Glycyrrhizic acid suppresses Cox-2-mediated anti-inflammatory responses during Leishmania donovani infection

Bhattacharjee, Surajit; Bhattacharjee, Amrita; Majumder, Saikat; Majumdar, Suchandra Bhattacharya; Majumdar, Subrata

doi:10.1093/jac/dks159

Cited by 89 publications

(93 citation statements)

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“…Equal amounts of protein (30 g) were subjected to 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were subsequently transferred to a nitrocellulose membrane (Millipore, Bedford, MA). The membrane was blocked overnight with 3% bovine serum albumin in Tris-saline buffer (pH 7.5), and immunoblotting was performed to detect Cox-2 (Santa Cruz Biotechnology), arginase I (abcam), iNOS (Santa Cruz Biotechnology), and GAPDH (Santa Cruz Biotechnology) as described previously (17). Densitometric analyses of bands were performed using Quantity One 4.6.1 (basic) software (Bio-Rad).…”

Section: Methodsmentioning

confidence: 99%

“…Enzyme-linked immunosorbent assays (ELISAs) were performed according to the manufacturer's instructions (17).…”

Section: Methodsmentioning

confidence: 99%

“…On the other hand, glycyrrhizic acid (GA), a predominant bioactive component of the root of Glycyrrhiza glabra, has been reported to evoke antileishmanial activity through regulation of Cox-2 production (17). MDSCs exert a suppressive function on T cells that is dependent on the production of arginase I (11,12).…”

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confidence: 99%

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Glycyrrhizic Acid-Mediated Subdual of Myeloid-Derived Suppressor Cells Induces Antileishmanial Immune Responses in a Susceptible Host

et al. 2015

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CD11b؉ Gr1 ؉ myeloid-derived suppressor cells (MDSCs), a heterogeneous population of precursor cells, modulate protective immunity against visceral leishmaniasis by suppressing T cell functions. We observed that CD11b ϩ cells have been shown to be essential for the production of early Th1 cytokines in murine draining lymph nodes (14). However, the suppression mechanism of MDSCs includes production of cyclooxygenase-2 (Cox-2) and arginase I and blocking of T cell function by depleting L-arginine (15). Interestingly, pharmacological inhibition of Cox-2 blocked the expression of arginase I in lung carcinoma (16), though it was not clear how suppression of Cox-2 in MDSCs could affect Leishmania infection in a susceptible host.On the other hand, glycyrrhizic acid (GA), a predominant bioactive component of the root of Glycyrrhiza glabra, has been reported to evoke antileishmanial activity through regulation of Cox-2 production (17). MDSCs exert a suppressive function on T cells that is dependent on the production of arginase I (11, 12). We aimed to investigate how MDSCs and their pharmacological manipulation affect the host immune response against L. donovani infection. Here we show that MDSCs from soluble leishmanial antigen (SLA)-immunized BALB/c mice are less immunosuppressive than infection-induced MDSCs and fail to inhibit the induction of Th1 cytokines. Immunization of BALB/c mice with SLA resulted in reduced production of arginase I, Cox-2, inducible nitric oxide synthase (iNOS), and prostaglandin E2 (PGE2) in MDSCs. Moreover, pharmacological inhibition of Cox-2 by GA in BALB/c mice rendered the MDSCs nonsuppressive. In summary, we demonstrated an antileishmanial effect of Cox-2 inhibition by GA in myeloid-derived suppressor cells, a strategy that may be useful for eliminating the suppressive effect of MDSCs in relevant pathological contexts.

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Section: Methodsmentioning

confidence: 99%

“…Enzyme-linked immunosorbent assays (ELISAs) were performed according to the manufacturer's instructions (17).…”

Section: Methodsmentioning

confidence: 99%

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Glycyrrhizic Acid-Mediated Subdual of Myeloid-Derived Suppressor Cells Induces Antileishmanial Immune Responses in a Susceptible Host

et al. 2015

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“…Another constituent of licorice, which serves as an antileishmanial compound, is glycyrrhizic acid (GA) [43]. The studies using this compound showed an increase in NO production with restoration of Th1 cytokine balance and inhibition of immunosuppressive prostaglandin E2(PGE2) production.…”

