PMID: 

Food Chem Toxicol. 2018 Oct ;120:407-417. Epub 2018 Jul 25. PMID: 30055311

Abstract Title: 

Licochalcone A from licorice root, an inhibitor of human hepatoma cell growth via induction of cell apoptosis and cell cycle arrest.

Abstract: 

We investigated the anti-cancer activity of Licochalcone A (LCA), extracted from licorice root. LCA inhibited the proliferation of HepGcells with IC(65.96 μM) for 24 h and IC(44.13 μM) for 48 h and caused significant morphological changes and also led to intracellular ROS generation. LCA affected HepGcell growth by terminating cell cycle development at G2/M transition and further induced the apoptosis process. The mRNA expression of genes involved in cell cycles such as Survivin, Cyclin B1, and CDK1 were reduced; while, Weel, P21, Cyclin D1, and JNK1 showed increased mRNA expression. Two pathways consisting of internal and external factors were responsible for LCA -induced apoptosis. The anti-cancer action involved increased mRNA expression of DR3, DR5, caspases-3, caspases-8, caspases-10, Fas, Bad, Bax, Bcl-2, Bak, and PUMA; besides, decreased level of PKCε, p70S6K, and Akt. This study provides mechanistic explanation for anti-cancer activity of LCA and also suggests its potential role in the treatment of hepatoma cancer.

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PMID: 

Food Funct. 2018 Aug 15 ;9(8):4500-4507. PMID: 30083664

Abstract Title: 

Licochalcone A attenuates glioma cell growth in vitro and in vivo through cell cycle arrest.

Abstract: 

Licochalcone A (LA), an active ingredient of licorice, has multiple biological activities, including antioxidative and anti-inflammatory activities. Although LA exerts antitumor effects in various cancer cells, its role in gliomas remains unclear. Therefore, this study determined whether LA inhibits glioma cell growth in vitro and in vivo. The present data revealed that LA effectively inhibited the growth of U87 glioma cells by inducing cell cycle arrest in the G0/G1 and G2/M phases; cell cycle arrest was attributed to the LA-mediated reduction of mRNA and protein levels of cyclins and cyclin-dependent kinases. Moreover, subcutaneous (flank) and orthotopic (brain) tumor models were used to determine the role of LA in gliomas. LA significantly alleviated tumor growth in both models. These findings indicate that LA exerts antitumor effects in gliomas in vitro and in vivo and that it is a potential agent for treating glioblastoma multiforme.

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PMID: 

Phytother Res. 2018 Dec ;32(12):2551-2559. Epub 2018 Oct 3. PMID: 30281174

Abstract Title: 

Licochalcone A attenuates acne symptoms mediated by suppression of NLRP3 inflammasome.

Abstract: 

Activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome by Propionibacterium acnes (P. acnes) is critical for inducing inflammation and aggravating the development of acne lesions. We searched for available small-molecule inhibitors of the NLRP3 inflammasome that could be topically administered for the treatment of acne. We found that licochalcone A, a chalconoid isolated from the root of Glycyrrhiza inflate, was an effective inhibitor for P. acnes-induced NLRP3 inflammasome activation. Licochalcone A blocked P. acnes-induced production of caspase-1(p10) and IL-1β in primary mouse macrophages and human SZ95 sebocytes, indicating the suppression of NLRP3 inflammasome. Licochalcone A suppressed P. acnes-induced ASC speck formation and mitochondrial reactive oxygen species. Topical application of licochalcone A to mouse ear skin attenuated P. acnes-induced skin inflammation as shown by histological assessment, ear thickness measurement, and inflammatory gene expression. Licochalcone A reduced caspase-1 activity and IL-1β production in mouse ear injected with P. acnes. This study demonstrated that licochalcone A is effective in the control of P. acnes-induced skin inflammation as an efficient inhibitor for NLRP3 inflammasome. Our study provides a new paradigm for the development of anti-acne therapy via targeting NLRP3 inflammasome.

