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1.
PLoS One ; 16(9): e0255198, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34547020

RESUMO

Disruption of lipolysis has widespread effects on intermediary metabolism and organismal phenotypes. Defects in lipolysis can be modeled in Drosophila melanogaster through genetic manipulations of brummer (bmm), which encodes a triglyceride lipase orthologous to mammalian Adipose Triglyceride Lipase. RNAi-mediated knock-down of bmm in all tissues or metabolic specific tissues results in reduced locomotor activity, altered sleep patterns and reduced lifespan. Metabolomic analysis on flies in which bmm is downregulated reveals a marked reduction in medium chain fatty acids, long chain saturated fatty acids and long chain monounsaturated and polyunsaturated fatty acids, and an increase in diacylglycerol levels. Elevated carbohydrate metabolites and tricarboxylic acid intermediates indicate that impairment of fatty acid mobilization as an energy source may result in upregulation of compensatory carbohydrate catabolism. bmm downregulation also results in elevated levels of serotonin and dopamine neurotransmitters, possibly accounting for the impairment of locomotor activity and sleep patterns. Physiological phenotypes and metabolomic changes upon reduction of bmm expression show extensive sexual dimorphism. Altered metabolic states in the Drosophila model are relevant for understanding human metabolic disorders, since pathways of intermediary metabolism are conserved across phyla.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiologia , Lipase/metabolismo , Locomoção , Metaboloma , Neurotransmissores/metabolismo , Sono/fisiologia , Animais , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/genética , Feminino , Lipase/antagonistas & inibidores , Lipase/genética , Longevidade , Masculino , Interferência de RNA , Caracteres Sexuais
2.
Int J Mol Sci ; 22(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34576044

RESUMO

α,ß-amyrenone (ABAME) is a triterpene derivative with many biological activities; however, its potential pharmacological use is hindered by its low solubility in water. In this context, the present work aimed to develop inclusion complexes (ICs) of ABAME with γ- and ß-cyclodextrins (CD), which were systematically characterized through molecular modeling studies as well as FTIR, XRD, DSC, TGA, and SEM analyses. In vitro analyses of lipase activity were performed to evaluate possible anti-obesity properties. Molecular modeling studies indicated that the CD:ABAME ICs prepared at a 2:1 molar ratio would be more stable to the complexation process than those prepared at a 1:1 molar ratio. The physicochemical characterization showed strong evidence that corroborates with the in silico results, and the formation of ICs with CD was capable of inducing changes in ABAME physicochemical properties. ICs was shown to be a stronger inhibitor of lipase activity than Orlistat and to potentiate the inhibitory effects of ABAME on porcine pancreatic enzymes. In conclusion, a new pharmaceutical preparation with potentially improved physicochemical characteristics and inhibitory activity toward lipases was developed in this study, which could prove to be a promising ingredient for future formulations.


Assuntos
Inibidores Enzimáticos/farmacologia , Lipase/antagonistas & inibidores , Triterpenos/farmacologia , beta-Ciclodextrinas/farmacologia , Animais , Varredura Diferencial de Calorimetria , Simulação por Computador , Inibidores Enzimáticos/química , Lipase/química , Orlistate/farmacologia , Solubilidade/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Suínos , Triterpenos/síntese química , Triterpenos/química , Difração de Raios X , beta-Ciclodextrinas/química
3.
Biomed Res Int ; 2021: 5577498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337029

