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1.
J Enzyme Inhib Med Chem ; 37(1): 2452-2477, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36093586

RESUMO

Arctium lappa L. is a prevalent medicinal herb and a health supplement that is commonly used in Asia. Over the last few decades, the bioactive component arctigenin has attracted the attention of researchers because of its anti-inflammatory, antioxidant, immunomodulatory, multiple sclerosis fighting, antitumor, and anti-leukemia properties. After summarising the research and literature on arctigenin, this study outlines the current status of research on pharmacological activity, total synthesis, and structural modification of arctigenin. The purpose of this study is to assist academics in obtaining a more comprehensive understanding of the research progress on arctigenin and to provide constructive suggestions for further investigation of this useful molecule.


Assuntos
Arctium , Lignanas , Anti-Inflamatórios , Arctium/química , Furanos/química , Furanos/farmacologia , Lignanas/química , Lignanas/farmacologia
2.
Sci Rep ; 12(1): 13990, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978012

RESUMO

Forkhead Box M1 (FOXM1) is known to regulate cell proliferation, apoptosis and tumorigenesis. The lignan, (-)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol (DFS), from Alnus japonica has shown anti-cancer effects against colon cancer cells by suppressing FOXM1. The present study hypothesized that DFS can have anti-cancer effects against glioblastoma (GBM) tumorspheres (TSs). Immunoprecipitation and luciferase reporter assays were performed to evaluate the ability of DFS to suppress nuclear translocation of ß-catenin through ß-catenin/FOXM1 binding. DFS-pretreated GBM TSs were evaluated to assess the ability of DFS to inhibit GBM TSs and their transcriptional profiles. The in vivo efficacy was examined in orthotopic xenograft models of GBM. Expression of FOXM1 was higher in GBM than in normal tissues. DFS-induced FOXM1 protein degradation blocked ß-catenin translocation into the nucleus and consequently suppressed downstream target genes of FOXM1 pathways. DFS inhibited cell viability and ATP levels, while increasing apoptosis, and it reduced tumorsphere formation and the invasiveness of GBM TSs. And DFS reduced the activities of transcription factors related to tumorigenesis, stemness, and invasiveness. DFS significantly inhibited tumor growth and prolonged the survival rate of mice in orthotopic xenograft models of GBM. It suggests that DFS inhibits the proliferation of GBM TSs by suppressing FOXM1. DFS may be a potential therapeutic agent to treat GBM.


Assuntos
Alnus , Glioblastoma , Lignanas , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Humanos , Lignanas/farmacologia , Lignanas/uso terapêutico , Camundongos , beta Catenina/metabolismo
3.
Anticancer Res ; 42(9): 4403-4410, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36039427

RESUMO

BACKGROUND/AIM: Osteosarcoma is an aggressive primary malignant bone tumor that occurs in childhood. Although the diagnostic and treatment options have been improved, osteosarcoma confers poor prognosis. Magnolol, an active component of Magnoliae officinalis cortex, has been widely applied in herb medicine and has been shown to have multiple pharmacological activities. However, whether magnolol possesses anti-osteosarcoma capacity remains unknown. MATERIALS AND METHODS: We examined magnolol is cytotoxicity, and whether it regulates apoptosis and oncogene expression using MTT, flow cytometry and Western blotting assays in osteosarcoma cells. RESULTS: Magnolol exerted toxicity towards U-2 OS cells by inducing intrinsic/extrinsic apoptosis pathways. Additionally, treatment of U-2 OS cells with magnolol inhibited MAPK1 mitogen-activated protein kinase 1 (ERK)/Nuclear factor kappa B (NF-B) signaling involved in tumor progression and reduced the expression of anti-apoptotic and metastasis-associated genes. CONCLUSION: Magnolol may induce apoptosis and inactivate ERK/NF-B signal transduction in osteosarcoma cells.


