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1.
Animal ; 17(1): 100696, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36587589

RESUMO

Some studies have suggested that dietary medicinal plants or herbs may have a variety of biological functions such as anti-inflammatory, antiallergic, antifungal, antioxidative stress, and anticarcinogenic activities. The present study was undertaken to assess the incorporation of the extract of licorice supplementation on the growth performance, carcass yield, blood indices, and antioxidative capacity in broilers. Three hundred twenty unsexed one-day-old Ross 308 broiler chicks were allocated randomly into four groups. Chicks in each group were randomly subdivided into eight replicates of ten chicks. The first group received a basal diet and was considered a control. The respective groups received a basal diet supplemented with 1, 2, and 3 g licorice extract/kg diet. The obtained results indicated that supplementation of licorice extract to broiler chicks resulted in heavier BW and weight gain and a better feed conversion ratio during the experimental periods compared with the control group. However, feed consumption increased during the entire growing period. Supplementing the broiler's diet with licorice extract led to a higher value of erythrocytes, leukocytes, haemoglobin, plasma total protein, albumin, and antioxidant concentration and a low value in plasma cholesterol, triglycerides, uric acid, urea, and total cholesterol. It could be concluded that the dietary addition of licorice extracts 2 and 3 g licorice extract/kg diet improved broiler chicks' growth performance and physiological status.


Assuntos
Antioxidantes , Glycyrrhiza , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Galinhas , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Suplementos Nutricionais , Dieta/veterinária , Glycyrrhiza/metabolismo , Colesterol/metabolismo
2.
Immun Inflamm Dis ; 11(1): e757, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36705402

RESUMO

PURPOSE: Study of the effects and mechanisms of licorice in the treatment of ulcerative colitis (UC) from the perspective of mitochondrial autophagy. METHODS: BALB/C mice were induced with 3% dextran sodium sulfate to build an animal model of UC. After 7 days of modeling, different doses of licorice were administered for 7 days. Hematoxylin and eosin staining is used to detect pathological changes in the colon. Mitochondrial membrane potentials and reactive oxygen species (ROS) contents were detected by flow cytometry, and autophagy of mitochondria was observed by transmission electron microscopy. Determination of inflammatory cytokines by enzyme-linked immunosorbent assay. The oxidizing factors are detected by the kits. Western blot analysis was used to detect expressions for nuclear factor called erythropoietin (Nrf2), pten-induced protein kinase 1 (PINK1), Parkin, HO-1, P62, and LC3. RESULTS: Licorice improved the pathological condition of UC mice, increasing the mitochondrial membrane potential and decreasing the ROS content. Promotes the emergence of autophagosomes and autophagosomes. The contents of interleukin (IL)-1ß, IL-6, IL-17, and tumor necrosis factor-alpha were downregulated, the contents of superoxide dismutase and glutathione peroxidase were upregulated and the contents of malondialdehyde were downregulated. In addition, licorice promotes the expression of Nrf2, PINK1, Parkin, HO-1, P62, and LC3. CONCLUSION: Licorice was shown to reduce levels of inflammatory factors and oxidative stress in mice with UC, possibly by promoting mitochondrial autophagy through the activation of the Nrf2/PINK1 pathway.


Assuntos
Colite Ulcerativa , Glycyrrhiza , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Quinases , Glycyrrhiza/metabolismo , Camundongos Endogâmicos BALB C , Autofagia , Mitocôndrias , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/farmacologia
3.
BMC Complement Med Ther ; 23(1): 22, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36709283

RESUMO

BACKGROUND: Streptococcus mutans is a bacterium that causes oral diseases. Plaque, a biofilm produced by S. mutans and other bacteria, makes it difficult to remove cariogenic oral microorganisms, including biofilm producers. Glucan synthesis by glucosyltransferase is one of the mechanisms underlying plaque formation. This study demonstrates the effectiveness of inhibiting biofilm formation by interfering with the glucosyltransferase activity of S. mutans using edible herbal medicines. METHODS: This study investigated the inhibitory activity of Glycyrrhizae Radix extract, Rubi Fructus extract, glycyrrhizin from Glycyrrhizae Radix, and ellagic acid from Rubi Fructus against glucosyltransferase activity of S. mutans. Enzyme kinetic analysis identified the mechanism by which glycyrrhizin and ellagic acid inhibit enzyme activity. RESULTS: The conditions for synergistically inhibiting biofilm formation by combining Glycyrrhizae Radix and Rubi Fructus extracts were identified. Biofilm formation was also synergistically inhibited by mixing their respective active constituents, glycyrrhizin and ellagic acid. Glycyrrhizin and ellagic acid inhibited glucosyltransferase via noncompetitive and uncompetitive mechanisms, respectively, indicating that they inhibit it via distinct mechanisms. CONCLUSIONS: This study presents an effective oral hygiene method using the synergistic activity of two natural plant extracts to inhibit biofilm formation through different inhibitory mechanisms against glucosyltransferase of S. mutans.


