licochalcone-a and Disease-Models--Animal

The gut epithelium is a mechanical barrier that protects the host from the luminal microenvironment and interacts with the gut microflora, which influences the development and progression of ulcerative colitis (UC). Licochalcone A (LA) exerts anti-inflammatory effects against UC; however, whether it also regulates both the gut barrier and microbiota during colitis is unknown. The current study was conducted to reveal the regulatory effects of LA on the intestinal epithelium and gut microflora in C57BL/6 mice subjected to dextran sodium sulfate (DSS). Sulfasalazine (SASP) was used as the positive control. Results of clinical symptoms evaluation, hematoxylin, and eosin (H&E) staining, and enzyme-linked immunosorbent (ELISA) assays showed that LA significantly inhibited DSS-induced weight loss, disease activity index (DAI) increase, histological damage, and gut inflammation. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemical (IHC) analysis showed that LA maintained the integrity of the intestinal barrier by suppressing cell apoptosis and preserving the expression of tight junction (TJ) proteins. Notably, the optimal dose of LA for gut barrier preservation was low, while that for anti-inflammatory effects was high, indicating that LA might preserve gut barrier integrity via direct effects on the epithelial cells (ECs) and TJ proteins. Furthermore, 16S rRNA analysis suggested that the regulatory effect of LA on the gut microbiota differed distinctly according to dose. Correlation analysis indicated that a low dose of LA significantly modulated the intestinal barrier-associated bacteria as compared with a moderate or high dose of LA. Western blot (WB) analysis indicated that LA exhibited anti-UC activity partly by blocking the mitogen-activated protein kinase (MAPK) pathway. Our results further elucidate the pharmacological activity of LA against UC and will provide valuable information for future studies regarding on the regulatory effects of LA on enteric diseases.

Topics: Animals; Chalcones; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Sulfasalazine; Tight Junction Proteins

Topics: Angiotensin II; Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Apolipoproteins E; Apoptosis; Chalcones; Cytokines; Disease Models, Animal; Heme Oxygenase-1; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; MicroRNAs; Signal Transduction; Sirtuin 1

Topics: Animals; Antibody Specificity; Asthma; Bronchoalveolar Lavage Fluid; Cell Adhesion; Chalcones; Chemokines; Collagen; Cyclooxygenase 2; Disease Models, Animal; DNA Damage; Eosinophils; Female; Glutathione; Goblet Cells; Humans; Hyperplasia; Inflammation Mediators; Lung; Malondialdehyde; Mice, Inbred BALB C; Ovalbumin; Oxidative Stress; Protective Agents; Reactive Oxygen Species; Respiratory Hypersensitivity; THP-1 Cells

Licorice has been used as an antitussive and expectorant herbal medicine for a long history. This work evaluated the activities of 14 major compounds and crude extracts of licorice, using the classical ammonia-induced cough model and phenol red secretion model in mice. Liquiritin apioside (1), liquiritin (2), and liquiritigenin (3) at 50 mg/kg (i.g.) could significantly decrease cough frequency by 30-78% (p < .01). The antitussive effects could be partially antagonized by the pretreatment of methysergide or glibenclamide, but not naloxone. Moreover, compounds 1-3 showed potent expectorant activities after 3 days treatment (p < .05). The water and ethanol extracts of licorice, which contain abundant 1 and 2, could decrease cough frequency at 200 mg/kg by 25-59% (p < .05), and enhance the phenol red secretion (p < .05), while the ethyl acetate extract showed little effect. These results indicate liquiritin apioside and liquiritin are the major antitussive and expectorant compounds of licorice. Their antitussive effects depend on both peripheral and central mechanisms.

