PMID: 

Oncol Lett. 2018 Nov ;16(5):6133-6139. Epub 2018 Aug 21. PMID: 30344755

Abstract Title: 

Isoliquiritigenin inhibits cell proliferation and migration through the PI3K/AKT signaling pathway in A549 lung cancer cells.

Abstract: 

The present study aimed to investigate the molecular mechanisms of inhibition of Isoliquiritigenin (ISL) on the proliferation and migration of A549 cells. A549 cells were cultured, and the effects of ISL inhibition were examined using cell counting kit-8, Transwell invasion and flow cytometric assays. Western blot analysis was also performed to detect cell apoptosis and the expression of phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway-associated proteins. The results demonstrated a significant inhibition of proliferation and migration of A549 cells when treated with ISL (P

read more

PMID: 

Int J Mol Sci. 2018 Oct 22 ;19(10). Epub 2018 Oct 22. PMID: 30360437

Abstract Title: 

Dietary Isoliquiritigenin at a Low Dose Ameliorates Insulin Resistance and NAFLD in Diet-Induced Obesity in C57BL/6J Mice.

Abstract: 

Isoliquiritigenin (ILG) is a flavonoid constituent ofplants. The current study investigated the effects of ILG on diet-induced obesity and metabolic diseases. C57BL/6J mice were fed a normal diet (AIN-76 purified diet), high-fat diet (40 kcal% fat), and high-fat diet +0.02% (/) ILG for 16 weeks. Supplementation of ILG resulted in decreased body fat mass and plasma cholesterol level. ILG ameliorated hepatic steatosis by suppressing the expression of hepatic lipogenesis genes and hepatic triglyceride and fatty acid contents, while enhancingβ-oxidation in the liver. ILG improved insulin resistance by lowering plasma glucose and insulin levels. This was also demonstrated by the intraperitoneal glucose tolerance test (IPGTT). Additionally, ILG upregulated the expression of insulin signaling-related genes in the liver and muscle. Interestingly, ILG elevated energy expenditure by increasing the expression of thermogenesis genes, which is linked to stimulated mitochondrial biogenesis and uncoupled cellular respiration in brown adipose tissue. ILG also suppressed proinflammatory cytokine levels in the plasma. These results suggest that ILG supplemented at 0.02% in the diet can ameliorate body fat mass, plasma cholesterol, non-alcoholic fatty liver disease, and insulin resistance; these effects were partly mediated by increasing energy expenditure in high-fat fed mice.

read more

PMID: 

Neurochem Res. 2018 Dec ;43(12):2435-2445. Epub 2018 Nov 16. PMID: 30446968

Abstract Title: 

Isoliquiritigenin Provides Protection and Attenuates Oxidative Stress-Induced Injuries via the Nrf2-ARE Signaling Pathway After Traumatic Brain Injury.

Abstract: 

Traumatic brain injury (TBI) is a serious public health and medical problem worldwide. Oxidative stress plays a vital role in the pathogenesis of TBI. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important factor in the cellular defense against oxidative stress, is activated following TBI. In this study, the protective effects of Isoliquiritigenin (ILG), a promising antioxidant stress drug, was evaluated as a protective agent against TBI. In a mouse model of controlled cortical impact Injury, we found that the ILG administration reduced the Garcia neuroscore, injury histopathology, brain water content, cerebral vascular permeability, the expression of cleaved caspase3, aquaporin-4, glial fibrillary acidic protein and the increased the expression of neurofilament light chain protein, indicating the protective effects against TBI in vivo. ILG treatment after TBI also restored the oxidative stress and promoted the Nrf2 protein transfer from the cytoplasm to the nucleus. We then used Nrf2-/- mice to test the protective effect of Nrf2 during ILG treatment of TBI. Our findings indicated that Nrf2-/- mice had greater brain injury and oxidative stress than wild-type (WT) mice and ILG was less effective at inhibiting oxidative stress and repairing the brain injury than in the WT mice. In vitro studies in SY5Y cells under oxygen glucose deprivation/re-oxygenation stimulation yielded results that were consistent with those obtained in vivo showing that ILG promotes Nrf2 protein transfer from the cytoplasm to the nucleus. Taken together, our findings demonstrate that Nrf2 is an important protective factor against TBI-induced injuries, which indicates that the protective effects of ILG are mediated by inhibiting oxidative stress after TBI via a mechanism that involves the promotion of Nrf2 protein transfer from the cytoplasm to the nucleus.