RESUMO

Postmenopausal women express great failure in their ovarian hormone production, especially estrogen. This deficiency may promote hypercholesterolemia and accelerate the redox imbalance. The present study was designed to evaluate the protective effect of Avena sativa against estrogen deficiency-induced liver and uterus oxidative injury in experimental ovariectomized mice. Female mice were randomly divided into five groups: group one (negative control) received normal diet and distilled water (C), group two (positive control) received daily enriched diet with oat grains and was kept on tap distilled water at a dose of 200 mg kg-1 d-1 (A), group three (ovariectomized mice) was nontreated fed with normal diet (O), group four includes ovariectomized mice treated daily with estradiol given by intraperitoneal injection at a dose of 100 µg kg-1 d-1 (OE), and the fifth group also includes ovariectomized mice which received enriched diet with oat grain parts with the same dose given to group two. The treatment period lasted two consecutive months. Both oat and hormonal treatments of ovariectomized groups resulted in a significant reduction in triglycerides and total cholesterol and increased high-density lipoprotein (HDL) levels in the plasma after 21 and 60 days of treatment. Besides, the coadministration of A. sativa has decreased the activities of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) and increased transaminase activities after 21 and 60 days of treatment. On the other hand, this cereal has restored the enzymatic (SOD, CAT, and GPx) and nonenzymatic antioxidant activities (GSH) as well as the elevated thiobarbituric acid reactive substances (AOPP and PCO) to near-normal values. The beneficial effects of this cereal were confirmed by a histological study of the liver and uterus of all previous cited groups. Our finding emphasized the antioxidant and antilipidemic effect of oat grain part, suggesting the use of this cereal in the prevention of liver and uterus diseases that occurred in postmenopausal women.


Assuntos
Avena/química , Fígado/patologia , Ovariectomia , Estresse Oxidativo , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/farmacologia , Biomarcadores/sangue , Inibidores Enzimáticos/farmacologia , Etanol/química , Feminino , Lipase/antagonistas & inibidores , Lipase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Carbonilação Proteica , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Útero/efeitos dos fármacos , Útero/patologia
4.
Molecules ; 26(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34279385

RESUMO

This work aimed to evaluate the phenolic content and in vitro antioxidant, antimicrobial and enzyme inhibitory activities of the methanol extracts and their fractions of two edible halophytic Limonium species, L. effusum (LE) and L. sinuatum (LS). The total phenolic content resulted about two-fold higher in the ethyl acetate fraction of LE (522.82 ± 5.67 mg GAE/g extract) than in that of LS (274.87 ± 1.87 mg GAE/g extract). LC-MS/MS analysis indicated that tannic acid was the most abundant phenolic acid in both species (71,439.56 ± 3643.3 µg/g extract in LE and 105,453.5 ± 5328.1 µg/g extract in LS), whereas hyperoside was the most abundant flavonoid (14,006.90 ± 686.1 µg/g extract in LE and 1708.51 ± 83.6 µg/g extract in LS). The antioxidant capacity was evaluated by DPPH and TAC assays, and the stronger antioxidant activity in ethyl acetate fractions was highlighted. Both species were more active against Gram-positive bacteria than Gram negatives and showed considerable growth inhibitions against tested fungi. Interestingly, selective acetylcholinesterase (AChE) activity was observed with LE and LS. Particularly, the water fraction of LS strongly inhibited AChE (IC50 = 0.199 ± 0.009 µg/mL). The ethyl acetate fractions of LE and LS, as well as the n-hexane fraction of LE, exhibited significant antityrosinase activity (IC50 = 245.56 ± 3.6, 295.18 ± 10.57 and 148.27 ± 3.33 µg/mL, respectively). The ethyl acetate fraction and methanol extract of LS also significantly inhibited pancreatic lipase (IC50 = 83.76 ± 4.19 and 162.2 ± 7.29 µg/mL, respectively). Taken together, these findings warrant further investigations to assess the potential of LE and LS as a bioactive source that can be exploited in pharmaceutical, cosmetics and food industries.


