RESUMEN

BACKGROUND: One of the most popular chemotherapy medications is doxorubicin (DOX), however it can have non-negligible damage. When the underlying mechanisms of damage are investigated, the most prominent pathways are oxidative stress, inflammation and apoptosis. AIM: We investigated the NF-κB/MAPK inflammatory pathway and cellular apoptosis to determine the efficacy of trigonelline alkaloid (TRIG) in preventing DOX-induced lung injury. METHODOLOGY: The study consisted of C, TRIG, DOX and TRIG+DOX groups. TRIG and TRIG+DOX groups received 50 mg/kg TRIG for 7 days. On day 8, DOX and TRIG+DOX groups received a single dose of 15 mg/kg DOX. RESULTS: Our results showed that apoptosis markers and inflammation were higher in the DOX group. In contrast, TRIG pretreatment partially suppressed apoptosis and decreased inflammation by blocking the activation of the MAPK/NF-κB pathway, lowering IL-6 levels, and protecting the lung from apoptotic cell death. CONCLUSION: Assessing TRIG's effectiveness in lung tissue injury, this study may be a crucial first step.

RESUMEN

Coffee, a universally consumed beverage, is known to contain thousands of bioactive constituents that have garnered interest due to their potential neuroprotective effects against various neurodegenerative disorders, including Alzheimer's disease (AD). Extensive research has been conducted on coffee constituents such as Caffeine, Trigonelline, Chlorogenic acid, and Caffeic acid, focusing on their neuroprotective properties. These compounds have potential to impact key mechanisms in AD development, including amyloidopathy, tauopathy, and neuroinflammation. Furthermore, apart from its neuroprotective effects, coffee consumption has been associated with anticancerogenic and anti-inflammatory effects, thereby enhancing its therapeutic potential. Studies suggest that moderate coffee intake, typically around two to three cups daily, could potentially contribute to mitigating AD progression and lowering the risk of related neurological disorders. This literature underscores the potential neuroprotective properties of coffee compounds, which usually perform their neuronal protective effects via modulating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nuclear factor erythroid-derived 2-like 2 (Nrf2), interleukins, tumor necrosis factor-alpha (TNF-α), and many other molecules.

Asunto(s)

Enfermedad de Alzheimer , Café , Fármacos Neuroprotectores , Humanos , Enfermedad de Alzheimer/prevención & control , Fármacos Neuroprotectores/farmacología , Animales

RESUMEN

BACKGROUND: Trigonella foenum-graecum, commonly known as fenugreek and it is used as a spice. It has antioxidant, anti-diabetic, antilipedemic and other pharmocological properties. OBJECTIVES: The aim of the study was to detect the cardio protective activity of Trigonelline (TG) a bioactive compound of Trigonella foenum-graecum (TF) in alcohol intoxicated rats. MATERIAL AND METHODS: The young wistar strain albino rats are divided in to 5 groups and treatment was given as per the experimental protocol. Antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), glutathione (GSH), malondialdehyde (MDA) levels are estimated in cardiac tissue of all experimental groups. Cardiac markers creatine kinase-MB (CK-MB), troponin-T (TT), troponin-I (TI), myoglobin (MG) and serum markers alanine transaminase (AAT), aspartate transaminase (AST) and alkaline phosphatase (ALP) are estimated. Free radical scavenging activities like 2,2-diphenylpicrylhydrazyl (DPPH), hydrogen peroxide (H2O2) and hydroxyl radical are estimated in ethanolic extract of Trigonella foenum-graecum. RESULTS: SOD, CAT, GPx, GR, GSH activities are depleted and MDA, CK-MB, TT, TI, MG and AAT, AST, ALP activities are elevated in alcohol intoxicated rats. Trigonelline supplementation to alcoholic rats for 30 days elevated antioxidant enzymes, depleted MDA, cardiac markers and serum markers in alcohol intoxicated rats. Free radical scavenging assay also reported that Trigonella foenum-graecum possess free radical scavenging activity. Furthermore, our histopathological evidence also proved that TG protected the cardiac tissue from alcohol induced toxicity in all the experimental rats. CONCLUSION: Our study concluded that TG may be useful to the alcoholic and myocardial infarction subjects.