read more

PMID: 

Chem Biol Interact. 2019 Feb 1 ;299:77-87. Epub 2018 Nov 28. PMID: 30502331

Abstract Title: 

Anti-proliferative and cytotoxic activities of the flavonoid isoliquiritigenin in the human neuroblastoma cell line SH-SY5Y.

Abstract: 

Neuroblastoma is a common childhood cancer with high mortality. We evaluated the capacity of the flavonoid, isoliquiritigenin (4,2',4'-trihydroxychalcone; ISL) to inhibit cellular proliferation and migration in the human neuroblastoma cell line SH-SY5Y. Incubation of cultured SH-SY5Y cells with 20-100 μM ISL decreased cell confluency (15-70%) after 24 h incubation, while 10-100 μM ISL (24 h) depleted intracellular ATP stores (15-90% vs vehicle-treated control) after 24 h incubation. ISL-mediated cell toxicity did not involve intracellular caspase 3/7 activation, externalization of phosphatidylserine on the cell membrane or stimulation of TNF and IL-1β release, all indicating that the flavonoid did not induce apoptosis. Pre-treatment of cells with necrostatin-1, a necroptosis inhibitor, significantly restored ATP levels (ATP levels increased 12-42%) in ISL-treated neuroblastomacells indicative of enhanced viability. By contrast, RIP1 phosphorylation status remained unchanged in cells treated with ISL although the intracellular ratio of phosphorylated/total parental RIP1 increased after ISL treatment on SH-SY5Y cells indicating that ISL decreased levels of native RIP1. Inaddition, ISL treatment inhibited SH-SY5Y cell migration/proliferation in a scratch assay and arrested cell cycle transition by significantly decreasing the number of cells in G0/G1 phase and increasing populations by ~10% in S (primarily) and G2/M (lesser extent) phases. The intracellular ratio ofphosphorylated/total ERK 1/2 and p38 remained unchanged after ISL treatment (up to 40 μM); ERK activation was only determined at ISL dose well above the experimental ICvalue as judged by ELISA analyses and this did not correlate with ISL cytotoxicity at lower dose

read more

PMID: 

Environ Sci Technol. 2019 Sep 25. Epub 2019 Sep 25. PMID: 31552738

Abstract Title: 

Plastic Teabags Release Billions of Microparticles and Nanoparticles into Tea.

Abstract: 

The increasing presence of micro- and nano-sized plastics in the environment and food chain is of growing concern. Although mindful consumers are promoting the reduction of single-use plastics, some manufacturers are creating new plastic packaging to replace traditional paper uses, such as plastic teabags. The objective of this study was to determine whether plastic teabags could release microplastics and/or nanoplastics during a typical steeping process. We show that steeping a single plastic teabag at brewing temperature (95°C) releases approximately 11.6 billion microplastics and 3.1 billion nanoplastics into a single cup of the beverage. The composition of the released particles is matched to the original teabags (nylon and polyethylene terephthalate) using Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The levels of nylon and polyethylene terephthalate particles released from the teabag packaging are several orders of magnitude higher than plastic loads previously reported in other foods. An initial acute invertebrate toxicity assessment shows that exposure to onlythe particles released from the teabags caused dose-dependent behavioral and developmental effects.

read more

PMID: 

Am J Transl Res. 2018 ;10(12):4141-4151. Epub 2018 Dec 15. PMID: 30662657

Abstract Title: 

Isoliquiritigenin attenuates LPS-induced AKI by suppression of inflammation involving NF-κB pathway.