Assuntos
Compostos Fitoquímicos/química , Extratos Vegetais/química , Plumbaginaceae/química , Polifenóis/análise , Acetilcolinesterase/metabolismo , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Proteínas de Peixes/antagonistas & inibidores , Proteínas de Peixes/metabolismo , Lipase/antagonistas & inibidores , Monofenol Mono-Oxigenase/antagonistas & inibidores , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia
5.
Molecules ; 26(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206066

RESUMO

The phytochemical composition of leaves, stems, pericarps and rhizomes ethanolic extracts of Asparagus acutifolius were characterized by HPLC-DAD-MS. A. acutifolius samples contain at least eleven simple phenolics, one flavonon, two flavonols and six steroidal saponins. The stem extracts showed the highest total phenolic acid and flavonoid contents, where cafeic acid and rutin were the main compounds. No flavonoids were detected in the leaf, pericarp or rhizome while caffeic acid and ferulic acid were the predominant. Steroidal saponins were detected in the different plant parts of A. acutifolius, and the highest contents were found in the rhizome extracts. The stem extracts exhibited the highest antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) and the highest 2,2-azino-bis (3 ethylbenzothiazoline-6-sulphonic acid) (ABTS) scavenging activity was found in the pericarp extracts. The rhizome and leaf extracts showed a potent cytotoxic activity against HCT-116 and HepG2 cell lines. Moreover, the pericarp and rhizome extracts revealed a moderate lipase inhibitory activity. The leaf and rhizome extracts were screened for their antimicrobial activity against human pathogenic isolates. The leaf extract exhibited a powerful inhibitory activity against all the bacteria and fungi tested.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Asparagus (Planta)/química , Lipase/antagonistas & inibidores , Compostos Fitoquímicos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Células HCT116 , Células Hep G2 , Humanos , Espectrometria de Massas , Especificidade de Órgãos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Folhas de Planta/química , Caules de Planta/química , Rizoma/química
6.
Molecules ; 26(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34299456

RESUMO

The inhibition of certain digestive enzymes by target food matrices represents a new approach in the treatment of socially significant diseases. Proving the ability of fruits to inhibit such enzymes can support the inclusion of specific varieties in the daily diets of patients with diabetes, obesity, Alzheimer's disease, etc., providing them with much more than just valuable micro- and macromolecules. The current study aimed atidentifying and comparing the GC-MS metabolic profiles of eight peach varieties ("Filina", "Ufo 4, "Gergana", "Laskava", "July Lady", "Flat Queen", "Evmolpiya", and "Morsiani 90") grown in Bulgaria (local and introduced) and to evaluate the inhibitory potential of their extracts towards α-glucosidase, α-amylase, lipase, and acetylcholinesterase. In order to confirm samples' differences or similarities, principal component analysis (PCA) and hierarchical cluster analysis (HCA) were also applied to the identified metabolites. The results provide important insights into the metabolomic profiles of the eight peach varieties and represent a first attempt to characterize the peels of the peach varieties with respect to α-glucosidase-, α-amylase-, lipase-, and acetylcholinesterase-inhibitory activities. All of the studied peach extracts displayed inhibitory activity towards α-glucosidase (IC50: 125-757 mg/mL) and acetylcholinesterase (IC50: 60-739 mg/mL), but none of them affected α-amylase activity. Five of the eight varieties showed inhibitory activity towards porcine pancreatic lipase (IC50: 24-167 mg/mL). The obtained results validate the usefulness of peaches and nectarines as valuable sources of natural agents beneficial for human health, although further detailed investigation should be performed in order to thoroughly identify the enzyme inhibitors responsible for each activity.


Assuntos
Extratos Vegetais/farmacologia , Prunus persica/metabolismo , Acetilcolinesterase/metabolismo , Amilases/metabolismo , Antioxidantes/farmacologia , Bulgária , Inibidores da Colinesterase/farmacologia , Inibidores Enzimáticos/farmacologia , Frutas/química , Frutas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Inibidores de Glicosídeo Hidrolases/farmacologia , Lipase/antagonistas & inibidores , Lipase/metabolismo , Metaboloma , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Prunus persica/química , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
7.
Food Funct ; 12(12): 5650-5657, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34018495

