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1.
J Ethnopharmacol ; 301: 115769, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36183952

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis fruit is a well-known traditional Chinese medicine (TCM) that has been used to treat various liver diseases. Our previous study revealed that its extract is effective against nonalcoholic fatty liver disease (NAFLD). AIM OF THIS STUDY: This study aimed to elucidate the active components and explore the underlying mechanisms of action of S. chinensis fruit in the treatment of NAFLD. MATERIALS AND METHODS: A HepG2 cell model was used to screen the anti-NAFLD activity of the fraction from S. chinensis fruit extract. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to determine the components of the active fraction. Active compounds, potential targets, and key pathways were predicted for the active fraction treatment of NAFLD using network pharmacology. The anti-NAFLD effects of the active fraction and core active compound 3 were further validated using a high-fat diet (HFD)-induced NAFLD mouse model, intraperitoneal glucose tolerance test (IPGTT), and intraperitoneal insulin tolerance test (IPITT). Related hepatic mRNA expression was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to preliminarily validate the mechanism. RESULTS: In vitro experiments showed that the active fraction of S. chinensis fruit ethanol (EtOH) extract was mainly concentrated in the soluble fraction of petroleum ether (PET). Thirty-seven lignans were identified in this active fraction using UPLC-Q-TOF/MS. Network pharmacology studies have indicated that its anti-NAFLD effects lie in three major active lignans (3, 24, and 27) contained in PET, which may regulate the insulin resistance signaling pathway. In vivo experiments demonstrated that PET and core active compound 3 treatment significantly attenuated hepatic steatosis and reduced the levels of serum alanine transaminase (ALT), aspartate transaminase (AST), insulin, malondialdehyde (MDA), hepatic triglyceride (TG), and total cholesterol (TC) in HFD-induced mice (P < 0.05). Moreover, treatment with PET and compound 3 alleviated glucose tolerance and insulin resistance. These beneficial effects can be achieved by regulating the expression of Pik3ca, Gsk3ß, Jnk1, and Tnf-α. CONCLUSION: This study identified the main active fraction and compounds responsible for the anti-NAFLD activity of S. chinensis fruit. This mechanism may be related to regulation of the resistance pathway.


Assuntos
Resistência à Insulina , Lignanas , Hepatopatia Gordurosa não Alcoólica , Schisandra , Camundongos , Animais , Schisandra/química , Frutas , Farmacologia em Rede , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Lignanas/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Insulina , Tecnologia
2.
Int J Food Microbiol ; 384: 109972, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36279642

RESUMO

Plant-derived substances as antifungal agents have received considerable attention in recent years to reduce the use of chemical fungicides in food preservatives. In this study, honokiol, a type of phenolic compound in Magnolia officinalis, was found to inhibit spore germination and mycelia growth of Aspergillus flavus at 100 µg/mL. In addition, a pathogenicity assay showed that honokiol had potent antifungal activity against A. flavus in corn flour by suppressing conidia production. Fluorescence staining, transmission electron microscopy and biochemical assays were performed to explore its possible inhibition mechanisms against A. flavus. The results showed that the destructive effect of honokiol on A. flavus appeared to be related to increased plasma membrane permeability, the inhibition of ATPase activity, mitochondrial dysfunction and the accumulation of reactive oxygen species. Furthermore, a transcriptomic analysis showed that honokiol treatment resulted in 1578 different expressed genes. Gen Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that some genes of A. flavus related to spore development, integrity of the cell wall and membrane, oxidative stress and energy metabolism were significantly downregulated. In addition, RNA-seq results were validated by quantitative real-time polymerase chain reactions. Our finding enhanced the understanding of the antifungal activity of honokiol and underlying mechanisms of action at the molecular level, supporting honokiol as a potential agent in preventing contamination by A. flavus.


