germination rate index; FW, Fresh weight; LA, Leaf area; MDA, Malondialdehyde; TBA, thiobarbituric acid; DPPH, 2,2-diphenyl-1-picrylhydrazyl; BSA, Bovine serum albumin; PAL, Phenylalanine ammonia-lyase. ...
Article
Fenugreek (Trigonella foenum-graecum L.) is an important source of trigonelline, a valuable anti-diabetic metabolite. The main objective of this study was to investigate the possibility of ultrasonication and nicotinic acid feeding in stimulating trigonelline biosynthesis and antioxidant system. For this purpose, the seeds were ultrasonicated in three groups for 0, 5, and 10 min at 40 kHz at 25 °C. Seedlings were treated after the emergence of the first true leaves (10 days) with Hoagland's solution complemented with 0, 2, 4 mg L⁻¹ nicotinic acid. The results showed that the 5 min ultrasound priming of fenugreek seeds improved germination-related traits compared with the control culture. However, the 10 min ultrasound priming negatively affected and reduced the germination traits. The highest values of growth indices of seedlings were recorded under effect of 5 min ultrasound and 4 mg L⁻¹ nicotinic acid. Ultrasound and nicotinic acid individually and as combined decreased photosynthetic pigments (chlorophylls and carotenoids). The interaction between the two factors increased the antioxidant compounds and biochemical levels of seedlings compared with the control treatment. The highest increase in trigonelline content (170.9 mg/100 g FW) was observed under 5 min ultrasound and 2 mg L⁻¹ nicotinic acid feeding. Generally, it appears that ultrasound potentiated the effect of nicotinic acid feeding on defense responses and the production of secondary metabolites, including trigonelline biosynthesis. Overall, it can be concluded that 5 min ultrasound seed priming and 2 mg L⁻¹ nicotinic acid can improve growth indices, and therefore to achieve optimal biomass yield and trigonelline production is recommended in fenugreek cultivation.
... Trigonelline was found at comparable levels (1.0 ± 0.9-3.1 ± 0.8 μg/mg) in nearly all examined species. Research studies revealed that trigonelline exhibited significant hypoglycemic activity in both animal models (50 mg/kg) and humans (500 mg oral daily dose) (Mishkinsky et al. 1967;Sharma et al. 1990;Zhou et al. 2012). Moreover, the antidiabetic action of fenugreek seed, well-known for its high trigonelline content (0.13-0.36%), has been attributed to its trigonelline as a major hypoglycemic agent (Barnes et al. 2002;Mishkinsky et al. 1974;O'Neil 2001). ...
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Cymbopogon species are widely distributed worldwide and known for their high essential oil content with potential commercial and medicinal benefits justifying for their inclusion in food and cosmetics. Most species received scant characterization regarding their full complement of bioactive constituents necessary to explain their medicinal activities. In this study, the metabolite profiles of 5 Cymbopogon species, C. citratus, C. flexuosus, C. procerus, C. martini, and C. nardus, were characterized via NMR-based metabolomics. The results of 13 shoot accessions revealed the identification and quantifica-tion of 23 primary and secondary metabolites belonging to various compound classes. Multivariate analyses were used for species classification, though found not successful in discrimination based on geographical origin. Nevertheless, C. citratus was found particularly enriched in neral, geranial, (E)-aconitic acid, isoorientin, and caffeic acid as the major characterizing metabolites compared to other species, while an unknown apigenin derivative appeared to discriminate C. martini. The high essential oil and phenolic content in C. citratus emphasizes its strong antioxidant activity, whereas (E)-aconitic acid accounts for its traditional use as insecticide. This study affords the first insight into metabolite compositional differences among Cymbopogon species. Moreover, antimicrobial, insecticidal, antidiabetic, and antioxidant compounds were identified that can be utilized as biomarkers for species authentication.
... Trigonelline is a derivative of nicotinic acid, rst isolated from fenugreek (Trigonella foenum-graecum). Trigonelline has several medicinal properties such as hypoglycaemic, neuroprotective, antibacterial, and anti-tumour activities 52 Fig. 4E) with a sequence identity of 92.6 %and a 100 %query coverage. Further this hit was validated through mapping of the FIRs (Supplementary Fig. 4A-D). ...