RESUMO

Chalcones, a class of natural lipase inhibitors, have received substantial attention from researchers in recent years. Although many kinds of chalcones are typically distributed in G. inflata, there is little literature about the anti-lipase activity of G. inflata extracts (GIEs). In the present study, a ligand fishing strategy for fast screening of lipase inhibitors from GIEs was thus proposed. Porcine pancreatic lipase (PPL) was firstly immobilized on carboxyl modified Fe3O4 magnetic nanoparticles (MNPs) to obtain PPL functionalized MNPs (PPL@MNPs), and then the PPL@MNPs were incubated with a bioactive fraction to fish out the ligands. Eight ligands were obtained and identified as one flavone together with seven chalcones. Licochalcone A, licochalcone D and licochalcone E inhibited pancreatic lipase (PL) with IC50 of 4.9, 3.2 and 5.8 µM, respectively. Meanwhile, investigation of the structure-activity relationship also revealed that isopentenyl and hydroxyl substituents at ring A were essential for the noncovalent inhibitory potency of the chalcones.


Assuntos
Enzimas Imobilizadas/química , Glycyrrhiza/química , Lipase/antagonistas & inibidores , Nanopartículas de Magnetita/química , Extratos Vegetais/farmacologia , Animais , Chalconas , Ligantes , Simulação de Acoplamento Molecular , Suínos
8.
Biosci Biotechnol Biochem ; 85(8): 1885-1889, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34048530

RESUMO

Young barley leaves (Hordeum vulgare L.) have various health effects and are employed as an ingredient in the production of health-promoting foods. Promoting antiobesity is one such health effect; however, the mechanism and bioactive compounds are unclear. In this research, young barley leaf extract (YB) was demonstrated to possess pancreatic lipase inhibitory activity. The addition of YB to a high-fat diet in mice increased fecal lipid content, indicating reduced absorption of lipids as the mechanism underlying antiobesity effect. The investigation of bioactive compounds in YB resulted in the identification of fructose-bisphosphate aldolase as a proteinous lipase inhibitor. Maximum inhibition of the protein was 45%, but inhibition was displayed at a concentration as low as 16 ng/mL, which is a characteristic inhibition compared with other reported proteinous lipase inhibitors.


Assuntos
Fármacos Antiobesidade/farmacologia , Inibidores Enzimáticos/farmacologia , Hordeum/química , Lipase/antagonistas & inibidores , Pâncreas/enzimologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Dieta Hiperlipídica , Masculino , Camundongos , Camundongos Endogâmicos BALB C
9.
Biophys Chem ; 274: 106607, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33957576

RESUMO

Obesity is a global health problem characterized by excessive fat deposition in adipose tissues and can be managed by targeting pancreatic lipase (PL) activity. In the present study, we investigated the in vitro antioxidant and anti-obesity potentials of methanolic leaf extract of Justicia carnea(MEJC) using lipase inhibition kinetics model. In silico evaluations of MEJC bioactive compounds as potential drug-like agents and inhibitors of PL were also investigated using SwissADME prediction tool, semi-empirical quantum mechanics(SQM), molecular electrostatic potential(MEP) and molecular docking analysis. Gas chromatography-mass spectrometry(GC-MS) revealed presence of campesterol, stigmasterol, beta-amyrin etc. MEJC scavenged reactive species and inhibited PL activity via a mixed inhibition pattern (Ki = 107.69 µg/mL; Kii = 398.00 µg/mL) with IC50 > orlistat's IC50. Molecular docking of GC-MS identified compounds with porcine PL showed compounds 8,10,12 and 14 having high PL-binding affinity and similar binding pose with orlistat. Hydrophobic interactions and van der Waals forces were predominantly involved in the ligands' interactions with some key catalytic site amino acid residues (Ser-153,His-264). Compounds 10,12,13 and 14 indicated high drug-likeness, bioavailability, electronegativity, ELUMO-EHOMO energy gaps and MEP. Our findings show that MEJC is a rich natural source of antioxidant and anti-obesity agents which could be optimized for development of new anti-obesity drugs.


