Long-Lasting Anti-Inflammatory and Antinociceptive Effects of Acute Ammonium Glycyrrhizinate Administration: Pharmacological, Biochemical, and Docking Studies

Μaione, Francesco; Minosi, Paola; Giannuario, A. Di; Raucci, Federica; Chini, Maria Giovanna; Vita, Simona De; Bifulco, Giuseppe; Mascolo, Nicola; Pieretti, Stefano

doi:10.3390/molecules24132453

Cited by 28 publications

(19 citation statements)

References 80 publications

(98 reference statements)

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“…In addition, we were also interested in exploring the other administration route, i.p., because several anti-inflammatory studies were conducted by i.p. administration [27,28], which is an useful way to demonstrate first-pass effect by liver without causing gastric acid stability issue. After p.o.…”

Section: Discussionmentioning

confidence: 99%

Profiling and Identification of Omeprazole Metabolites in Mouse Brain and Plasma by Isotope Ratio-Monitoring Liquid Chromatography-Mass Spectrometric Method

Shin

Park

et al. 2020

Life

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Neuro–inflammation is known to be one of the pathogenesis for the degenerative central nervous system (CNS) disease. Recently various approaches for the treatment of brain diseases by controlling neuro-inflammation in the brain have been introduced. In this respect, there is a continuous demand for CNS drugs, which could be safer and more effective. Omeprazole, a well-known proton-pump inhibitor (PPI) is generally prescribed for the treatment of peptic ulcer. In addition to the anti-gastric acid secretion mechanism, recent studies showed that omeprazole or PPIs would likely have anti-inflammation effects in vitro and in vivo, but their effects on anti-inflammation in brain are still unknown. In this study, omeprazole and its metabolites in a mouse’s brain after various routes of administration have been explored by stable isotope ratio-patterning liquid chromatography–mass spectrometric method. First, a simple liquid chromatography–mass spectrometric (LC–MS) method was established for the quantification of omeprazole in mouse plasma and brain. After that, omeprazole and its stable isotope (D3–omeprazole) were concomitantly administered through various routes to mice in order to identify novel metabolites characteristically observed in the mouse brain and were analyzed using a different LC–MS method with information-dependent analysis (IDA) scan. With this unique approach, several new metabolites of omeprazole were identified by the mass difference between omeprazole and stable isotope in both brain and plasma samples. A total of seventeen metabolites were observed, and the observed metabolites were different from each administration route or each matrix (brain or plasma). The brain pharmacokinetic profiles and brain-to-plasma partition coefficient (Kp) were also evaluated in a satellite study. Overall, these results provide better insights to understand the CNS-related biological effects of omeprazole and its metabolites in vivo.

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Section: Discussionmentioning

confidence: 99%

Profiling and Identification of Omeprazole Metabolites in Mouse Brain and Plasma by Isotope Ratio-Monitoring Liquid Chromatography-Mass Spectrometric Method

Shin

Park

et al. 2020

Life

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“…Compounds were freshly diluted in saline 0.1% v / v DMSO and were injected at 10 µg/10 µL for intracerebroventricular (i.c.v.) administrations, as previously reported [42,43].…”

Section: Methodsmentioning

confidence: 57%

Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity

et al. 2019

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The endocannabinoid system represents an integrated neuronal network involved in the control of several organisms’ functions, such as feeding behavior. A series of hybrids of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (mimonabant), a well-known inverse agonist of the type-1 cannabinoid receptor (CB1), once used as an antiobesity drug, and the N-(2S)-substitutes of 1-[(4-fluorophenyl)methyl]indazole-3-carboxamide with 1-amino-3-methyl-1-oxobutane (AB-Fubinaca), 1-amino-3,3-dimethyl-1-oxobutane (ADB-Fubinaca), and 3-methylbutanoate (AMB-Fubinaca), endowed with potent agonistic activity towards cannabinoid receptors CB1 and CB2 were in solution as C-terminal amides, acids, methyl esters and N-methyl amides. These compounds have been studied by binding assays to cannabinoid receptors and by functional receptor assays, using rat brain membranes in vitro. The most active among them as an agonist, (S)-1-(2,4-dichlorobenzyl)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-1H-indazole-3-carboxamide (LONI11), and an antagonist, (S)-2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoic acid (LONI4), were tested in vivo in mic, to evaluate their ability to stimulate or suppress feeding behavior after intraperitoneal (i.p.) administration. For a LONI11 formalin test and a tail flick test after an administration by the subcutaneous (s.c.) and intracerebroventricular (i.c.v.) routes, respectively, were also carried out in vivo in mice to investigate the antinociceptive property at the central and peripheral levesl. We observed a significant orexant effect for LONI11 and an intense anorexant effect for (S)-methyl 2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (LONI2) and LONI4. In zymosan-induced edema and hyperalgesia, LONI11 reduced the percent of paw volume increase and paw latency after s.c. administration, also suggesting a possible peripheral anti-inflammatory activity.

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“…The early neurogenic pain phase is stimulated by formalin to activate substance P after its injection. The late inflammatory pain phase is mediated through serotonin, histamine, prostaglandins, and bradykinin release [40]. The central antinociceptive agents equally suppress both stages, while peripheral agents inhibit only the later phase [34,41].…”

Section: Discussionmentioning

confidence: 99%

Antipyretic, Antinociceptive, and Anti-Inflammatory Activities from Pogostemon benghalensis Leaf Extract in Experimental Wister Rats

et al. 2019

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Background: Pogostemon benghalensis leaves have traditionally been utilized for relieving body aches, headaches and fever. Based on its uses, the present study was designed to investigate the antinociceptive, antipyretic and anti-edematogenic activities from P. benghalensis leaves’ methanol extract (PBME) in Wister rats. Methods: The thermal (hot plate) and chemical (acetic acid-induced writhing and formalin test) models for antinociceptive effects, and the Brewer's yeast induced hyperthermia test for antipyretic action and rat paw edema by carrageenan for anti-edematogenic activity, were applied for PBME at different dose levels. The acute toxicity of PBME through the oral route was performed to determine the lethal dose. Results: PBME significantly and dose-dependently reduced pyrexia and diminished edema volume, which depicted its antipyretic and anti-edematogenic effects respectively. The inhibition of writhing reflex, increased reaction latency and reduced frequency of licking indicated that PBME has significant dose-dependent antinociceptive activity. P. benghalensis methanol extract at 4000 mg/kg shows no sign of toxicity, which is a considerable, good margin of safety. Conclusions: The study illustrated the antipyretic, antinociceptive and anti-inflammatory potential of P. benghalensis leaf extract with a safety margin, and validated its traditional use to alleviate fever, pain, and inflammation.

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Long-Lasting Anti-Inflammatory and Antinociceptive Effects of Acute Ammonium Glycyrrhizinate Administration: Pharmacological, Biochemical, and Docking Studies

Cited by 28 publications

References 80 publications

Profiling and Identification of Omeprazole Metabolites in Mouse Brain and Plasma by Isotope Ratio-Monitoring Liquid Chromatography-Mass Spectrometric Method

Profiling and Identification of Omeprazole Metabolites in Mouse Brain and Plasma by Isotope Ratio-Monitoring Liquid Chromatography-Mass Spectrometric Method

Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity

Antipyretic, Antinociceptive, and Anti-Inflammatory Activities from Pogostemon benghalensis Leaf Extract in Experimental Wister Rats

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