Licochalcone A

The roots of Glycyrrhiza glabra L.

Licochalcone A, a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, presents obvious anti-cancer effects. The IC50 value is 0.97 μM for UGT1A1.

References:
[1]. Tang ZH, et al. Induction of C/EBP homologous protein-mediated apoptosis and autophagy by licochalcone A in non-small cell lung cancer cells. Sci Rep. 2016 May 17;6:26241. [2]. Hong Xin, et al. Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases. Food and Chemical Toxicology Volume 90, April 2016, Pages 112–122 [3]. Egler J, et al. Licochalcone A Induced Suicidal Death of Human Erythrocytes. Cell Physiol Biochem. 2015;37(5):2060-70.

Antimetastatic effects of licochalcone A on oral cancer via regulating metastasis-associated proteases.[Pubmed:24789273]

Tumour Biol. 2014 Aug;35(8):7467-74.

Licochalcone A, a major phenolic constituent of the licorice species Glycyrrhiza inflata, has been proven to possess various biological benefits including anti-cancer activity. However, the detailed effects and molecular mechanisms of Licochalcone A on the invasiveness and metastasis of oral cancer cells have not been fully understood. Thus, SCC-25 oral cancer cells were subjected to a treatment with Licochalcone A at indicated concentrations (25, 50, and 100 mug/mL) for 36 h and then analyzed for the effect of Licochalcone A on the cell migration and invasion. In vitro assays, including wound healing, cell adhesion, and cell invasion/migration assays, revealed that Licochalcone A treatment significantly inhibited the cell migration/invasion capacities of SCC-25 cells. Also, results of zymography and Western blotting showed that activity and protein level of matrix metalloproteinase-2 (MMP-2) was suppressed, but TIMP-2 level was increased, indicating the important role of MMP-2 and TIPM-2 in anti-metastatic regulation of SCC-25 cells. Furthermore, Licochalcone A was shown to suppress the nuclear factor-kappa B (NF-kappaB) signal, as evidenced by the decreased expression of phosphorylated p65 (p-65) protein in Licochalcone A-treated SCC-25 cells. Notably, we also found that Licochalcone A treatment increased the expression of the epithelial marker E-cadherin and decreased the expression of mesenchymal markers N-cadherin in SCC-25 cells. This is the first report describing the effects and possible mechanisms of Licochalcone A on tumor invasion and metastasis of SCC-25 cells. Taken together, our findings support that Licochalcone A can be developed to a potent anti-metastatic candidate for oral cancer therapy.

Antibacterial activity of licochalcone A against spore-forming bacteria.[Pubmed:11959549]

Antimicrob Agents Chemother. 2002 May;46(5):1226-30.

Licochalcone A was isolated from the roots of licorice, Glycyrrhiza inflata, which has various uses in the food and pharmaceutical industries; isolation was followed by extraction with ethanol and column chromatography with silica gel. In this study, the activities of Licochalcone A against some food contaminant microorganisms were evaluated in vitro. The vegetative cell growth of Bacillus subtilis was inhibited in a Licochalcone A concentration-dependent manner and was completely prevented by 3 micrograms of Licochalcone A/ml. Licochalcone A showed a high level of resistance to heating at 80 to 121 degrees C for 15 min. Licochalcone A did not inhibit the germination of heat-treated spores of B. subtilis induced by L-alanine. Licochalcone A showed effects against all gram-positive bacteria tested and especially was effective against all Bacillus spp. tested, with MICs of 2 to 3 micrograms/ml, but was not effective against gram-negative bacteria or eukaryotes at 50 micrograms/ml. Although the cationic antimicrobial peptides protamine and epsilon-poly-L-lysine resulted in the loss of antimicrobial activity in the presence of either 3% (wt/vol) NaCl or protease at 20 micrograms/ml, the antibacterial activity of Licochalcone A was resistant to these conditions. Thus, Licochalcone A could be a useful compound for the development of antibacterial agents for the preservation of foods containing high concentrations of salts and proteases, in which cationic peptides might be less effective.

The effect of licochalcone A on cell-aggregates ECM secretion and osteogenic differentiation during bone formation in metaphyseal defects in ovariectomized rats.[Pubmed:24439395]

Biomaterials. 2014 Mar;35(9):2789-97.

