PMID: 

Food Funct. 2019 Sep 1 ;10(9):5644-5655. Epub 2019 Aug 21. PMID: 31433413

Abstract Title: 

Fucoxanthin modulates cecal and fecal microbiota differently based on diet.

Abstract: 

Obesity is a major health concern worldwide and is considered to be associated with disruption of host-microbial homeostasis, especially microbiota composition in the gastrointestinal tract. Use of microbiota-directed foods or nutraceuticals therefore represents a promising approach for the control of obesity. Fucoxanthin, a marine carotenoid, has been proven to be one of the most effective anti-obesity natural products. However, its action mechanism is yet to be unraveled, especially with respect to its role in the modulation of gut microbiota composition. In the present study, profiles of microbiota in both the cecal and fecal samples from BALB/c mice given respectively the following treatments were examined: normal chow diet (NCD), NCD + fucoxanthin (NCDF), high-fat-diet (HFD), and HFD + fucoxanthin (HFDF). The results showed that fucoxanthin supplementation for 4 weeks significantly changed the composition of both cecal and fecal microbiota. In addition, a differential effect was observed between the supplementation to NCD and to HFD. The changes in the Firmicutes/Bacteroidetes ratio and the abundance of S24-7 and Akkermansia were identified to be among the major gut microbiota modulating events associated with the anti-obesity bioactivity of fucoxanthin. Hence, our results suggested that fucoxanthin could be a promising microbiota-targeted functional-food ingredient.

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PMID: 

Int J Mol Sci. 2019 Sep 11 ;20(18). Epub 2019 Sep 11. PMID: 31514311

Abstract Title: 

Fucoxanthin-Rich Brown Algae Extract Improves Male Reproductive Function on Streptozotocin-Nicotinamide-Induced Diabetic Rat Model.

Abstract: 

Hypogonadism and oxidative stress are occurring commonly in men with diabetes and associated male infertility. This study aimed to investigate the capability of anti-oxidative and anti-inflammatory properties of fucoxanthin as well as to evaluate its protective effects on male reproduction in diabetic rats. The RAW 264.7 macrophage cells were used to evaluate the anti-oxidative and anti-inflammatory activity. Thirty male Sprague-Dawley rats were induced by streptozotocin-nicotinamide for a diabetes model and fed either with three different doses of fucoxanthin (13, 26, and 65 mg/kg) or rosiglitazone (0.571 mg/kg) for four weeks. The fucoxanthin significantly inhibited nitric oxide production and reduced reactive oxygen species level in lipopolysaccharide-induced RAW 264.7 cells. In the animal study, fucoxanthin administration improved insulin resistance, restored sperm motility, decreased abnormal sperm number, and inhibited lipid peroxidation. Moreover, it restored GPR54 and SOCS-3 mRNA expression in the hypothalamus and recovered luteinizing hormone level, as well as the testosterone level. In conclusion, fucoxanthin not only possessed antioxidant and anti-inflammatory properties but also decreased the diabetes signs and symptoms as well as improved spermatogenesis and male reproductive function.

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PMID: 

Front Pharmacol. 2019 ;10:906. Epub 2019 Aug 28. PMID: 31555126

Abstract Title: 

Fucoxanthin, a Marine Xanthophyll Isolated FromND-8: Preventive Anti-Inflammatory Effect in a Mouse Model of Sepsis.

Abstract: 