Assuntos
Aspergillus flavus , Lignanas , Antifúngicos/metabolismo , Transcriptoma , Lignanas/farmacologia , Lignanas/metabolismo
3.
Sci Rep ; 12(1): 19320, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369516

RESUMO

Schistosomiasis, a parasitic disease caused by the blood fluke of the genus Schistosoma, affects over 230 million people, especially in developing countries. Despite the significant economic and public health consequences, only one drug is currently available for treatment of schistosomiasis, praziquantel. Thus, there is an urgent demand for new anthelmintic agents. Based on our continuous studies involving the chemical prospection of floristic biodiversity aiming to discover new bioactive compounds, this work reports the in vitro antiparasitic activity against Schistosoma mansoni adult worms of neolignans threo-austrobailignan-6 and verrucosin, both isolated from Saururus cernuus L. (Saururaceae). These neolignans showed a significant in vitro schistosomicidal activity, with EC50 values of 12.6-28.1 µM. Further analysis revealed a pronounced reduction in the number of S. mansoni eggs. Scanning electron microscopy analysis revealed morphological alterations when schistosomes were exposed to either threo-austrobailignan-6 or verrucosin. These relevant antischistosomal properties were accompanied by low cytotoxicity potential against the animal (Vero) and human (HaCaT) cell lines, resulting in a high selectivity index. Considering the promising chemical and biological properties of threo-austrobailignan-6 and verrucosin, this research should be of interest to those in the area of neglected diseases and in particular antischistosomal drug discovery.


Assuntos
Lignanas , Saururaceae , Esquistossomose mansoni , Esquistossomose , Animais , Humanos , Schistosoma mansoni , Saururaceae/química , Esquistossomose mansoni/tratamento farmacológico
4.
J Agric Food Chem ; 70(44): 14157-14169, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36349542

RESUMO

Based on the current results, they showed that Schisandra chinensis lignans (SCL) ameliorated depressive-like behaviors in chronic unpredictable mild stress (CUMS) mice, alleviated neuroinflammation, and improved neuronal injury. This study aimed to explore whether SCL exerted antidepressant effects through inhibiting neuroinflammation, in turn improving neuronal injury. In vitro studies revealed that SCL blocked lipopolysaccharide-increased BV2 microglial M1 but promoted the M2 phenotype. The BV2-N2a interaction model suggested that increasing the M2 phenotype of BV2 played neuroprotective effects. The current studies demonstrated that SCL up-regulated the expression of CUMS- and LPS-decreased cannabinoid receptor type-2 (CB2R) mRNA. In vitro studies showed that the transfection of BV2 with siCrn2 blocked the SCL-increased M2 phenotype via the inactivating signal transducer and activator of transcription 6 (STAT6) pathway, further decreasing the viability of N2a cells. Finally, the possible pharmacodynamic compounds, γ-schisandrin and schisantherin A, were indicated by AutoDuck analysis. Overall, our study showed that SCL promoted microglia polarization toward the M2 phenotype, in turn exerting neuroprotective effects by activating CB2R-STAT6 signaling further to play antidepressant roles.


Assuntos
Lignanas , Fármacos Neuroprotetores , Schisandra , Camundongos , Animais , Microglia/metabolismo , Schisandra/metabolismo , Fármacos Neuroprotetores/metabolismo , Fator de Transcrição STAT6/metabolismo , Lignanas/farmacologia , Lignanas/metabolismo , Lipopolissacarídeos/farmacologia , Antidepressivos/farmacologia , Antidepressivos/metabolismo , Fenótipo , Receptores de Canabinoides/metabolismo
5.
Zhongguo Gu Shang ; 35(11): 1087-94, 2022 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-36415197

