Liquiritigenin

1 Pterocarpus sp.

Liquiritigenin exhibits antitumour action in pituitary adenoma cells via Ras/ERKs and ROS-dependent mitochondrial signalling pathways.[Pubmed:24491032]

J Pharm Pharmacol. 2014 Mar;66(3):408-17.

OBJECTIVE: The purpose of this study was to investigate antitumour effects of Liquiritigenin (LQ) on pituitary adenoma in in-vitro and in-vivo models. METHODS: The effects of LQ on cell viability, apoptosis rate, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) level and various apoptosis-related mediators were examined in MMQ and GH3 cells that are derived from rat pituitary adenoma. Antitumour effect of LQ was also examined in the mouse model of GH3-xenografted tumour. KEY FINDINGS: LQ inhibited cell viability, caused G1 phase arrest and initiated apoptosis in both MMQ and GH3 cells. LQ dissipated MMP, increased intracellular ROS level and cytosol cytochrome C, and reduced the expression of Ras, B-cell lymphoma 2 and B-cell lymphoma-extra large. LQ also inhibited the activation of extracellular signalling-regulated kinases (ERKs) and the translocation of from cytoplasm to nucleus. LQ markedly reduced tumour size without affecting bodyweight in mice with GH3 cells xenograft. CONCLUSIONS: LQ effectively inhibits pituitary adenoma tumour growth and induces cell apoptotic death mainly via Ras/ERKs and ROS-dependent mitochondrial pathways, suggesting that LQ is a potential suppressor of pituitary adenoma.

Liquiritigenin alleviates mechanical and cold hyperalgesia in a rat neuropathic pain model.[Pubmed:25022218]

Sci Rep. 2014 Jul 14;4:5676.

This study assessed the potential antinociceptive effects of Liquiritigenin, a plant-derived compound with transient receptor potential melastatin 3 blocking activity in a rat model of persistent neuropathic pain. Chronic constriction injury (CCI) to the sciatic nerve was induced in male Sprague-Dawley rats to model human peripheral neuropathic pain. Liquiritigenin (1, 3, or 9 mg/kg) was administered intraperitoneally to examine the effects on mechanical, thermal, and cold hyperalgesia using the von Frey test, plantar test, and cold plate test, respectively. A rotarod test was also conducted to examine motor function. Liquiritigenin dose dependently alleviated mechanical, thermal and cold hyperalgesia. In addition, daily repeated treatment with Liquiritigenin did not demonstrate significant antinociceptive tolerance in the measures of hyperalgesia. Within the doses studied, Liquiritigenin did not significantly affect motor performance. These results suggest that Liquiritigenin may be potentially useful novel treatments for neuropathic pain.

Amelioration of trinitrobenzene sulfonic acid-induced colitis in mice by liquiritigenin.[Pubmed:25311527]

J Gastroenterol Hepatol. 2015 May;30(5):858-65.

BACKGROUND AND AIM: The anti-inflammatory effects of Liquiritigenin, a major flavonoid isolated from Glycyrrhizae uralensis, have been reported in many inflammation models. However, its protective effects have not been reported in a colitis model. This study investigated the anti-inflammatory effect and mechanism of Liquiritigenin for trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. METHODS: Male mice imprinting control regions (ICR) were randomly divided into five groups: normal, TNBS-induced colitis, colitis treated with Liquiritigenin at low dose (10 mg/kg) and high dose (20 mg/kg), or mesalazine (10 mg/kg). TNBS colitis induction was performed except for in the normal group, and they were treated with Liquiritigenin or mesalazine except control group. The treatment effect was measured after three days treatment, by body weight, colon length, macroscopic score, histological score, levels of cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, and IL-10) in colon tissue as well as the nuclear factor kappa-light-chain-enhancer pathway of activated B cells (NF-kappaB) activation. RESULTS: Mice treated with high-dose Liquiritigenin showed significant body weight gain, inhibition of colon shortening, protective effect on histological damages, and myeloperoxidase activity of colon tissue compared with the control group. Furthermore, mice treated with high-dose Liquiritigenin experienced significantly suppressed tumor necrosis factor-alpha, IL-1beta, and IL-6 as well as enhanced IL-10 expression (all P < 0.05). High-dose Liquiritigenin treatment group showed significant decreases in TNBS-induced phosphorylation of IKKbeta, p65, and IkappaB-alpha. CONCLUSION: Liquiritigenin may ameliorate TNBS-induced colitis in mice by suppressing expression of pro-inflammatory cytokines through NF-kappaB pathway.

Tacrine, an oral acetylcholinesterase inhibitor, induced hepatic oxidative damage, which was blocked by liquiritigenin through GSK3-beta inhibition.[Pubmed:25747977]

Biol Pharm Bull. 2015;38(2):184-92.

Although the cholinesterase inhibitor tacrine has been successfully used for the treatment of Alzheimer's disease, it is known to have hepatotoxic effects. Liquiritigenin (LQ), an active flavonoid in Glycyrrhizae radix, exerts protective effects against liver damage. This study investigated the toxic effect of tacrine on hepatocytes and the beneficial effect of LQ on tacrine intoxication in vivo and in vitro, and the underlying mechanism involved. In hepatocyte cell lines, tacrine induced cell death and oxidative stress, as indicated by decreases in cell viability and glutathione (GSH) contents, which were blocked by pretreatment with LQ. Fluorescent activated cell sorter (FACS) analysis revealed that LQ inhibited cellular H2O2 production and mitochondrial dysfunction induced by tacrine in HepG2 cells. Furthermore, LQ promoted inhibitory phosphorylation of glycogen synthase kinase-3beta (GSK3beta) and prevented decreases in GSK3beta phosphorylation induced by tacrine. In rats treatment with tacrine at 30 mg/kg increased hepatic damage as assessed by blood biochemistry and histopathology. Administration of LQ (10 or 30 mg/kg/d, per os (p.o.)) or the hepatoprotective drug sylimarin (100 mg/kg/d) for 3 d inhibited elevations in alanine aminotransferase, aspartate aminotransferase, and histological changes induced by tacrine. These results show that LQ efficaciously protects the rat liver against tacrine-induced liver damage, and suggest that LQ is a therapeutic candidate for ameliorating the hepatotoxic effects of tacrine.