Fucoxanthin (FX), a xanthophyll pigment which occurs in marine brown algae with remarkable biological properties, has been proven to be safe for consumption by animals. Although FX has various pharmacological effects including anti-inflammatory, anti-tumor, anti-obesity, antioxidant, anti-diabetic, anti-malarial, and anti-lipid,protective effect against sepsis has not been reported. In this study, we aimed at evaluation the efficacy of the FX in a model of sepsis mouse.FX was successfully isolated fromND-8 for the first time. The FX was identified by thin-layer chromatography (TLC), high-performance liquid chromatography-mass spectrometry (HPLC-MS), and nuclear magnetic resonance (NMR). Animals were randomly divided into 9 groups, including Sham group (mouse received an intraperitoneal injection of normal saline 1.0 ml/kg), FX-treated (0.1-1.0 ml/kg), Lipopolysaccharide (LPS)-treated (20 mg/kg), FX+LPS-treated (0.1-10.0 mg/kg and 20 mg/kg, respectively), and urinastatin groups (10U/kg). Nuclear factor (NF)-κB activation could be potential treatment for sepsis. NF-κB signaling components were determined by western-blotting. IL-6, IL-1β, TNF-α production, and NF-κB activation were evaluated by ELISA and immunofluorescent staining.FX was found to decrease the expression of inflammatory cytokines including IL-6, IL-1β, and TNF-α, in a prophylactic manner in the LPS-induced sepsis mouse model. Meanwhile, FX significantly inhibits phosphorylation of the NF-κB signaling pathway induced by LPS at the cellular level and reduces the nuclear translocation of NF-κB. The ICfor suppressing the expression of NF-κB was 11.08 ± 0.78 μM in the THP1-Lucia™ NF-κB cells. Furthermore, FX also inhibits the expression of inflammatory factors in a dose-dependent manner with the ICinhibition of IL-6 production was 2.19± 0.70 μM in Raw267.4 macrophage cells. It is likely that the molecules with the ability of targeting NF-κB activation and inflammasome assembly, such as fucoxanthin, are interesting subjects to be used for treating sepsis.

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PMID: 

Biomed Pharmacother. 2019 Sep 18 ;120:109443. Epub 2019 Sep 18. PMID: 31541884

Abstract Title: 

Rosmarinic acid inhibits proliferation and invasion of hepatocellular carcinoma cells SMMC 7721 via PI3K/AKT/mTOR signal pathway.

Abstract: 

OBJECTIVE: To investigate the effect of rosmarinic acid (RosA) on hepatocellular carcinoma cell in vivo and in vitro and to explore its possible mechanism of anti-hepatocarcinoma.METHODS: The hepatocellular carcinoma cell line SMMC-7721 was treated with different concentrations of RosA (0, 20, 50, 100 μmol/L) to detect cell proliferation, cell cycle, apoptosis and invasion.PI3K pathway-specific activator IGF-1 was used to explore whether the mechanism for RosA action relates to PI3K/AKT signal pathway.Nude mice inoculated with SMMC-7721 cells were treated with different doses of RosA (0, 5, 10 and 20 mg/kg) to detect the tumor formation of cancer cells in vivo.RESULTS: RosA significantly inhibited the proliferation of SMMC-7721 cells and induced G1 arrest and apoptosis in a dose-dependent manner. RosA might inhibit cell invasion by regulating epithelial-mesenchymal transition. Rescue experiments showed that IGF-1 could reverse the inhibition of PI3K/AKT/mTOR signal pathway by RosA and the effect on proliferation, apoptosis, cell cycle, invasion and EMT by IGF-1 in SMMC-7721 cells;RosA could inhibit tumor formation of SMMC-7721 cells in vivo.CONCLUSION: RosA can inhibit the proliferation and invasion of hepatocellular carcinoma cell in vitro and inhibit tumour growth in vivo and the mechanism may relate to inhibiting the activation of PI3K/AKT signal pathway.

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PMID: 

Diabetologia. 2018 06 ;61(6):1282-1294. Epub 2018 Apr 18. PMID: 29671031

Abstract Title: 

Short-term decreased physical activity with increased sedentary behaviour causes metabolic derangements and altered body composition: effects in individuals with and without a first-degree relative with type 2 diabetes.

Abstract: 

AIMS/HYPOTHESIS: Low physical activity levels and sedentary behaviour are associated with obesity, insulin resistance and type 2 diabetes. We investigated the effects of a short-term reduction in physical activity with increased sedentary behaviour on metabolic profiles and body composition, comparing the effects in individuals with first-degree relatives with type 2 diabetes (FDR+ve) vs those without (FDR-ve).METHODS: Forty-five habitually active participants (16 FDR+ve [10 female, 6 male] and 29 FDR-ve [18 female, 11 male]; age 36 ± 14 years) were assessed at baseline, after 14 days of step reduction and 14 days after resuming normal activity. We determined physical activity (using a SenseWear armband), cardiorespiratory fitness ([Formula: see text]), body composition (dual-energy x-ray absorptiometry/magnetic resonance spectroscopy) and multi-organ insulin sensitivity (OGTT) at each time point. Statistical analysis was performed using a two-factor between-groups ANCOVA, with data presented as mean ± SD or (95% CI).RESULTS: There were no significant between-group differences in physical activity either at baseline or following step reduction. During the step-reduction phase, average daily step count decreased by 10,285 steps (95% CI 9389, 11,182; p 

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PMID: 

Br J Pharmacol. 2008 May ;154(1):165-73. Epub 2008 Mar 10. PMID: 18332856

Abstract Title: 

Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-kappaB-dependent iNOS and proinflammatory cytokines production.