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PMID: 

Zhongguo Zhong Yao Za Zhi. 2018 Sep ;43(17):3545-3552. PMID: 30347925

Abstract Title: 

[Effect of licochalcone A on autophagy in renal cell carcinoma via PI3K/Akt/mTOR signaling pathway].

Abstract: 

To investigate the effect of licochalcone (LCA) on autophagy in renal cell carcinoma (RCC), and further determine whether the mechanism is correlated with the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of mTOR pathway, RCC 786-O and 769-P were used as study subjects. MTT assay was used to examine cell proliferation. The abilities of migration and invasion were detected by Transwell. The autophagy was observed under the fluorescence microscope through acridine orange staining. Green fluorescence spots were observed in Ad-GFP-LC3 transfection experiment. The protein expression was detected by Western blot. MTT assay results showed a dose and time-dependent cytotoxicity in the two cell lines treated with LCA. LCA inhibited migration and invasion in 786-O and 769-P cells. LCA increased the expression levels of LC3-Ⅱ, beclin 1, Atg5, and down-regulated the expression of p62. In addition, LCA inhibited the PI3K/Akt/mTOR pathway. Furthermore, the inhibition of PI3K/Akt by LY294002 or that of mTOR by rapamycin augmented LCA-induced autophagy. The findings demonstrated that LCA inhibited the proliferation, migration, invasion, and induced autophagy by inactivating PI3K/Akt/mTOR signaling pathway in 786-O and 769-P cells.

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PMID: 

Food Funct. 2018 Dec 13 ;9(12):6196-6204. PMID: 30465574

Abstract Title: 

Licochalcone A inhibits the invasive potential of human glioma cells by targeting the MEK/ERK and ADAM9 signaling pathways.

Abstract: 

Licochalcone A (LicA) has been reported to possess antitumor properties. However, its effect on human glioma cells remains unknown. In this study, we observed that LicA significantly suppressed the ADAM9 expression and the migration and invasion activities of human glioma cells (M059K, U-251 MG, and GBM8901) and exhibited no cell cytotoxicity. The human proteinase antibody array and immunoblot analysis indicated that the LicA treatment inhibited the expression of ADAM9 protein in human glioma cells. Recombinant human ADAM-9 (Rh-ADAM9) treatment significantly reversed the LicA-induced reduction in the ADAM9 level and the migration and invasion activities of human glioma cells. Additionally, the phosphorylation/activation of the mitogen-activated protein kinase kinase (MEK)-extracellularly responsive kinases (ERK) signaling pathway was significantly suppressed in LicA-treated human glioma cells. Cotreatment with LicA and PD98059 synergistically inhibited the ADAM9 expression, cell migration, and cell invasion, which suggested that the MEK-ERK signaling pathway was involved in the LicA-induced inhibition of the ADAM9 expression and the invasion activity of human glioma cells. These findings are the first evidence of LicA's anti-invasive properties against human glioma cells.

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PMID: 

Cells. 2019 03 5 ;8(3). Epub 2019 Mar 5. PMID: 30841634

Abstract Title: 

Licochalcone A Inhibits Cellular Motility by Suppressing E-cadherin and MAPK Signaling in Breast Cancer.

Abstract: 