Assuntos
Glycyrrhiza , Streptococcus mutans , Ácido Glicirrízico/farmacologia , Ácido Elágico/farmacologia , Cinética , Extratos Vegetais/farmacologia , Biofilmes
4.
Drug Des Devel Ther ; 17: 15-37, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36647530

RESUMO

Glabridin is a prenylated isoflavan from the roots of Glycyrrhiza glabra Linne and has posed great impact on the areas of drug development and medicine, due to various biological properties such as anti-inflammation, anti-oxidation, anti-tumor, anti-microorganism, bone protection, cardiovascular protection, neuroprotection, hepatoprotection, anti-obesity, and anti-diabetes. Many signaling pathways, including NF-κB, MAPK, Wnt/ß-catenin, ERα/SRC-1, PI3K/AKT, and AMPK, have been implicated in the regulatory activities of glabridin. Interestingly, glabridin has been considered as an inhibitor of tyrosinase, P-glycoprotein (P-gp), and CYP2E1 and an activator of peroxisome proliferator-activated receptor γ (PPARγ), although their molecular regulating mechanisms still need further investigation. However, poor water solubility and low bioavailability have greatly limited the clinical applications of glabridin. Hopefully, several effective strategies, such as nanoemulsions, microneedles, and smartPearls formulation, have been developed for improvement.


Assuntos
Glycyrrhiza , Isoflavonas , Fosfatidilinositol 3-Quinases , Isoflavonas/farmacologia , Fenóis/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP
5.
J Ethnopharmacol ; 303: 116005, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36516906

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Euodiae Fructus (EF) has been used to treat stomachache, belching, and emesis for more than a thousand years. Ancient records and modern research have shown that EF has mild toxicity, which needs to be processed with licorice juice to reduce its toxicity. Research suggested that the toxicity of EF can be caused by in vivo metabolism, but whether its metabolites are related to hepatotoxicity and whether licorice can affect the metabolism of EF have not been reported, which needed an effective strategy to clarify the correlation between metabolites and toxicity and the attenuation mechanism of licorice processing. AIM OF THE STUDY: The poisonous substances and metabolic pathways were clarified by comparing the mechanism in vivo process of the main alkaloids of EF in normal rats and rats treated with dexamethasone (DXMS), ketoconazole (KTC), and EF processed with licorice (EFP). MATERIALS AND METHODS: Rats were given EF and EFP by oral administration, respectively. The EF + DXMS and EF + KTC groups were pretreated with DXMS and KTC, respectively, by i. p. for seven days, and their toxicity differences were compared. The comprehensive strategy based on UPLC-Q-Exactive-MS and Orthogonal Partial Least Squares Discriminant Analysis was developed to compare the types and contents of metabolites and clarify the metabolic pathways of alkaloids among EF, EFP, EF + KTC, and EF + DXMS groups. RESULTS: EF + DXMS group significantly increased the hepatotoxicity, whereas the EF + KTC and EFP groups reduced the hepatotoxicity compared with the EF group. One hundred and thirty-five metabolites were detected, and the metabolic pathways of the main alkaloid components related to toxicity were inferred in the plasma, urine, feces, and bile of rats. KTC and licorice similarly inhibited the production of toxic metabolites, changed metabolism in vivo, and produced many new II and a few phases I metabolites, while the contents of toxic metabolites increased in the DXMS group. CONCLUSION: Licorice and KTC could inhibit the production of metabolites of EF related to toxicity, increase the production of other metabolites and promote the excretion of alkaloids, which may be why licorice and KTC can minimize EF toxicity.


