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1.
Int J Biol Macromol ; 259(Pt 2): 129344, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38218282

RESUMO

This study aimed to investigate the influence of incorporating Lepidium perfoliatum seed gum (LPSG) into wheat starch (WS) at various mixing ratios on its FTIR, DSC, steady and dynamic rheological properties, pasting attributes, syneresis, and particle size distributions characteristics. The interaction between WS and LPSG was purely based on hydrogen-bonding. It was found that the onset (To) and peak (Tp) temperatures of the LPSG-rich mixtures increased by 10 % and 8 %, respectively, while the enthalpy (ΔH) decreased by 70 % compared to WS. A higher LPSG ratio led to a decrease in the frequency dependence of storage modulus (G'), as well as an increase in the pseudoplasticity of the mixtures. The in-shear structural recovery test showed that the rate of recovery (R, %) increased with an increasing LPSG ratio. The pasting results demonstrated that the 9/1 ratio had the highest final viscosity and the lowest relative breakdown. Applying 1 to 5 freeze-thaw cycles resulted in a 50 % to 70 % decrease in syneresis for the 9/1 mixing ratio in comparison to WS, respectively. The incorporation of LPSG into WS resulted in higher static and dynamic magnitudes of yield stress, as well as an increase in particle size when compared to WS.


Assuntos
Lepidium , Amido , Amido/química , Lepidium/química , Triticum/química , Viscosidade , Sementes/química , Reologia
2.
Fitoterapia ; 168: 105521, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37146736

RESUMO

Macathioureas A-D (1-4), four new thiourea derivatives with a carbamothioylpyrrolidine-2-carboxamide framework, were isolated from the roots of Lepidium meyenii (Maca) collected from Qujing, Yunnan Province of China. Their structures were identified based on extensive spectroscopic data, including 1D NMR, 2D NMR, and HRESIMS techniques. Their absolute configurations were assigned as 7S by the comparison of the experimental and predicted electronic circular dichroism (ECD) spectra. All the thiourea analogues were tested for their cytotoxicities against five human cancer cell lines. However, no significant activities were detected at concentrations up to 40 µM.


Assuntos
Lepidium , Humanos , Lepidium/química , China , Estrutura Molecular , Raízes de Plantas/química , Linhagem Celular Tumoral , Extratos Vegetais/química
3.
Molecules ; 28(9)2023 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-37175353

RESUMO

Macamides are a class of amide alkaloids that are only found in maca and are widely considered to be its bioactive marker compounds. More than thirty macamide monomers have been identified in recent years; however, it is difficult to obtain a single macamide monomer from the maca plant because of their similar structures and characteristics. We used the carbodiimide condensation method (CCM) to efficiently synthesize five typical macamides, including N-benzyl-hexadecanamide (NBH), N-benzyl-9Z,12Z,15Z-octadecenamide, N-(3-methoxybenzyl)-9Z,12Z-octadecenamide, N-benzyl-9Z,12Z-octadecenamide, and N-(3-methoxybenzyl)-9Z,12Z,15Z-octadecadienamide. All the synthesized macamides were purified by a one-step HPLC with a purity of more than 95%. NBH is the most abundant macamide monomer in natural maca, and it was selected to evaluate the anti-fatigue effects of macamides. The results indicated that NBH could enhance the endurance capacity of mice by increasing liver glycogen levels and decreasing blood urea nitrogen, lactate dehydrogenase, blood ammonia, and blood lactic acid levels. Macamides might be the active substances that give maca its anti-fatigue active function.


Assuntos
Lepidium , Animais , Camundongos , Lepidium/química , Amidas/farmacologia , Amidas/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Estado Nutricional
4.
Molecules ; 28(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37241805

RESUMO

Testicular dysfunction (TDF) is characterized by testosterone deficiency and is caused by oxidative stress injury in Leydig cells. A natural fatty amide named N-benzylhexadecanamide (NBH), derived from cruciferous maca, has been shown to promote testosterone production. Our study aims to reveal the anti-TDF effect of NBH and explore its potential mechanism in vitro. This study examined the effects of H2O2 on cell viability and testosterone levels in mouse Leydig cells (TM3) under oxidative stress. In addition, cell metabolomics analysis based on UPLC-Q-Exactive-MS/MS showed that NBH was mainly involved in arginine biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, the TCA cycle and other metabolic pathways by affecting 23 differential metabolites, including arginine and phenylalanine. Furthermore, we also performed network pharmacological analysis to observe the key protein targets in NBH treatment. The results showed that its role was to up-regulate ALOX5, down-regulate CYP1A2, and play a role in promoting testicular activity by participating in the steroid hormone biosynthesis pathway. In summary, our study not only provides new insights into the biochemical mechanisms of natural compounds in the treatment of TDF, but also provides a research strategy that integrates cell metabolomics and network pharmacology in order to promote the screening of new drugs for the treatment of TDF.