RESUMEN

A rapid, simple, effective, and green method for the determination of betaine and trigonelline from Lycium chinense Mill. (LCM) and the quantification of the trigonelline in coffee was proposed and validated by matrix-assisted laser desorption ionization time-of-flight mass spectrometric (MALDI-TOF MS) detection. Due to without chromatographic separation, the method greatly shortened the detection time. The detection of betaine and trigonelline concentration showed good linearity in the range of 1-100 µg/mL and 0.01-100 µg/mL, with correlation coefficients r2 = 0.9962 and 0.9946, respectively. The good reproducibility and reliability of the method were demonstrated by excellent intraday and interday precisions with RSD <8.3%, and the recovery of betaine and trigonelline ranged from 92.2% to 116.0%. Analysis of LCM and coffee extracts (raw, light-roasted, and dark-roasted coffee beans) gave results in agreement with the literature. The method appeared as a fast and reliable alternative method for routine Lycium chinense and coffee analysis.

RESUMEN

The intricate nature of Alzheimer's disease (AD) has presented significant hurdles in the development of effective interventions. Sulforaphane (SFN) is of interest due to its antioxidative, anti-inflammatory, and neuroprotective properties, which could address various aspects of AD pathology. This study explores the potential of SFN in a rat model of AD induced by Aß (1-42) peptides. AD symptoms were triggered in rats by injecting Aß (1-42) peptides directly into their cerebral ventricles. SFN (10 mg/kg and 20 mg/kg), Trigonelline (10 mg/kg), and Pioglitazone (10 mg/kg) were administered in Aß (1-42) treated animals. Behavioral assessments were performed using the Novel Object Recognition tests. Various biochemical parameters, such as soluble Aß (1-42), IRS-S312, GSK-3ß, TNF-α, acetylcholinesterase, nitrite levels, lipid peroxidation, and reduced glutathione activity, were quantified using ELISA kits and spectrophotometric assays. Histopathological analyses included Hematoxylin and Eosin, Crystal Violet, Congo red, and IRS-1 Immunohistochemistry staining. Quantification was performed to assess neuronal loss and Aß plaque burden. The novelty of this study lies in its comprehensive evaluation of SFN's impact on multiple AD-related pathways at dual doses. The Novel Object Recognition test revealed that SFN, especially at higher doses, improved memory deficits induced by Aß (1-42). Biochemically, SFN reduced hippocampal Aß levels, IRS-S312, GSK-3ß, TNF-α, and acetylcholinesterase activity, while increasing glutathione levels, all in a dose-dependent manner. Histopathological analyses further confirmed SFN's protective role against Aß-induced neuronal damage, amyloidosis, and changes in insulin signaling. These results highlight SFN's potential as a multifaceted therapeutic agent for AD, offering a promising avenue for treatment due to its antioxidative, anti-inflammatory, and neuroprotective properties. The inclusion of combination treatments with Trigonelline and Pioglitazone alongside SFN offers insights into potential synergistic effects, which could pave the way for developing combination therapies for AD.

Asunto(s)

Enfermedad de Alzheimer , Péptidos beta-Amiloides , Modelos Animales de Enfermedad , Isotiocianatos , Fármacos Neuroprotectores , Fragmentos de Péptidos , Sulfóxidos , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/toxicidad , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Isotiocianatos/farmacología , Isotiocianatos/uso terapéutico , Fragmentos de Péptidos/toxicidad , Masculino , Ratas , Sulfóxidos/farmacología , Ratas Wistar

