PMID: 

Food Chem Toxicol. 2014 Mar ;65:242-51. Epub 2013 Dec 31. PMID: 24384411

Abstract Title: 

Licochalcone B inhibits growth of bladder cancer cells by arresting cell cycle progression and inducing apoptosis.

Abstract: 

To examine the mechanisms by which licochalcone B (LCB) inhibits the proliferation of human malignant bladder cancer cell lines (T24 and EJ) in vitro and antitumor activity in vivo in MB49 (murine bladder cancer cell line) tumor model. Exposure of T24 or EJ cells to LCB significantly inhibited cell lines proliferation in a concentration-dependent and time-dependent manner, and resulted in S phase arrest in T24 or EJ cells, respectively. LCB treatment decreased the expression of cyclin A, cyclin-dependent kinase (CDK1 and CDK2) mRNA, cell division cycle 25 (Cdc25A and Cdc25B) protein. In addition, LCB treatment down-regulated Bcl-2 and survivin expression, enhanced Bax expression, activated caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) protein. Consistently, the tumorigenicity of LCB-treated MB49 cells was limited significantly by using the colony formation assay in vitro and the MB49 tumor model performed in C57BL/6 mice in vivo. These findings provide support for the use of LCB in chemoprevention and bladder cancer therapy.

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PMID: 

J Pharm Pharmacol. 2014 Jun ;66(6):886-94. Epub 2014 Jan 22. PMID: 24447171

Abstract Title: 

Immunomodulatory effects of licochalcone A on experimental autoimmune encephalomyelitis.

Abstract: 

OBJECTIVES: Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. Herein, we have investigated the immunomodulatory effect of licochalcone A (LicoA) on NO, H2 O2 , tumour necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ) and IL-17 production in cultured cells from EAE mice.METHODS: EAE was induced in C57Bl/6 mice with myelin oligodendrocyte glycoprotein peptide (MOG35-55 ). LicoA was isolated from the roots of Glycyrrhiza inflata. Splenocytes were obtained from EAE mice and incubated with LicoA (4, 20 and 40 μm). Peritoneal cells were obtained from EAE mice treated with LicoA (15 and 30 mg/kg/day. p.o.). H2 O2 , NO, IFN-γ, TNF-α and IL-17 production was determined in the presence or absence of concanavalin (ConA) or MOG35-55 stimulation.KEY FINDINGS: LicoA (40 μm) inhibited H2 O2 , NO, IFN-γ, TNF-α and IL-17 production in splenocytes spontaneously or after both ConA and MOG35-55 stimulation. LicoA (30 mg/kg/day) reduced clinical score and severity of EAE mice, and inhibited TNF-α, IFN-γ and IL-17 production in peritoneal cells.CONCLUSIONS: LicoA possesses immunomodulatory effects on H2 O2 , NO, IFN-γ, TNF-α and IL-17 production in cells from EAE mice. It is suggested that LicoA acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells.

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PMID: 

Basic Clin Pharmacol Toxicol. 2014 Dec ;115(6):527-33. Epub 2014 Jul 1. PMID: 25099010

Abstract Title: 

Antimetastatic effects of licochalcone B on human bladder carcinoma T24 by inhibition of matrix metalloproteinases-9 and NF-кB activity.

Abstract: 