Assuntos
Neoplasias Ósseas , Lignanas , Osteossarcoma , Apoptose , Compostos de Bifenilo/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Lignanas/farmacologia , NF-kappa B/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Transdução de Sinais
4.
Chem Biodivers ; 19(9): e202200618, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35972824

RESUMO

Three rare spirocyclohexadienone-type neolignans, magnoflorins A-C (1-3), and three known analogs (4-6), were isolated from the leaves of Magnolia liliiflora. Magnoflorin D (4) was obtained from natural resources for the first time. The chemical structures and absolute configurations of 1-4 were elucidated through detailed analysis of HR-ESI-MS, IR, 1 H, 13 C, and 2D NMR, and ECD experiments. The absolute configuration of 5 were characterized by X-ray crystallography in present study. Moreover, compounds 4 and 5 displayed moderate neuroprotective activity against corticosterone-induced PC12 cells injury at 20 µM with cell viability of 71.5±0.99 % and 73.0±1.42 %, respectively, compared to the model group with 60.83±0.93 %. Compound 6 could enhance neurite outgrowth of nerve growth factor (NGF)-induced PC12 cells at 10 µM with the differentiation rate of 11.98 %, compared with 20.49 % of 50 ng/ml NGF.


Assuntos
Lignanas , Magnolia , Animais , Corticosterona/metabolismo , Lignanas/metabolismo , Lignanas/farmacologia , Magnolia/química , Fator de Crescimento Neural/metabolismo , Neuritos/metabolismo , Crescimento Neuronal , Células PC12 , Ratos
5.
Viruses ; 14(7)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35891401

RESUMO

Micropterus salmoides rhabdovirus (MSRV) is a primary viral pathogen in largemouth bass aquaculture, which leads to tremendous economic losses yearly. Currently, there are no approved drugs for the treatment and control of this virus. Our previous studies screened the herb Magnolia officinalis from many traditional Chinese medicines, and we isolated and identified magnolol as its main active compound against multiple rhabdoviruses, including MSRV. On the basis of the structure-activity relationship and pharmacophore model of magnolol, two new magnolol derivatives, namely, hydrogenated magnolol and 2,2'-dimethoxy-magnolol, were designed and synthesized. Their anti-MSRV activities were systematically investigated both in vitro and in vivo. By comparing the half-maximal inhibitory concentration (IC50), it was found that hydrogenated magnolol possessed a higher anti-MSRV activity than magnolol and 2,2'-dimethoxy-magnolol, with an IC50 of 13.37 µM. Furthermore, hydrogenated magnolol exhibited a protective effect on the grass carp ovary (GCO) cell line by reducing the cytopathic effect induced by MSRV. Further studies revealed that hydrogenated magnolol did not directly impact virions or interfere with MSRV adsorption. It worked within the 6-8 h of the phase of virus replication. In vivo treatment of MSRV infection with magnolol and hydrogenated magnolol showed that they significantly improved the survival rate by 44.6% and 62.7%, respectively, compared to MSRV-infected groups. The viral load measured by the expression of viral glycoprotein in the organs including the liver, spleen, and kidney also significantly decreased when fish were intraperitoneally injected at a dose of 20 mg/kg. Altogether, the structural optimization of magnolol via hydrogenation of the propylene groups increased its anti-MSRV activity both in vitro and in vivo. These results may provide a valuable reference for anti-MSRV drug discovery and development in aquaculture.


Assuntos
Bass , Doenças dos Peixes , Lignanas , Rhabdoviridae , Animais , Compostos de Bifenilo/farmacologia , Feminino , Doenças dos Peixes/tratamento farmacológico , Lignanas/farmacologia , Lignanas/uso terapêutico
6.
Chin J Physiol ; 65(3): 151-157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35775534