RESUMEN

INTRODUCTION: Understanding why subjects with overweight and with obesity vary in their response to dietary interventions is of major interest for developing personalized strategies for body mass regulation. OBJECTIVES: The aim of this study was to investigate the relationship between changes in the urine metabolome and body mass during a breakfast meal intervention. Furthermore, we aimed to elucidate if the baseline urine metabolome could predict the response to the two types of breakfast meals (high versus low protein) during the intervention. METHODS: A total of 75 young, women with overweight were randomly allocated to one of two intervention groups: (1) High-protein (HP) or (2) low-protein (LP) breakfast as part of their habitual diet during a 12-week intervention. Beside the breakfast meal, participants were instructed to eat their habitual diet and maintain their habitual physical activity level. Nuclear magnetic resonance-based metabolomics was conducted on urine samples collected at baseline (wk 0), mid-intervention (wk 6), and at endpoint (wk 12). At baseline and endpoint, body mass was measured and DXA was used to measure lean body mass and fat mass. RESULTS: The baseline urine metabolite profile showed a slightly higher correlation (R2 = 0.56) to body mass in comparison with lean body mass (R2 = 0.51) and fat mass (R2 = 0.53). Baseline 24-h urinary excretion of trigonelline (p = 0.04), N, N-dimethylglycine (p = 0.02), and trimethylamine (p = 0.03) were significantly higher in individuals who responded with a reduction in body mass to the HP breakfast. CONCLUSIONS: Differences in the urine metabolome were seen for women that obtained a body weight loss in the response to the HP breakfast intervention and women who did not obtain a body weight loss, indicating that the urine metabolome contains information about the metabolic phenotype that influences the responsiveness to dietary interventions.

Asunto(s)

Composición Corporal , Desayuno , Metaboloma , Sobrepeso , Humanos , Femenino , Sobrepeso/orina , Sobrepeso/metabolismo , Sobrepeso/dietoterapia , Adulto , Índice de Masa Corporal , Metabolómica/métodos , Adulto Joven , Proteínas en la Dieta/administración & dosificación

RESUMEN

Rotenone (RTN) induces neurotoxicity and motor dysfunction in rats, mirroring the pathophysiological traits of Parkinson's disease (PD), including striatal oxidative stress, mitochondrial dysfunction, and changes in neural structure. This makes RTN a valuable model for PD research. Berberine (BBR), an isoquinoline alkaloid recognized for its antioxidative, anti-inflammatory, and neuroprotective properties, was evaluated for its ability to counteract RTN-induced impairments. Rats received subcutaneous RTN at 0.5 mg/kg for 21 days, resulting in weight loss and significant motor deficits assessed through open-field, bar catalepsy, beam-crossing, rotarod, and grip strength tests. BBR, administered orally at 30 or 100 mg/kg doses, one hour prior to RTN exposure for the same duration, effectively mitigated many of the RTN-induced motor impairments. Furthermore, BBR treatment reduced RTN-induced nitric oxide (NO) and lipid peroxidation (LPO) levels, bolstered antioxidative capacity, enhanced mitochondrial enzyme activities (e.g., succinate dehydrogenase (SDH), ATPase, and the electron transport chain (ETC)), and diminished striatal neuroinflammation and apoptosis markers. Notably, the co-administration of trigonelline (TGN), an inhibitor of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway, significantly attenuated BBR's protective effects, indicating that BBR's neuroprotective actions are mediated via the Nrf2 pathway. These results underscore BBR's potential in ameliorating motor impairments akin to PD, suggesting its promise in potentially delaying or managing PD symptoms. Further research is warranted to translate these preclinical findings into clinical settings, enhancing our comprehension of BBR's therapeutic prospects in PD.

RESUMEN

Glutamatergic neurotransmission and oxidative stress are involved in the pathophysiology of seizures. Some anticonvulsants exert their effects through modulation of these pathways. Trigonelline (TRG) has been shown to possess various pharmacological effects like neuroprotection. Therefore, this study was performed to determine TRG's anticonvulsant effects, focusing on its potential effects on N-methyl-D-aspartate (NMDA) receptors, a type of glutamate receptor, and oxidative stress state in the prefrontal cortex (PFC) in PTZ-induced seizure in mice. Seventy-two male mice were randomly divided into nine groups. The groups included mice that received normal saline, TRG at doses of 10, 50, and 100 mg/kg, diazepam, NMDA (an agonist), ketamine (an antagonist), the effective dose of TRG with NMDA, as well as sub-effective dose of TRG with ketamine, respectively. All agents were administrated intraperitoneally 60 min before induction of seizures by PTZ. Latency to seizure, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels in serum and PFC were measured. Furthermore, the gene expression of NR2A and NR2B, subunits of NMDA receptors, was measured in the PFC. TRG administration increased the latency to seizure onset and enhanced TAC while reducing MDA levels in both the PFC and serum. TRG also decreased the gene expression of NR2B in the PFC. Unexpectedly, the findings revealed that the concurrent administration of ketamine amplified, whereas NMDA mitigated, the impact of TRG on latency to seizure. Furthermore, NMDA diminished the positive effects of TRG on antioxidant capacity and oxidative stress, while ketamine amplified these beneficial effects, indicating a complex interaction between TRG and NMDA receptor modulation. In the gene expression of NMDA receptors, results showed that ketamine significantly decreased the gene expression of NR2B when co-administrated with a sub-effective dose of TRG. It was found that, at least partially, the anticonvulsant effect of TRG in PTZ-induced seizures in male mice was mediated by the attenuation of glutamatergic neurotransmission as well as the reduction of oxidative stress.