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Fenugreek ( Trigonella foenum-graecum L.) is a self-pollinated leguminous crop belonging to the Fabaceae family. It is a multipurpose crop used as herb, spice, vegetable and forage. It is a traditional medicinal plant in India attributed with several nutritional and medicinal properties including antidiabetic and anticancer. We have performed a combined transcriptome assembly from RNA sequencing data derived from leaf, stem and root tissues. Around 2,09,831 transcripts were deciphered from the assembly of 92% completeness and an N50 of 1382 bases. Whilst secondary metabolites of medicinal value, such as trigonelline, diosgenin, 4-hydroxyisoleucine and quercetin, are distributed in several tissues, we report transcripts that bear sequence signatures of enzymes involved in the biosynthesis of such metabolites and are highly expressed in leaves, stem and roots. One of the antidiabetic alkaloid, trigonelline and its biosynthesising enzyme, is highly abundant in leaves. These findings are of value to nutritional and the pharmaceutical industry.
... Research groups universally study the efficiency of natural compounds in treating diabetes [55,56]. Alkaloids [57], glycosides [58], polyphenols [59], carotenoids [60], terpenoids [60], flavonoids [61], anthocyanins [62], tocopherol [63], peptidoglycans [64], steroids [65], saponins [66], xanthones [67], and polysaccharides [68] have been presented as antidiabetic properties. Forty-two natural products were analyzed for their potency to treat diabetes by lowering in vivo blood glucose levels and activating in vitro GLUT4 translocation (Table 1). ...
Article
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The growing smooth talk in the field of natural compounds is due to the ancient and current interest in herbal medicine and their potentially positive effects on health. Dozens of antidiabetic natural compounds were reported and tested in vivo, in silico, and in vitro. The role of these natural compounds, their actions on the insulin signaling pathway, and the stimulation of the glucose transporter-4 (GLUT4) insulin-responsive translocation to the plasma membrane (PM) are all crucial in the treatment of diabetes and insulin resistance. In this review, we collected and summarized a group of available in vivo and in vitro studies which targeted isolated phytochemicals with possible antidiabetic activity. Moreover, the in silico docking of natural compounds with some of the insulin signaling cascade key proteins is also summarized based on the current literature. In this review, hundreds of recent studies on pure natural compounds that alleviate type II diabetes mellitus (type II DM) were revised. We focused on natural compounds that could potentially regulate blood glucose and stimulate GLUT4 translocation through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. On attempt to point out potential new natural antidiabetic compounds, this review also focuses on natural ingredients that were shown to interact with proteins in the insulin signaling pathway in silico, regardless of their in vitro/in vivo antidiabetic activity. We invite interested researchers to test these compounds as potential novel type II DM drugs and explore their therapeutic mechanisms.
... Ferreira (2018) reports the presence of trigonelline in crowberry leaves (10.2 μg/100 mg) and fruits (2.5 μg/100 mg). This alkaloid is effective in the treatment of diabetes-associated neuropathy (Zhou et al., 2012) and various types of cancer (Hirakawa et al., 2005;Liao et al., 2015). ...
Thesis
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Pesticides are chemical substances, or a biological agents intentionally released into the environment, capable of deterring, preventing or controlling populations of harmful pests such as animals, weeds, fungi, bacteria or viruses. These pests are defined as organisms that can be hazardous to our food and health, and are liable for yearly expenses of billions of dollars through the production of costly synthetic chemicals. The urge for new environmentally friendly solutions to the pesticides has led to a recent increasing interest in the research and production of plant-based biopesticides and the compounds they produce. In the present study, leaves of the species Solanum betaceum Cav. and Corema album (L.) D. Don were used to create crude ethanol extracts which were subsequently fractioned using organic solvents. The species leaf fractions were tested in vitro for their anti-oomycete activity on the growth of Phytophthora cinnamomi Rands. The initial extract of the leaf material was prepared with ethanol and the fractionation was carried out with n-hexane, chloroform, ethyl acetate and butanol, in that order, through a biphasic separation system. P. cinnamomi shows sensitivity to the butanolic fraction of S. betaceum and to all fractions of C. album, particularly to the initial C. album ethanolic extract. The butanolic fraction of S. betaceum proves to be rich in polyphenols, polysaccharides and esters. The various fractions of C. album contain pectins, esters, triterpenoids and aromatic compounds such as phenols.