RESUMO

Gomisin A is a dietary lignan compound isolated from the fruit of Schisandra chinensis and has many pharmacological properties, including hepato-protective, anti-diabetic, and anti-oxidative activities. However, the benefit of gomisin A is still not well understood. The action of gomisin A is diverse. However, the effect of gomisin A on Ca2+ signaling in prostate cancer cells is unknown. Ca2+ is a pivotal second envoy that triggers and regulates cellular processes such as apoptosis, fertilization, energy transduction, secretion, and protein activation. The goal of this study was to explore the action of gomisin A on [Ca2+]i and cytotoxicity in PC3 prostate cancer cells. Gomisin A at 100-200 µM provoked [Ca2+]i raises. 20% of the response was reduced by removing external Ca2+. The Ca2+ influx provoked by gomisin A was suppressed by 20% by store-caused Ca2+ entry suppressors: econazole, SKF96365, nifedipine; also by phorbol 12-myristate 13 acetate and GF109203X. Without external Ca2+, gomisin A-caused [Ca2+]i raises were abolished by thapsigargin. In contrast, gomisin A suppressed the [Ca2+]i raises caused by thapsigargin. U73122 fell short to change gomisin A-caused [Ca2+]i responses. Gomisin A (20-100 µM) elicited cytotoxicity in a dose-associated fashion. Blockade of [Ca2+] elevations with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl failed to inhibit cytotoxicity of gomisin A. Collectively, gomisin A evoked [Ca2+]i raises and provoked cytotoxicity in a Ca2+-dissociated fashion in prostate cancer cells.


Assuntos
Lignanas , Neoplasias da Próstata , Cálcio/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Ciclo-Octanos , Dioxóis , Humanos , Lignanas/farmacologia , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Tapsigargina/farmacologia , Fosfolipases Tipo C/metabolismo
7.
Commun Biol ; 5(1): 680, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804021

RESUMO

Radiation affects not only cognitive function but also gut microbiota. Eleutheroside E (EE), a principal active compound of Acanthopanax senticosus, has a certain protective effect on the nervous system. Here, we find a four-week EE supplementation to the 60Co-γ ray irradiated mice improves the cognition and spatial memory impairments along with the protection of hippocampal neurons, remodels the gut microbiota, especially changes of Lactobacillus and Helicobacter, and altered the microbial metabolites including neurotransmitters (GABA, NE, ACH, 5-HT) as well as their precursors. Furthermore, the fecal transplantation of EE donors verifies that EE alleviated cognition and spatial memory impairments, and activates the PKA/CREB/BDNF signaling via gut microbiota. Our findings provide insight into the mechanism of EE effect on the gut-brain axis and underpin a proposed therapeutic value of EE in cognitive and memory impairments induced by radiation.


Assuntos
Disfunção Cognitiva , Microbioma Gastrointestinal , Lignanas , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Suplementos Nutricionais , Glucosídeos , Lignanas/farmacologia , Camundongos
8.
Eur J Med Chem ; 240: 114593, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35820350

RESUMO

Infections caused by drug-resistant bacteria have emerged to be one of the greatest threats to global public health, and new antimicrobial agents with novel mechanisms of action hence are in an urgent need to combat bacterial resistance. Herein, we reported the design, synthesis, and antibacterial evaluation of novel honokiol derivatives as mimics of antimicrobial peptides (AMPs). These mimics showed potent antimicrobial properties against Gram-positive bacteria. Among them, the most promising compound 13b exhibited excellent antibacterial activity, rapid bactericidal properties, avoidance of antibiotic resistance, and weak hemolytic and cytotoxic activities. In addition, compound 13b not only inhibited the biofilm formation but also destroy the preformed biofilm. Mechanism studies further revealed that compound 13b killed bacteria rapidly by interrupting the bacterial membrane. More intriguingly, compound 13b exhibited potent in vivo antibacterial efficacy in a mouse septicemia model induced by Staphylococcus aureus ATCC43300. These results highlight the potential of 13b to be used as therapeutic agents.