RESUMO

OBJECTIVE: To compare the effects of different concentrations of linolenin on inhibiting apoptosis of chondrocytes in the growth plate, and to screen the optimal concentration of linolenin, so as to provide theoretical support for delaying epiphyseal closure and promoting long bone growth in rats. METHODS: Two 4-week-old male SD rats (SPF grade) with a body mass of 80 g were selected. The growth plate cartilage of rat tibia and femur was dissected and isolated in vitro to obtain growth plate chondrocytes for culture. The chondrocytes were observed and identified by inverted phase contrast microscope and typeⅡ collagen immunofluorescence test, and then 20 ng/ml IL-1ß was used to induce apoptosis of growth plate chondrocytes as model group, and added with 1, 10, 20, 40 µM linolenin as the experimental group, and 5 µM letrozole as the positive control group. The cells were cultured for 24 and 48 hours respectively. The drug promoted cell proliferation was observed by MTT method, and the drug inhibited cell apoptosis was detected by flow cytometry. RESULTS: Contents 1, 10, 20, 40 µM could promote cell proliferation in varying degrees, and the principle was that the drug inhibits IL-1ß induced chondrocyte apoptosis in the growth plate, and the optimal concentration of drugs to inhibit apoptosis was 20 µM. CONCLUSION: The appropriate concentration of linseed lignans can significantly inhibit the apoptosis of chondrocytes in the growth plate of rats, and the optimal drug concentration is 20 µM. It provides possibility for delayed bone closure and longer growth time to promote bone growth during development.


Assuntos
Linho , Lignanas , Masculino , Ratos , Animais , Lâmina de Crescimento , Condrócitos , Ratos Sprague-Dawley , Apoptose , Lignanas/farmacologia
6.
Biomolecules ; 12(11)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36421734

RESUMO

Rhaponticum uniflorum (L.) DC. (syn. Leuzea uniflora (L.) Holub) is a plant species of the Compositae (Asteraceae) family that is widely used in Asian traditional medicines in China, Siberia, and Mongolia as an anti-inflammatory and stimulant remedy. Currently, R. uniflorum is of scientific interest to chemists, biologists, and pharmacologists, and this review includes information from the scientific literature from 1991 to 2022. The study of the chemodiversity of R. uniflorum revealed the presence of 225 compounds, including sesquiterpenes, ecdysteroids, triterpenes, sterols, thiophenes, hydroxycinnamates, flavonoids, lignans, nucleosides and vitamins, alkanes, fatty acids, and carbohydrates. The most studied groups of substances are phenolics (76 compounds) and triterpenoids (69 compounds). Information on the methods of chromatographic analysis of selected compounds, as well as on the quantitative content of some components in various organs of R. uniflorum, is summarized in this work. It has been shown that the extracts and some compounds of R. uniflorum have a wide range of biological activities, including anti-inflammatory, antitumor, immunostimulatory, anxiolytic, stress-protective, actoprotective, antihypoxic, anabolic, hepatoprotective, inhibition of PPARγ receptors, anti-atherosclerotic, and hypolipidemic. Published research on the metabolites and bioactivity of R. uniflorum does not include clinical studies of extracts and pure compounds; therefore, an accurate study of this traditional medicinal plant is needed.


Assuntos
Asteraceae , Leuzea , Lignanas , Triterpenos , Etnofarmacologia , Flavonoides
7.
Int J Mol Sci ; 23(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36232918

RESUMO

Cyclophosphamide is an anticancer drug with a wide spectrum of clinical uses, but its typical side effects are multiple complications, including nephron toxicity. The possible molecular mechanism of the nephroprotective action of sesamin (SM) against cyclophosphamide (CP) induced renal toxicity was investigated in rats by understanding oxidative stress and inflammatory cytokines. In this study, rats were arbitrarily grouped into the following four groups: a normal control group (CNT); a CP-induced toxicity group; a treatment group with two doses of sesamin SM10 and SM20; a group with sesamin (SM20) alone. A single dose of CP (150 mg/kg body, i.p.) was administered on day 4 of the experiments, while treatment with SM was given orally for seven days from day 1. The group treated with SM showed a significant protective effect against CP-induced renal damage in rats. Treatment with SM significantly increased the antioxidant enzymes (GSH, CAT, and SOD) and reduced malondialdehyde (MDA) levels. Thus, SM significantly overcame the elevated kidney function markers (creatinine, blood urea nitrogen, and uric acid) by attenuating oxidative stress. The SM also significantly reduced the elevated cytokines (IL-1ß and TNFα) and caspase-3 in the treated group. Histopathological studies confirmed the protective effect of sesamin (SM) on CP-induced nephrotoxicity. In conclusion, the current findings support the nephroprotective effect of sesamin against CP-induced renal injury.