Asunto(s)

Alcaloides , Anticonvulsivantes , Estrés Oxidativo , Receptores de N-Metil-D-Aspartato , Convulsiones , Animales , Receptores de N-Metil-D-Aspartato/metabolismo , Estrés Oxidativo/efectos de los fármacos , Anticonvulsivantes/farmacología , Ratones , Masculino , Alcaloides/farmacología , Convulsiones/tratamiento farmacológico , Convulsiones/metabolismo , Convulsiones/inducido químicamente , Corteza Prefrontal/metabolismo , Corteza Prefrontal/efectos de los fármacos , Malondialdehído/metabolismo , Ketamina/farmacología , Pentilenotetrazol/toxicidad , Antioxidantes/farmacología

RESUMEN

BACKGROUND: The combination of compost and biochar (CB) plays an important role in soil restoration and mitigation strategies against drought stress in plants. In the current study, the impact of CB was determined on the characteristics of saline calcareous soil and the productivity of fenugreek (Trigonella foenum-graecum L.) plants. The field trials examined CB rates (CB0, CB10 and CB20 corresponding to 0, 10, and 20 t ha‒1, respectively) under deficit irrigation [DI0%, DI20%, and DI40% receiving 100, 80, and 60% crop evapotranspiration (ETc), respectively] conditions on growth, seed yield (SY), quality, and water productivity (WP) of fenugreek grown in saline calcareous soils. RESULTS: In general, DI negatively affected the morpho-physio-biochemical responses in plants cultivated in saline calcareous soils. However, amendments of CB10 or CB20 improved soil structure under DI conditions. This was evidenced by the decreased pH, electrical conductivity of soil extract (ECe), and bulk density but increased organic matter, macronutrient (N, P, and K) availability, water retention, and total porosity; thus, maintaining better water and nutritional status. These soil modifications improved chlorophyll, tissue water contents, cell membrane stability, photosystem II photochemical efficiency, photosynthetic performance, and nutritional homeostasis of drought-stressed plants. This was also supported by increased osmolytes, non-enzymatic, and enzymatic activities under DI conditions. Regardless of DI regimes, SY was significantly (P ≤ 0.05) improved by 40.0 and 102.5% when plants were treated with CB10 and CB20, respectively, as similarly observed for seed alkaloids (87.0, and 39.1%), trigonelline content (43.8, and 16.7%) and WP (40.9, and 104.5%) over unamended control plants. CONCLUSIONS: Overall, the application of organic amendments of CB can be a promising sustainable solution for improving saline calcareous soil properties, mitigating the negative effects of DI stress, and enhancing crop productivity in arid and semi-arid agro-climates.

Asunto(s)

Carbón Orgánico , Compostaje , Semillas , Suelo , Trigonella , Trigonella/metabolismo , Trigonella/fisiología , Trigonella/crecimiento & desarrollo , Suelo/química , Semillas/crecimiento & desarrollo , Compostaje/métodos , Deshidratación , Agua/metabolismo , Salinidad

RESUMEN

BACKGROUND: Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it's unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear. METHODS: To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions. RESULTS: In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO2-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO2 group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-ß/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts. CONCLUSION: In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.