Abstract: 

BACKGROUND AND PURPOSE: Glycyrrhizae radix has been widely used as a cytoprotective, plant-derived medicine. We have identified a flavanoid, liquiritigenin, as an active component in extracts of Glycyrrhizae radix. This research investigated the effects of liquiritigenin on the induction of inducible NOS (iNOS) and proinflammatory cytokines by lipopolysaccharide (LPS) in Raw264.7 cells, and on paw oedema in rats.EXPERIMENTAL APPROACH: iNOS expression was determined by western blotting, real-time reverse transcription-PCR and reporter gene analyses. Tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 were assayed by ELISA. Gel shift assay and immunoblotting were used to assess NF-kappaB activation. The effect of liquiritigenin on acute inflammation in vivo was evaluated using carrageenan-induced paw oedema.KEY RESULTS: Treatment of Raw264.7 cells with liquiritigenin caused inhibition of LPS-induced NF-kappaB DNA binding activity, due to repression of I-kappaBalpha phosphorylation and degradation. Liquiritigenin treatment prevented LPS from increasing the levels of iNOS protein and mRNA in a concentration-dependent manner. Liquiritigenin also suppressed the production of TNF-alpha, IL-1beta and IL-6 from Raw264.7 cells after LPS. In rats, liquiritigenin treatment inhibited formation of paw oedema induced by carrageenan.CONCLUSION AND IMPLICATIONS: These results demonstrate that liquiritigenin exerts anti-inflammatory effects, which results from the inhibition of NF-kappaB activation in macrophages, thereby decreasing production of iNOS and proinflammatory cytokines. Our findings showing inhibition by liquiritigenin of paw oedema as well as inflammatory gene induction will help to understand the pharmacology and mode of action of liquiritigenin, and of the anti-inflammatory use of Glycyrrhizae radix.

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PMID: 

Int Immunopharmacol. 2009 May ;9(5):632-8. Epub 2009 Mar 3. PMID: 19264152

Abstract Title: 

Liquiritigenin, a licorice flavonoid, helps mice resist disseminated candidiasis due to Candida albicans by Th1 immune response, whereas liquiritin, its glycoside form, does not.

Abstract: 

Licorice (the root of Glycyrrhizae plant) has been used as an oriental herbal medicine for thousands of years. The licorice flavonoid components are reported to possess immunomodulatory activities. In this present study, we investigated the immunomodulatory effects of liquiritigenin (LG) and liquiritin (LQ), licorice flavonoid components, against disseminated candidiasis due to Candida albicans, a dimorphic fungus, that causes severe disease via hematogenous dissemination and local diseases such as vaginitis and thrush. Results showed that direct interaction of LG or LQ with C. albicans yeast cells resulted in no growth-inhibition, in vitro. When tested in a murine model of disseminated candidiasis, mice given LQ intraperitoneally before intravenous challenge with live C. albicans yeast cells had similar mean survival times (MST) as untreated mice groups. On the contrary, mice given LG in the same manner as LQ above had longer MST than the untreated mice groups (P

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PMID: 

Acta Pharmacol Sin. 2009 Jul ;30(7):899-906. PMID: 19574995

Abstract Title: 

Liquiritigenin inhibits Abeta(25-35)-induced neurotoxicity and secretion of Abeta(1-40) in rat hippocampal neurons.