Treatment of weight-bearing bones fractures with defects is critical for patients with osteoporosis's rehabilitation. Although various tissue engineering methods were reported, the best treating strategy for tissue engineering remains to be identified as the limitation of enhancing the ability of the osteogenetic differentiation potential of seed cell is one of the cardinal issues to be solved. The objective of this study is to investigate the feasibility of applying licochalcone-A (L-A) and bone marrow mesenchymal stem cells (BMSC)-aggregate in bone repairing tissue engineering and further study the biological effects of L-A on the cell aggregate formation and osteogenic properties. 80 female Sprague Dawley rats underwent bilateral ovariectomy were made with a 3.5 mm femurs bone defects without any fixation. These rats were then randomly assigned to five different treatment groups: (1) empty defect (n = 16), (2) CA-LA (n = 16), (3) CA-N (n = 16), (4) CA-L (n = 16), (5) CA-S (n = 16) and 16 female SD rats were treated as a control. Data showed that L-A administrated cell aggregate had a stronger osteogenic differentiation and mineralized formation potential than non-administrated group both in vitro and in vivo. For in vitro study, L-A administrated group had a more significant expression of ECM, osteogenic associated maker in addition with more mineralized area and higher ALP activity compared with the control group. For in vivo study, 3D reconstruction of micro-CT, HE staining and bone strength results showed that newly formed bone in groups administrated by L-A was significant higher than that in Sham group at 2, 4, 8 and 12 weeks after transplantation, especially for groups which was systematically injected with L-A at 8 weeks. Results of our study demonstrated that LA could positively affect cell behavior in cell-aggregate engineering and could be a promising strategy in treating osteoporotic weight-bearing bones fractures with defects.

Antileishmanial activity of licochalcone A in mice infected with Leishmania major and in hamsters infected with Leishmania donovani.[Pubmed:8092835]

Antimicrob Agents Chemother. 1994 Jun;38(6):1339-44.

This study was designed to examine the antileishmanial activity of the oxygenated chalcone Licochalcone A in mice and hamsters infected with Leishmania parasites. Intraperitoneal administration of Licochalcone A at doses of 2.5 and 5 mg/kg of body weight per day completely prevented lesion development in BALB/c mice infected with Leishmania major. Treatment of hamsters infected with L. donovani with intraperitoneal administration of Licochalcone A at a dose of 20 mg/kg of body weight per day for 6 consecutive days resulted in a > 96% reduction of parasite load in the liver and the spleen compared with values for untreated control animals. The [3H]thymidine uptake by the parasites isolated from the treated hamsters was only about 1% of that observed in parasites isolated from the controls. Oral administration of Licochalcone A at concentrations of 5 to 150 mg/kg of body weight per day for 6 consecutive days resulted in > 65 and 85% reductions of L. donovani parasite loads in the liver and the spleen, respectively, compared with those of untreated control hamsters. These data clearly demonstrate that Licochalcone A is a promising lead for the development of a new drug against leishmaniases.

Licochalcone A as a potent antitumor agent suppresses growth of human oral cancer SCC-25 cells in vitro via caspase-3 dependent pathways.[Pubmed:24691971]

Tumour Biol. 2014 Jul;35(7):6549-55.

The majority of anticancer drugs are of natural origin. However, it is unknown whether Licochalcone A is cytotoxic towards oral squamous cell carcinoma (OSCC) cells. The goal of this study was to investigate the cytotoxic effects of Licochalcone A on the human OSCC SCC-25 cells and to identify the underlying molecular mechanism. Exposure of SCC-25 cells to Licochalcone A dose- and time-dependently decreased cell viability by arresting cell cycle at the S and G2/M phase as well as inducing apoptosis. Furthermore, the proapoptotic activity of Licochalcone A was revealed by DNA fragmentation. Concomitantly, we observed activation of the effector caspases-3, induced by activation of the initiator caspases -8 and -9, which subsequent trigger both death receptor pathway and the mitochondrial apoptotic pathway in Licochalcone A-mediated SCC-25 cell apoptosis. Besides, treatment with 50 mug/mL of Licochalcone A for 36 h led to the cleavage of PARP, an indicator of apoptosis induction. Therefore Licochalcone A may be a good candidate for development as a possible chemopreventive agent against OSCC.

Licochalcone A, a new antimalarial agent, inhibits in vitro growth of the human malaria parasite Plasmodium falciparum and protects mice from P. yoelii infection.[Pubmed:7979274]

Antimicrob Agents Chemother. 1994 Jul;38(7):1470-5.

Licochalcone A, isolated from Chinese licorice roots, inhibited the in vitro growth of both chloroquine-susceptible (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum strains in a [3H]hypoxanthine uptake assay. The growth inhibition of the chloroquine-resistant strain by Licochalcone A was similar to that of the chloroquine-susceptible strain. To examine the activity of Licochalcone A on the different asexual blood stages of the parasite, Licochalcone A was added to highly synchronized cultures containing rings, trophozoites, and schizonts. The growth of the parasites at all stages was inhibited by Licochalcone A. The in vivo activity of Licochalcone A was tested in a mouse model of infection with P. yoelii. Licochalcone A administered either intraperitoneally or orally for 3 to 6 days protected the mice from the otherwise lethal P. yoelii infection. These results demonstrate that Licochalcone A exhibits potent antimalarial activity and might be developed into a new antimalarial drug.