Assuntos
Antineoplásicos , Insuficiência Renal , Animais , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Apoptose , Caspase 3/metabolismo , Creatinina/metabolismo , Ciclofosfamida/toxicidade , Citocinas/metabolismo , Dioxóis , Rim/metabolismo , Lignanas , Malondialdeído/metabolismo , Estresse Oxidativo , Ratos , Insuficiência Renal/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ácido Úrico/metabolismo
8.
Molecules ; 27(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36234864

RESUMO

Lignans are known to exhibit a broad spectrum of biological activities, indicating their potential as constituents of feed supplements. This study investigated two extracts derived from the feed supplements 'ROI' and 'Protect'-which contain the wood lignans magnolol and honokiol ('ROI'), or soluble tannins additional to the aforementioned lignans ('Protect')-and their impact on selected parameters of intestinal functionality. The antioxidant and anti-inflammatory properties of the extracts were determined by measuring their effects on reactive oxygen species (ROS) and pro-inflammatory cytokine production in vitro. The impact on intestinal barrier integrity was evaluated in Caco-2 cells and Drosophila melanogaster by examining leaky gut formation. Furthermore, a feeding trial using infected piglets was conducted to study the impact on the levels of superoxide dismutase, glutathione and lipid peroxidation. The Protect extract lowered ROS production in Caco-2 cells and reversed the stress-induced weakening of barrier integrity. The ROI extract inhibited the expression or secretion of interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNFα). Moreover, the ROI extract decreased leaky gut formation and mortality rates in Drosophila melanogaster. Dietary supplementation with Protect improved the antioxidant status and barrier integrity of the intestines of infected piglets. In conclusion, wood lignan-enriched feed supplements are valuable tools that support intestinal health by exerting antioxidant, anti-inflammatory and barrier-strengthening effects.


Assuntos
Interleucina-8 , Lignanas , Ração Animal/análise , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Células CACO-2 , Suplementos Nutricionais , Drosophila melanogaster/metabolismo , Glutationa , Humanos , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lignanas/farmacologia , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Suínos , Taninos , Fator de Necrose Tumoral alfa/metabolismo , Madeira/metabolismo
9.
Molecules ; 27(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36234885

RESUMO

Five new furofurans lignans, Brasesquilignan A-E (1-5), were isolated from the aqueous ethanol extract of Selaginella braunii Baker. Their structures were elucidated by extensive analysis of NMR and HRESIMS data. Their absolute configurations were determined by CD spectra, enzymatic hydrolysis, and GCMS analysis. Furthermore, all compounds were evaluated for anti-proliferative activities against various human cancer cellsin vitro. Compounds 2 and 3 exhibited weak inhibitorypotency against five human cancer cells.


Assuntos
Lignanas , Selaginellaceae , Etanol , Humanos , Lignanas/química , Lignanas/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Selaginellaceae/química
10.
Molecules ; 27(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36234977

RESUMO

Cancer is a serious disease with high mortality and morbidity worldwide. Natural products have served as a major source for developing new anticancer drugs during recent decades. Magnolol, a representative natural phenolic lignan isolated from Magnolia officinali, has attracted considerable attention for its anticancer properties in recent years. Accumulating preclinical studies have demonstrated the tremendous therapeutic potential of magnolol via a wide range of pharmacological mechanisms against cancer. In this review, we summarized the latest advances in preclinical studies investigating anticancer properties of magnolol and described the important signaling pathways explaining its underlying mechanisms. Magnolol was capable of inhibiting cancer growth and metastasis against various cancer types. Magnolol exerted anticancer effects through inhibiting proliferation, inducing cell cycle arrest, provoking apoptosis, restraining migration and invasion, and suppressing angiogenesis. Multiple signaling pathways were also involved in the pharmacological actions of magnolol against cancer, such as PI3K/Akt/mTOR signaling, MAPK signaling and NF-κB signaling. Based on this existing evidence summarized in the review, we have conclusively confirmed magnolol had a multi-target anticancer effect against heterogeneous cancer disease. It is promising to develop magnolol as a drug candidate for cancer therapy in the future.