Asunto(s)

Alcaloides , Diferenciación Celular , Fibroblastos , Ratones Endogámicos C57BL , Miofibroblastos , Fibrosis Pulmonar , Dióxido de Silicio , Silicosis , Animales , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/prevención & control , Alcaloides/farmacología , Dióxido de Silicio/toxicidad , Ratones , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patología , Diferenciación Celular/efectos de los fármacos , Silicosis/patología , Silicosis/metabolismo , Silicosis/tratamiento farmacológico , Masculino

RESUMEN

Female germline stem cells (FGSCs) are renewable sources of oocytes that play an indispensable role in re-establishing mammal fertility. Here, we have established FGSCs from neonatal mice, which exhibit characteristics of germline stem cells. We show that compared with monomeric trigonelline and diosgenin, macromolecular compounds Cistanche deserticola polysaccharides (CDPs) in Chinese herbal medicine can enhance the ability of FGSCs to differentiate into oocytes at appropriate concentrations while maintaining self-renewal in vitro. In contrast, trigonelline and diosgenin inhibited the expression of germ cell-specific genes while reducing cell proliferation activity. In summary, CDPs could induce the differentiation and self-renewal of FGSCs in vitro. The comparison of the effects of the active components of different types of Chinese medicine will provide a reference for the development of clinical drugs in the future, and help to elucidate the development process of FGSCs.

RESUMEN

Trigonelline (TRG) is a natural polar hydrophilic alkaloid that is found in many plants such as green coffee beans and fenugreek seeds. TRG potentially acts on multiple molecular targets, including nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor γ, glycogen synthase kinase, tyrosinase, nerve growth factor, estrogen receptor, amyloid-ß peptide, and several neurotransmitter receptors. In this review, we systematically summarize the pharmacological activities, medicinal properties, and mechanistic actions of TRG as a potential therapeutic agent. Mechanistically, TRG can facilitate the maintenance and restoration of the metabolic homeostasis of glucose and lipids. It can counteract inflammatory constituents at multiple levels by hampering pro-inflammatory factor release, alleviating inflammatory propagation, and attenuating tissue injury. It concurrently modulates oxidative stress by the blockage of the detrimental Nrf2 pathway when autophagy is impaired. Therefore, it exerts diverse therapeutic effects on a variety of pathological conditions associated with chronic metabolic diseases and age-related disorders. It shows multidimensional effects, including neuroprotection from neurodegenerative disorders and diabetic peripheral neuropathy, neuromodulation, mitigation of cardiovascular disorders, skin diseases, diabetic mellitus, liver and kidney injuries, and anti-pathogen and anti-tumor activities. Further validations are required to define its specific targeting molecules, dissect the underlying mechanistic networks, and corroborate its efficacy in clinical trials.

Asunto(s)

Alcaloides , Diabetes Mellitus , Humanos , Factor 2 Relacionado con NF-E2 , Alcaloides/farmacología , Alcaloides/uso terapéutico , Alcaloides/química , Diabetes Mellitus/tratamiento farmacológico , Estrés Oxidativo

RESUMEN

This article addresses the bioactive components in coffee aroma, their metabolism, and the mechanism of action in lowering the risk of various potential health problems. The main bioactive components involved in the perceived aroma of coffee and its related health benefits are caffeine, chlorogenic acid (CGA), trigonelline, diterpenes, and melanoids. These compounds are involved in various physiological activities. Caffeine has been shown to have anticancer properties, as well as the ability to prevent the onset and progression of hepatocellular carcinoma and to be anti-inflammatory. CGA exhibits antioxidant action and is implicated in gut health, neurodegenerative disease protection, type 2 diabetes, and cardiovascular disease prevention. Furthermore, together with diterpenes, CGA has been linked to anticancer activity. Trigonelline, on the other side, has been found to lower oxidative stress by increasing antioxidant enzyme activity and scavenging reactive oxygen species. It also prevents the formation of kidney stones. Diterpenes and melanoids possess anti-inflammatory and antioxidant properties, respectively. Consuming three to four cups of filtered coffee per day, depending on an individual's physiological condition and health status, has been linked to a lower risk of several degenerative diseases. Despite their health benefits, excessive coffee intake above the recommended daily dosage, calcium and vitamin D deficiency, and unfiltered coffee consumption all increase the risk of potential health concerns. In conclusion, moderate coffee consumption lowers the risk of different noncommunicable diseases.