Role of licochalcone A on thymic stromal lymphopoietin expression: implications for asthma.[Pubmed:25055998]

Exp Biol Med (Maywood). 2015 Jan;240(1):26-33.

Asthma is a common chronic inflammatory disease characterized by the infiltration and accumulation of memory-like Th2 cells and eosinophils. Viral infection has emerged as the most common cause of severe episodes of asthma. For the treatment of bronchial asthma, the root of liquorice (Glycyrrhiza glabra) has been used as a traditional medicine in the East and West. Licochalcone A is the predominant, characteristic chalcone in liquorice root. To determine whether Licochalcone A possesses an anti-inflammatory effect, we tested its effect on the expression and production of thymic stromal lymphopoietin (TSLP) in BEAS 2B cells and primary bronchial epithelial cells. We found that polyinosinic-polycytidylic acid (poly-IC)-induced TSLP expression was suppressed by treatment with Licochalcone A in a dose- and time-dependent manner. We also found that poly-IC-induced mRNA expression of other proinflammatory mediators such as MCP-1, RANTES, and IL-8 was suppressed by Licochalcone A. Furthermore, Licochalcone A suppressed poly-IC-induced nuclear factor kappa B (NF-kappaB) nuclear translocation and DNA-binding activity by suppressing the Ikappabeta kinase (IKK) activity but not by direct phosphorylation of p65 at serine 276. Collectively, our findings suggest that Licochalcone A suppresses poly-IC-induced TSLP expression and production by inhibiting the IKK/NF-kappaB signaling pathway, which might be involved in the pathogenesis of virus-exacerbated asthma. Further elucidation of the mechanisms underlying these observations can help develop therapeutic strategies for virally induced asthma.

Effects of licochalcone A on the bioavailability and pharmacokinetics of nifedipine in rats: possible role of intestinal CYP3A4 and P-gp inhibition by licochalcone A.[Pubmed:24903704]

Biopharm Drug Dispos. 2014 Oct;35(7):382-90.

The purpose of this study was to investigate the possible effects of Licochalcone A (a herbal medicine) on the pharmacokinetics of nifedipine and its main metabolite, dehydronifedipine, in rats. The pharmacokinetic parameters of nifedipine and/or dehydronifedipine were determined after oral and intravenous administration of nifedipine to rats in the absence (control) and presence of Licochalcone A (0.4, 2.0 and 10 mg/kg). The effect of Licochalcone A on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was also evaluated. Nifedipine was mainly metabolized by CYP3A4. Licochalcone A inhibited CYP3A4 enzyme activity in a concentration-dependent manner with a 50% inhibition concentration (IC50 ) of 5.9 mum. In addition, Licochalcone A significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. The area under the plasma concentration-time curve from time 0 to infinity (AUC) and the peak plasma concentration (Cmax ) of oral nifedipine were significantly greater and higher, respectively, with Licochalcone A. The metabolite (dehydronifedipine)-parent AUC ratio (MR) in the presence of Licochalcone A was significantly smaller compared with the control group. The above data could be due to an inhibition of intestinal CYP3A4 and P-gp by Licochalcone A. The AUCs of intravenous nifedipine were comparable without and with Licochalcone A, suggesting that inhibition of hepatic CYP3A4 and P-gp was almost negligible.

Licochalcone A significantly suppresses LPS signaling pathway through the inhibition of NF-kappaB p65 phosphorylation at serine 276.[Pubmed:19168128]

Cell Signal. 2009 May;21(5):778-85.

Licorice root, Glycyrrhiza inflata, has been used as a traditional medicine for the treatment of bronchial asthma and inflammation; however, the mechanism of its anti-inflammatory activity has not been clarified. Here, we investigated the effect of Licochalcone A, a major component of G. inflata, on the LPS signaling pathway. We found that Licochalcone A remarkably inhibited LPS-induced NO production, and TNFalpha expression and MCP-1 expression in both RAW264.7 cells and primary macrophages. Furthermore, when injected with Licochalcone A prior to injection of LPS, the serum level of TNFalpha and MCP-1 in C57BL/6 mice was clearly decreased, indicating that Licochalcone A has a potent anti-inflammatory effect both in vitro and in vivo. Strikingly, Licochalcone A significantly inhibited LPS-induced NF-kappaB transcriptional activation; however, it had no effect on not only the phosphorylation and degradation of IkappaBalpha but also nuclear translocation and DNA binding activity of NF-kappaB p65. Interestingly, Licochalcone A markedly inhibited the phosphorylation of p65 at serine 276. As a result, it reduced NF-kappaB transactivation by preventing the interaction of p65 with p300. Taken together, Licochalcone A might contribute to the potent anti-inflammatory effect of G. inflata through the unique mechanism of NF-kappaB inhibition.

Licochalcone A, a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, presents obvious anti-cancer effects.

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