A compound isolated from, licochalcone A (LA) exhibits anti-inflammatory and anti-tumor properties in various cell lines. LA has been found to promote autophagy and suppress specificity protein 1, inducing apoptosis in breast cancer cells. However, the regulation of breast cancer cell invasion and migration by LA is elusive. Thus, the present study investigated whether LA induces apoptosis and cellular motility in MDA-MB-231 breast cells, and investigated the underlying molecular mechanisms. MDA-MB-231 cells treated with LA and cell viability measured by cell counting kit-8 assay. Apoptotic signal proteins checked by flow cytometry, fluorescent staining, and Western blot. LA effectively suppressed cell migration, and modulated E-cadherin and vimentin expression by blocking MAPK and AKT signaling. LA inhibited cell proliferation and cell cycle, modulated mitochondrial membrane potential and DNA damage, and reduced oxidative stress in MDA-MB-231 cells. LA also activated cleaved-caspase 3 and 9, significantly decreased Bcl-2 expression, ultimately causing the release of cytochrome c from the mitochondria into the cytoplasm. Overall, our findings suggest that LA decreases cell proliferation and increases reactive oxygen species production for induced apoptosis, and regulates E-cadherin and vimentin by reducing MAPK and AKT signaling, resulting in suppressed MDA-MB-231 cell migration and invasion.

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PMID: 

Environ Toxicol. 2019 Jul ;34(7):853-860. Epub 2019 Apr 14. PMID: 30983163

Abstract Title: 

Licochalcone A induces apoptotic cell death via JNK/p38 activation in human nasopharyngeal carcinoma cells.

Abstract: 

Licochalcone A is widely studied in different fields and possesses antiasthmatic, antibacterial, anti-inflammatory, antioxidative, and anticancer properties. Its antimalignancy activity on renal, liver, lung, and oral cancer has been explored. However, limited studies have been conducted on the inhibitory effects of licochalcone A in human nasopharyngeal carcinoma cells. We determined cell viability using MTT assay. Cell cycle distribution and apoptotic cell death were measured via flow cytometry. Caspase activation and mitogen-activated protein kinase-related proteins in nasopharyngeal cancer cells in response to licochalcone A were identified by Western blot analysis. Results indicated that licochalcone A reduces cell viability and induces apoptosis, as evidenced by the upregulation of caspase-8 and caspase-9, caspase-3 activation, and cleaved-poly ADP-ribose polymerase expression. Treatment with licochalcone A significantly increases ERK1/2, p38, and JNK1/2 activation. Co-administration of a JNK inhibitor (JNK-IN-8) or p38 inhibitor (SB203580) abolishes the activation of caspase-9, caspase-8, and caspase-3 protein expression during licochalcone A treatment. These findings indicate that licochalcone A exerts a cytostatic effect through apoptosis by targeting the JNK/p38 pathway in human nasopharyngeal carcinoma cells. Therefore, licochalcone A is a promising therapeutic agent for the treatment of human nasopharyngeal cancer cells.

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PMID: 

Pharmacol Res. 2019 06 ;144:210-226. Epub 2019 Apr 22. PMID: 31022523

Abstract Title: 

Natural products in licorice for the therapy of liver diseases: Progress and future opportunities.

Abstract: 

Liver diseases related complications represent a significant source of morbidity and mortality worldwide, creating a substantial economic burden. Oxidative stress, excessive inflammation, and dysregulated energy metabolism significantly contributed to liver diseases. Therefore, discovery of novel therapeutic drugs for the treatment of liver diseases are urgently required. Licorice is one of the most commonly used herbal drugs in Traditional Chinese Medicine for the treatment of liver diseases and drug-induced liver injury (DILI). Various bioactive components have been isolated and identified from the licorice, including glycyrrhizin, glycyrrhetinic acid, liquiritigenin, Isoliquiritigenin, licochalcone A, and glycycoumarin. Emerging evidence suggested that these natural products relieved liver diseases and prevented DILI through multi-targeting therapeutic mechanisms, including anti-steatosis, anti-oxidative stress, anti-inflammation, immunoregulation, anti-fibrosis, anti-cancer, and drug-drug interactions. In the current review, we summarized the recent progress in the research of hepatoprotective and toxic effects of different licorice-derived bioactive ingredients and also highlighted the potency of these compounds as promising therapeutic options for the treatment of liver diseases and DILI. We also outlined the networks of underlying molecular signaling pathways. Further pharmacology and toxicology research will contribute to the development of natural products in licorice and their derivatives as medicines with alluring prospect in the clinical application.