Assuntos
Antineoplásicos , Produtos Biológicos , Lignanas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Produtos Biológicos/farmacologia , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/uso terapêutico , Lignanas/farmacologia , Lignanas/uso terapêutico , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
11.
Molecules ; 27(19)2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36235047

RESUMO

Brunfelsia grandiflora is an ancient plant widely used for its promising medicinal properties, although little explored scientifically. Despite being a rich source of phenolic compounds responsible in part for the proven anti-inflammatory activity, its characterization has not been carried out to date. The present work deals with the exhaustive identification and quantification of its phenolic fraction, along with its antioxidant activity. Decoction resulting from the bark as fine powder was filtered and lyophilized, and polyphenols were extracted from the resulting product by aqueous-organic solvents. Seventy-nine polyphenols were identified using LC-MSn. Hydroxycinnamates was the most abundant group of compounds (up to 66.8%), followed by hydroxycoumarins (15.5%), lignans (6.1%), flavonols (5.7%), phenolic simples (3.1), gallates (2.3%), flavanols (0.3%), and flavanones (0.2%). About 64% of the characterized phenols were in their glycosylated forms. The quantification of these phytochemicals by LC-QToF showed that this medicinal plant contained 2014.71 mg of phenolic compounds in 100 g dry matter, which evidences a great antioxidant potency determined by ABTS and DPPH assays. Therefore, Brunfelsia grandiflora represents an important source of polyphenols which supports its therapeutic properties scientifically proven.


Assuntos
Flavanonas , Lignanas , Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides , Flavonóis , Fenóis , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Pós , Solventes/química
12.
Molecules ; 27(19)2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36235155

RESUMO

Siraitia grosvenorii (Swingle) C. Jeffrey ex Lu et Z. Y. Zhang is a unique economic and medicinal plant of Cucurbitaceae in Southern China. For hundreds of years, Chinese people have used the fruit of S. grosvenorii as an excellent natural sweetener and traditional medicine for lung congestion, sore throat, and constipation. It is one of the first species in China to be classified as a medicinal food homology, which has received considerable attention as a natural product with high development potential. Various natural products, such as triterpenoids, flavonoids, amino acids, and lignans, have been released from this plant by previous phytochemical studies. Phar- macological research of the fruits of S. grosvenorii has attracted extensive attention, and an increasing number of extracts and compounds have been demonstrated to have antitussive, expectorant, antiasthmatic, antioxidant, hypoglycemic, immunologic, hepatoprotective, antibacte- rial, and other activities. In this review, based on a large number of previous studies, we summarized the related research progress of the chemical components and pharmacological effects of S. grosvenorii, which provides theoretical support for further investigation of its biological functions and potential clinical applications.


Assuntos
Antiasmáticos , Antitussígenos , Produtos Biológicos , Cucurbitaceae , Lignanas , Triterpenos , Aminoácidos/análise , Antioxidantes/análise , Antioxidantes/farmacologia , Produtos Biológicos/análise , Cucurbitaceae/química , Expectorantes , Flavonoides/análise , Frutas/química , Humanos , Hipoglicemiantes/farmacologia , Lignanas/análise , Edulcorantes , Triterpenos/química
13.
Molecules ; 27(19)2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36235218

RESUMO

The study investigated the effect of elicitation with: chitosan (CH) (200 mg/L), yeast extract (YeE) (3000 mg/L), ethephon (ETH) (25 µM/L), and methyl jasmonate (MeJA) (50 µM/L), on lignan accumulation in agitated and bioreactor (Plantform temporary immersion systems) microshoot cultures of female (F) and male (M) Schisandra rubriflora Rehd. et Wils. (Schisandraceae) lines. The elicitors were supplemented on the 10th day of culture. Biomasses were collected at 24 h and 48 h, and 4, 6, and 8 days after the addition of each elicitor. The 24 compounds from the dibenzocyclooctadiene, aryltetralin, dibenzylbutane, and tetrahydrofuran lignans and neolignans were determined qualitatively and quantitatively in biomass extracts using the UHPLC-MS/MS method. The highest total contents [mg/100 g DW] of lignans were: for CH-95.00 (F, day 6) and 323.30 (M, 48 h); for YeE 104.30 (F, day 8) and 353.17 (M, day 4); for ETH 124.50 (F, 48 h) and 334.90 (M, day 4); and for MeJA 89.70 (F, 48 h) and 368.50 (M, 24 h). In the biomass extracts of M cultures grown in bioreactors, the highest total lignan content was obtained after MeJA elicitation (153.20 mg/100 g DW). The maximum total lignan contents in the biomass extracts from agitated and bioreactor cultures were 3.29 and 1.13 times higher, respectively, than in the extracts from the non-elicited cultures. The poor understanding of the chemical composition and the lack of studies in the field of plant biotechnology of S. rubriflora emphasize the innovativeness of the research.


