Phytomedicine 18 (2011) 278–284 Contents lists available at ScienceDirect Phytomedicine journal homepage: www.elsevier.de/phymed Short communication Dual inhibitory effect of Glycyrrhiza glabra (GutGard TM ) on COX and LOX products C.V. Chandrasekaran ∗ , H.B. Deepak, P. Thiyagarajan, S. Kathiresan, Gopal Krishna Sangli, M. Deepak, Amit Agarwal R&D Centre, Natural Remedies Pvt. Ltd., Bangalore, India article info Keywords: Glycyrrhiza glabra Phytoconstituents (glabridin, isoliquiritigenin, glycyrrhizin) Inflammation COX products (PGE2, TXB2) LOX product (LTB4) abstract Glycyrrhiza glabra and its phytoconstituents have been known to possess widespread pharmacological properties as an anti-inflammatory, anti-viral, antitumour and hepatoprotective drug. In this study, we examined the inhibitory potential of extract of G. glabra (GutGard TM ) root and its phytoconstituents (glabridin, glycyrrhizin, and isoliquiritigenin) on both cyclooxygenase (COX) and lipoxygenase (LOX) products in order to understand the mechanism of its anti-inflammatory action. Inhibitory effect of GutGard TM and its phytoconstituents on lipopolysaccharide (LPS) induced prostaglandin E 2 (PGE 2 ), cal- cimycin (A23187) induced thromboxane (TXB 2 ), and leukotriene (LTB 4 ) release was studied using murine macrophages (J774A.1) and human neutrophil (HL-60) cells. Results revealed that, G. glabra and glabridin significantly inhibited PGE 2 , TXB 2 (COX) and LTB 4 (LOX), while, isoliquiritigenin exerted inhibitory effect only against COX products but failed to suppress LOX product. However, glycyrrhizin at the tested con- centrations failed to exhibit inhibitory effect on both COX and LOX products. Here, we report for the first time that G. glabra (almost devoid of glycyrrhizin) exhibits anti-inflammatory property likely through the inhibition of PGE 2 , TXB 2 and LTB 4 in mammalian cell assay system, which could be influenced in part by glabridin and isoliquiritigenin. © 2010 Elsevier GmbH. All rights reserved. Introduction Glycyrrhiza glabra (G. glabra L.; Family: Papilionaceae/Fabaceae) is a well-known medicinal herb that has long been used in the traditional medicinal system for multiple pharmaco- logical activities (Khattak and Simpson 2010). It is a highly reputed ayurvedic plant used in the herbal preparations as a tonic, expectorant and demulcent (Ambawade et al. 2002). It has been reported to have antioxidant (Toshio et al. 2003), immunostimulant, and anti-allergenic (Zore et al. 2008) activ- ities. Recently, Mukherjee et al. (2010) reported the anti-ulcer and anti-oxidant activity of standardized extract of G. glabra (GutGard TM ). Phytochemical investigation has demonstrated that major bioactive components of licorice root are flavonoids and penta- cyclic triterpene saponin, including isoliquiritigenin, glycyrrhizin, glabridin and glycyrrhizic acid (Kamei et al. 2003). Isoliquiriti- genin is a flavonoid from licorice having diverse biological activities ∗ Corresponding author at: Plot No. 5B, Veerasandra Indl. Area, 19th K. M. Stone, Hosur Road, Bangalore 560100, Karnataka, India. Tel.: +91 80 40209999; fax: +91 80 40209817. E-mail addresses: cvc@naturalremedy.com, cvctox@gmail.com (C.V. Chandrasekaran). such as antiallergic (Kakegawa et al. 1992), antioxidant (Vaya et al. 1997), etc. Apparently, the major pharmacological action of the plant is mainly attributed to glabridin, a chief active flavonoid, which exhibits wide range of biological activities (Kang et al. 2005). However, little is known about the pharmacological mechanisms underlying these actions, although some of its anti-inflammatory effects have been investigated. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are both key enzymes involved in the arachidonic acid (AA) cascade (Funk 2001). The prostaglandins (PGs) and thromboxanes (TXs) produced by COX plays a major role in inflammatory reactions and are respon- sible for the characteristic inflammatory symptoms (Smith et al. 1996; Gaddi et al. 2004). Considering the potent pro-inflammatory properties of LTB 4 , the modulation of this pathway should be interesting in the treatment of numerous diseases such as allergic and inflammatory disorders (Brain and Williams 1990). Previous reports have suggested that G. glabra inhibits both COX-2 and 5-LOX enzymes in cell free system (Herold et al. 2003). In order to elucidate the mechanism of its anti-inflammatory activity, we investigated the inhibitory effect of extract of G. glabra root and its active prin- ciples (glabridin, glycyrrhizin, and isoliquiritigenin) on COX and LOX products in cell based assays. We examined LPS induced PGE 2 release in murine macrophages (J774A.1) and A23187 stimulated LTB 4 and TXB 2 levels in human promyelocytic leukemic (HL-60) cells. 0944-7113/$ – see front matter © 2010 Elsevier GmbH. All rights reserved. doi:10.1016/j.phymed.2010.08.001