Liquiritigenin induces tumor cell death through mitogen-activated protein kinase- (MPAKs-) mediated pathway in hepatocellular carcinoma cells.[Pubmed:24738081]

Biomed Res Int. 2014;2014:965316.

Liquiritigenin (LQ), separated from Glycyrrhiza radix, possesses anti-inflammatory, antihyperlipidemic, and antiallergic effects. Our present study aims to investigate the antihepatocellular carcinoma effects of LQ both in cell and animal models. LQ strikingly reduced cell viability, enhanced apoptotic rate, induced lactate dehydrogenase over-release, and increased intracellular reactive oxygen species (ROS) level and caspase 3 activity in both PLC/PRL/5 and HepG2 cells. The expression of cleaved PARP, the hall-marker of apoptosis, was enhanced by LQ. LQ treatment resulted in a reduction of the expressions of B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL), and an increase of the phosphorylation of c-Jun N-terminal kinases (JNK) and P38. LQ-mediated cell viability reduction, mitochondrial dysfunction, apoptosis related protein abnormal expressions, and JNK and P38 activation were partially abolished by N-Acetyl-L-cysteine (a ROS inhibitor) pretreatment. Moreover, LQ suppressed the activation of extracellular signaling-regulated kinase (ERKs) and reduced the translocation of phosphor-ERKs from cytoplasm to nucleus. This antitumor activity was further confirmed in PLC/PRL/5-xenografted mice model. All these data indicate that the antihepatocellular carcinoma effects of LQ are related to its modulation of the activations of mitogen-activated protein kinase (MAPKs). The study provides experimental evidence supporting LQ as a potential therapeutic agent for hepatocellular carcinoma treatment.

Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-kappaB-dependent iNOS and proinflammatory cytokines production.[Pubmed:18332856]

Br J Pharmacol. 2008 May;154(1):165-73.

BACKGROUND AND PURPOSE: Glycyrrhizae radix has been widely used as a cytoprotective, plant-derived medicine. We have identified a flavanoid, Liquiritigenin, as an active component in extracts of Glycyrrhizae radix. This research investigated the effects of Liquiritigenin on the induction of inducible NOS (iNOS) and proinflammatory cytokines by lipopolysaccharide (LPS) in Raw264.7 cells, and on paw oedema in rats. EXPERIMENTAL APPROACH: iNOS expression was determined by western blotting, real-time reverse transcription-PCR and reporter gene analyses. Tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 were assayed by ELISA. Gel shift assay and immunoblotting were used to assess NF-kappaB activation. The effect of Liquiritigenin on acute inflammation in vivo was evaluated using carrageenan-induced paw oedema. KEY RESULTS: Treatment of Raw264.7 cells with Liquiritigenin caused inhibition of LPS-induced NF-kappaB DNA binding activity, due to repression of I-kappaBalpha phosphorylation and degradation. Liquiritigenin treatment prevented LPS from increasing the levels of iNOS protein and mRNA in a concentration-dependent manner. Liquiritigenin also suppressed the production of TNF-alpha, IL-1beta and IL-6 from Raw264.7 cells after LPS. In rats, Liquiritigenin treatment inhibited formation of paw oedema induced by carrageenan. CONCLUSION AND IMPLICATIONS: These results demonstrate that Liquiritigenin exerts anti-inflammatory effects, which results from the inhibition of NF-kappaB activation in macrophages, thereby decreasing production of iNOS and proinflammatory cytokines. Our findings showing inhibition by Liquiritigenin of paw oedema as well as inflammatory gene induction will help to understand the pharmacology and mode of action of Liquiritigenin, and of the anti-inflammatory use of Glycyrrhizae radix.

Liquiritigenin is a plant-derived highly selective estrogen receptor beta agonist.[Pubmed:18177995]

Mol Cell Endocrinol. 2008 Feb 13;283(1-2):49-57.

After the Women's Health Initiative found that the risks of hormone therapy outweighed the benefits, a need for alternative drugs to treat menopausal symptoms has emerged. We explored the possibility that botanical agents used in Traditional Chinese Medicine for menopausal symptoms contain ERbeta-selective estrogens. We previously reported that an extract containing 22 herbs, MF101 has ERbeta-selective properties. In this study we isolated Liquiritigenin, the most active estrogenic compound from the root of Glycyrrhizae uralensis Fisch, which is one of the plants found in MF101. Liquiritigenin activated multiple ER regulatory elements and native target genes with ERbeta but not ERalpha. The ERbeta-selectivity of Liquiritigenin was due to the selective recruitment of the coactivator steroid receptor coactivator-2 to target genes. In a mouse xenograph model, Liquiritigenin did not stimulate uterine size or tumorigenesis of MCF-7 breast cancer cells. Our results demonstrate that some plants contain highly selective estrogens for ERbeta.

Liquiritigenin, a flavanone isolated from Glycyrrhiza uralensis, is a highly selective estrogen receptor β (ERβ) agonist with an EC50 of 36.5 nM for activation of the ERE tk-Luc.

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