RESUMEN

Plants employ a multilayered immune system to combat pathogens. In one layer, recognition of Pathogen- or Microbe-Associated Molecular Patterns or elicitors, triggers a cascade that leads to defence against the pathogen and Pattern Triggered Immunity. Secondary or specialised metabolites (SMs) are expected to play a role, because they are potentially anti-fungal compounds. Tomato (Solanum lycopersicum) plants inoculated with Alternaria solani s.l. show symptoms of infection after inoculation. Plants inoculated with Alternaria alternata remain symptomless. We hypothesised that pattern-triggered induction of resistance related metabolites in tomato contributes to the resistance against A. alternata. We compared the metabolomic profile (metabolome) of tomato after treatments with A. alternata, A. solani and the fungal elicitor chitin, and identified SMs involved in early defence of tomato plants. We revealed differential metabolome fingerprints. The composition of A. alternata and chitin induced metabolomes show larger overlap with each other than with the A. solani induced metabolome. We identify 65 metabolites possibly associated with PTI in tomato plants, including NAD and trigonelline. We confirm that trigonelline inhibits fungal growth in vitro at physiological concentrations. Thus, a true pattern-triggered, chemical defence is mounted against A. alternata, which contains anti-fungal compounds that could be interesting for crop protection strategies.

Asunto(s)

Proteínas de Plantas , Solanum lycopersicum , Proteínas de Plantas/metabolismo , Resistencia a la Enfermedad , Enfermedades de las Plantas/microbiología , Alternaria/metabolismo , Quitina

RESUMEN

Pseudomonas aeruginosa, a vivid biofilm-producing bacterium, is considered a dreadful opportunistic pathogen, and thus, management of biofilm-associated infections due to multidrug resistant strains by traditional drugs currently is of great concern. This study was aimed to assess the impact of trigonelline hydrochloride, a pyridine alkaloid, on P. aeruginosa PAO1, in search of an alternative therapeutant. The effect of trigonelline on colony morphology and motility was studied along with its role on biofilm and expression virulence factors. Trigonelline influenced the colony structure, motility, biofilm architecture, and the production of virulence factors in a dose-dependent manner. Alterations in quorum sending (QS)-regulated gene expression after treatment and molecular docking analysis for certain regulator proteins confirmed its effect on the QS-system network by affecting Las, Rhl, and Pqs signaling pathways and as possible molecular targets. Thus, trigonelline might be considered as a potential chemical lead to manage biofilm-associated pathogenesis or to develop other analogues with enhanced pharmacokinetic actions.

Asunto(s)

Alcaloides , Antiinfecciosos , Virulencia , Pseudomonas aeruginosa , Simulación del Acoplamiento Molecular , Percepción de Quorum , Biopelículas , Alcaloides/farmacología , Factores de Virulencia/metabolismo , Antiinfecciosos/farmacología

RESUMEN

Trigonella foenum-graecum L. (Fenugreek) is an annual herb that belongs to Fabaceae family. The compositional make-up of microgreens depends on prevailing environmental conditions. So, Trigonella microgreens were cultivated under different photoperiod and temperature conditions and evaluated for plant height, total chlorophyll content (TCC), targeted compound analysis and non-targeted UHPLC-QTOF-IMS based metabolomic profile. The plant height and TCC of Trigonella microgreens increased by approximately 22 % and 20 %, respectively under T1 conditions (longer photoperiod of 22 h with 22 °C in light and 17 °C in dark). The targeted phenolic profile analysis revealed the dominant presence of gallic acid, p-coumaric acid and apigenin in Trigonella microgreens. Also, the concentration of p-coumaric acid concentration raised from 3.51 mg/g to 5.83 mg/g as a response of T1 conditions. The sugar profile revealed augmented concentration of myo-inositol, glucose, fructose, xylose, maltose, and sucrose in longer photoperiod with T1 conditions. The microgreens were also rich in amino acids like aspartic acid, glutamic acid, leucine, isoleucine, and phenylalanine. Notably, the concentration of proline increased from 10.40 mg/g to 16.92 mg/g as a response to T1 growth conditions. The concentration of these metabolites varied significantly under different photoperiod and temperature conditions. The comprehensive non-targeted UHPLC-QTOF-IMS analysis of microgreens revealed different class of metabolites like organic compounds, alkaloids, coumarin-derivatives, phenolic and flavonoid derivatives, terpenoids, sugars, amino acids and few nucleic acid derivatives. The multivariate PLS-DA explained different expression level of metabolites under different growing conditions. The T1 growing condition resulted in the increased biosynthesis of phenolic compounds and various metabolites. The expression level of terpenoid derivatives specifically of Trigonelloside C and Trigoneoside XIIa/b increased under T1 conditions. The substantial alteration in the metabolites due to growing conditions may alter the microgreen's dietary benefits. So, additional research may be warranted.