Assuntos
Lepidium , Espectrometria de Massas em Tandem , Camundongos , Masculino , Animais , Lepidium/química , Farmacologia em Rede , Peróxido de Hidrogênio , Alcamidas Poli-Insaturadas , Testosterona , Metabolômica
5.
Food Chem ; 419: 136035, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37027970

RESUMO

Lepidium latifolium L. is an established phytofood of the Ladakh Himalayas that contains differential content of important glucosinolates (GLS) in specific stages of sprouts. Therefore, in order to harness its nutraceutical potential, a comprehensive mass spectrometry-based stage-specific untargeted metabolomic analysis was performed. A total of 318 metabolites were detected, out of which 229 were significantly (p ≤ 0.05) changed during different stages. The Principal Component Analysis plot clearly differentiated different growth stages into three clusters. The nutritionally important metabolites, including amino acids, sugars, organic acids, and fatty acids, were found significantly (p ≤ 0.05) higher in the first cluster consisting of 1st, 2nd and 3rd week sprouts. The higher energy requirements during the early growth stages were observed with the higher metabolites of glycolysis and the TCA cycle. Further, the trade-off between primary and secondary sulfur-containing metabolites was observed, which may explain the differential GLS content in different growth stages.


Assuntos
Lepidium , Lepidium/química , Metabolômica , Ácidos Graxos
6.
J Asian Nat Prod Res ; 25(10): 976-982, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36946084

RESUMO

Two previously undescribed flavonoid thioglucosides lepidiumflavonosides A and B (1-2) and two known megastigmane compounds (7E,9S)-9-hydroxy-5,7-megastigmadien-4-one 9-O-ß-D-glucopyranoside (3) and (9S)-4-oxo-ß-inol ß-D-glucopyranoside (4) were isolated from the water extract of the seeds of Lepidium apetalum Willd. The structural elucidation of isolated compounds was unambiguously determined based on extensive 1D and 2D NMR spectroscopic analyses. All compounds were evaluated for their estrogen-like effects on MCF-7 cells in vitro. The results showed that compounds 1-4 significantly promoted the proliferation of MCF-7 cells, and the proliferation was antagonized by the specific ER antagonist ICI182,780, suggesting that compounds 1-4 might have the estrogen-like effect in vitro potentially.


Assuntos
Flavonoides , Lepidium , Flavonoides/farmacologia , Flavonoides/química , Tioglucosídeos/análise , Lepidium/química , Estrogênios/farmacologia , Sementes/química
7.
J Anim Physiol Anim Nutr (Berl) ; 107(1): 286-297, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36102208

RESUMO

Heat stress (HS) is the most substantial environmental issue in rabbit health status impairment, which can lower productivity. Maca is a common medicinal plant with important biological activities including antioxidant, anti-inflammatory, anti-fatigue, and neuroprotective effects. The present research explored the alleged protective role of Maca extract in alleviating the adverse impact of HS on rabbits. Growing V-line 6-week-old buck rabbits (N = 48) were orally administered Maca extract at levels of 0 (MAC0), 200 (MAC2), 400 (MAC4), or 600 (MAC6) mg/head twice per week. Compared to the control groups, rabbits provided Maca had better growth performance, feed intake and feed conversion ratio. Liver and tests weights were significantly higher (p < 0.05) in Maca treated groups compared to the control. hemoglobin, white blood cell, red blood corpuscles, platelet count, hematocrit, and lymphocytes were significantly increased in the MAC4 group compared with the control group. MAC4 treatment significantly reduced aspartate aminotransferase and malondialdehyde levels compared with other groups. Moreover, the concentrations of total bilirubin, creatinine, glucose, total cholesterol, and triglycerides were lower (p < 0.05) in the MAC4 group than in the controls. Oral administration of Maca improved cortisol and testosterone values, total antioxidant capacity, and superoxide dismutase. The MAC4 group exhibited significant improvement (p < 0.05) in sperm motility, survival, membrane functionality, concentration, and libido, with a significant decrease in abnormal sperm compared with the control group. Also, aforementioned group showed sperm cells with a normal structure and intact plasma membranes, acrosomes, and well-organised axonemal components. Histopathological screening of liver sections showed moderate to severe degenerative and necrotic changes in rabbits exposed to HS, which were alleviated with Maca oral administration. In conclusion, oral administration of Maca extract at 400 or 600 mg/head-weekly enhanced growth performance, hemato-biochemical attributes, antioxidant status, and semen quality in rabbits during the hot season.