Assuntos
Anti-Infecciosos , Lignanas , Compostos Alílicos , Animais , Antibacterianos/química , Anti-Infecciosos/farmacologia , Bactérias , Compostos de Bifenilo/farmacologia , Lignanas/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Fenóis
9.
Anticancer Res ; 42(8): 3825-3833, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35896265

RESUMO

BACKGROUND/AIM: Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer worldwide, and treatment outcomes are still poor. Magnolol, a hydroxylated biphenyl isolated from Magnolia officinalis, was found to be effective against hepatocellular carcinoma via inactivating nuclear-factor-kappa B (NF-B) signaling. However, whether magnolol targets not only NF-B but also other factors in NSCLC and may contribute to the suppression of tumor progression is unclear. MATERIALS AND METHODS: Cell viability, flow cytometry, and western blotting assays were used to identify the mechanism of magnolol action in human lung adenocarcinoma cell lines A549 and CL1-5-F4. RESULTS: Our results indicated that magnolol induced cytotoxicity through extrinsic/intrinsic apoptosis signaling and suppressed phosphorylation of signal transducer and activator of transcription 3 (STAT3)/NF-B and expression of their downstream proteins. CONCLUSION: Magnolol not only induced extrinsic and intrinsic apoptosis signaling but also inactivated STAT3/NF-B and attenuated their signaling of epithelial-mesenchymal transition and metastasis-related protein expression in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Lignanas , Neoplasias Pulmonares , Apoptose , Compostos de Bifenilo/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Humanos , Lignanas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo
10.
J Agric Food Chem ; 70(28): 8767-8775, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35796683

RESUMO

3-(7'-Aryl-9'-hydroxyprop-8'-yl)coumarin, which is a structural isomer of a Z-2-hydroxybenzylidene-γ-butyrolactone-type lignan, was stereoselectively synthesized and subjected to plant growth regulation examination. (R)-4'-Methoxyphenyl derivative 3 showed stereospecific plant growth suppressive activity. The significance of the presence of hydroxy group at the 9'-position for the activity was clarified. The effect of the substituent at the 7'-aryl group was also shown. The 3'-methoxy, 4'-methoxy, and 4'-trifluoromethyl derivatives 10, 3, and 22 led to the most significant growth suppression of Italian ryegrass roots. The 2'-methoxy derivative 9 and 4'-methoxy derivative 3 provided the most growth suppressive activity against lettuce shoots and roots, respectively.


Assuntos
Lignanas , 4-Butirolactona/farmacologia , Cumarínicos/farmacologia , Alface , Lignanas/química , Lignanas/farmacologia , Desenvolvimento Vegetal
11.
Sci Rep ; 12(1): 11505, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35798810

RESUMO

This is the first comprehensive study of the influence of plant growth regulators (PGRs) on the development of shoots and accumulation of biologically active lignans-phyllanthin and hypophyllanthin, in the shoot culture of P. amarus Schum. & Thonn. (Euphorbiaceae) obtained by direct organogenesis. The following PGRs were included in the experiments-cytokinins: kinetin (Kin), 6-benzylaminopurine (BAP), 2-isopentenyladenine (2iP), 1-phenyl-3-(1,2,3-thiadiazol-5-yl)urea, thidiazuron (TDZ) and auxin, indole-3-butyric acid (IBA) and used at various concentrations. Depending on PGRs and their concentrations, differences in the culture response and lignan accumulation were observed. The highest content of the investigated compounds was found in the shoot culture grown on Murashige and Skoog's (MS) medium supplemented with Kin 0.25 mg/L. The sum of phyllanthin and hypophyllanthin was ~ 10 mg/g of dry weight (DW), which was similar or even higher than that in the plant material obtained from natural conditions. The results of the research provide new data on the selection of the optimal growth medium for the production of plant material with a significant level of phyllanthin and hypophyllanthin biosynthesis. The obtained data may also be valuable in designing systems for large-scale cultivation of P. amarus shoots with high productivity of hepatoprotective lignans.