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PMID: 

Cells. 2019 05 11 ;8(5). Epub 2019 May 11. PMID: 31083505

Abstract Title: 

Protective Effects of Licochalcone A Ameliorates Obesity and Non-Alcoholic Fatty Liver Disease Via Promotion of the Sirt-1/AMPK Pathway in Mice Fed a High-Fat Diet.

Abstract: 

Licochalcone A is a chalcone isolated from. It showed anti-tumor and anti-inflammatory properties in mice with acute lung injuries and regulated lipid metabolism through the activation of AMP-activated protein kinase (AMPK) in hepatocytes. However, the effects of licochalcone A on reducing weight gain and improving nonalcoholic fatty liver disease (NAFLD) are unclear. Thus, the present study investigated whether licochalcone A ameliorated weight loss and lipid metabolism in the liver of high-fat diet (HFD)-induced obese mice. Male C57BL/6 mice were fed an HFD to induce obesity and NAFLD, and then were injected intraperitoneally with licochalcone A. In another experiment, a fatty liver cell model was established by incubating HepG2 hepatocytes with oleic acid and treating the cells with licochalcone A to evaluate lipid metabolism. Our results demonstrated that HFD-induced obese mice treated with licochalcone A had decreased body weight as well as inguinal and epididymal adipose tissue weights compared with HFD-treated mice. Licochalcone A also ameliorated hepatocyte steatosis and decreased liver tissue weight and lipid droplet accumulation in liver tissue. We also found that licochalcone A significantly regulated serum triglycerides, low-density lipoprotein, and free fatty acids, and decreased the fasting blood glucose value. Furthermore, in vivo and in vitro, licochalcone A significantly decreased expression of the transcription factor of lipogenesis and fatty acid synthase. Licochalcone A activated the sirt-1/AMPK pathway to reduce fatty acid chain synthesis and increased lipolysis andβ-oxidation in hepatocytes. Licochalcone A can potentially ameliorate obesity and NAFLD in mice via activation of the sirt1/AMPK pathway.

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PMID: 

Cells. 2019 06 20 ;8(6). Epub 2019 Jun 20. PMID: 31226782

Abstract Title: 

Protective Effects of Licochalcone A Improve Airway Hyper-Responsiveness and Oxidative Stress in a Mouse Model of Asthma.

Abstract: 

Licochalcone A was isolated fromand previously reported to have antitumor and anti-inflammatory effects. Licochalcone A has also been found to inhibit the levels of Th2-associated cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. However, the molecular mechanism underlying airway inflammation and how licochalcone A regulates oxidative stress in asthmatic mice are elusive. In this study, we investigated whether licochalcone A could attenuate inflammatory and oxidative responses in tracheal epithelial cells, and whether it could ameliorate oxidative stress and airway inflammation in asthmatic mice. Inflammatory human tracheal epithelial (BEAS-2B) cells were treated with licochalcone A to evaluate oxidative responses and inflammatory cytokine levels. In addition, BALB/c mice were sensitized with ovalbumin (OVA) and injected intraperitoneally with licochalcone A (5 or 10 mg/kg). Licochalcone A significantly inhibited reactive oxygen species, eotaxin, and proinflammatory cytokines in BEAS-2B cells. Licochalcone A also decreased intercellular adhesion molecule 1 levels in inflammatory BEAS-2B cells, blocking monocyte cell adherence. We also found that licochalcone A significantly decreased oxidative responses, reduced malondialdehyde levels, and increased glutathione levels in the lungs of OVA-sensitized mice. Furthermore, licochalcone A decreased airway hyper-responsiveness, eosinophil infiltration, and Th2 cytokine production in the BALF. These findings suggest that licochalcone A alleviates oxidative stress, inflammation, and pathological changes by inhibiting Th2-associated cytokines in asthmatic mice and human tracheal epithelial cells. Thus, licochalcone A demonstrated therapeutic potential for improving asthma.

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