Abstract: 

AIM: To examine whether liquiritigenin, a newly found agonist of selective estrogen receptor-beta, has neuroprotective activity against beta-amyloid peptide (Abeta) in rat hippocampal neurons.METHODS: Primary cultures of rat hippocampal neurons were pretreated with liquiritigenin (0.02, 0.2, and 2 micromol/L) prior to Abeta(25-35) exposure. Following treatment, viability of the cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis and by a lactate dehydrogenase activity-based cytotoxicity assay. Intracellular Ca(2+) concentration ([Ca(2+)](i)) and levels of reactive oxygen species (ROS), as well as apoptotic rates, were determined. Our studies were extended in tests of whether liquiritigenin treatment could inhibit the secretion of Abeta(1-40) as measured using an ELISA method. In order to analyze which genes may be involved, we used a microarray assay to compare gene expression patterns. Finally, the levels of specific proteins related to neurotrophy and neurodenegeration were detected by Western blotting.RESULTS: Pretreated neurons with liquiritigenin in the presence of Abeta(25-35) increased cell viability in a concentration-dependent manner. Liquiritigenin treatment also attenuated Abeta(25-35)-induced increases in [Ca(2+)](i) and ROS level and decreased the apoptotic rate of neurons. Some genes, including B-cell lymphoma/leukemia-2 (Bcl-2), neurotrophin 3 (Ntf-3) and amyloid beta (A4) precursor protein-binding, family B, member 1 (Apbb-1) were regulated by liquiritigenin; similar results were shown at the protein level by Western blotting.CONCLUSION: Our results demonstrate that liquiritigenin exhibits neuroprotective effects against Abeta(25-35)-induced neurotoxicity and that it can decrease the secretion of Abeta(1-40). Therefore, liquiritigenin may be useful for further study as a prodrug for treatment of Alzheimer's disease.Acta Pharmacologica Sinica (2009) 30: 899-906; doi: 10.1038/aps.2009.74.

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PMID: 

Behav Brain Res. 2010 Jun 26 ;210(1):24-31. Epub 2010 Feb 1. PMID: 20117143

Abstract Title: 

Effects of liquiritigenin treatment on the learning and memory deficits induced by amyloid beta-peptide (25-35) in rats.

Abstract: 

Considerable evidence has emerged supporting the neuroprotective and cognition-preserving effects of estrogen, but these benefits are complicated by the evidence that estrogen increases the risk of certain cancers. Selective estrogen receptor modulators (SERMs) that specifically target the brain while avoiding peripheral organs offer a way to allow the application of estrogen treatment to neurodegenerative diseases with fewer undesirable effects. In an attempt to find such estrogen substitutes, liquiritigenin was discovered as a relatively selective estrogen receptor beta (ERbeta) agonist. In the present study, we extend our previous findings to investigate the effects of liquiritigenin on the learning and memory deficits and related neuropathology in Abeta(25-35) hippocampal-injected rats. Our results show that liquiritigenin treatment improves the behavioral performance of the model rats and attenuates neuronal loss in the brain. More importantly, liquiritigenin treatment decreases mRNA levels and protein expression of Notch-2, an effect that could promote the generation of new neurons. These findings provide evidence for the beneficial activity of liquiritigenin in a brain-injured rat model and support the continued investigation of SERMs such as liquiritigenin as an alternative to estrogen-based hormone therapy in reducing the risk of neurodegenerative diseases such as Alzheimer's disease.

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PMID: 

Phytother Res. 2011 Feb ;25(2):277-83. PMID: 20658471

Abstract Title: 

Liquiritigenin induces mitochondria-mediated apoptosis via cytochrome c release and caspases activation in HeLa Cells.

Abstract: 

It has been demonstrated that many flavonoids possess a potent and broad spectrum of antitumor activity. Liquiritigenin is a flavanone extracted from Glycyrrhizae. This study investigated the effects of liquiritigenin on cell viability and apoptosis induction in human cervical carcinoma (HeLa) cells. The results show that liquiritigenin significantly suppressed cell proliferation in a dose- and time-dependent manner in HeLa cells. In addition, liquiritigenin promoted apoptosis in HeLa cells, evidenced by apoptotic morphological changes and Annexin-V binding. The apoptosis induction with liquiritigenin is associated with the up-regulation of p53 and Bax, along with down-regulation of Bcl-2 and survivin. Finally, examination of the mitochondrial pathway of apoptosis revealed that cytochrome c is released from mitochondria to cytosol, associated with the activation of caspase-9 and -3, and the cleavage of poly (ADP-ribose) polymerase (PARP). Overall, the results indicate that liquiritigenin induces apoptosis in part via the mitochondrial pathway, which is associated with p53 up-regulation, release of cytochrome c and elevated activity of caspase-9 and -3 in HeLa cells.

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