Assuntos
Lignanas , Phyllanthus , Citocininas/farmacologia , Ácidos Indolacéticos , Cinetina , Lignanas/farmacologia , Reguladores de Crescimento de Plantas/farmacologia
12.
Fitoterapia ; 160: 105228, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35667521

RESUMO

A pair of new diastereoisomers neolignans (1-2) and a new alkaloid (7) were isolated from the stems of Nauclea officinalis: naucleaoxyneolignoside A (1), naucleaoxyneolignoside B (2), (2S,3S)-javaniside (7), together with nine known compounds, 2S-3,3-di-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol (3), threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)-propane-1,3-diol (4), nauclefine (5), angustidine (6), naucleoxoside A (8), naucleoxoside B (9), angustoline (10), (3S,19S)-3,14-dihydroangustoline (11), and (3S,19R)-3,14-dihydroangustoline (12).The structures of 1, 2 and 7 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparison of their data with those reported in the literature. The absolution configurations of 1, 2, 7,11 and 12 were confirmed by the quantum chemical CD calculation method. Compounds 1-9 showed weak to moderate inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC50 values comparable to that of dexamethasone. In addition, compounds 1-9 were evaluated for the antibacterial and cytotoxic effects, and the results revealed that these compounds showed no anti-bacterial activity, and compounds 3-6 showed modest cytotoxic activity.


Assuntos
Lignanas , Rubiaceae , Animais , Alcaloides Indólicos , Lignanas/farmacologia , Camundongos , Estrutura Molecular , Propano , Rubiaceae/química
13.
Phytomedicine ; 103: 154209, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35689901

RESUMO

BACKGROUND: Leaky gut symptoms and inflammatory bowel disease (IBD) are associated with damaged intestinal mucosa, intestinal permeability dysfunction by epithelial cell cytoskeleton contraction, disrupted intercellular tight junction (TJ) protein expression, and abnormal immune responses and are intractable diseases. PURPOSE: We evaluated the effects of schisandrin C, a dibenzocyclooctadiene lignan from Schisandra chinensis, on intestinal inflammation and permeability dysfunction in gut mimetic systems: cultured intestinal cells, intestinal organoids, and a Caenorhabditis elegans model. METHODS: Schisandrin C was selected from 9 lignan compounds from S. chinensis based on its anti-inflammatory effects in HT-29 human intestinal cells. IL-1ß and Pseudomonas aeruginosa supernatants were used to disrupt intestinal barrier formation in vitro and in C. elegans, respectively. The effects of schisandrin C on transepithelial electrical resistance (TEER) and intestinal permeability were evaluated in intestinal cell monolayers, and its effect on intestinal permeability dysfunction was tested in mouse intestinal organoids and C. elegans by measuring fluorescein isothiocyanate (FITC)-dextran efflux. The effect of schisandrin C on TJ protein expression was investigated by western blotting and fluorescence microscopy. The signaling pathway underlying these effects was also elucidated. RESULTS: Schisandrin C ameliorated intestinal permeability dysfunction in three IBD model systems and enhanced epithelial barrier formation via upregulation of ZO-1 and occludin in intestinal cell monolayers and intestinal organoids. In Caco-2 cells, schisandrin C restored IL-1ß-mediated increases in MLCK and p-MLC expression, in turn blocking cytoskeletal contraction and subsequent intestinal permeabilization. Schisandrin C inhibited NF-ĸB and p38 MAPK signaling, which regulates MLCK expression and structural reorganization of the TJ complex in Caco-2 cells. Schisandrin C significantly improved abnormal FITC-dextran permeabilization in both intestinal organoids and C. elegans. CONCLUSION: Schisandrin C significantly improves abnormal intestinal permeability and regulates the expression of TJ proteins, long MLCK, p-MLC, and inflammation-related proteins, which are closely related to leaky gut symptoms and IBD development. Therefore, schisandrin C is a candidate to treat leaky gut symptoms and IBDs.