... It possesses also hypoglycaemic, hypolipidemic, neuroprotective, antimigraine, sedative, and memoryimproving activities, and may also reduce diabetic auditory neuropathy and platelet aggregation. It has been established that trigonelline affects β-cell regeneration, insulin secretion, activities of enzymes related to glucose metabolism, reactive oxygen species, axonal extension, and neuron excitability [26]. ...
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Stachys thracica Davidov is a Balkan endemic species distributed in Bulgaria, Greece, and Turkey. In Bulgaria, it is classified as “rare” and is under the protection of the Bulgarian biodiversity law. The aim of our study was to develop an efficient protocol for ex situ conservation of S. thracica and to perform comparative NMR-based metabolite profiling and bioactivity assays of extracts from in situ grown, in vitro cultivated, and ex vitro acclimated plants. Micropropagation of S. thracica was achieved by in vitro cultivation of mono-nodal segments on basal MS medium. Ex Vitro adaptation was accomplished in the experimental field with 83% survival while conserved genetic identity between in vitro and ex vitro plants as shown by the overall sequence-related amplified polymorphism marker patterns was established. Verbascoside, chlorogenic acid, and trigonelline appeared the main secondary metabolites in in situ, in vitro cultivated, and ex vitro acclimated S. thracica. High total phenolic and flavonoid content as well as antioxidant and radical scavenging activity were observed in in situ and ex vitro plants. Further, the anti-inflammatory activity of S. thracica was tested by hemolytic assay and a high inhibition of the complement system was observed. Initiated in vitro and ex vitro cultures offer an effective tool for the management and better exploitation of the Stachys secondary metabolism and the selection of lines with high content of bioactive molecules and nutraceuticals.
... For instance, Berberis vulgaris, rich in berberine alkaloids, is traditionally used as a herb that is effective in preventing coronary artery disease and shows anti-inflammatory and immunomodulatory effects. e trigonelline alkaloid, isolated from Trigonella foenum-graecum in China, is effective for curing diabetes and central nervous system (CNS) diseases [48]. Due to synergistic actions of secondary ingredients, such as oxindole and L-stachydrine from Capparis tomentosa has been traditionally used for inflammation in Tanzania [49]. ...
Article
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Alkaloids are a type of natural compound possessing different pharmacological activities. Natural products, including alkaloids, which originate from plants, have emerged as potential protective agents against neurodegenerative disorders (NDDs) and chronic inflammations. A wide array of prescription drugs are used against these conditions, however, not free of limitations of potency, side effects, and intolerability. In the context of personalized medicine, further research on alkaloids to unravel novel therapeutic approaches in reducing complications is critical. In this review, a systematic survey was executed to collect the literature on alkaloids and their health complications, from which we found that majority of alkaloids exhibit anti-inflammatory action via nuclear factor-κB and cyclooxygenase-2 (COX-2), and neuroprotective interaction through acetylcholinesterase (AChE), COX, and β-site amyloid precursor protein activity. In silico ADMET and ProTox-II-related descriptors were calculated to predict the pharmacological properties of 280 alkaloids isolated from traditional medicinal plants towards drug development. Out of which, eight alkaloids such as tetrahydropalmatine, berberine, tetrandrine, aloperine, sinomenine, oxymatrine, harmine, and galantamine are found to be optimal within the categorical range when compared to nicotine. ese alkaloids could be exploited as starting materials for novel drug synthesis or, to a lesser extent, manage inflammation and neurodegenerative-related complications.
... There were 97 alkaloids found in fresh AMM roots, stems and leaves, including isoquinoline alkaloids, amines, pyridine alkaloids, and piperidine alkaloids. Trigonelline (metab_6362 and metab_1296) has therapeutic potential for diabetes and central nervous system diseases (Zhou et al., 2012). Corydaline (metab_1681) could be used to treat tachyarrhythmia (Zhang et al., 2012). ...