Asunto(s)

Trigonella , Temperatura , Fotoperiodo , Cromatografía Líquida de Alta Presión/métodos , Fenoles/análisis

RESUMEN

In recent years, exploring natural compounds with functional properties to ameliorate aging-associated cognitive decline has become a research priority to ensure healthy aging. In the present study, we investigated the effects of Trigonelline (TG), a plant alkaloid, on memory and spatial learning in 16-week-old senescence-accelerated mouse model SAMP8 using an integrated approach for cognitive and molecular biology aspects. After 30 days of oral administration of TG at the dose of 5 mg/kg/day, the mice were trained in Morris Water Maze task. TG-treated SAMP8 mice exhibited significant improvement in the parameters of escape latency, distance moved, and annulus crossing index. Next, we performed a whole-genome transcriptome profiling of the mouse hippocampus using microarrays. Gene ontology analyses showed that a wide range of biological processes, including nervous system development, mitochondrial function, ATP synthesis, and several signaling pathways related to inflammation, autophagy, and neurotransmitter release, were significantly enriched in TG-treated SAMP8 compared to nontreated. Further, a nonlinear dimensionality reduction technique, Uniform Manifold Approximation and Projection (UMAP), was applied to identify clusters of functions that revealed TG primarily regulated pathways related to inflammation, followed by those involved in neurotransmitter release. In addition, a protein-protein interaction network analysis indicated that TG may exert its biological effects through negatively modulating Traf6-mediated NF-κB activation. Finally, ELISA test showed that TG treatment significantly decreased proinflammatory cytokines- TNFα and IL6 and increased neurotransmitters- dopamine, noradrenaline, and serotonin in mouse hippocampus. Altogether, our integrated bio-cognitive approach highlights the potential of TG in alleviating age-related memory and spatial impairment.

Asunto(s)

Alcaloides , Citocinas , Ratones , Animales , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Alcaloides/farmacología , Alcaloides/uso terapéutico , Trastornos de la Memoria/tratamiento farmacológico , Neurotransmisores/uso terapéutico , Inflamación

RESUMEN

AIMS: Pulmonary fibrosis (PF) is a chronic interstitial lung disease with an increasing incidence following the COVID-19 outbreak. Pirfenidone (Pirf), an FDA-approved pulmonary anti-fibrotic drug, is poorly tolerated and exhibits limited efficacy. Trigonelline (Trig) is a natural plant alkaloid with diverse pharmacological actions. We investigated the underlying prophylactic and therapeutic mechanisms of Trig in ameliorating bleomycin (BLM)-induced PF and the possible synergistic antifibrotic activity of Pirf via its combination with Trig. MATERIALS AND METHODS: A single dose of BLM was administered intratracheally to male Sprague-Dawley rats for PF induction. In the prophylactic study, Trig was given orally 3 days before BLM and then for 28 days. In the therapeutic study, Trig and/or Pirf were given orally from day 8 after BLM until the 28th day. Biochemical assay, histopathology, qRT-PCR, ELISA, and immunohistochemistry were performed on lung tissues. KEY FINDINGS: Trig prophylactically and therapeutically mitigated the inflammatory process via targeting NF-κB/NLRP3/IL-1ß signaling. Trig activated the autophagy process which in turn attenuated alveolar epithelial cells apoptosis and senescence. Remarkably, Trig attenuated lung SPHK1/S1P axis and its downstream Hippo targets, YAP-1, and TAZ, with a parallel decrease in YAP/TAZ profibrotic genes. Interestingly, Trig upregulated lung miR-375 and miR-27a expression. Consequently, epithelial-mesenchymal transition in lung tissues was reversed upon Trig administration. These results were simultaneously associated with profound improvement in lung histological alterations. SIGNIFICANCE: The current study verifies Trig's prophylactic and antifibrotic effects against BLM-induced PF via targeting multiple signaling. Trig and Pirf combination may be a promising approach to synergize Pirf antifibrotic effect.