Assuntos
Doenças Inflamatórias Intestinais , Lignanas , Animais , Células CACO-2 , Caenorhabditis elegans/metabolismo , Ciclo-Octanos , Humanos , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/metabolismo , Lignanas/farmacologia , Camundongos , Quinase de Cadeia Leve de Miosina/metabolismo , Organoides/metabolismo , Permeabilidade , Compostos Policíclicos , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas
14.
Dermatol Ther ; 35(8): e15658, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35726011

RESUMO

Honokiol is one of the natural extracts of Magnolia officinalis. It is a small molecule, lipophilic compound with extensive biological effects. It has been used in the treatment of multisystem diseases, including digestive diseases, endocrine diseases, nervous system diseases, and various tumors. This paper reviews the biological effects of honokiol on the treatment of skin diseases in recent years, including anti-microbial, anti-oxidant, anti-inflammatory, anti-tumor, anti-fibrosis, anti-allergy, photo-protection, and immunomodulation. Most current researches are focused on the effects of anti-melanoma and photo-protection. Therefore, we summarized the specific mechanisms about these two effects. On the other side of treating skin diseases, the advantages of topical drugs cannot be replaced. As a small molecule fat-soluble compound, honokiol is suitable for external use. We reviewed the advantages and disadvantages of the topical mixed cream and various improved methods. These improvements include physical and chemical penetration enhancers, drug carriers, and chemical derivatives. In conclusion, honokiol has a wide range of effects, and its topical preparation provides a safe and effective way for treating skin diseases.


Assuntos
Dermatologia , Lignanas , Dermatopatias , Compostos Alílicos , Antioxidantes , Compostos de Bifenilo/farmacologia , Humanos , Lignanas/química , Lignanas/farmacologia , Lignanas/uso terapêutico , Fenóis , Dermatopatias/tratamento farmacológico
15.
Metab Brain Dis ; 37(6): 2039-2052, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35731324

RESUMO

Arctigenin (Arc) is a phenylpropanoid dibenzylbutyrolactone lignan in Arctium lappa L, which has been widely applied as a traditional Chinese herbal medicine for treating inflammation. In the present study, we explored the neuroprotective effect and the potential mechanisms of arctigenin against LPS-evoked neuroinflammation, neurodegeneration, and memory impairments in the mice hippocampus. Daily administration of arctigenin (50 mg/kg per day, i.g.) for 28 days revealed noticeable improvements in spatial learning and memory deficits after exposure to LPS treatment. Arctigenin prevented LPS-induced neuronal/synaptic injury and inhibited the increases in Abeta (Aß) generation and the levels of amyloid precursor protein (APP) and ß-site amyloid precursor protein cleavage enzyme 1 (BACE1). Moreover, arctigenin treatment also suppressed glial activation and reduced the production of proinflammatory cytokines. In LPS-treated BV-2 microglial cells and mice, activation of the TLR4 mediated NF-κB signaling pathway was significantly suppressed by arctigenin administration. Mechanistically, arctigenin reduced the LPS-induced interaction of adiponectin receptor 1 (AdipoR1) with TLR4 and its coreceptor CD14 and inhibited the TLR4-mediated downstream inflammatory response. The outcomes of the current study indicate that arctigenin mitigates LPS-induced apoptotic neurodegeneration, amyloidogenesis and neuroinflammation as well as cognitive impairments, and suggest that arctigenin may be a potential therapeutic candidate for neuroinflammation/neurodegeneration-related diseases.