Assuntos
Antioxidantes , Lepidium , Masculino , Coelhos , Animais , Antioxidantes/química , Análise do Sêmen/veterinária , Lepidium/química , Contagem de Espermatozoides/veterinária , Motilidade dos Espermatozoides , Sementes , Extratos Vegetais/química , Resposta ao Choque Térmico
8.
Plant Foods Hum Nutr ; 77(3): 460-466, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35932411

RESUMO

Lepidium meyenii Walp (red maca) is a high Andean plant cultivated since the Incas and has innumerable therapeutic properties. The study aims to identify its phytochemical composition using UHPLC-ESI-MS/MS, and evaluate its effects on acrylamide-induced oxidative stress. The lyophilized aqueous extract of red maca (LAqE-RM) was orally administered in doses of 1 and 2 g/kg body weight for 4 weeks. Malondialdehyde (MDA) levels in erythrocytes, brain, and liver, as well as hepatic levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Administration of acrylamide for 2 and 4 weeks significantly increased (p < 0.001) MDA levels in erythrocytes, brain, and liver. However, LAqE-RM prevented (p < 0.001) an increase in MDA levels in all tissues studied. Likewise, the groups treated with LAqE-RM presented significantly (p < 0.001) lower levels of ALT and AST compared to the control. Treatment with LAqE-RM ameliorated the acrylamide-induced oxidative stress by reducing MDA levels in erythrocytes, brain, and liver and by lowering liver levels of ALT and AST in a dose-dependent manner. Twenty-five secondary metabolites were identified and characterized from LAqE-RM based on UHPLC mass spectrophotometry. These include carbolines, alkamides, fatty acids, and macamides, which are probably involved in their antioxidant protective role.


Assuntos
Lepidium , Acrilamida/toxicidade , Animais , Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais , Lepidium/química , Fígado , Estresse Oxidativo , Compostos Fitoquímicos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Espectrometria de Massas em Tandem
9.
Int J Mol Sci ; 23(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35563248

RESUMO

The aim of the study was to present the fingerprint of different Lepidium peruvianum tuber extracts showing glucosinolates-containing substances possibly playing an important role in preventinting dementia and other memory disorders. Different phenotypes of Lepidium peruvianum (Brassicaceae) tubers were analysed for their glucosinolate profile using a liquid chromatograph coupled with mass spectrometer (HPLC-ESI-QTOF-MS/MS platform). Qualitative analysis in 50% ethanolic extracts confirmed the presence of ten compounds: aliphatic, indolyl, and aromatic glucosinolates, with glucotropaeolin being the leading one, detected at levels between 0-1.57% depending on phenotype, size, processing, and collection site. The PCA analysis showed important variations in glucosinolate content between the samples and different ratios of the detected compounds. Applied in vitro activity tests confirmed inhibitory properties of extracts and single glucosinolates against acetylcholinesterase (AChE) (15.3-28.9% for the extracts and 55.95-57.60% for individual compounds) and butyrylcholinesterase (BuChE) (71.3-77.2% for the extracts and 36.2-39.9% for individual compounds). The molecular basis for the activity of glucosinolates was explained through molecular docking studies showing that the tested metabolites interacted with tryptophan and histidine residues of the enzymes, most likely blocking their active catalytic side. Based on the obtained results and described mechanism of action, it could be concluded that glucosinolates exhibit inhibitory properties against two cholinesterases present in the synaptic cleft, which indicates that selected phenotypes of L. peruvianum tubers cultivated under well-defined environmental and ecological conditions may present a valuable plant material to be considered for the development of therapeutic products with memory-stimulating properties.