This study investigated the mechanisms by which licochalcone B (LCB) inhibits the adhesion,invasion and metastasis of human malignant bladder cancer T24 cells. Cell viability was evaluated using a sulforhodamine B (SRB) assay. Cell migration and invasion ability were conducted using wound-healing assay and matrigel transwell invasion assay. The activities of matrix metalloproteinases (MMP)-2 and MMP-9 were measured by gelatin zymography protease assays. The expression in protein level of NF-κBP65 and AP-1 was determined using the ELISA method; the protein levels of MMP-9, NF-κBP65, IκBα and P-IκBα were detected by Western blot. The expression in mRNA level of MMP-9 was assessed using quantitative real-time polymerase chain reaction (PCR) and reverse transcription PCR. The resultsindicated that LCB attenuated T24 cell migration, adhesion and invasion in a concentration-dependent manner. LCB treatment down-regulated the mRNA expression, protein expression and activity of MMP-9 but had no effect on MMP-2. In addition, LCB treatment decreased the protein level of NF-кBP65 andnuclear translocation of NF-кB. These findings suggested that LCB attenuated migration of bladder cancer T24 cells and adhesion and invasion accompanied with down-regulated protein expression of MMP-9 and the nuclear translocation of NF-кB. Our results provide support that LCB may be a potent adjuvant therapeutic agent in the prevention and therapy of bladder cancer.

PMID: 

Life Sci. 2015 Jul 1 ;132:27-33. Epub 2015 Apr 25. PMID: 25921769

Abstract Title: 

Role of licochalcone C in cardioprotection against ischemia/reperfusion injury of isolated rat heart via antioxidant, anti-inflammatory, and anti-apoptotic activities.

Abstract: 

AIMS: This study aimed to evaluate the protective effect of licochalcone C against myocardial ischemia/reperfusion injury in rats.MAIN METHODS: Left ventricular developed pressure (LVDP) and its maximum up/down rate (±dp/dtmax) were recorded as myocardial function. Levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined by using enzyme-linked immunosorbent assay. Cell morphology was observed and mitochondrial damage was assessed by HE coloration and transmission electron microscopy, respectively. Cardiomyocyte apoptosis was determined by using terminal deoxynucleotidyl transferased UTP nick-end labeling (TUNEL).KEY FINDINGS: Pretreatment with licochalcone C significantly improved the recovery of LVDP and±dp/dtmax, and increased the levels of SOD and GSH/GSSG ratio. However, pretreatment with licochalcone C not only decreased the TUNEL-positive cell ratio and morphological changes, but also weaken the mitochondrial injury and the levels of CK, LDH, MDA, and TNF-α.SIGNIFICANCE: These results suggested an important function of licochalcone C extracted from traditional Chinese medicine in the cardioprotection via antioxidant, anti-inflammatory, and anti-apoptotic activities.

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PMID: 

Acta Trop. 2009 Mar ;109(3):194-8. Epub 2008 Nov 20. PMID: 19063856

Abstract Title: 

Phytochemical licochalcone A enhances antimalarial activity of artemisinin in vitro.

Abstract: 

Resistance to synthetic first-line antimalarial drugs is considered to be a major cause of increased malaria morbidity and mortality. Use of artemisinin-based combination therapies (ACTs) is being encouraged to reduce the malaria mortality in areas of falciparum resistance. Artemisinin is a natural product at times in short supply. With projected rise in demand of artemisinin there is an unmet need for alternate ACTs. Novel compounds that reduce dependence on artemisinin are required. In vitro cultures of Plasmodium falciparum provide a screen system for identifying and evaluating new drug combinations. Interactions of two phytochemicals, artemisinin and licochalcone A, has been studied against synchronized erythrocytic stages of chloroquine-sensitive 3D7 and chloroquine-resistant RKL 303 strains of P. falciparum. These two compounds in combination show synergistic antiplasmodial activity in vitro on these strains. Artemisinin but not licochalcone A interferes with hemozoin formation. Neither of the phytochemicals alone or in combination obstructs sorbitol-induced hemolysis.

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PMID: 

J Nutr Biochem. 2012 Jul ;23(7):759-67. Epub 2011 Aug 12. PMID: 21840191

Abstract Title: 

Licochalcone E has an antidiabetic effect.

