Inflammatory responses bridge comorbid cardiac disorder in experimental model of IBD induced by DSS: protective effect of the trigonelline

Omidi-Ardali, Hossein; Lorigooini, Zahra; Soltani, Amin; Balali-Dehkordi, Shima; Amini‐Khoei, Hossein

doi:10.1007/s10787-019-00581-w

Cited by 35 publications

(27 citation statements)

References 39 publications

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“…In line, we also observed decreased level of IL‐4; a proinflammatory marker of T‐helper 2 (Th2) immune response, which is considered to preserve inflammatory reactions . Cancer associated chronic inflammation is a main director in tumor progression and angiogenesis …”

Section: Discussionsupporting

confidence: 70%

Tropisetron attenuates tumor growth and progression in an experimental model of mouse lung cancer

Rashidi

Bazi

Shiran

et al. 2019

J of Cellular Biochemistry

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The antineoplastic effects of 5‐hydroxytryptamine (5‐HT) receptor antagonists have been shown in previous studies. However, the exact underlying mechanisms mediating these antineoplastic effects are unclear. In the present study, we assessed the antineoplastic effects of tropisetron, a 5‐HT receptor antagonist, in an experimental model of lung cancer in BALB/c mouse. Lewis lung carcinoma cell line was used to induce lung cancer. Mice were divided into four groups (n = 6) as follows: tumor‐bearing mice + tropisetron (5 mg/kg intraperitoneally [IP]), tumor‐bearing mice + tropisetron (10 mg/kg IP), tumor‐bearing mice + saline, healthy mice + tropisetron (10 mg/kg). Tumor burden, interferon‐γ (IFN‐γ), interleukin (IL)‐4, pathological response, Ki‐67, and E‐cadherin were assessed using enzyme‐linked immunosorbent assay, and real‐time polymerase chain reaction. Comet assay was used to assess DNA toxicity. Tropisetrone‐treated animals (either 5 or 10 mg/kg) showed significantly lower tumor sizes at the day 24th after tumor induction. Tropisetron received animals also showed significantly higher levels of IFN‐γ, E‐cadherin, pathologic response, and necrotic cells compared to the saline‐treated counterparts. In addition, the levels of IL‐4, and Ki‐67 were significantly lower in tropisetrone treated mice in comparison with control. Furthermore, tropisteron coadministration signifcantly reduced H2O2‐induced DNA toxicity while treatment with tropisteron alone showed no adverse effect on DNA. Tropisetrone can be used as a potential antineoplastic drug in lung cancer. This agent can promote its antineoplastic effects in part through modulating inflammatory and proliferating markers.

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Section: Discussionsupporting

confidence: 70%

Tropisetron attenuates tumor growth and progression in an experimental model of mouse lung cancer

Rashidi

Bazi

Shiran

et al. 2019

J of Cellular Biochemistry

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“…We also found that trigonelline, another activator of HCAR2, was overrepresented. Trigonelline has protective effects in IBD DSS mice models 27 , but is also involved in lipid metabolism, suggesting its role in the HCAR2 upregulation 28 .…”

Section: Discussionmentioning

confidence: 99%

Expanding the drug discovery space with predicted metabolite–target interactions

et al. 2021

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Metabolites produced in the human gut are known modulators of host immunity. However, large-scale identification of metabolite–host receptor interactions remains a daunting challenge. Here, we employed computational approaches to identify 983 potential metabolite–target interactions using the Inflammatory Bowel Disease (IBD) cohort dataset of the Human Microbiome Project 2 (HMP2). Using a consensus of multiple machine learning methods, we ranked metabolites based on importance to IBD, followed by virtual ligand-based screening to identify possible human targets and adding evidence from compound assay, differential gene expression, pathway enrichment, and genome-wide association studies. We confirmed known metabolite–target pairs such as nicotinic acid–GPR109a or linoleoyl ethanolamide–GPR119 and inferred interactions of interest including oleanolic acid–GABRG2 and alpha-CEHC–THRB. Eleven metabolites were tested for bioactivity in vitro using human primary cell-types. By expanding the universe of possible microbial metabolite–host protein interactions, we provide multiple drug targets for potential immune-therapies.

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“…Tohda et al [57], reported that TRG stimulates functional neurite outgrowth. Literature searching showed that the TRG has various pharmacological effects including hypoglycemic, hypolipidemic, neuroprotective, antimigraine, sedative, and memory-improving activities [24,[58][59][60]. Recently, it has been determined that TRG through the attenuation of oxidative stress and mitigation of neuroinflammation exerted a neuroprotective effect against LPS-mediated cognitive impairment [27].…”

Section: Discussionmentioning

confidence: 99%

Trigonelline through the Attenuation of Oxidative Stress Exerts Antidepressant- and Anxiolytic-Like Effects in a Mouse Model of Maternal Separation Stress

et al. 2019

Self Cite

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Depression and anxiety are common psychiatric disorders accounting for social and economic burdens. Previous studies have shown that oxidative stress and oxidant/antioxidant imbalance are involved in the pathophysiology of psychiatric disorders. Experiencing early-life adversities (like maternal separation [MS] stress) provoked psychiatric disorders. Trigonelline (TRG) is a pyridine alkaloid that has various pharmacological effects including hypoglycemic, neuroprotective and memory-improving properties. To investigate the antidepressant-and anxiolytic-like effects of TRG focusing oxidative stress, we applied the MS paradigm to male mice at postnatal day (PND) 2-14 (3 h daily, 9-12 a.m.) and investigated the behaviors at PND 45-47. Using valid behavioral tests including a forced swimming test (FST), splash test, open field test (OFT) and elevated plus maze (EPM), we investigated behavioral modifications. Additionally, we examined the effects of MS and TRG treatment on the level of malondialdehyde (MDA), nitric oxide (NO) and also antioxidant capacity in the brain and serum. Our results showed that MS provoked depressive-and anxiety-like behaviors in the FST, OFT, EPM and splash test, which are associated with an increase in MDA and NO levels as well as a decrease in antioxidant capacity in the brain and serum samples. Findings determined that TRG significantly reversed the negative effects of MS on behavior that is accompanied by a decrease in MDA and NO as well as an increase in antioxidant capacity. Findings of the present study showed that beneficial effects of TRG may be, at least partially, mediated via the reduction of oxidative stress and an increase of antioxidant capacity.

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Inflammatory responses bridge comorbid cardiac disorder in experimental model of IBD induced by DSS: protective effect of the trigonelline

Cited by 35 publications

References 39 publications

Tropisetron attenuates tumor growth and progression in an experimental model of mouse lung cancer

Tropisetron attenuates tumor growth and progression in an experimental model of mouse lung cancer

Expanding the drug discovery space with predicted metabolite–target interactions

Trigonelline through the Attenuation of Oxidative Stress Exerts Antidepressant- and Anxiolytic-Like Effects in a Mouse Model of Maternal Separation Stress

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