Assuntos
Lepidium , Acetilcolinesterase , Butirilcolinesterase , Inibidores da Colinesterase/farmacologia , Glucosinolatos/análise , Lepidium/química , Simulação de Acoplamento Molecular , Fenótipo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espectrometria de Massas em Tandem
10.
J Agric Food Chem ; 70(14): 4328-4341, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35357828

RESUMO

Maca is a protein-enriched edible plant with immunomodulatory activity. However, the role of proteins in the immunomodulatory activity of maca is unclear. In this study, peptide products of maca proteins obtained through in vitro gastrointestinal digestion were isolated and purified, and the immunomodulatory activities of these peptides were assessed in macrophages (RAW 264.7 cells). The results show that the maca protein hydrolysate enhanced the phagocytic capacity and NO, TNF-α, and IL-6 secretion of RAW 264.7 cells. Forty-five peptides from known proteins of maca or the cruciferous family were identified by ultraperformance liquid chromatography-tandem mass spectrometry in the hydrolysate, and the peptide RNPFLP exhibited the strongest immunomodulatory activity. Antibody blocking, siRNA, pathway inhibitors, and western blot assays showed that RNPFLP-activated RAW 264.7 cells through the NF-κB and MAPK signaling pathways mediated by TLR2 and TLR4 receptors. An analysis of the structure-activity relationship showed that the N9-H60 active site in arginine plays an important role in the immunomodulatory activity of RNPFLP. This study provides a new understanding of the immunomodulatory activity of maca.


Assuntos
Lepidium , Animais , Lepidium/química , Camundongos , NF-kappa B/metabolismo , Peptídeos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Hidrolisados de Proteína/farmacologia , Células RAW 264.7
11.
J Ethnopharmacol ; 289: 115056, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35104576

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lepidium virginicum L. (Brassicaceae) is a plant widely used in traditional Mexican medicine as an expectorant, diuretic, and as a remedy to treat diarrhea and dysentery, infection-derived gastroenteritis. However, there is no scientific study that validates its clinical use as an anti-inflammatory in the intestine. AIM OF THE STUDY: This study aimed to investigate the anti-inflammatory properties of the ethanolic extract of Lepidium virginicum L. (ELv) in an animal model of inflammatory bowel disease (IBD)-like colitis. MATERIALS AND METHODS: The 2,4-dinitrobenzene sulfonic acid (DNBS) animal model of IBD was used. Colitis was induced by intrarectal instillation of 200 mg/kg of DNBS dissolved vehicle, 50% ethanol. Control rats only received the vehicle. Six hours posterior to DNBS administration, ELv (3, 30, or 100 mg/kg) was administered daily by gavage or intraperitoneal injection. The onset and course of the inflammatory response were monitored by assessing weight loss, stool consistency, and fecal blood. Colonic damage was evaluated by colon weight/length ratio, histopathology, colonic myeloperoxidase (MPO) activity, and gene expression of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), chemokine C-X-C motif ligand 1 (CXCL-1), and interleukin-6 (IL-6). RESULTS: Rats treated with DNBS displayed significant weight loss, diarrhea, fecal blood, colon shortening, a significant increase in immune cell infiltration and MPO activity, as well as increased proinflammatory cytokine expression. Intraperitoneal administration of ELv significantly reduced colon inflammation, whereas oral treatment proved to be ineffective. In fact, intraperitoneal ELv significantly attenuated the clinical manifestations of colitis, immune cell infiltration, MPO activity, and pro-inflammatory (CXCL-1, TNF-α, and IL-1ß) gene expression in a dose-dependent manner. CONCLUSION: Traditional medicine has employed ELv as a remedy for common infection-derived gastrointestinal symptoms; however, we hereby present the first published study validating its anti-inflammatory properties in the mitigation of DNBS-induced colitis.


Assuntos
Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Lepidium/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Colite/genética , Colite/fisiopatologia , Dinitrofluorbenzeno/análogos & derivados , Relação Dose-Resposta a Droga , Etanol/química , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/fisiopatologia , Medicina Tradicional , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar
12.
Molecules ; 27(3)2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35163986

RESUMO

Four new benzoylamide derivatives, lepidiumamide B-E (1-4), were isolated from the seeds of Lepidium apetalum Willd. The structures were determined by a combination of MS and NMR analyses. All compounds were evaluated for their protective effects against NRK-52e cell injury induced by lipopolysaccharide (LPS) in vitro. These compounds showed significantly protective activity and ameliorated LPS-induced NRK52e cells via the Nrf2/Keap1 pathway. The discovery of these active compounds is important for the prevention and treatment of renalinjury.