Abstract: 

Licochalcone E (lico E) is a retrochalcone isolated from the root of Glycyrrhiza inflata. Retrochalcone compounds evidence a variety of pharmacological profiles, including anticancer, antiparasitic, antibacterial, antioxidative and superoxide-scavenging properties. In this study, we evaluated the biological effects of lico E on adipocyte differentiation in vitro and obesity-related diabetes in vivo. We employed 3T3-L1 preadipocyte and C3H10T1/2 stem cells for in vitro adipocyte differentiation study and diet-induced diabetic mice for in vivo study. The presence of lico E during adipogenesis induced adipocyte differentiation to a significant degree, particularly at the early induction stage. Licochalcone E evidenced weak, but significant, peroxisome proliferator-activated receptor gamma (PPARγ) ligand-binding activity. Two weeks of lico E treatment lowered blood glucose levels and serum triglyceride levels in the diabetic mice. Additionally, treatment with lico E resulted in marked reductions in adipocyte size and increases in the mRNA expression levels of PPARγ in white adipose tissue (WAT). Licochalcone E was also shown to significantly stimulate Akt signaling in epididymal WAT. In conclusion, lico E increases the levels of PPARγ expression, at least in part, via the stimulation of Akt signals and functions as a PPARγ partial agonist, and this increased PPARγ expression enhances adipocyte differentiation and increases the population of small adipocytes, resulting in improvements in hyperglycemia and hyperlipidemia under diabetic conditions.

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PMID: 

Immunopharmacol Immunotoxicol. 2013 Dec ;35(6):653-61. Epub 2013 Sep 12. PMID: 24028304

Abstract Title: 

Attenuation of allergic airway inflammation in a murine model of asthma by Licochalcone A.

Abstract: 

CONTEXT: Licochalcone A (Lico A) is a major and biogenetically characteristic chalcone isolated from the root of Xinjiang liquorice, Glycyrrhiza inflata.OBJECTIVE: We focused on investigating whether Lico A possesses distinct anti-inflammatory activity on a non-infectious mouse model of asthma, and we aimed to elucidate its involvement with the mitogen-activated protein kinases pathway.METHODS: BALB/c mice that were sensitized and challenged to ovalbumin (OVA) were treated with Lico A (50 mg/kg) 1 h before they were challenged with OVA.RESULTS: Our study demonstrated that Lico A may effectively inhibit the increase in T-helper type 2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid, and reduced serum levels of OVA-specific IgE and IgG. Furthermore, Lico A substantially inhibited OVA-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells in the airway. Meanwhile, pretreatment with Lico A resulted in a significant reduction in mRNA expression of acidic mammalian chitinase, chitinase 3-like protein 4 (Ym2), E-selectin, Muc5ac, CCL11 and CCR3 in lung tissues and airway hyper-responsiveness to methacholine.CONCLUSIONS: These findings suggest that Lico A may effectively delay the progression of airway inflammation and could be used as a therapy for patients with allergic airway inflammation.

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PMID: 

Mol Med Rep. 2015 Nov ;12(5):7623-8. Epub 2015 Sep 22. PMID: 26397392

Abstract Title: 

Licochalcone C induces apoptosis via B-cell lymphoma 2 family proteins in T24 cells.

Abstract: 

The current study investigated the mechanisms by which licochalcone C induces apoptosis of T24 human malignant bladder cancer cells. Cell viability was evaluated using an MTT assay. Apoptosis was investigated using a morphological assay, flow cytometry and a caspase‑3 activity assay. Alterations in the gene expression levels of Bcl‑2 family members were measured by semi‑quantitative reverse transcription‑polymerase chain reaction assays. The protein levels of pro‑caspase‑3 and cleaved poly(ADP ribose) polymerase were measured using western blotting. The results indicated that licochalcone C induced T24 cell apoptosis in a concentration‑dependent manner. Licochalcone C treatment reduced the levels of the anti‑apoptotic mRNAs (Bcl‑2, Bcl‑w and Bcl‑XL) and increased expression of the pro‑apoptotic mRNAs (Bax and Bim). The Bcl‑2 family inhibitor (ABT‑737) reduced apoptosis induced by licochalcone C in T24 cells. The current study demonstrated that licochalcone C may be a potential adjuvant therapeutic agent for bladder cancer.