Assuntos
Alcaloides , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Glycyrrhiza , Ratos , Animais , Inibidores do Citocromo P-450 CYP3A , Indutores do Citocromo P-450 CYP3A , Alcaloides/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Cetoconazol , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cromatografia Líquida de Alta Pressão
6.
J Ethnopharmacol ; 305: 116108, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36586524
7.
Pak J Pharm Sci ; 35(5): 1321-1326, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36451559

RESUMO

The aim of this study was to determine the effects of licorice gargle juice on aphthous ulcers, which is a common and painful disease that causes loss of normal mucous tissues and results in inflammatory ulcers in the oral mucosa. A randomized double-blind placebo-controlled trial involving primary care patients suffering from aphthous ulcer was performed. The intervention group received licorice gargle juice for 1 and 2 days. Of the 54 patients that participated in the study, 30 were included in the intervention group and 24 in the placebo group. A 10-point visual analog scale (VAS) was used to assess the patients' self-assessed pain levels before and after treatment. Statistical analyses were performed by using the nonparametric Mann-Whitney test. The licorice gargle juice group had a significantly reduced pain level rate compared with the placebo group at day 1 (mean VAS, 2.47 [95% CI, 1.95-2.98] vs. 4.75 [3.96-5.54]; P<0.001) and day 2 (mean VAS, 1.07 [95% CI, 0.81-1.32] vs. 4.08 [3.23-4.94]; P<0.001).The current study indicates that licorice gargle juice rapidly reduce pain and healing time and thus can improve the quality of life of a patient with aphthous ulcer.


Assuntos
Glycyrrhiza , Estomatite Aftosa , Triterpenos , Humanos , Estomatite Aftosa/tratamento farmacológico , Manejo da Dor , Qualidade de Vida , Antissépticos Bucais/uso terapêutico , Extratos Vegetais/uso terapêutico , Método Duplo-Cego , Dor
8.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6146-6154, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36471939

RESUMO

Since exploding rates of modern mental diseases, application of antidepressants has increased. Worryingly, the antidepressant-induced liver injury has gradually become a serious health burden. Furthermore, since most of the knowledge about antidepressant hepatotoxicity are from pharmacovigilance and clinical case reports and lack of observational studies, the underlying mechanisms are poorly understood and there is a lack of efficient treatment strategies. In this study, antidepressant paroxetine directly triggered inflammasome activation evidenced by caspase-1 activation and downstream effector cytokines interleukin(IL)-1ß secretion. The pretreatment of echinatin, a bioactive component of licorice, completely blocked the activation. This study also found that echinatin effectively inhibited the production of inflammasome-independent tumor necrosis factor α(TNF)-α induced by paroxetine. Mechanistically, the accumulation of mitochondrial reactive oxygen species(mtROS) was a key upstream event of paroxetine-induced inflammasome activation, which was dramatically inhibited by echinatin. In the lipopolysaccharide(LPS)-mediated idiosyncratic drug-induced liver injury(IDILI) model, the combination of LPS and paroxetine triggered aberrant activation of the inflammasome to induce idiosyncratic hepatotoxicity, which was reversed by echinatin pretreatment. Notably, this study also found that various bioactive components of licorice had an inhibitory effect on paroxetine-triggered inflammasome activation. Meanwhile, multiple antidepressant-induced aberrant activation of the inflammasome could be completely blocked by echinatin pretreatment. In conclusion, this study provides a novel insight for mechanism of antidepressant-induced liver injury and a new strategy for the treatment of antidepressant-induced hepatotoxicity.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Glycyrrhiza , Triterpenos , Humanos , Animais , Camundongos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Lipopolissacarídeos/toxicidade , Paroxetina/efeitos adversos , Interleucina-1beta , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Extratos Vegetais , Antidepressivos , Fator de Necrose Tumoral alfa , Camundongos Endogâmicos C57BL
9.
Acta Cir Bras ; 37(10): e371002, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36542040

RESUMO

PURPOSE: The active melanocytes in the skin were affected by hormones and ultraviolet (UV) irradiation. Licorice zinc has a whitening effect, which may have a prominent potential in the treatment of pigmented skin disease. METHODS: Modeling chloasma C57BL/6J mice by daily progesterone injection (15 mg/kg) and ultraviolet B (UVB) irradiation (λ = 312 nm, 2 h/day) for 30 days. Then, mice were given 0.65, 1.3, and 2.6 (g/kg) of licorice zinc and tranexamic acid 250 mg daily by oral administration for 14 days, respectively. Hematoxylin and eosin and Fontana-Masson staining, and Western blotting (WB) were performed to test the inhibitory of melanogenesis and activation of c-Jun-N-terminal (JNK)/p38 mitogen-activated protein kinases (MAPK) for licorice zinc. Melanogenesis was induced by α-melanocyte-stimulating hormone in vitro. Cell counting kit-8, melanin content determination, and WB were performed to verify the inhibitory effect of licorice zinc on melanogenesis. RESULTS: The present study showed that licorice zinc decreased melanin formation, cutaneous tissue injury, and the phosphorylation of JNK and P38MAPK, which was caused by UVB irradiation in vivo. In vitro, licorice zinc showed opposite effects from JNK/p38 activator. Meanwhile, tyrosinase-related protein-1, tyrosinase, and microphthalmia-associated transcription factor were decreased too. CONCLUSIONS: Licorice zinc induced a decrease in melanin synthesis by inhibiting the JNK and the P38MAPK signaling pathway, suggesting licorice zinc is a potential agent of anti-chloasma.