Assuntos
Fármacos Antiobesidade/farmacologia , Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Lipase/antagonistas & inibidores , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Justicia, Planta/química , Cinética , Lipase/metabolismo , Simulação de Acoplamento Molecular , Obesidade/metabolismo , Picratos/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Teoria Quântica
10.
Molecules ; 26(7)2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33916551

RESUMO

Vaccinium dunalianum Wight, usually processed as a traditional folk tea beverage, is widely distributed in the southwest of China. The present study aimed to investigate the antioxidant, α-glucosidase and pancreatic lipase inhibitory activities of V.dunalianum extract and isolate the bioactive components. In this study, the crude extract (CE) from the buds of V. dunalianum was prepared by the ultrasound-assisted extraction method in 70% methanol and then purified with macroporous resin D101 to obtain the purified extract (PM). Five fractions (Fr. A-E) were further obtained by MPLC column (RP-C18). Bioactivity assays revealed that Fr. B with 40% methanol and Fr. D with 80% methanol had better antioxidant with 0.48 ± 0.03 and 0.62 ± 0.01 nM Trolox equivalent (TE)/mg extract for DPPH, 0.87 ± 0.02 and 1.58 ± 0.02 nM TE/mg extract for FRAP, 14.42 ± 0.41 and 19.25 ± 0.23 nM TE/mg extract for ABTS, and enzyme inhibitory effects with IC50 values of 95.21 ± 2.21 and 74.55 ± 3.85 for α-glucosidase, and 142.53 ± 11.45 and 128.76 ± 13.85 µg/mL for pancreatic lipase. Multivariate analysis indicated that the TPC and TFC were positively related to the antioxidant activities. Further phytochemical purification led to the isolation of ten compounds (1-10). 6-O-Caffeoylarbutin (7) showed significant inhibitory effects on α-glucosidase and pancreatic lipase enzymes with values of 38.38 ± 1.84 and 97.56 ± 7.53 µg/mL, and had the highest antioxidant capacity compared to the other compounds.


Assuntos
Antioxidantes/isolamento & purificação , Arbutina/análogos & derivados , Ácidos Cafeicos/isolamento & purificação , Flavonoides/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Lipase/química , Vaccinium/química , alfa-Glucosidases/química , Antioxidantes/química , Arbutina/química , Arbutina/isolamento & purificação , Benzotiazóis/antagonistas & inibidores , Benzotiazóis/química , Compostos de Bifenilo/química , Ácidos Cafeicos/química , Flavonoides/química , Inibidores de Glicosídeo Hidrolases/química , Lipase/antagonistas & inibidores , Lipase/metabolismo , Extração Líquido-Líquido/métodos , Metanol/química , Picratos/química , Extratos Vegetais/química , Folhas de Planta/química , Solventes/química , Sonicação , Ácidos Sulfônicos/antagonistas & inibidores , Ácidos Sulfônicos/química , alfa-Glucosidases/metabolismo
11.
Mar Drugs ; 19(3)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803803

