Pharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3385 - 3385

Published: March 16, 2024

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

Language: Английский

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Electroacupuncture combined with trigonelline inhibits pyroptosis in cerebral ischemia-reperfusion by suppressing autophagy via the PI3K/AKT/mTOR signaling pathway

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111200 - 111200

Published: Jan. 1, 2025

Electroacupuncture (EA) and trigonelline (TG) have been reported to be beneficial in alleviating cerebral ischemia/reperfusion injury (CIRI). However, the synergistic effects of EA TG CIRI underlying mechanism not demonstrated. Rats were subjected middle artery occlusion (MCAO) surgery reperfusion (MCAO/R) establish a model. Neurological deficit score was evaluated using Garcia's scale. Cerebral infarction rats determined TTC staining. Brain tissue morphology assessed by HE The expression various proteins measured IF assay western blot. or treatment could effectively ameliorate neurological disorders, attenuate reduce neuronal damage brain rats. In addition, suppressed autophagy pyroptosis More importantly, intervention observed ameliorating suppressing pyroptosis, while Rapa, an inducer autophagy, strengthened these MCAO/R-induced Furthermore. Rapa reversed combination with TG-mediated improvement suppression Notably, PI3K/AKT/mTOR pathway inactivated combined enhanced activation pathway. LY294002, inhibitor pathway, stimulated pyroptosis. which dependent on inhibition through signaling

Language: Английский

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Hippocampal gray matter volume alterations in patients with first-episode and recurrent major depressive disorder and their associations with gene profiles

BMC Psychiatry, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 15, 2025

Recent studies indicate that patients with first-episode drug-naïve (FEDN) and recurrent major depressive disorder (R-MDD) exhibit distinct atrophy patterns in the hippocampal subregions along proximal-distal axis. However, it remains unclear whether such differences occur long axis how they may relate to specific genes. In present study, we analyzed T1-weighted images from 421 (FEDN: n = 232; R-MDD: 189) 544 normal controls (NC) as part of REST-meta-MDD consortium. Additionally, transcriptome maps structural Magnetic Resonance Imaging (MRI) data six donated brains were obtained Allen Human Brain Atlas (AHBA). We first identified changes gray matter volume (GMV) within hippocampus both FEDN R-MDD then integrated these findings AHBA investigate genes associated GMV changes. Compared NC, displayed reduced left tail, whereas exhibited decreased bilateral body increased tail. Further analysis revealed expression levels SYTL2 positively correlated patients, while SORCS3 SLIT2 those R-MDD. Our results suggest alterations subfields differ between R-MDD, reflecting progressive deterioration prolonged depression, potentially supported by These offer valuable insights into neural genetic mechanisms underlying which aid development more targeted effective treatment strategies for MDD subtypes.

Language: Английский

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Compositional analysis of baru (Dipteryx alata Vog.) pulp highlighting its industrial potential

Food Research International, Journal Year: 2025, Volume and Issue: 201, P. 115548 - 115548

Published: Jan. 2, 2025

Language: Английский

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Senescence Accelerated Mouse-Prone 8: a Model of Neuroinflammation and Aging with Features of Sporadic Alzheimer’s disease

Stem Cells, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract The large majority of Alzheimer’s disease (AD) cases are sporadic with unknown genetic causes. In contrast, only a small percentage AD familial, known Paradoxically, there few validated mouse models but many familial AD. Senescence Accelerated Mouse-Prone 8 (SAMP8) mice model accelerated aging features They exhibit more complete suite human AD-relevant pathologies than most models. SAMP8 brains characterized by inflammation, glial activation, β-amyloid deposits, and hyperphosphorylated Tau. excess amyloid deposits congregate around blood vessels leading to vascular impairment leaky BBBs in these mice. also neuronal cell death, feature not typically seen Additionally, adult hippocampal neurogenesis is decreased correspondingly, they have reduced cognitive ability. line this, LTP significantly compromised No perfect limited the lack clarity about their genomic differences from control SAMR1 (Senescence Mouse-Resistant 1) although transcriptomics changes being revealed. To further complicate matters, multiple substrains emerged over years, sometimes making comparisons studies difficult. Despite challenges, we argue that can be useful for studying symptoms propose important experiments strengthen this already model.