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PMID: 

Int J Oncol. 2016 Apr ;48(4):1749-57. Epub 2016 Feb 1. PMID: 26847145

Abstract Title: 

Licochalcone B induces apoptosis of human oral squamous cell carcinoma through the extrinsic- and intrinsic-signaling pathways.

Abstract: 

Licochalcone B (Lico B), which belongs to the retrochalcone family, is isolated from the roots of Chinese licorice. Lico B has been reported to have several other useful pharmacological properties, such as anti-inflammatory, antibacterial, antioxidant, antiulcer, anticancer, and anti-metastasis activities. We elucidated the underlying mechanism by which Lico B can induce apoptosis in oral squamous cell carcinoma (OSCC). Our results showed that exposure of OSCC cells (HN22 and HSC4) to Lico B significantly inhibited cell proliferation in a time- and concentration-dependent manner. Lico B caused cell cycle arrest at G1 phase along with downregulation of cyclin D1 and upregulation of p21 and p27 proteins. Lico B also facilitated the diffusion of phospholipid phosphatidylserine (PS) from inner to outer leaflets of the plasma membrane with chromatin condensation, DNA fragmentation, accumulated sub-G1 population in a concentration-dependent manner. Moreover, Lico B promoted the generation of reactive oxygen species (ROS), which, in turn, can induce CHOP, death receptor (DR) 4 and DR5. Lico B treatment induced downregulation of anti-apoptotic proteins (Bid and Bcl-xl and Mcl-1), and up-regulation of pro-apoptotic protein (Bax). Lico B also led to the loss of mitochondrial membrane potential (MMP), resulting in cytochrome c release. As can be expected from the above results, the apoptotic protease activating factor-1 (Apaf-1) and survivin were oppositely expressed in favor of apoptotic cell death. This notion was supported by the fact that Lico B activated multi-caspases with cleavage of poly (ADP-ribose) polymerase (PARP) protein. Therefore, it is suggested that Lico B is a promising drug for the treatment of human oral cancer via the induction of apoptotic cell death.

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PMID: 

Recent Pat Anticancer Drug Discov. 2016 ;11(4):444-452. PMID: 27719653

Abstract Title: 

Licochalcone B Arrests Cell Cycle Progression and Induces Apoptosis in Human Breast Cancer MCF-7 Cells.

Abstract: 

BACKGROUND: Recent patent of licochalcone B (LCB) as an antiinflammatory agent has been developed. Emerging evidence shows that LCB may be a promising alternative compound with anti-cancer activities. However, the anticancer mechanism of LCB in MCF-7 cells has not been fully investigated.OBJECTIVE: We aimed to unearth the anti-cancer effect and mechanism of LCB in MCF-7 cells.METHOD: Cell proliferation activity and cell-cycle progression were determined by sulforhodamine B assay and flow cytometry, respectively. The mRNA and protein levels of cell cycle-related proteins and apoptosis-associated proteins were examined by RT-qPCR and western blot, respectively. Mitochondrial membrane potential (MMP) was measured by flow cytometry after JC-1 staining.RESULTS: We found that LCB inhibited MCF-7 cells proliferation in a concentration- and time-dependent manner. Moreover, LCB-treatment led to S phase arrest in MCF-7 cells, which could be elucidated by the decreased mRNA and protein levels of Cyclin A, Cdk2 and Cdc25 A, and the increased protein level of p21. LCB also induced such apoptosis morphology as phosphatidylserine externalization, chromatin condensation and DNA fragmentation. Moreover, LCB led to the loss of MMP, resulting in the release of cytochrome C. The above apoptotic events were supported by the fact that LCB upregulated the mRNA and protein levels of Caspase 3, Caspase 9 and Bax, and downregulated the mRNA and protein level of Bcl-2, which was triggered by the increased p53 protein level in LCB-treated MCF-7 cells.CONCLUSION: These findings suggested that LCB could be a promising agent for treatment of human breast cancer.

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