Assuntos
Glycyrrhiza , Melaninas , Animais , Camundongos , Melaninas/metabolismo , Melaninas/farmacologia , Sistema de Sinalização das MAP Quinases , Proteínas Quinases p38 Ativadas por Mitógeno , Glycyrrhiza/metabolismo , Zinco/farmacologia , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral
10.
Braz J Biol ; 84: e265447, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36383787

RESUMO

The present study aimed to evaluate the in vitro antibacterial and antioxidant activities and the in vivo wound healing performance of a polysaccharide isolated from Glycyrrhiza glabra named PSG. It was structurally characterized by Fourier transformed infrared (FT-IR) spectroscopy, which confirmed the presence of different polysaccharides functional bands. The antioxidant capacity of PSG was determined in vitro and evaluated in vivo through the examination of wound healing capacity. Thirty two rats were randomly divided into four groups: group I was treated with physiological serum (negative control); group II was treated with "CYTOL CENTELLA®"; group III was treated with glycerol and group IV was treated with polysaccharide. The response to treatments was assessed by macroscopic, histologic, and biochemical parameters. Data revealed that our sample exhibited potential antioxidant activities and accelerated significantly the wound healing process, after ten days of treatment, proved by the higher wound appearance scores and a higher content of collagen confirmed by histological examination, when compared with control and "CYTOL CENTELLA®". Overall, these findings proved that this polysaccharide isolated from Glycyrrhiza glabra could be considered as a natural bioactive polymer for therapeutic process in wound healing applications.


Assuntos
Glycyrrhiza , Ratos , Animais , Ratos Wistar , Antioxidantes/farmacologia , Antioxidantes/química , Água , Espectroscopia de Infravermelho com Transformada de Fourier , Cicatrização/fisiologia , Polissacarídeos/farmacologia , Polissacarídeos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química
11.
Food Funct ; 13(23): 12105-12120, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36377761

RESUMO

Prenylated phenolics are antimicrobials found in liquorice (Glycyrrhiza spp.). Liquorice spent is a by-product rich in prenylated phenolics obtained after water extraction of roots, and is currently not valorised. We analysed the prenylated phenolics composition of spent extracts from Glycyrrhiza glabra, G. inflata, and G. uralensis, their antimicrobial activity, cytotoxicity, and effects on Caco-2 cell viability. G. glabra, G. inflata, and G. uralensis spent extracts showed distinct phytochemical profiles. Antibacterial activity (Lactobacillus buchneri, Streptococcus mutans, and Staphylococcus aureus) of G. uralensis and G. inflata (MICs 25-250 µg mL-1) was higher than of G. glabra (MICs 75-1000 µg mL-1). Marker compounds glabridin, licochalcone A, and glycycoumarin were equally potent (MICs 12.5-25 µg mL-1). G. inflata and G. uralensis showed cytotoxicity at 500 µg mL-1, whereas G. glabra was not toxic up to 1000 µg mL-1, but showed reduced viability between 50-500 µg mL-1. Linking antibacterial activity of the liquorice spent extracts with cell viability showed that MICs against S. aureus coincide with concentrations where cell viability was not reduced, whereas for the other bacteria and yeasts MICs concurred at concentrations where cell viability was reduced. In this study we show that liquorice spent is a by-product rich in antibacterial prenylated phenolics that offers interesting oppurtunities for e.g. control of microorganisms and the discovery of novel plant-derived antimicrobials.