Assuntos
Arctium , Disfunção Cognitiva , Lignanas , Secretases da Proteína Precursora do Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Arctium/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Furanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Lignanas/farmacologia , Lignanas/uso terapêutico , Lipopolissacarídeos/farmacologia , Transtornos da Memória/metabolismo , Camundongos , Microglia/metabolismo , NF-kappa B/metabolismo , Doenças Neuroinflamatórias , Receptor 4 Toll-Like/metabolismo
16.
J Nutr Biochem ; 108: 109093, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35724814

RESUMO

Lignans are plant-derived compounds that act as partial estrogen agonists. Chondroitin sulfate proteoglycans (CSPGs) represent one of the major components of the extracellular matrix. Here we aimed to understand the role of sesamin (SES), a major lignan compound, in the biosynthesis and degradation of CSPGs in the mouse hippocampus because CSPGs play a key role in the regulation of cognitive functions through the promotion of adult neurogenesis. The expression of the pro-inflammatory cytokine interleukin-1ß was decreased by SES administration in the hippocampus of lipopolysaccharide (LPS)-treated mice, a model of neuroinflammation-induced cognitive deficits. The expression of genes related to biosynthesis and degradation of CSPGs in the hippocampus of LPS-treated mice was both increased and decreased by SES administration. Further, the diffuse extracellular matrix labeling of CSPGs by Wisteria floribunda agglutinin (WFA) in the hippocampus of LPS-treated mice was increased by SES administration. The densities of neural stem cells, late transit-amplifying cells, and newborn-granule cells in the hippocampus of LPS-treated mice were also increased by SES administration. Moreover, SES-induced alterations in gene expression, WFA labeling, and adult neurogenesis in LPS-treated mice were more evident in the dorsal hippocampus (center of cognition) than in the ventral hippocampus (center of emotion). Neither LPS nor SES administration affected locomotor activity, anxiety-like behavior, and depression-related behavior. However, impairments in contextual memory and sensorimotor gating in LPS-treated mice were recovered by SES administration. Our results show that SES can promote adult hippocampal neurogenesis through the upregulation of CSPGs, which may alleviate cognitive deficits induced by neuroinflammation.


Assuntos
Sulfatos de Condroitina , Lignanas , Animais , Proteoglicanas de Sulfatos de Condroitina , Cognição , Dioxóis , Modelos Animais de Doenças , Hipocampo , Lignanas/farmacologia , Lignanas/uso terapêutico , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias , Regulação para Cima
17.
J Ethnopharmacol ; 296: 115478, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35716920

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Forsythiae fructus, the dried fruit of Oleaceae plant Forsythia suspensa (Thunb.) Vahl, is a traditional Chinese medicine widely used in clinical practice and has a variety of pharmacological activities, such as anti-inflammation, antioxidation, and hepatoprotection. AIM OF THE STUDY: Phillygenin (PHI), an important fingerprint lignan component of Forsythiae fructus, has prominent hepatoprotective, anti-inflammatory and antioxidant effects. Previously, it was shown that PHI could exert anti-fibrotic effects by modulating inflammation and gut microbiota. Therefore, given the important roles of SCFAs and BAs in the development of liver fibrosis, as well as their close links with gut microbiota, we aimed to determine the protective effects of PHI on carbon tetrachloride (CCl4)-induced liver fibrosis and its effects on the metabolism of SCFAs and BAs based on metabolomics. MATERIALS AND METHODS: In C57BL/6J mice, liver fibrosis model was established by intraperitoneal injection of olive oil containing 10% CCl4 for 4 weeks. Firstly, the mouse liver tissues were subjected to histological analysis and biochemical index assay to evaluate the protective effect of PHI on CCl4-induced liver fibrosis. Subsequently, the effects of PHI on the metabolism of SCFAs and BAs in CCl4-induced liver fibrosis mice were determined using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) for metabolomics analysis. Finally, the levels of the closely related proteins and genes were detected by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) to explore the underlying mechanisms of the protective effect of PHI on CCl4-induced liver fibrosis. RESULTS: The histological analysis and the determination of relevant biochemical indexes of liver tissues showed that PHI could attenuate CCl4-induced liver fibrosis. The metabolomic analysis on SCFAs showed that PHI could promote SCFA production in the gut of mice with CCl4-induced liver fibrosis, especially acetic acid, propionic acid and butyric acid. It has been reported that the increased production of SCFAs was possibly beneficial to health. The metabolomic analysis on BAs found that PHI could restore the disturbance of BA metabolism in mice with CCl4-induced liver fibrosis. The immunohistochemistry and RT-qPCR results confirmed that PHI could ameliorate intestinal epithelial barrier disruption, and reverse the expression of BA metabolism-related genes in mice with CCl4-induced liver fibrosis. CONCLUSIONS: Promoting the production of SCFAs in the gut and restoring the disturbance of BA metabolism may be the potential mechanisms by which PHI alleviated CCl4-induced liver fibrosis.