Assuntos
Quitosana , Lignanas , Schisandra , Acetatos , Quitosana/farmacologia , Ciclopentanos , Furanos/farmacologia , Lignanas/química , Oxilipinas , Brotos de Planta/química , Schisandra/química , Espectrometria de Massas em Tandem
14.
Chem Biodivers ; 19(11): e202200414, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36200645

RESUMO

A pair of new lignan conformers (1-2), one new flavonoid glycoside (3), as well as nineteen known compounds were purified from the twigs and leaves of Cajanus cajan (L.) Millsp.. The planar structures of the unknown compounds were determined via NMR and high-resolution mass spectrometry, while their absolute configurations were elucidated via comparison between their experimental and calculated electronic circular dichroism (ECD) values. All the isolated compounds were assayed for their α-glucosidase inhibitory activities. The results demonstrated that compounds 8-12, 15-16, 18-19, 21-22 had strong inhibition activities, with compound 10 (IC50 =0.4±0.21 µM) most active. The structure-activity relationships were preliminarily summarized. Enzyme kinetics showed that compounds 8, 9, 15-16, 18-19, 21-22 were non-competitive inhibitors and compounds 10-12 were anti-competitive ones.


Assuntos
Cajanus , Lignanas , Cajanus/química , Flavonoides/química , Lignanas/farmacologia , Lignanas/análise , alfa-Glucosidases , Folhas de Planta/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química
15.
Molecules ; 27(20)2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36296420

RESUMO

Flavonoids, stilbenes, lignans, and phenolic acids, classes of polyphenols found in grape pomace (GP), were investigated as an important alternative source for active substances that could be used in the management of oxidative stress and inflammation. The benefic antioxidant and anti-inflammatory actions of GP are presented in the literature, but they are derived from a large variety of experimental in vitro and in vivo settings. In these in vitro works, the decrease in reactive oxygen species, malondialdehyde, and thiobarbituric acid reactive substances levels and the increase in glutathione levels show the antioxidant effects. The inhibition of nuclear factor kappa B and prostaglandin E2 inflammatory pathways and the decrease of some inflammatory markers such as interleukin-8 (IL-8) demonstrate the anti-inflammatory actions of GP polyphenols. The in vivo studies further confirmed the antioxidant (increase in catalase, superoxide dismutase and glutathione peroxidase levels and a stimulation of endothelial nitric oxide synthase -eNOS gene expression) and anti-inflammatory (inhibition of IL-1𝛼, IL-1ß, IL-6, interferon-𝛾, TNF-α and C-reactive protein release) activities. Grape pomace as a whole extract, but also different individual polyphenols that are contained in GP can modulate the endogenous pathway responsible in reducing oxidative stress and chronic inflammation. The present review analyzed the effects of GP in oxidative stress and inflammation, suggesting that it could become a valuable therapeutic candidate capable to reduce the aforementioned pathological processes. Grape pomace extract could become an adjuvant treatment in the attempt to reduce the side effects of the classical anti-inflammatory medication like non-steroidal anti-inflammatory drugs (NSAIDs).