Assuntos
Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Rim/efeitos dos fármacos , Lepidium/química , Lipopolissacarídeos/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Fitoquímicos/farmacologia , Sementes/química , Animais , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Rim/metabolismo , Rim/patologia , Fator 2 Relacionado a NF-E2/genética , Extratos Vegetais/farmacologia
13.
Nutr Cancer ; 74(4): 1322-1337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34282687

RESUMO

The consumption of glucosinolate (GL)-rich foods, including Brassica vegetables, such as mustard, broccoli, and maca, is associated with decreased risk of developing cancer. The GL content in maca, which is recognized as a "superfood", is approximately 100-times higher than that in other brassicas. Although maca is a potential dietary source of GLs, limited studies have examined the bioactivity of maca GLs using the combination of chemical characterization and bioassays. In this study, the fractions (Lm-II and Lm-III) rich in intact GLs (glucotropaeolin and glucolimnanthin) were isolated and characterized from maca ethanolic extracts using chromatography and mass spectrometry. Additionally, the growth-inhibitory effects of Lm-II and Lm-II fractions against hepatocellular carcinoma (HepG2/C3A) and colon adenocarcinoma (HT29) cell lines were examined in the absence or presence of myrosinase (MYR). Fractions lacking low molecular weight sugars dose-dependently exerted cytotoxic effects in the presence of MYR. The half-maximal inhibitory concentration values of Lm-II and Lm-III against HepG2/C3A were 118.8 and 69.9 µg/mL, respectively, while those against HT29 were 102.6 and 71.5 µg/mL, respectively. These results suggest that the anticancer properties of maca can be attributed to GLs and corroborate the categorization of maca as a "superfood."Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1952444.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Lepidium , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Glucosinolatos/análise , Glucosinolatos/farmacologia , Glicosídeo Hidrolases , Humanos , Lepidium/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia
14.
Cells ; 10(11)2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34831102

RESUMO

Loss of myofibers during muscle atrophy affects functional capacity and quality of life. Dexamethasone, an inducer of rapid atrophy of skeletal myofibers, has been studied as a glucocorticoid receptor in muscle atrophy or motor neurodegeneration. In this study, we examined dexamethasone-induced muscle atrophy using zebrafish (Danio rerio), a vertebrate model, and assessed whether administration of Lepidium meyenii (maca) as a dietary supplement can prevent muscle atrophy. Changes in skeletal myofibers in zebrafish were evaluated after exposure to dexamethasone for different periods and at different concentrations. Under optimized conditions, zebrafish pre-fed with maca for 3 days were exposed to 0.01% dexamethasone for 1 h/day for 7 days. Thereafter, myofiber loss, damaged muscle contractile proteins, and abnormal exploratory behavior due to the structural and functional impairment of skeletal muscle associated with muscle atrophy were investigated using hematoxylin-eosin, immunofluorescence staining, and behavioral analyses. Our findings suggest that dexamethasone induces muscle atrophy in zebrafish, inhibiting exploratory behavior by inducing myofiber loss, inhibiting muscle contraction, and causing changes in endurance and velocity. Thus, the zebrafish model can be used to screen pharmaceutical agents and to study muscle atrophy. Furthermore, maca is a potential dietary supplement to prevent muscle atrophy, as it protects muscle fibers.


Assuntos
Dexametasona/efeitos adversos , Lepidium/química , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/prevenção & controle , Extratos Vegetais/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Proteínas Musculares/metabolismo , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Extratos Vegetais/farmacologia , Natação/fisiologia , Peixe-Zebra
15.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500622