Abstract: 

Septic acute kidney injury (AKI) characterized as acute infection and renal inflammation, still lacks of effective therapies. Isoliquiritigenin (ISL) as a small molecular from licorice, is able to inhibit the expression of HMGB1. However, the role and mechanism of ISL in septic AKI has not been investigated. In this study, we used LPS injection to induce murine septic AKI. One hour before LPS injection, 50 mg/kg ISL was once orally given to the mice. For thestudy, HKhuman tubular cells were respectively treated with 50μM and 100 μM ISL 5 hrs before 2 μg/ml LPS stimulation. Then we observed that ISL ameliorated renal dysfunction and attenuated renal tubular injury. ISL inhibited the phosphorylation of IκB-α and NF-κB p65 after LPS induction bothand. ISL also inhibited NF-κB p65 translocation from cytoplasm to the nucleus upon LPS stimulation. Further, NF-κB p65 translocation could trigger macrophage polarization, neutrophil activation and pro-inflammatory cytokines secretion in LPS-induced inflammation. These results showed that ISL could alleviate LPS-induced AKIby suppressing NF-κB p65 translocation and inhibiting inflammatory responses, indicating protective effects of ISL in LPS-induced acute renal inflammation. This study might be useful for designing potential clinical trials to prevent and treat sepsis induced AKI in patients with serious illness.

read more

PMID: 

Drug Dev Res. 2019 06 ;80(4):461-470. Epub 2019 Jan 30. PMID: 30698296

Abstract Title: 

Mechanisms underlying isoliquiritigenin-induced apoptosis and cell cycle arrest via ROS-mediated MAPK/STAT3/NF-κB pathways in human hepatocellular carcinoma cells.

Abstract: 

Isoliquiritigenin (ISL), a natural flavonoid isolated from plant licorice, has various pharmacological properties, including anticancer, anti-inflammatory, and antiviral effects. However, the underlying mechanisms and signaling pathways of ISL in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we evaluated the effects of ISL on the apoptosis of human HCC cells with a focus on reactive oxygen species (ROS) production. Our results showed that ISL exhibited cytotoxic effects on two human liver cancer cells in a dose-dependent manner. ISL significantly induced mitochondrial-related apoptosis and cell cycle arrest at the G2/M phase, which was accompanied by ROS accumulation in HepG2 cells. However, pretreatment with an ROS scavenger, N-acetyl-l-cysteine (NAC), inhibited ISL-induced apoptosis. In addition, ISL increased the phosphorylation levels of c-Jun N-terminal kinase (JNK), p38 kinase and inhibitor of NF-κB (IκB), and decreased the phosphorylation levels of extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-κB), these effects were blocked by NAC and mitogen-activated protein kinase (MAPK) inhibitors. Taken together,the findings of this study indicate that ISL induced HepG2 cell apoptosis via ROS-mediated MAPK, STAT3, and NF-κB signaling pathways. Therefore, ISL may be a potential treatment for human HCC, as well as other cancer types.

read more

PMID: 

Oncol Rep. 2019 Apr ;41(4):2502-2510. Epub 2019 Feb 4. PMID: 30720124

Abstract Title: 

Isoliquiritigenin inhibits the proliferation, apoptosis and migration of osteosarcoma cells.