Article
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Astragalus membranaceus var. mongolicus (AMM) is an edible and medicinal material and is commonly used in East Asia. According to the pharmacopeia of China, the dried root of AMM is medicinal. However, the aerial parts of AMM are always directly discarded after harvest. The stems and leaves are also rich in active compounds, including saponins, flavonoids, terpenoids, and polysaccharides. To rationally use resources, waste products from AMM stems and leaves are useful substrates for edible fungus cultivation. Here, oyster mushroom ( Pleurotus ostreatus var. florida ) was cultivated on a basal substrate supplemented with AMM stems and leaves (AMM group). The nutritional and chemical composition of the fruiting body were analyzed by metabolomics and chemometrics. Our results showed that AMM addition to the substrate affected the fresh weight, moisture, fat, protein, and element concentrations, and amino acid composition of oyster mushroom. Moreover, 2,156 metabolites were detected and annotated based on the metabolomics data, of which 680 were identified as differentially expressed metabolites. Many active phytometabolites previously identified in AMM herbs were also detected in the metabolomics of oyster mushroom from AMM group, including 46 terpenoids, 21 flavonoids, 17 alkaloids, 14 phenylpropanoids, and 3 fatty acids. In summary, our results imply that oyster mushroom cultured with AMM stems and leaves might have very high nutritional therapy health care value.
... Trigonelline is an alkaloid derived from a traditional Chinese herbal, Trigonella foenumgraecum L., present in coffee and fenugreek seeds in considerable amounts . Trigonelline has been believed to be of great benefits in the prevention and treatment of diabetes and central nervous system disorders (Zhou et al., 2012). Recent studies have revealed that trigonelline exerts antitumor efficiency as a pharmacological inhibitor of NRF2. ...
Article
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Ferroptosis, a newly discovered form of regulatory cell death (RCD), has been demonstrated to be distinct from other types of RCD, such as apoptosis, necroptosis, and autophagy. Ferroptosis is characterized by iron-dependent lipid peroxidation and oxidative perturbation, and is inhibited by iron chelators and lipophilic antioxidants. This process is regulated by specific pathways and is implicated in diverse biological contexts, mainly including iron homeostasis, lipid metabolism, and glutathione metabolism. A large body of evidence suggests that ferroptosis is interrelated with various physiological and pathological processes, including tumor progression (neuro)degenerative diseases, and hepatic and renal failure. There is an urgent need for the discovery of novel effective ferroptosis-modulating compounds, even though some experimental reagents and approved clinical drugs have been well documented to have anti- or pro-ferroptotic properties. This review outlines recent advances in molecular mechanisms of the ferroptotic death process and discusses its multiple roles in diverse pathophysiological contexts. Furthermore, we summarize chemical compounds and natural products, that act as inducers or inhibitors of ferroptosis in the prevention and treatment of various diseases. Herein, it is particularly highlighted that natural products show promising prospects in ferroptosis-associated (adjuvant) therapy with unique advantages of having multiple components, multiple biotargets and slight side effects.
... Mirabilis jalapa commonly known as "four o'clock" plant (Holdsworth, 1992) and locally as tonaposo in Yoruba language (Elufioye et al., 2012) belongs to the family Nyctaginaceae. It is commonly used in Chinese folk medicine to treat diabetes (Zhou et al., 2012a), constipation (Lee et al., 2008), genitourinary system disorder and injuries (Weckerle et al., 2009). It is also widely used to treat dysentery, diarrhea (Sadiq et al., 2016) muscular pain, and abdominal colics (Walker et al., 2008). ...
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The present study demonstrates the postprandial hypoglycemic effects of methanol root extract of Mirabilis jalapa. Alloxan induced diabetic rats were treated with 200 mg/kg body weight of the extract for 9 days at 12 hourly intervals. The experiment was designed to assess both fasting and 2 hour postprandial blood glucose levels. Lipid profile and liver function biochemical analyses were conducted using serum obtained from the experimental animals sacrificed after 10 days. The results showed a marked difference in blood glucose levels postprandial in the diabetic group treated with the extract (DTM) (11.02 ± 1.42 mmol/L) when compared with the diabetic untreated group (DU) (19.80 ± 5.37 mmol/L). Similar trends were observed for the fasting blood glucose which remained elevated in the DU group throughout the experiment but was maintained at comparable levels (4.70-6.82 mmol/L) between healthy control group (HU) and all other groups treated both with extract and standard drug metformin. Triglyceride levels of diabetic groups treated with the extract were also observed to fall within comparable limits with the HU group (30.79 ±4.76-65.95 ± 2.42 mg/L). In conclusion, treatment with methanol root extract of Mirabilis jalapa suppresses hyperglycemia postprandial and probably promotes slow progression to dyslipidemia in experimentally induced diabetes in rats.
