Abstract
The object of the study was to estimate the long-lasting effects induced by ammonium glycyrrhizinate (AG) after a single administration in mice using animal models of pain and inflammation together with biochemical and docking studies. A single intraperitoneal injection of AG was able to produce anti-inflammatory effects in zymosan-induced paw edema and peritonitis. Moreover, in several animal models of pain, such as the writhing test, the formalin test, and hyperalgesia induced by zymosan, AG administered 24 h before the tests was able to induce a strong antinociceptive effect. Molecular docking studies revealed that AG possesses higher affinity for microsomal prostaglandin E synthase type-2 compared to type-1, whereas it seems to locate better in the binding pocket of cyclooxygenase (COX)-2 compared to COX-1. These results demonstrated that AG induced anti-inflammatory and antinociceptive effects until 24–48 h after a single administration thanks to its ability to bind the COX/mPGEs pathway. Taken together, all these findings highlight the potential use of AG for clinical treatment of pain and/or inflammatory-related diseases.
Highlights
The most prevalent medical issues strongly affecting people in terms of health and quality of life are acute and chronic pain [1]
Molecular docking studies revealed that ammonium glycyrrhizinate (AG) possesses higher affinity for microsomal prostaglandin E synthase type-2 compared to type-1, whereas it seems to locate better in the binding pocket of cyclooxygenase (COX)-2 compared to COX-1
In animals treated with vehicle (Hepes, 10 mL/kg, i.p.) 10 min before zymosan, we discovered a rise in paw volume that achieved the maximal value 3–4 h after the injection, followed by a slight reduction in the following 48 h (Figure 1)
Summary
The most prevalent medical issues strongly affecting people in terms of health and quality of life are acute and chronic pain [1]. Acute and chronic pain are different clinical entities. A considerable number of studies have demonstrated that several mediators, including cytokines (Interleukin (IL) -1β, IL-6, IL-17, IL-10, tumor necrosis factor (TNF) -α), chemokines (chemokine (CXCL1), Motif Chemokine Ligand (CCL2), C-X-C chemokine receptor type 2 (CXCR2)), lipid mediators (prostaglandins and leukotrienes) and growth factors (nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF)), play an important role in inflammatory pain [2]. Two types of treatments can be used to treat inflammatory pain: nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. Very often there are several side effects, such as gastrointestinal lesions [3]
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