Assuntos
Chalcona , Chalconas , Glycyrrhiza , Triterpenos , Humanos , Glycyrrhiza/química , Flavonoides/farmacologia , Flavonoides/análise , Chalconas/farmacologia , Chalconas/análise , Staphylococcus aureus , Células CACO-2 , Raízes de Plantas/química , Extratos Vegetais/química , Triterpenos/análise , Antibacterianos/farmacologia , Antibacterianos/análise
12.
BMC Complement Med Ther ; 22(1): 313, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36447209

RESUMO

BACKGROUND: To date, treating nasal polyps (NPs) is still a medical challenge. However, we have developed an innovative therapy using licorice extract (LE: Glycyrrhiza glabra) to treat rhinitis and sinusitis via nasal irrigation and have discovered that it significantly affects treatment of NPs. HYPOTHESIS/PURPOSE: This study investigated the mechanism of LE on NPs. STUDY DESIGN: NPs were collected from three patients using tissue biopsies before and 2 weeks after nasal irrigation with licorice for histopathological analysis. Additionally, NPs from two patients were collected, and nasal polyp-derived fibroblasts (NPDF) were isolated and cultured. METHODS: The TGF-ß1-stimulated NPDF model was used to examine the effect of LE on fibroblast differentiation (biomarker: α-SMA), the consequent production of extracellular matrix (ECM; biomarkers: fibronectin, FBN), and the functional signaling pathway. RESULTS: Immunohistochemistry (IHC) revealed that the number of eosinophils and the expression of α-SMA and interstitial collagen of polyps after licorice treatment significantly decreased. Additionally, RT-PCR, western blotting, and immunofluorescence (IF) showed that α-SMA and FBN expressions were significantly increased in the NPDF, which was stimulated by TGF-ß1, and LE dose-dependently could effectively reduce this effect. Furthermore, western blotting showed that LE could attenuate α-SMA and FBN expressions by preventing the signaling pathway of MAPK/ERK-1/2, which IHC and IF further confirmed. In addition, LE effectively suppressed the cell migration of NPDF, which is related to polyp expansion. CONCLUSION: LE is clinically used to treat sinusitis with NPs through nasal irrigation, which significantly reduces the size of NPs. This effect could attenuate fibroblast differentiation, ECM production and cell migration, and one of the functional mechanisms may be through inhibition of the MAPK/ERK-1/2 signaling pathway. TRIAL REGISTRATION: ISRCTN (No. 51425529) registered on 17/04/2020 (retrospectively registered) - http://www.isrctn.com/ISRCTN51425529.


Assuntos
Glycyrrhiza , Pólipos Nasais , Triterpenos , Humanos , Fator de Crescimento Transformador beta1 , Pólipos Nasais/tratamento farmacológico , Matriz Extracelular , Fibroblastos , Lavagem Nasal , Extratos Vegetais/farmacologia
13.
Molecules ; 27(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36431791

RESUMO

The roots of licorice (Glycyrrhiza glabra L.) have been widely used in traditional and officinal medicines for the treatment of different diseases. Natural deep eutectic solvents (NADES) have become popular for the extraction of active principles from medicinal plants. However, the ability of NADES to co-extract trace elements during the isolation of target active compounds is rarely investigated. The aim of this study was to analyze the content of trace elements in acid-based NADES extracts from the roots of G. glabra and the health risks associated with them. In this study, we have tested for the first time the ability of several acid-based NADES to co-extract glycyrrhizic acid (GA) and trace elements from the roots of G. glabra. GA has been identified as the dominant phytochemical in G. glabra NADES extracts (0.145-0.495 mg/g). Due to the close pKa of lactic acid and GA, the yield of GA in lactic acid-based NADES was higher in comparison with other tested NADES. The yield of GA in NADES3-NADES5 was statistically significant and surpassed the yield of GA in water. The recovery of all elements (except Li) by all tested NADES was low (less than 6%). According to an ANOVA test, the hydrogen bond donor type plays a decisive role in the extraction of elements. A strong positive correlation between the recovery of GA and MPI was noted. The metal pollution index, hazard quotient, hazard index, and chronic daily intake were calculated and suggest that all tested NADES extracts of G. glabra roots were nontoxic and possess no health risk for both ingestion and topical application.