Chapter
O presente volume contém monografias completas de 11 plantas medicinais amplamente empregadas no país, sendo apenas duas exóticas. Nenhuma dessas espécies possui monografia farmacopeica nas seis edições já publicadas da Farmacopeia Brasileira; portanto, é significativa a contribuição desta obra para o desenvolvimento de fitoterápicos, importantes para a Atenção Primária à Saúde, principalmente quando se considera que 82% da população brasileira utiliza produtos à base de plantas medicinais.
Chapter
Diabetes is a metabolic disorder in which lack of insulin production or disturbances in the utilization of insulin lead to high concentrations of glucose in the blood and urine. In recent years, diabetes has reached almost epidemic proportions, possibly because of the changes in human lifestyle, which include dietary habits and a more sedentary form of living. Scientists are taking a closer look at both plants and animals, including marine entities, as sources of compounds for more efficacious and safer antidiabetic drugs at a cheaper cost. A number of promising leads have emerged and are covered in this chapter. The chapter also discusses two important factors that are now recognized in the pathophysiology of diabetes and diabetes-induced loss of vision, kidney function, and dementia, namely oxidative stress and gut dysbiosis. It is possible that a fresh approach towards diabetes in the breaking of the diabetes-oxidative stress/dysbiosis-diabetes cycle with the aid of better glucose-lowering drugs, antioxidants, and probiotic symbionts may enable us to finally conquer this dread disease.
Article
Chaya (Cnidoscolus chayamansa and C. aconitifolius) is a fast-growing medicinal plant, and its leaves exhibit a strong umami taste. Here metabolite variation and umami-related compounds in the leaves of two chaya species were determined using a multiplatform untargeted-metabolomics approach, electronic tongue, and in silico screening. Metabolite profiles varied between the leaves of the two species and among leaf maturation stages. Young leaves exhibited the highest umami taste intensity, followed by mature and old leaves. Partial least square regression and computational molecular docking analyses revealed five potent umami substances (quinic acid, trigonelline, alanyl–tyrosine, leucyl–glycyl–proline, and leucyl–aspartyl–glutamine) and three known umami compounds (l-glutamic acid, pyroglutamic acid, and 5′-adenosine monophosphate). The five substances were validated as novel umami compounds using electronic tongue assay; leucyl–glycyl–proline exhibited synergism with monosodium glutamate, thereby enhancing the umami taste. Thus, substances contributing to the taste of chaya leaves were successfully identified.
Article
Background: Pinang yaki has bioactive compounds that have potential as a new herbal supplement, but their metabolites profil is lack of data. A better understanding of the bioactive compounds of pinang yaki using untargeted metabolomic profiling studies will provide clearer insight into the health benefits of pinang yaki in further. Methods: Fresh samples of pinang yaki ( Areca vestiaria ) are obtained from forests in North Sulawesi Province, Indonesia. Samples were used for untargeted metabolomics analysis by UHPLC-MS. Results: Based on an untargeted metabolomic profiling study of pinang yaki, 2504 compounds in ESI- and 2645 compounds in ESI+ were successfully obtained. After the analysis, 356 compounds in ESI- and 543 compounds in ESI+ were identified successfully. Major compounds Alpha-Chlorohydrin (PubChem ID: 7290) and Tagatose (PubChem ID: 439312) were found in ESI+ and ESI-. Discussion: The 10 metabolites from pinang yaki extract (ESI+) also have been indicated in preventing viral infection and have exhibited good neuroprotective immunity. Benzothiazole (PubChem ID: 7222), L-isoleucine (PubChem ID: 6306), D-glucono-delta-lactone (PubChem ID: 736), Diethylpyrocarbonate (PubChem ID: 3051), Bis(2-Ethylhexyl) amine (PubChem ID: 7791), Cinnamic acid (PubChem ID: 444539), and Trigonelline (PubChem ID: 5570) also had potential effects as an antiviral and anti-inflammatory. Conclusion: Untargeted metabolomic profiling showed many bioactive compounds contained in pinang yaki ( Areca vestiaria ) extract. The top 10 compounds capable to ionize well have been identified and explored for their potential benefits as antiviral supplement products by literature study. This is a preliminary study which still needs further research such as in vitro, preclinical, and clinical trials.