Assuntos
Lignanas , Estilbenos , Vitis , Polifenóis/farmacologia , Polifenóis/metabolismo , Vitis/metabolismo , Interleucina-8/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Catalase/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Glutationa Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , NF-kappa B/metabolismo , Proteína C-Reativa/metabolismo , Dinoprostona/metabolismo , Interleucina-6/metabolismo , Estresse Oxidativo , Flavonoides/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Superóxido Dismutase/metabolismo , Estilbenos/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/metabolismo , Lignanas/metabolismo , Glutationa/metabolismo , Interferons
16.
Bioorg Med Chem ; 73: 116999, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36191547

RESUMO

Among the sirtuin enzymes, Sirt3 is one of the most important deacetylases as it regulates acetylation levels in mitochondria, which are linked to the metabolism of multiple organs and therefore involved in many types of age-related human diseases such as cancer, heart diseases and metabolic diseases. Given the dearth of direct activators of Sirt3, the identification of new modulators could be a key step in the development of new therapeutics. Here we report the discovery of Sirt3 modulators, including activators, through the use of DNA encoded library technology (DEL) and computational high-throughput screening methodologies. Top hits from both screenings against Sirt3 were evaluated according to their activity and affinity. Our best activator is more potent than the previously reported activator Honokiol. Docking studies suggest that our activators identified from virtual screening interact with Sirt3 at a site similar to Honokiol, whereas the activators identified from DEL selection interact with Sirt3 at an atypical site. Our results establish the attractiveness of these high-throughput screening technologies in identifying novel and potent Sirt3 activators and, therefore, in associated therapeutic applications.


Assuntos
Lignanas , Sirtuína 3 , Sirtuínas , Acetilação , Compostos Alílicos , Compostos de Bifenilo/farmacologia , Humanos , Fenóis , Sirtuína 3/metabolismo , Sirtuínas/metabolismo
17.
Food Funct ; 13(22): 11733-11743, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36281695

RESUMO

Physalis peruviana L. is a common edible fruit in Egypt and other regional countries. In the present study, we investigated its crude extract as a potential source of antiproliferative secondary metabolites. Upon bioactivity guided solvent fractionation, ethyl acetate extract showed preferential activity toward the human pancreatic cancer cell line PANC-1 with an IC50 value of 5.23 ± 0.2 µg mL-1. The subsequent HR-LCMS-guided and biological activity-guided isolation revealed magnolin as a potent preferential antiproliferative agent against PANC-1 with an IC50 of 0.51 ± 0.46 µM that was comparable to that of the positive control doxorubocin (IC50 of 0.17 ± 0.15 µM). Moreover, magnolin showed much less cytotoxicity in comparison with the positive control doxorubicin (6.96% and 30.48% growth inhibition, respectively, at 5 µg mL-1) towards normal human cells (i.e. dermal fibroblasts; HDFa). Furthermore, magnolin was able to induce a concentration-dependent suppression of the formation of PANC-1 colonies, where the treatment of the tumor cells with 25 nM, 50 nM, and 100 nM concentrations of the compound resulted in a 36%, 57, and 78% reduction, respectively, in the PANC-1 colony formation. Additionally, magnolin was observed to limit PANC-1 tumor cell migration in the tumor cell wound healing assay, indicating a substantial anti-migratory effect against the PANC-1 cell line. A subsequent in silico-based study of this compound structure putatively suggested matrix metalloproteinase-3 (MMP3) as the molecular target that mediates these observed effects on PANC-1 cells. Absolute binding free energy estimation (ΔGbinding) and 100 ns long molecular dynamics simulation (MDS) experiments indicated that the magnolin structure has good affinity towards the MMP3's active site and can achieve significantly stable binding inside it. Accordingly, upon experimental validation, magnolin was found to inhibit the catalytic activity of MMP3 in a dose-dependent manner with a nanomolar IC50 value of 185 nm ± 4.86 and a Ki of 112 nm ± 6.31. In conclusion, our results clearly revealed that magnolin derived from P. peruviana is an interesting antiproliferative and antimetastatic agent against PANC-1 cells with potent inhibitory activity against MMP3. Further in vivo evaluation will be of great interest in the future.