Assuntos
Tetracloreto de Carbono , Lignanas , Animais , Ácidos e Sais Biliares/metabolismo , Tetracloreto de Carbono/farmacologia , Ácidos Graxos Voláteis/metabolismo , Lignanas/farmacologia , Fígado , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL
18.
Nutrients ; 14(12)2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35745107

RESUMO

High-fiber plant foods contain lignans that are converted to bioactive enterolignans, enterolactone (ENL) and enterodiol (END) by gut bacteria. Previously, we conducted an intervention study to gain mechanistic insight into the potential chemoprotective effects of flaxseed lignan supplementation (secoisolariciresinol diglucoside; SDG) compared to a placebo in 42 men and women. Here, we expand on these analyses to further probe the impact of the microbial metabolite phenotype on host gene expression in response to lignan exposure. We defined metabolic phenotypes as high- or low-ENL excretion based on the microbial metabolism of SDG. RNA-seq was used to assess host gene expression in fecal exfoliated cells. Stratified by microbial ENL excretion, differentially expressed (DE) genes in high- and low-ENL excreter groups were compared. Linear discriminant analysis using the ENL phenotypes identified putative biomarker combinations of genes capable of discriminating the lignan treatment from the placebo. Following lignan intervention, a total of 165 DE genes in high-ENL excreters and 1450 DE genes in low-ENL excreters were detected. Functional analysis identified four common upstream regulators (master genes): CD3, IFNG, IGF1 and TNFRSF1A. Our findings suggest that the enhanced conversion of flaxseed lignan to ENL is associated with a suppressed inflammatory status.


Assuntos
Linho , Lignanas , 4-Butirolactona , Estudos Cross-Over , Suplementos Nutricionais , Feminino , Linho/metabolismo , Humanos , Lignanas/metabolismo , Lignanas/farmacologia , Masculino , Fenótipo
19.
Int J Mol Sci ; 23(11)2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35682715

RESUMO

Plant lignans exhibit a wide range of biological activities, which makes them the research objects of potential use as therapeutic agents. They provide diverse naturally-occurring pharmacophores and are available for production by chemical synthesis. A large amount of accumulated data indicates that lignans of different structural groups are apt to demonstrate both anti-inflammatory and antioxidant effects, in many cases, simultaneously. In this review, we summarize the comprehensive knowledge about lignan use as a bioactive agent in disorders associated with oxidative stress and inflammation, pharmacological effects in vitro and in vivo, molecular mechanisms underlying these effects, and chemical synthesis approaches. This article provides an up-to-date overview of the current data in this area, available in PubMed, Scopus, and Web of Science databases, screened from 2000 to 2022.


Assuntos
Lignanas , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Lignanas/química , Lignanas/farmacologia , Estresse Oxidativo
20.
Molecules ; 27(11)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35684476

RESUMO

Two new neolignans jatrolignans, C (1) and D (2), a pair of epimers, were isolated from the whole plants of Jatropha curcas L. (Euphorbiaceae). Their structures were determined with HRESIMS, IR, and NMR data analysis, and electronic circular dichroism (ECD) experiments via a comparison of the experimental and the calculated ECD spectra. Their antichlamydial activity was evaluated in Chlamydia abortus. They both showed dose-dependent antichlamydial effects. Significant growth inhibitory effects were observed at a minimum concentration of 40 µM.


Assuntos
Euphorbiaceae , Jatropha , Lignanas , Jatropha/química , Lignanas/química , Lignanas/farmacologia
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