RESUMO

Obesity is a complex metabolic disease, which is increasing worldwide. The reduction of dietary lipid intake is considered an interesting pathway to reduce fat absorption and to affect the chronic energy imbalance. In this study, zebrafish larvae were used to analyze effects of cyanobacteria on intestinal lipid absorption in vivo. In total, 263 fractions of a cyanobacterial library were screened for PED6 activity, a fluorescent reporter of intestinal lipases, and 11 fractions reduced PED6 activity > 30%. Toxicity was not observed for those fractions, considering mortality, malformations or digestive physiology (protease inhibition). Intestinal long-chain fatty acid uptake (C16) was reduced, but not short-chain fatty acid uptake (C5). Alteration of lipid classes by high-performance thin-layer chromatography (HPTLC) or lipid processing by fluorescent HPTLC was analyzed, and 2 fractions significantly reduced the whole-body triglyceride level. Bioactivity-guided feature-based molecular networking of LC-MS/MS data identified 14 significant bioactive mass peaks (p < 0.01, correlation > 0.95), which consisted of 3 known putative and 11 unknown compounds. All putatively identified compounds were known to be involved in lipid metabolism and obesity. Summarizing, some cyanobacterial strains repressed intestinal lipid absorption without any signs of toxicity and could be developed in the future as nutraceuticals to combat obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Cianobactérias/metabolismo , Inibidores Enzimáticos/farmacologia , Absorção Intestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Lipase/antagonistas & inibidores , Metabolismo dos Lipídeos/efeitos dos fármacos , Proteínas de Peixe-Zebra/antagonistas & inibidores , Peixe-Zebra/metabolismo , Animais , Fármacos Antiobesidade/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Intestinos/enzimologia , Lipase/metabolismo , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/metabolismo
12.
Food Funct ; 12(6): 2644-2659, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33645616

RESUMO

The purpose of this study was to perform a parallel and comparative investigation of the effects of a Myrciaria jaboticaba (common name jabuticaba) peel extract and of its constituent cyanidin-3-O-glucoside on the overall process of starch and triglyceride intestinal absorption. The peel extract inhibited both the porcine pancreactic α-amylase and the pancreatic lipase but was 13.6 times more potent on the latter (IC50 values of 1963 and 143.9 µg mL-1, respectively). Cyanidin-3-O-glucoside did not contribute significantly to these inhibitions. The jabuticaba peel extract inhibited starch absorption in mice at doses that were compatible with its inhibitory action on the α-amylase. No inhibition of starch absorption was found with cyanidin-3-O-glucoside doses compatible with its content in the extract. The extract also inhibited triglyceride absorption, but at doses that were considerably smaller than those predicted by its strength in inhibiting the pancreatic lipase (ID50 = 3.65 mg kg-1). In this case, cyanidin-3-O-glucoside was also strongly inhibitory, with 72% inhibition at the dose of 2 mg kg-1. When oleate + glycerol were given to mice, both the peel extract and cyanidin-3-O-glucoside strongly inhibited the appearance of triglycerides in the plasma. The main mechanism seems, thus, not to be the lipase inhibition but rather the inhibition of one or more steps (e.g., transport) in the events that lead to the transformation of free fatty acids in the intestinal tract into triglycerides. Due to the low active doses, the jabuticaba peel extract presents many favourable perspectives as an inhibitor of fat absorption and cyanidin-3-O-glucoside seems to play a decisive role.


Assuntos
Antocianinas/farmacologia , Myrtaceae/química , Extratos Vegetais/farmacologia , Amido/metabolismo , Triglicerídeos/metabolismo , Animais , Antocianinas/química , Frutas/química , Inibidores de Glicosídeo Hidrolases , Lipase/antagonistas & inibidores , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Extratos Vegetais/química , Amido/química , Suínos , Triglicerídeos/sangue , Triglicerídeos/química
13.
Artigo em Inglês | MEDLINE | ID: mdl-33713950