Topics: Administration, Oral; Ammonia; Animals; Antitussive Agents; Cough; Disease Models, Animal; Dose-Response Relationship, Drug; Expectorants; Glyburide; Glycyrrhiza; Male; Methysergide; Mice; Mice, Inbred ICR; Molecular Structure; Phenolsulfonphthalein; Plant Extracts; Structure-Activity Relationship

Licochalcone A (LCA) is derived from glycyrrhizae radix with antimicrobial, antitumor and anti-inflammatory activities. However, the anti-arthritic function of LCA and underlying mechanism has not been yet explored. The current study investigated the anti-arthritic effect of LCA and elucidated the underlying mechanism. The results showed that LCA significantly suppressed arthritis via the activation of SQSTM1 (p62)/nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling in the collagen-induced arthritis (CIA) model of DBA mice. In coincided with the results, this anti-arthritic effect of LCA was remarkably diminished in the collagen antibody-induced arthritis (CAIA) model of Nrf2-/- mice. These findings indicate that p62/Nrf2 signaling is a crucial pathway for the induction and treatment of arthritis. To further validate the effect of LCA on the arthritis, rheumatoid arthritis synovial fibroblasts (RASFs) isolated from the synovium of RA patients were employed in the study. In coincided with in vivo results, LCA inhibited the cell proliferation and arrested the cell cycle, induced apoptosis, suppressed pro-inflammatory cytokine secretion and increased expression of antioxidant enzymes via the activation of Keap1-Nrf2 signaling by enhancing p62 phosphorylation and expression, Nrf2 accumulation and Nrf2 nucleus translocation. Findings in the current study provide evidence that p62-Keap1-Nrf2 axis is a pivotal signaling pathway in development of arthritis and therapeutic efficacy of drugs, and LCA activates of Keap1-Nrf2 signaling to suppress arthritis by phosphorylation of p62 at Ser349. Collectively, LCA is valuable to be further investigated as a lead compound for application in anti-arthritis, and interference with the interaction between Nrf2 and Keap1 by phosphorylation of p62 may be a promising strategy for the discovery of anti-arthritic agents.

Topics: Animals; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Proliferation; Cells, Cultured; Chalcones; Disease Models, Animal; Fibroblasts; Glycyrrhiza; Kelch-Like ECH-Associated Protein 1; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Knockout; NF-E2-Related Factor 2; Phosphorylation; Sequestosome-1 Protein; Signal Transduction

The main function of brown adipose tissue is to dissipate surplus caloric intake into heat energy by thermogenesis, increasing energy expenditure. Inducible brown adipocytes can develop within white adipose tissue (WAT) through a process referred to as browning. Browning of white fat represents a promising strategy for treatment of obesity and the related complications. We investigated whether Glycyrrhiza uralensis and its ingredients modulated adipogenesis through adipocyte browning using 3T3-L1 adipocytes and a high-fat diet (HFD)-induced obesity mice model. Amongst extracts and fractions of G. uralensis, methyl dichloride (MeCl

Topics: 3T3-L1 Cells; Adipocytes, Brown; Animals; Chalcones; Diet, High-Fat; Disease Models, Animal; Glycyrrhiza uralensis; Injections, Intraperitoneal; Metabolic Diseases; Mice; Obesity; Plant Extracts; Plant Roots

Topics: Administration, Oral; Animals; Carbon Tetrachloride; Cell Survival; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Dose-Response Relationship, Drug; Glycyrrhiza; Hep G2 Cells; Humans; Male; Mice; Mice, Inbred ICR; Molecular Structure; NF-E2-Related Factor 2; Plant Extracts; Plant Roots; Rats; Rats, Sprague-Dawley

Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra), has been reported to have anti-inflammatory activity. However, the protective effects of Lico A on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) remains unclear. In this study, using a mouse model of LPS-induced AKI, we investigated the protective effects and mechanism of Lico A on LPS-induced AKI in mice. LPS-induced kidney injury was assessed by detecting kidney histological study, blood urea nitrogen (BUN), and creatinine levels. The production of inflammatory cytokines TNF-α, IL-6, and IL-1β in serum and kidney tissues was detected by ELISA. The activation of NF-κB was measured by western blot analysis. Our results showed that Lico A dose-dependently attenuated LPS-induced kidney histopathologic changes, serum BUN, and creatinine levels. Lico A also suppressed LPS-induced TNF-α, IL-6, and IL-1β production both in serum and kidney tissues. Furthermore, our results showed that Lico A significantly inhibited LPS-induced NF-κB activation. In conclusion, our results suggest that Lico A has protective effects against LPS-induced AKI and Lico A exhibits its anti-inflammatory effects through inhibiting LPS-induced NF-κB activation.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents; Blood Urea Nitrogen; Chalcones; Creatinine; Disease Models, Animal; Enzyme Activation; Fabaceae; Female; Interleukin-1beta; Interleukin-6; Kidney; Lipopolysaccharides; Mice; Mice, Inbred C57BL; NF-kappa B; Plant Preparations; Tumor Necrosis Factor-alpha

Both phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase (MAPK) signaling cascades play an important role in cell proliferation, survival, angiogenesis, and metastasis of tumor cells. In the present report, we investigated the effects of licochalcone A (LA), a flavonoid extracted from licorice root, on the PI3K/AKT/mTOR and MAPK activation pathways in human gastric cancer BGC-823 cells. LA increased reactive oxygen species (ROS) levels, which is associated with the induction of apoptosis as characterized by positive Annexin V binding and activation of caspase-3, and cleavage of poly-ADP-ribose polymerase (PARP). Inhibition of ROS generation by N-acetylcysteine (NAC) significantly prevented LA-induced apoptosis. Interestingly, we also observed that LA caused the activation of ERK, JNK, and p38 MAPK in BGC-823 cells. The antitumour activity of LA-treated BGC-823 cells was significantly distinct in KM mice in vivo. All the findings from our study suggest that LA can interfere with MAPK signaling cascades, initiate ROS generation, induce oxidative stress and consequently cause BGC cell apoptosis.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chalcones; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Humans; JNK Mitogen-Activated Protein Kinases; Mice; Mitogen-Activated Protein Kinases; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction; Stomach Neoplasms; Xenograft Model Antitumor Assays

Licochalcone A (Lico A) is a major and biogenetically characteristic chalcone isolated from the root of Xinjiang liquorice, Glycyrrhiza inflata.. 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.. 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.. 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.. 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.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Chalcones; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Immunoglobulin E; Immunoglobulin G; Lung; Mice; Mice, Inbred BALB C; Receptors, CCR3

Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra), is known for its antimicrobial activity and its reported ability to inhibit cancer cell proliferation. In the present study, we found that Lico A exerted potent anti-inflammatory effects in in vitro and in vivo models induced by lipopolysaccharide (LPS). The concentrations of TNF-α, interleukin (IL)-6, and IL-1β in the culture supernatants of RAW 264.7 cells were determined at different time points following LPS administration. LPS (0.5 mg/kg) was instilled intranasally (i.n.) in phosphate-buffered saline to induce acute lung injury, and 24 h after LPS was given, bronchoalveolar lavage fluid was obtained to measure pro-inflammatory mediator and total cell counts. The phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) p65 protein was analyzed by Western blotting. Our results showed that Lico A significantly reduced the amount of inflammatory cells, the lung wet-to-dry weight (W/D) ratio, protein leakage, and myeloperoxidase activity and enhances oxidase dimutase activity in mice with LPS-induced acute lung injury (ALI). Enzyme-linked immunosorbent assay results indicated that Lico A can significantly down-regulate TNF-α, IL-6, and IL-1β levels in vitro and in vivo, and treatment with Lico A significantly attenuated alveolar wall thickening, alveolar hemorrhage, interstitial edema, and inflammatory cells infiltration in mice with ALI. In addition, we further demonstrated that Lico A exerts an anti-inflammation effect in an in vivo model of acute lung injury through suppression of NF-κB activation and p38/ERK MAPK signaling in a dose-dependent manner.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Cell Line; Chalcones; Disease Models, Animal; Down-Regulation; Glycyrrhiza; Humans; Interleukin-6; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Plant Extracts; Tumor Necrosis Factor-alpha