RESUMO

Glucosinolates (GSLs) from Lepidium graminifolium L. were analyzed qualitatively and quantitatively by their desulfo-counterparts using UHPLC-DAD-MS/MS technique and by their volatile breakdown products-isothiocyanates (ITCs) using GC-MS analysis. Thirteen GSLs were identified with arylaliphatic as the major ones in the following order: 3-hydroxybenzyl GSL (glucolepigramin, 7), benzyl GSL (glucotropaeolin, 9), 3,4,5-trimethoxybenzyl GSL (11), 3-methoxybenzyl GSL (glucolimnanthin, 12), 4-hydroxy-3,5-dimethoxybenzyl GSL (3,5-dimethoxysinalbin, 8), 4-hydroxybenzyl GSL (glucosinalbin, 6), 3,4-dimethoxybenzyl GSL (10) and 2-phenylethyl GSL (gluconasturtiin, 13). GSL breakdown products obtained by hydrodistillation (HD) and CH2Cl2 extraction after hydrolysis by myrosinase for 24 h (EXT) as well as benzyl ITC were tested for their cytotoxic activity using MTT assay. Generally, EXT showed noticeable antiproliferative activity against human bladder cancer cell line UM-UC-3 and human glioblastoma cell line LN229, and can be considered as moderately active, while IC50 of benzyl ITC was 12.3 µg/mL, which can be considered as highly active.


Assuntos
Proliferação de Células/efeitos dos fármacos , Glucosinolatos/química , Glucosinolatos/farmacologia , Lepidium/química , Linhagem Celular Tumoral , Cromatografia Gasosa-Espectrometria de Massas/métodos , Glioblastoma/tratamento farmacológico , Humanos , Hidrólise , Isotiocianatos/química , Isotiocianatos/farmacologia , Espectrometria de Massas em Tandem/métodos , Tiocianatos/química , Tiocianatos/farmacologia , Tioglucosídeos/química , Tioglucosídeos/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico
16.
Molecules ; 26(16)2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34443522

RESUMO

Five new thiohydantoin derivatives (1-5) were isolated from the rhizomes of Lepidium meyenii Walp. NMR (1H and 13C NMR, 1H-1H COSY, HSQC, and HMBC), HRESIMS, and ECD were employed for the structure elucidation of new compounds. Significantly, the structure of compound 1 was the first example of thiohydantoins with thioxohexahydroimidazo [1,5-a] pyridine moiety. Additionally, compounds 2 and 3 possess rare disulfide bonds. Except for compound 4, all isolates were assessed for neuroprotective activities in corticosterone (CORT)-stimulated PC12 cell damage. Among them, compound (-)-3 exhibited moderate neuroprotective activity (cell viability: 68.63%, 20 µM) compared to the positive control desipramine (DIM) (cell viability: 88.49%, 10 µM).


Assuntos
Lepidium/química , Fármacos Neuroprotetores/química , Extratos Vegetais/química , Tioidantoínas/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Corticosterona/farmacologia , Desipramina/farmacologia , Humanos , Fármacos Neuroprotetores/farmacologia , Células PC12 , Extratos Vegetais/farmacologia , Piridinas/química , Ratos , Tioidantoínas/isolamento & purificação
17.
Int J Biol Macromol ; 189: 577-589, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34450149

RESUMO

Here, we fabricated amphiphilic polysaccharide micelles for synergistic cancer immunotherapy targeting tumor-associated macrophages (TAMs). Lepidium meyenii Walp. (maca) polysaccharide (MP), a naturally derived macromolecule with a strong TAM-remodeling effect, was grafted on a hydrophobic poly(lactic-co-glycolic acid) (PLGA) segment, with a disulfide bond for redox-sensitive linkage. The amphiphilic polysaccharide derivatives could self-assemble into core (PLGA)-shell (MP)-structured micelles and encapsulate chloroquine (CQ) into the hydrophobic core. By using a 4T1-M2 macrophage co-culture model and a 4T1 tumor xenograft mouse model, we showed that the prepared micelles could co-deliver MP and CQ to the tumor sites and selectively accumulate at TAMs because of the specific properties of MP. Furthermore, the nanoparticles exerted synergistic tumor immunotherapeutic and antimetastatic effects, which might be attributable to the enhanced cell internalization of the micelles and the multiple regulatory mechanisms of MP and CQ. Thus, immunomodulatory MP may be a promising biomaterial for cancer immunotherapy.