Assuntos
Glycyrrhiza , Oligoelementos , Solventes Eutéticos Profundos , Solventes/química , Extratos Vegetais/química , Ácido Glicirrízico , Ácido Láctico
14.
Molecules ; 27(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36431839

RESUMO

Licorice (Gan-Cao, licorice) is a natural antioxidant and roasted licorice is the most common processing specification used in traditional Chinese medicine prescriptions. Traditional Chinese medicine theory deems that the honey-roasting process can promote the efficacy of licorice, including tonifying the spleen and augmenting "Qi" (energy). The antioxidant activity and mechanisms underlying roasted licorice have not yet been reported. In this study, we found that roasted licorice could relieve the oxidative stress injury induced by metronidazole (MTZ) and could restrain the production of excessive reactive oxygen species (ROS) induced by 2,2'-azobis (2-methylpropionamidine) dihydrochloride (AAPH) in a zebrafish model. It was further found that roasted licorice could exert its oxidative activity by upregulating the expression of key genes such as heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC) in the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway both in vivo and in vitro. Furthermore, consistent results were obtained showing that rat serum containing roasted licorice was estimated to reduce cell apoptosis induced by H2O2. Then, the UHPLC-Q-Exactive Orbitrap MS analysis results elucidated the chemical composition of rat plasma containing roasted licorice extracts, including ten prototype chemical components and five metabolic components. Among them, six compounds were found to have binding activity with Kelch-like ECH-associated protein 1 (KEAP1), which plays a crucial role in the transcriptional activity of NRF2, using a molecular docking simulation. The results also showed that liquiritigenin had the strongest binding ability with KEAP1. Immunofluorescence further confirmed that liquiritigenin could induce the nuclear translocation of NRF2. In summary, this study provides a better understanding of the antioxidant effect and mechanisms of roasted licorice, and lays a theoretical foundation for the development of a potential antioxidant for use in clinical practice.


Assuntos
Glycyrrhiza , Triterpenos , Ratos , Animais , Glycyrrhiza/química , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Peixe-Zebra/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Peróxido de Hidrogênio/metabolismo , Simulação de Acoplamento Molecular , Extratos Vegetais
15.
Int J Mol Sci ; 23(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36232674

RESUMO

Platelets are crucial for hemostasis and arterial thrombosis, which may lead to severe cardiovascular diseases (CVDs). Thus, therapeutic agents must be developed to prevent pathological platelet activation. Glabridin, a major bioalkaloid extracted from licorice root, improves metabolic abnormalities (i.e., obesity and diabetes) and protects against CVDs and neuronal disorders. To the best of our knowledge, no studies have focused on glabridin's effects on platelet activation. Therefore, we investigated these effects in humans and mice. Glabridin exhibited the highest inhibitory effects on collagen-stimulated platelet aggregation and moderate effects on arachidonic-acid-stimulated activation; however, no effects were observed for any other agonists (e.g., thrombin or U46619). Glabridin evidently reduced P-selectin expression, ATP release, and intracellular Ca2+ ([Ca2+]i) mobilization and thromboxane A2 formation; it further reduced the activation of phospholipase C (PLC)γ2/protein kinase C (PKC), phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3ß (GSK3ß), mitogen-activated protein kinase (MAPK), and NF-κB. In mice, glabridin reduced the mortality rate caused by acute pulmonary thromboembolism without altering bleeding time. Thus, glabridin effectively inhibits the PLCγ2/PKC cascade and prevents the activation of the PI3K/Akt/GSK3ß and MAPK pathways; this leads to a reduction in [Ca2+]i mobilization, which eventually inhibits platelet aggregation. Therefore, glabridin may be a promising therapeutic agent for thromboembolic disorders.


Assuntos
Glycyrrhiza , Selectina-P , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Plaquetas/metabolismo , Colágeno/metabolismo , Flavonoides/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Isoflavonas , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Selectina-P/metabolismo , Fenóis , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfolipase C gama/metabolismo , Fosforilação , Ativação Plaquetária , Agregação Plaquetária , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Trombina/metabolismo , Tromboxanos/metabolismo
16.
Nutrients ; 14(19)2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36235833