Asunto(s)

Alcaloides , MicroARNs , Neumonía , Fibrosis Pulmonar , Ratas , Animales , Bleomicina/farmacología , Inflamasomas/metabolismo , Vía de Señalización Hippo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Sprague-Dawley , Pulmón/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/prevención & control , Neumonía/patología , Alcaloides/uso terapéutico , MicroARNs/metabolismo

RESUMEN

Triphenyltin chloride (TPT-Cl) is an organometallic organotin. This study aimed to investigate the role of trigonelline (TG) along with the impact of TPT withdrawal on the testicular toxicity induced by TPT-Cl. Thirty-six adult male albino rats were divided into control, TG (40 mg/kg/day), TPT-Cl (0.5 mg/kg/day), TG + TPT-Cl, and recovery groups. Animals were daily gavaged for 12 weeks. Both TG and TPT-Cl withdrawal improved TPT-Cl-induced testicular toxicity features involving testis and relative testis weight reduction, luteinizing hormone, follicular stimulating hormone, and sex hormone-binding globulin elevation, reduction of inhibin B, free testosterone levels, and sperm count reduction with increased abnormal sperm forms. Moreover, both TG and TPT-Cl withdrawal reduced inflammatory activin A, follistatin, tumor necrosis factor α, interleukin-1ß, and proapoptotic Bax and elevated antiapoptotic Bcl2 in testicular tissues mediated by TPT-Cl. TG and TPT-Cl withdrawal restored the excessive autophagy triggered by TPT-Cl via elevation of mTOR, AKT, PI3K, and P62/SQSTM1 and reduction of AMPK, ULK1, Beclin1, and LC3 mRNA gene expressions and regained the deteriorated testicular structure. In conclusion, TG and TPT-Cl withdrawal had an ameliorative role in partially reversing TPT-Cl-induced testicular toxicity. However, the findings indicated that the use of TG as an adjunctive factor is more favorable than TPT-Cl withdrawal, suggesting the capability of the testis for partial self-improvement.

Asunto(s)

Alcaloides , Compuestos Orgánicos de Estaño , Testículo , Testosterona , Ratas , Animales , Masculino , Testículo/patología , Testosterona/metabolismo , Semen/metabolismo , Apoptosis , Autofagia , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Estrés Oxidativo

RESUMEN

Trigonelline, an alkaloid found in the seeds of Trigonella foenum-graecum L. (fenugreek), has been recognized for its potential in treating various diseases. Notably, trigonelline has demonstrated a neuroprotective impact by reducing intrasynaptosomal calcium levels, inhibiting the production of reactive oxygen species (ROS), and regulating cytokines. Kainic acid, an agonist of kainic acid receptors, is utilized for inducing temporal lobe epilepsy and is a common choice for establishing kainic acid-induced status epilepticus, a widely used epileptic model. The neuroprotective effect of trigonelline in the context of kainic acid-induced epilepsy remains unexplored. This study aimed to induce epilepsy by administering kainic acid (10 mg/kg, single subcutaneous dose) and subsequently evaluate the potential anti-epileptic effect of trigonelline (100 mg/kg, intraperitoneal administration for 14 days). Ethosuccimide (ETX) (187.5 mg/kg) served as the standard drug for comparison. The anti-epileptic effect of trigonelline over a 14-day administration period was examined. Behavioral assessments, such as the Novel Object Recognition (NOR) test, Open Field Test (OFT), and Plus Maze tests, were conducted 2 h after kainic acid administration to investigate spatial and non-spatial acquisition abilities in rats. Additionally, biochemical analysis encompassing intrasynaptosomal calcium levels, LDH activity, serotonin levels, oxidative indicators, and inflammatory cytokines associated with inflammation were evaluated. Trigonelline exhibited significant behavioral improvements by reducing anxiety in open field and plus maze tests, along with an amelioration of memory impairment. Notably, trigonelline substantially lowered intrasynaptosomal calcium levels and LDH activity, indicating its neuroprotective effect by mitigating cytotoxicity and neuronal injury within the hippocampus tissue. Moreover, trigonelline demonstrated a remarkable reduction in inflammatory cytokines and oxidative stress indicators. In summary, this study underscores the potential of trigonelline as an anti-epileptic agent in the context of kainic acid-induced epilepsy. The compound exhibited beneficial effects on behavior, neuroprotection, and inflammation, shedding light on its therapeutic promise for epilepsy management.