Assuntos
Lignanas , Neoplasias Pancreáticas , Physalis , Humanos , Metaloproteinase 3 da Matriz , Lignanas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células
18.
Org Lett ; 24(42): 7812-7816, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36222500

RESUMO

The first enantioselective total synthesis of aryltetralin lignan acetals, (-)-formosanol, (+)-tsugacetal, (+)-methyl ß-conidendral, and their enantiomers have been accomplished on the basis of the Pd-catalyzed asymmetric allylic cycloaddition as a key step. Six stereoisomers of the lignan acetals have been synthesized via a 7-8 step sequence in up to 14% overall yield. The in vitro cytotoxicity against several cancer cells has preliminarily been examined for the obtained six stereoisomers of lignan acetals.


Assuntos
Acetais , Lignanas , Estereoisomerismo , Reação de Cicloadição , Lignanas/farmacologia
19.
J Agric Food Chem ; 70(42): 13602-13614, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36239029

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease, characterized by memory loss and cognitive deficits accompanied by neuronal damage and cholinergic disorders. Sesamol, a lignan component in sesame oil, has been proven to have neuroprotective effects. This research aimed to investigate the preventive effects of sesamol on scopolamine (SCOP)-induced cholinergic disorders in C57BL/6 mice. The mice were pretreated with sesamol (100 mg/kg/d, p.o.) for 30 days. Behavioral tests indicated that sesamol supplement prevented SCOP-induced cognitive deficits. Sesamol enhanced the expression of neurotrophic factors and postsynaptic density (PSD) in SCOP-treated mice, reversing neuronal damage and synaptic dysfunction. Importantly, sesamol could balance the cholinergic system by suppressing the AChE activity and increasing the ChAT activity and M1 mAChR expression. Sesamol treatment also inhibited the expression of inflammatory factors and overactivation of microglia in SCOP-treated mice. Meanwhile, sesamol improved the antioxidant enzyme activity and suppressed oxidative stress in SCOP-treated mice and ameliorated the oxidized cellular status and mitochondrial dysfunction in SCOP-treated SH-SY5Y cells. In conclusion, these results indicated that sesamol attenuated SCOP-induced cognitive dysfunction via balancing the cholinergic system and reducing neuroinflammation and oxidative stress.


Assuntos
Disfunção Cognitiva , Lignanas , Neuroblastoma , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Animais , Humanos , Camundongos , Antioxidantes/metabolismo , Colinérgicos , Cognição , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/genética , Lignanas/farmacologia , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Camundongos Endogâmicos C57BL , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/farmacologia , Fatores de Crescimento Neural/uso terapêutico , Doenças Neuroinflamatórias , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Escopolamina , Óleo de Gergelim
20.
Cells ; 11(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36291197

RESUMO

Many species from the Pinaceae family have been recognized as a rich source of lignans, flavonoids, and other polyphenolics. The great common occurrence of conifers in Europe, as well as their use in the wood industry, makes both plant material and industrial waste material easily accessible and inexpensive. This is a promising prognosis for both discovery of new active compounds as well as for finding new applications for wood and its industry waste products. This study aimed to analyze and phytochemically profile 13 wood extracts of the Pinaceae family species, endemic or introduced in Polish flora, using the LC-DAD-ESI-MS/MS method and compare their respective metabolite profiles. Branch wood methanolic extracts were phytochemically profiled. Lignans, stilbenes, flavonoids, diterpenes, procyanidins, and other compounds were detected, with a considerable variety of chemical content among distinct species. Norway spruce (Picea abies (L.) H.Karst.) branch wood was the most abundant source of stilbenes, European larch (Larix decidua Mill.) mostly contained flavonoids, while silver fir (Abies alba Mill.) was rich in lignans. Furthermore, 10 lignans were isolated from the studied material. Our findings confirm that wood industry waste materials, such as conifer branches, can be a potent source of different phytochemicals, with the plant matrix being relatively simple, facilitating future isolation of target compounds.


Assuntos
Lignanas , Proantocianidinas , Estilbenos , Traqueófitas , Proantocianidinas/análise , Madeira , Espectrometria de Massas em Tandem/métodos , Resíduos Industriais/análise , Compostos Fitoquímicos/química , Flavonoides , Extratos Vegetais/química
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