RESUMO

As a traditional Chinese medicine, licorice is often used in functional foods for its health benefits. However, the role of gut microbiota in the efficacy of licorice has not yet been fully elucidated. We hypothesized that the involvement of intestinal flora may be a key link in licorice ethanol extract (LEE)-induced health benefits. The aim of this study was to investigate whether LEE improves hepatic lipid accumulation in obese mice fed a high-fat diet (HFD) and whether the gut microbiota plays a key role in LEE treatment. Male C57BL/6J mice were fed HFD for liver fat accumulation and then treated with LEE. The same experiments were later performed using pseudo-sterile mice to verify the importance of gut flora. Supplementation with LEE improved the obesity profile, lipid profile and liver fat accumulation in HFD mice. In addition, LEE treatment improved intestinal flora dysbiosis caused by HFD in mice, as evidenced by a decrease in the percentage of Firmicutes/Bacteroidetes and an increase in the abundance of known anti-obesity-related bacteria. However, LEE failed to exhibit a therapeutic effect in pseudo-sterile mice. The results of the cellular assay showed that glycyrrhetic acid (GA), the main conversion product of glycyrrhizin (GL), was more effective in reducing fat accumulation and intracellular TG content in hepatocytes compared to GL. In conclusion, our data suggest that LEE attenuates obesity and hepatic fat accumulation in HFD mice, which may be associated with modulating the composition of gut microbiota and the conversion of LLE by the intestinal flora.


Assuntos
Microbioma Gastrointestinal , Ácido Glicirretínico , Glycyrrhiza , Animais , Dieta Hiperlipídica/efeitos adversos , Disbiose/microbiologia , Etanol/farmacologia , Ácido Glicirretínico/farmacologia , Ácido Glicirrízico/farmacologia , Lipídeos/farmacologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Extratos Vegetais/uso terapêutico
17.
Front Immunol ; 13: 1007186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238291

RESUMO

A component of licorice polysaccharide (GPS-1) was extracted from licorice, its primary structure was identified and characterized for the first time, and its immunomodulatory activity was studied. Crude licorice polysaccharide was isolated and purified by DEAE sepharose FF ion-exchange column chromatography and Chromdex 200 PG gel filtration column chromatography to obtain a purified Glycyrrhiza polysaccharide named GPS-1. NMR and methylation analysis revealed that GPS-1 is composed of homogalacturonan (HG)-type pectin with 4)-D-GalpA-(1 as the backbone. This study of GPS-1 also examined its significant role in regulating immune activity in vitro and in vivo. As a result, GPS-1 promoted the secretion of IFN-γ and IL-4 in mice and increased the proportion of CD3+CD4+ and CD3+CD8+ T lymphocytes in their spleens. Dendritic cells (DCs) treated with GPS-1 showed promotion of DC maturation, antigen presentation, and phagocytic capacity. The results suggest that GPS-1 is a potential immunomodulator that stimulates the immune system by regulating multiple signaling pathways. Combined with our characterization of the primary structure of GPS-1, the present investigation provides the basis for future study of the form-function relationship of polysaccharides.


Assuntos
Glycyrrhiza , Triterpenos , Animais , Glycyrrhiza/química , Fatores Imunológicos/química , Interleucina-4 , Camundongos , Pectinas , Polissacarídeos/química
18.
Front Immunol ; 13: 945583, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238303

RESUMO

Severe coronavirus disease (COVID-19) is accompanied by acute respiratory distress syndrome and pulmonary pathology, and is presented mostly with an inflammatory cytokine release, a dysregulated immune response, a skewed neutrophil/lymphocyte ratio, and a hypercoagulable state. Though vaccinations have proved effective in reducing the COVID-19-related mortality, the limitation of the use of vaccine against immunocompromised individuals, those with comorbidity, and emerging variants remains a concern. In the current study, we investigate for the first time the efficacy of the Glycyrrhiza glabra (GG) extract, a potent immunomodulator, against SARS-CoV-2 infection in hamsters. Prophylactic treatment with GG showed protection against loss in body weight and a 35%-40% decrease in lung viral load along with reduced lung pathology in the hamster model. Remarkably, GG reduced the mRNA expression of pro-inflammatory cytokines and plasminogen activator inhibitor-1 (PAI-1). In vitro, GG acted as a potent immunomodulator by reducing Th2 and Th17 differentiation and IL-4 and IL-17A cytokine production. In addition, GG also showed robust potential to suppress ROS, mtROS, and NET generation in a concentration-dependent manner in both human polymorphonuclear neutrophils (PMNs) and murine bone marrow-derived neutrophils (BMDNs). Taken together, we provide evidence for the protective efficacy of GG against COVID-19 and its putative mechanistic insight through its immunomodulatory properties. Our study provides the proof of concept for GG efficacy against SARS-CoV-2 using a hamster model and opens the path for further studies aimed at identifying the active ingredients of GG and its efficacy in COVID-19 clinical cases.