Assuntos
Cloroquina/farmacologia , Imunoterapia , Lepidium/química , Micelas , Nanopartículas/química , Neoplasias/terapia , Polissacarídeos/farmacologia , Macrófagos Associados a Tumor/patologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Polaridade Celular/efeitos dos fármacos , Cloroquina/administração & dosagem , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Neoplasias/imunologia , Neoplasias/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/síntese química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polissacarídeos/administração & dosagem , Células RAW 264.7 , Espectroscopia de Infravermelho com Transformada de Fourier , Microambiente Tumoral/efeitos dos fármacos , Macrófagos Associados a Tumor/efeitos dos fármacos
18.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202092

RESUMO

(1) Background: The COVID-19 pandemic lacks treatments; for this reason, the search for potential compounds against therapeutic targets is still necessary. Bioinformatics tools have allowed the rapid in silico screening of possible new metabolite candidates from natural resources or repurposing known ones. Thus, in this work, we aimed to select phytochemical candidates from Peruvian plants with antiviral potential against three therapeutical targets of SARS-CoV-2. (2) Methods: We applied in silico technics, such as virtual screening, molecular docking, molecular dynamics simulation, and MM/GBSA estimation. (3) Results: Rutin, a compound present in Peruvian native plants, showed affinity against three targets of SARS-CoV-2. The molecular dynamics simulation demonstrated the high stability of receptor-ligand systems during the time of the simulation. Our results showed that the Mpro-Rutin system exhibited higher binding free energy than PLpro-Rutin and N-Rutin systems through MM/GBSA analysis. (4) Conclusions: Our study provides insight on natural metabolites from Peruvian plants with therapeutical potential. We found Rutin as a potential candidate with multiple pharmacological properties against SARS-CoV-2.


Assuntos
Antivirais/química , Antivirais/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Plantas/química , Plantas/metabolismo , Asteraceae/química , Asteraceae/metabolismo , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/química , Proteínas do Nucleocapsídeo de Coronavírus/antagonistas & inibidores , Proteínas do Nucleocapsídeo de Coronavírus/química , Proteases Semelhantes à Papaína de Coronavírus/antagonistas & inibidores , Proteases Semelhantes à Papaína de Coronavírus/química , Bases de Dados Factuais , Humanos , Lepidium/química , Lepidium/metabolismo , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Peru , Fosfoproteínas/antagonistas & inibidores , Fosfoproteínas/química , Rutina/química , Rutina/farmacologia , SARS-CoV-2
19.
Fitoterapia ; 152: 104916, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33945874

RESUMO

Macamides are a class of bioactive amide alkaloids found only in maca (Lepidium meyenii). Recent studies have shown that macamide-rich extracts possess various biological activities, such as antioxidative, immune-enhancing, and reproductive health-improving activities. In the present study, N-benzyl docosahexaenamide (NB-DHA), a newly identified macamide with the highest degree of unsaturation among all identified macamides, was identified from the maca extract. Microalgae oil, a docosahexaenoic acid-rich substance, was used as the starting material for the synthesis of NB-DHA. The effects of NB-DHA in colitis-induced mice were evaluated. NB-DHA significantly alleviated weight loss, shortening of colon length, and occult blood occurrence in mice with dextran sulfate sodium-induced colitis. Histological analysis revealed that following the administration of NB-DHA in mice with colitis, the infiltration of inflammatory cells and levels of proinflammatory factors, such as tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and myeloperoxidase, decreased, whereas the level of the anti-inflammatory factor IL-10 increased. Furthermore, the decreased expression of intestinal tight junction proteins caused by colitis was upregulated by the administration of NB-DHA. These results indicate that NB-DHA could be developed as a therapeutic agent for ulcerative colitis.


Assuntos
Alcaloides/farmacologia , Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Lepidium/química , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , China , Colite/induzido quimicamente , Sulfato de Dextrana , Modelos Animais de Doenças , Frutas/química , Mucosa Intestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química
20.
Bioorg Chem ; 112: 104834, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33813309

RESUMO

Nine new pyrrole alkaloids, including two undescribed dimeric pyrrole 2­carbaldehyde alkaloids, lepipyrrolins A-B (1-2), seven pyrrole-alkaloid derivatives, macapyrrolins D-J (3-9), along with three known ones (10-12) were isolated from the rhizomes of Lepidium meyenii. Their structures and absolute configurations were demonstrated by extensive spectroscopic data (1D, 2D NMR, HRESIMS), and calculated electronic circular dichroism (ECD) experiment. Compounds 1, 3-12 were tested for their nitric oxide inhibitory effects. Furthermore, compound 1 was evaluated for its cytotoxic activity against five human tumor cell lines (HL-60, SMMC-7221, A549, MCF-7, and SW480) in vitro, and displayed selective cytotoxicity against SMMC-7721 with IC50 value of 16.78 ± 0.49 µM.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Lepidium/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-Atividade
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