Article
The global epidemic of diabetes has brought heavy pressure on public health. New effective anti-diabetes strategies are urgently needed. Trigonelline is the main component of fenugreek, which has been proved to have a good therapeutic effect on diabetes and diabetic complications. Trigonelline achieves amelioration of diabetes, the mechanisms of which include the modulation of insulin secretion, a reduction in oxidative stress, and the improvement of glucose tolerance and insulin resistance. Besides, trigonelline has been reported to be a neuroprotective agent against many neurologic diseases including Alzheimer's disease, Parkinson's disease, stroke, and depression. Concerning the potential therapeutic effects of trigonelline, comprehensive clinical trials are warranted to evaluate this valuable molecule.
Article
Aims: This study aimed to perform molecular docking studies to identify possibilities of the inhibitory potential of the trigonelline present in fenugreek seeds on the human tyrosinase, standardize fenugreek extract, formulate, and characterize an emulgel-containing fenugreek extract-entrapped niosomal vesicles. Materials and methods: The docking study was performed using AutoDock software. The extract was standardized by the RP-HPLC method. Emulgels containing fenugreek extract and fenugreek extract-entrapped niosomes were optimized by the D-optimal method. In vitro characterization and stability studies were also carried out. Results: The lowest energy docked poses of trigonelline on the human tyrosinase complex was calculated -5.8 kcal/mol. Also, in vitro assessment of the tyrosinase inhibitory effect of trigonelline and comparison of IC50 values of trigonelline and kojic acid revealed that the enzyme inhibition efficacy of trigonelline was stronger than that of kojic acid. Optimization led to emulgels with desired viscosity, droplet size, and spreadability values. The release study showed that trigonelline was released from the niosomes at a lower rate compared with extract containing emulgel. Permeation investigations revealed that trigonelline in niosomes has a higher ability to permeate through the skin. Conclusion: In conclusion, in silico and in vitro studies have shown that trigonelline can be assumed as an appropriate candidate for developing new cosmetic preparations and nonionic surfactant vesicles help trigonelline to permeate through the skin to a higher extent. However, clinical trials should be performed to confirm these findings.
Chapter
Heterocyclic moieties form important constituents of biologically active natural products and synthetic compounds of medicinal interest. Nitrogen heterocycles constitute important pharmacophores in drug design, especially pyridine derivatives, which are among the most frequently cited heterocyclic compounds. The isolated as well as synthesized pyridine compounds exhibited various pharmacological properties due to their diverse physiochemical properties like water solubility, weak basicity, chemical stability, hydrogen bond-forming ability, protein-binding capacity, cell permeability, and size of the molecules attracted the attention of medicinal chemists for the past few years. Their interesting molecular architecture seeks attention to isolate derivatives of medicinal interest from natural source. In this chapter, we plan to describe the isolated natural products having pyridine moiety and their pharmacological importance.
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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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Coffee and caffeine are known to affect the limbic system, but data on the influence of coffee and coffee constituents on neurotransmitter release is limited. We investigated dopamine release and Ca(2+)-mobilization in pheochromocytoma cells (PC-12 cells) after stimulation with two lyophilized coffee beverages prepared from either Coffea arabica (AR) or Coffea canephora var. robusta (RB) beans and constituents thereof. Both coffee lyophilizates showed effects in dilutions between 1:100 and 1:10,000. To identify the active coffee compound, coffee constituents were tested in beverage and plasma representative concentrations. Caffeine, trigonelline, N-methylpyridinium, chlorogenic acid, catechol, pyrogallol and 5-hydroxytryptamides increased calcium signaling and dopamine release, although with different efficacies. While N-methylpyridinium stimulated the Ca(2+)-mobilization most potently (EC(200): 0.14±0.29μM), treatment of the cells with pyrogallol (EC(200): 48±14nM) or 5-hydroxytryptamides (EC(200): 10±3nM) lead to the most pronounced effect on dopamine release. In contrast, no effect was seen for the reconstituted biomimetic mixture. We therefore conclude that each of the coffee constituents tested stimulated the dopamine release in PC-12 cells. Since no effect was found for their biomimetic mixture, we hypothesize other coffee constituents being responsible for the dopamine release demonstrated for AR and RB coffee brews.
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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).
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.