Assuntos
COVID-19 , Glycyrrhiza , Animais , Cricetinae , Citocinas/metabolismo , Glycyrrhiza/metabolismo , Humanos , Interleucina-17 , Interleucina-4 , Camundongos , Inibidor 1 de Ativador de Plasminogênio , RNA Mensageiro , Espécies Reativas de Oxigênio , SARS-CoV-2
19.
PLoS One ; 17(10): e0275181, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36251689

RESUMO

BACKGROUND: Glycyrrhizin, an active component of liquorice root extract, exhibits antiviral and immunomodulatory properties by direct inhibition of the pro-inflammatory alarmin HMGB1 (High-mobility group box 1). OBJECTIVE: The aim of this study was to explore the role of liquorice intake on the viral entry receptor ACE2 (angiotensin-converting enzyme 2) and the immunoregulatory HMGB1 in healthy individuals and to explore HMGB1 expression in coronavirus disease 2019 (COVID-19) or non-COVID-19 in ARDS (acute respiratory distress syndrome patients). MATERIAL AND METHODS: This study enrolled 43 individuals, including hospitalised patients with i) acute respiratory distress syndrome (ARDS) due to COVID-19 (n = 7) or other underlying causes (n = 12), ii) mild COVID-19 (n = 4) and iii) healthy volunteers (n = 20). Healthy individuals took 50 g of liquorice (containing 3% liquorice root extract) daily for 7 days, while blood samples were collected at baseline and on day 3 and 7. Changes in ACE2 and HMGB1 levels were determined by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Additionally, HMGB1 levels were measured in hospitalised COVID-19 patients with mild disease or COVID-19 associated acute respiratory distress syndrome (ARDS) and compared with a non-COVID-19-ARDS group. RESULTS: Liquorice intake significantly reduced after 7 days both cellular membranous ACE2 expression (-51% compared to baseline levels, p = 0.008) and plasma HMGB1 levels (-17% compared to baseline levels, p<0.001) in healthy individuals. Half of the individuals had a reduction in ACE2 levels of at least 30%. HMGB1 levels in patients with mild COVID-19 and ARDS patients with and without COVID-19 were significantly higher compared with those of healthy individuals (+317%, p = 0.002), but they were not different between COVID-19 and non-COVID-19 ARDS. CONCLUSIONS: Liquorice intake modulates ACE2 and HMGB1 levels in healthy individuals. HMGB1 is enhanced in mild COVID-19 and in ARDS with and without COVID-19, warranting evaluation of HMGB1 as a potential treatment target and glycyrrhizin, which is an active component of liquorice root extract, as a potential treatment in COVID-19 and non-COVID-19 respiratory disease.


Assuntos
Glycyrrhiza , Proteína HMGB1 , Síndrome do Desconforto Respiratório , Alarminas , Enzima de Conversão de Angiotensina 2 , Antivirais/uso terapêutico , Glycyrrhiza/metabolismo , Ácido Glicirrízico/farmacologia , Ácido Glicirrízico/uso terapêutico , Proteína HMGB1/metabolismo , Humanos , Projetos Piloto , Receptores Virais/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico
20.
Molecules ; 27(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36296445

RESUMO

Nowadays, subcritical water extraction (SWE) techniques are extensively investigated worldwide, while the thermal reactions that inevitably occur under subcritical water conditions are rarely studied. In order to investigate the behaviors of the different reactions during SWE of bioactive compounds from licorice, the Maillard reaction process was accessed via their products and the hydrolytic reaction was analyzed according to the kinetic parameters. In addition, the contents of total phenolics and flavonoids in the extracts obtained at the different temperatures were determined and total antioxidant capacities were evaluated by HPLC-ABTS+. The results showed that flavonoids and phenolics from licorice as well as new compounds generated via the Maillard reaction contributed to the antioxidant activity of the extracts. The fluorescence, color and absorbance of the extracts showed that the degree of the Maillard reaction increased with the rise of the extraction temperature. The kinetics of extraction for glycyrrhizic acid showed that it was firstly extracted by diffusion, and then was hydrolyzed into glycyrrhetinic acid 3-O-mono-ß-D-glucuronide and glycyrrhetinic acid following a first-order mechanism. These findings could provide deep insights into the SWE process and a new method for producing glycyrrhetinic acid 3-O-mono-ß-D-glucuronide and glycyrrhetinic acid.


Assuntos
Ácido Glicirretínico , Glycyrrhiza , Triterpenos , Água , Antioxidantes/análise , Ácido Glicirrízico , Glucuronídeos , Extratos Vegetais , Flavonoides , Fenóis
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