Language: Английский

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Gut-Brain Axis-Based Polygala Tenuifolia and Magnolia Officinalis Improve D-gal-Induced Cognitive Impairment in Mice Through cAMP and NF-κB Signaling Pathways

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 1869 - 1894

Published: March 1, 2025

Polygala tenuifolia Willd. (PT) is commonly used to address cognitive impairment (CI), while Magnolia officinalis Rehd. et Wils (MO) often prescribed for gastrointestinal issues as well CI. This study seeks explore the impacts and mechanisms behind combined therapy of PT MO (PM) in treating CI, based on concept gut-brain axis. The characteristic components PT, MO, PM were identified using ultra-high performance liquid chromatography-tandem triple quadrupole mass Spectrometry (UPLC-MS/MS). A mouse model was established by D-gal induction, effects CI evaluated through behavioral tests, pathological staining, Enzyme-Linked Immunosorbent Assay (ELISA). Subsequently, network pharmacology analyze potential which improves followed validation Western blotting (WB), traditional Chinese medicine (TEM), Immunofluorescence (IF), 16S rRNA. can each alleviate decline neuropathological damage mice varying degrees, reduce expression pro-inflammatory factors (TNF-α, IL-1β, IL-6, IFN-γ, LPS) serum or hippocampal tissue, increase SOD GSH levels. Network analysis molecular experiments confirmed that upregulates tight junction s (TJs), enhances proteins cAMP pathway, inhibits p-NF-κB-p65 expression. reverses D-gal-induced gut microbiota dysbiosis, increases abundance SCFA-producing bacteria, decreases LPS-producing bacteria. alleviates reducing inflammation oxidative stress, protecting blood-brain barrier (BBB) intestinal barrier, inhibiting NF-κB activating regulating microbiota.

Language: Английский

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The inhibitory effects of proteins secreted from trigonelline-treated renal cells on calcium oxalate crystals in vitro: Implications for kidney stone prevention

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 186, P. 118003 - 118003

Published: March 24, 2025

Language: Английский

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Trigonelline mitigates bleomycin-induced pulmonary inflammation and fibrosis: Insight into NLRP3 inflammasome and SPHK1/S1P/Hippo signaling modulation

Life Sciences, Journal Year: 2023, Volume and Issue: 336, P. 122272 - 122272

Published: Nov. 18, 2023

Language: Английский

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Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6793 - 6793

Published: June 20, 2024

Aging is a complex and time-dependent decline in physiological function that affects most organisms, leading to increased risk of age-related diseases. Investigating the molecular underpinnings aging crucial identify geroprotectors, precisely quantify biological age, propose healthy longevity approaches. This review explores pathways are currently being investigated as intervention targets biomarkers spanning molecular, cellular, systemic dimensions. Interventions target these hallmarks may ameliorate process, with some progressing clinical trials. Biomarkers used estimate aging-associated disease. Utilizing biomarkers, clocks can be constructed predict state abnormal aging, diseases, mortality. Biological age estimation therefore provide basis for fine-grained stratification by predicting all-cause mortality well ahead onset specific thus offering window intervention. Yet, despite technological advancements, challenges persist due individual variability dynamic nature biomarkers. Addressing this requires longitudinal studies robust biomarker identification. Overall, utilizing discover new drug develop opens frontiers medicine. Prospects involve multi-omics integration, machine learning, personalized approaches targeted interventions, promising healthier population.

Language: Английский

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A High-Throughput Screening of a Natural Products Library for Mitochondria Modulators

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 440 - 440

Published: April 4, 2024

Mitochondria, the energy hubs of cell, are progressively becoming attractive targets in search for potent therapeutics against neurodegenerative diseases. The pivotal role mitochondrial dysfunction pathogenesis various diseases, including Parkinson’s disease (PD), underscores urgency discovering novel therapeutic strategies. Given limitations associated with available treatments dysfunction-associated new alternatives has become imperative. In this report, we embarked on an extensive screening 4224 fractions from 384 Australian marine organisms and plant samples to identify natural products protective effects mitochondria. Our initial using PD patient-sourced olfactory neurosphere-derived (hONS) cells rotenone as a mitochondria stressor resulted 108 promising 11 different biota. To further assess potency efficacy these hits, biotas were subjected subsequent round human neuroblastoma (SH-SY5Y) cells, 6-hydroxydopamine induce stress, complemented by membrane potential assay. This rigorous process yielded 35 active eight biotas. Advanced analysis orbit trap mass spectrophotometer facilitated identification molecular constituents most fraction each meticulous approach led discovery 57 unique compounds, among which 12 previously recognized their mitoprotective effects. findings highlight vast derived plants quest innovative targeting

Language: Английский

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