Section: Glycyrrhizic Acidmentioning

confidence: 99%

Bioactive Component of Licorice as an Antileishmanial Agent

Gupta¹,

Ukil²,

Das³

2017

Biological Activities and Action Mechanisms of Licorice Ingredients

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The term leishmaniasis encompasses a spectrum of vector-borne protozoan parasitic diseases ranging from self-healing cutaneous to fatal visceral leishmaniasis. The disease affects 12 million people worldwide with 0.5 million new cases per annum. Present antileishmanial chemotherapeutic drugs project limitations because of severe toxicity, lengthy regime and occurrence of resistance, thereby making development of newer, gentler and efficacious therapeutics an urgent need for treatment of leishmaniasis. Application of medicinal plants in treatment of refractory diseases is valued for its clinical efficacy and nontoxicity. The biologically active components derived from them continue to play important roles as chemopreventive agents. Licorice has been known for its medicinal property from ancient times for treatment of various ailments. 18β-Glycyrrhetinic acid, glycyrrhizic acid and licochalcone A are the most extensively studied constituents of licorice in terms of antileishmanial agent. Overall, this chapter is dedicated to highlight the current understanding of the mechanism of these bioactive constituents of licorice, which potentiates them as antileishmanial agents. Furthermore, it also brings to light the importance of folk medicine in curing diseases and thereby gives impetus to explore ancient medicines and thier mode of actions to use them progressively to cure diseases.

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“…GA or GE, and in some cases, both acids, have exerted in many in vitro and in vivo studies, antiulcer [2], anti-inflammatory [2], hepatoprotective [17], anticancer [37,47], antibacterial [25], antiviral [3,10,13], antileishmanial [6,42] and neuroprotective activities, as well as cell-protective and chemopreventive effects [1,50]. Moreover, GE and its analogues have demonstrated anticoagulant activity as inhibitors of blood coagulation factor Xa, and have shown antifilarial properties against microfilariae and adult worms of Brugia malayi [18,19].…”

mentioning

confidence: 99%

Glycyrrhetinic acid and its derivatives in infectious diseases

Langer

Czarczyńska-Goślińska

Gośliński

2016

Current Issues in Pharmacy and Medical Sciences

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Introduction. Licorice or liquorice (Glycyrrhiza glabra, Leguminosae) is a perennial plant naturally occurring or cultivated in Europe and Asia. It was appreciated by many ancient cultures, and was employed within Arabic medicine and (beginning in the Middle Ages) in Europe folk medicine as a remedy for many diseases. Currently, the sweet flavoured root of this plant – Radix Glycyrrhizae (Liquirtiae), is widely taken for the treating of various upper respiratory tract diseases, as well as for gastric ulcer disease. It is also utilized as a sweetening and flavouring agent in the food, tobacco and pharmacy industries. The main active ingredient of liquorice is the triterpenoid saponin, glycyrrhizin, which is a mixture of calcium, magnesium and potassium salts of glycyrrhizic acid (GA). Glycyrrhizic acid is composed of an aglycone, that is 18β-glycyrrhetinic acid (GE), and a D-glucuronic acid dimer. The aim of this review is to discuss some aspects of the activity of glycyrrhetinic acid and its derivatives in infectious diseases.State of knowledge. The pentacyclic system of glycyrrhetinic acid consists of condensed six-membered rings with a hydroxyl group at C-3, a carboxyl moiety at C-30 and a ketone functional group at C-11. Considering the presence of the above mentioned functional groups, many structural transformations have been proposed, including those by way of esterification, alkylation and reduction reactions. The introduction of various chemical residues into its structure, as well as the modification of the glycyrrhetinic acid in its pentacyclic triterpene skeleton, has led to the generation of compounds with many valuable antimicrobial, anti-parasitic, antiviral properties and modified lipophilic parameters.Summary. In summary, glycyrrhetinic acid derivatives appear to have promise as active pharmaceutical ingredients that contain a wide range of biological and pharmacological properties.

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Glycyrrhizic acid suppresses Cox-2-mediated anti-inflammatory responses during Leishmania donovani infection

Abstract: These results provide a mechanistic understanding of GA-mediated protection against leishmanial parasites within the host.

Cited by 89 publications

References 41 publications

Glycyrrhizic Acid-Mediated Subdual of Myeloid-Derived Suppressor Cells Induces Antileishmanial Immune Responses in a Susceptible Host

Glycyrrhizic Acid-Mediated Subdual of Myeloid-Derived Suppressor Cells Induces Antileishmanial Immune Responses in a Susceptible Host

Bioactive Component of Licorice as an Antileishmanial Agent

Glycyrrhetinic acid and its derivatives in infectious diseases

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