Abstract: 

The overall survival rate of patients with osteosarcoma has remained unchanged for the last several decades. Therefore, novel drugs for osteosarcoma treatment are required. Isoliquiritigenin (ISL), a natural compound, has been demonstrated to inhibit the growth of various tumors. However, it is unclear whether ISL is able to inhibit the growth of osteosarcoma. In the present study, it was identified that ISL was able to inhibit the growth of the osteosarcoma cell line Saos‑2 cells in vitro and in xenograft tumors primarily by attenuating tumor cell proliferation and, cell migration and promoting tumor cell apoptosis. Decreased tumor cell proliferation induced by ISL was associated with downregulation of cyclin D1 and upregulation of p53, p21 and p27. Increased tumor cell apoptosis triggered by ISL was associated with downregulation of apoptosis regulator Bcl‑2, upregulation of apoptosis regulator Bax and damaged mitochondrial function evidenced by a low level of ATP‑synthesis. In addition, ISL was able to inhibit the migratory capacity of Saos‑2 cells by modulating the expression of matrix metalloproteinase (MMP)2 and MMP9. Mechanistic analysis revealed that the tumor growth‑inhibitory effect of ISL may depend on the action of ISL on the phosphorylation of PI3K and AKT. However, it remains to be investigated whether the inhibitory effect of ISLon the migration of Saos‑2 cells was associated with downregulated PI3K/AKT signaling. Overall, the present study provided evidence for the potential use of ISL against osteosarcoma.

read more

PMID: 

Neuroimmunomodulation. 2019 ;26(2):102-110. Epub 2019 Feb 15. PMID: 30783039

Abstract Title: 

Isoliquiritigenin Attenuates Neuroinflammation in Traumatic Brain Injury in Young Rats.

Abstract: 

OBJECTIVES: Inflammation and apoptosis play a critical role in the pathological progress of traumatic brain injury (TBI). Isoliquiritigenin is a bioactive component extracted from licorice roots, which possesses anti-inflammatory and anti-apoptotic properties. This study aims to investigate the potential effects of isoliquiritigenin on neuroinflammation in a rat model of TBI.METHODS: The SH-SY5Y cells were subjected to cell injury induced by shear stress and the effect of isoliquiritigenin on cell apoptosis was measured. Male rats received a controlled cortical impact to induce TBI and were then treated with isoliquiritigenin (20 mg/kg). Brain edema and contusion volume were measured to assess brain damage. Morris water maze, the beam-balance test, and the beam-walk test were performed to evaluate the cognitive and motor functions.RESULTS: Levels of proinflammatory cytokines and apoptotic regulators were measured. Results showed that isoliquiritigenin reduced shear stress-induced cell apoptosis in vitro. In young rats subjected to TBI, treatment of isoliquiritigenin reduced brain damage and attenuated motor and cognitive impairments. Isoliquiritigenin also reduced the level of proinflammatory cytokines and Bax and increased Bcl-2 and Bcl-xL in TBI rats.CONCLUSIONS: These findings suggest that isoliquiritigenin possesses beneficial effects in TBI by inhibiting inflammation and apoptosis.

read more

PMID: 

Oxid Med Cell Longev. 2019 ;2019:9817576. Epub 2019 Jan 21. PMID: 30805086

Abstract Title: 

Isoliquiritigenin Induces Mitochondrial Dysfunction and Apoptosis by Inhibiting mitoNEET in a Reactive Oxygen Species-Dependent Manner in A375 Human Melanoma Cells.

Abstract: 

The mitochondrial protein mitoNEET is a type of iron-sulfur protein localized to the outer membrane of mitochondria and is involved in a variety of human pathologies including cystic fibrosis, diabetes, muscle atrophy, and neurodegeneration. In the current study, we found that isoliquiritigenin (ISL), one of the components of the root of, could decrease the expression of mitoNEET in A375 melanoma cells. We also demonstrated that mitoNEET could regulate the content of reactive oxygen species (ROS), by showing that the ISL-mediated increase in the cellular ROS content could be mitigated by the mitoNEET overexpression. We also confirmed the important role of ROS in ISL-treated A375 cells. The increased apoptosis rate and the decreased mitochondrial membrane potential were mitigated by the overexpression of mitoNEET in A375 cells. These findings indicated that ISL could decrease the expression of mitoNEET, which regulated ROS content and subsequently induced mitochondrial dysfunction and apoptosis in A375 cells. Our findings also highlight mitoNEET as a promising mitochondrial target for cancer therapy.

read more