RESUMO

Lipase inhibitors are an attractive class of hypolipidemic compounds, which inhibit the activity of human pancreatic lipase, thereby preventing the absorption of triglycerides in vivo. As a library of promising lead compounds for drug development, traditional Chinese medicine (TCM) has gained growing attention in quick discovery and identification of enzyme inhibitors of natural-origin. The purpose of this work was to discover unknown lipase inhibitors from Alisma orientale by the activity oriented analysis method thin-layer chromatography-bioautography, then use electrospray ionization mass spectrometry technology via the elution based TLC-MS interface to identify their structures. As a result, eleven natural lipase inhibitors from Alisma orientale extracts were identified based on molecular mass and fragment ions obtained by HPTLC-MS, and further confirmed by a series of complementary means including UV spectra, 1H NMR characteristic proton signals and polarity of compounds, eleven lipase inhibitors were tentatively assigned as triterpenoids: alisol B (m/z 495.50 [M + Na]+), alisol B 23-acetate (m/z 537.58 [M + Na]+), 11-deoxy-alisol B (m/z 479.50 [M + Na]+), 11-deoxy-alisol B 23-acetate (m/z 521.50 [M + Na]+), alisol A/epialisol A (m/z 513.50 [M + Na]+), 16-oxo-11-deoxy-alisol A (m/z 511.50 [M + Na]+), 16-oxo-alisol A (527.50 [M + Na] +), alisol C (m/z 509.58 [M + Na]+), alisol C 23-acetate (m/z 551.50 [M + Na]+), alisol M 23-acetate (m/z 567.50 [M + Na]+), and alismanol Q/neoalisol (m/z 493.42 [M + Na]+). The integrated approach is an efficient method for rapid screening lipase inhibitors from complex plant extracts and provides a reasonable and favorable basis for the identification and separation of other enzymatic system and other important compounds with therapeutic values.


Assuntos
Alisma/química , Cromatografia em Camada Delgada/métodos , Inibidores Enzimáticos , Lipase/antagonistas & inibidores , Espectrometria de Massas/métodos , Extratos Vegetais/química , Colestenonas/análise , Colestenonas/química , Colestenonas/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/análise , Inibidores Enzimáticos/química , Triterpenos/análise , Triterpenos/química , Triterpenos/isolamento & purificação
14.
Bioorg Chem ; 110: 104783, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33714021

RESUMO

Paeonone A (1), a unique nonanortriterpenoid, and a new octanortriterpenoid, paeonone B (2), were isolated from the roots of Paeonia lactiflora, together with a known analogue, palbinone (3). Paeonone A (1) is the first example of naturally occurring nonanortriterpenoid with a diketo acid group. Extensive NMR and HRESIMS experiments were applied to identify the structures of 1 and 2, and their absolute configurations were solved by single-crystal X-ray diffraction and ECD data. Biological properties of 1-3 were explored against pancreatic lipase and cancer cell lines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Inibidores Enzimáticos/farmacologia , Lipase/antagonistas & inibidores , Paeonia/química , Raízes de Plantas/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Lipase/metabolismo , Estrutura Molecular , Pâncreas/enzimologia , Relação Estrutura-Atividade
15.
Carbohydr Polym ; 260: 117839, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33712174

RESUMO

The efficacy and mode of action of biodegradable chitosan (CS) and carboxymethyl chitosan (CMCS) organic polymer nanoparticles (NPs) on insects were studied. The prepared CS/CMCS-NPs were spherical with a particle size of 142.1 ± 2.0 nm. The swelling test showed that they were pH-sensitive, and the swelling rate was 554 % at pH 4.5. It was found that CS/CMCS-NPs had insecticidal efficacy against red fire ants (S. invicta). The mortality of red fire ants on the 6th day after treatment with 0.2 % and 0.06 % CS/CMCS-NPs suspensions was 98.33 ± 1.67 % and 48.33 ± 3.33 %, respectively. After CS/CMCS-NPs treatment, the food intake, growth, and development of red fire ants were inhibited; the midgut was significantly expanded; and the activity of digestive enzymes in the midgut was decreased. Our findings suggest that CS/CMCS-NPs mainly inhibited the digestion function of the midgut, leading to the death of red fire ants.


Assuntos
Quitosana/análogos & derivados , Quitosana/química , Inseticidas/química , Nanopartículas/química , Animais , Formigas/efeitos dos fármacos , Formigas/fisiologia , Peso Corporal/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Lipase/antagonistas & inibidores , Lipase/metabolismo , Nanopartículas/toxicidade , Peptídeo Hidrolases/química , Peptídeo Hidrolases/metabolismo
16.
Eur J Med Chem ; 216: 113358, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33725656

RESUMO

Pancreatic triglyceride lipase (PTL) and Niemann-Pick C1-like 1 (NPC1L1) have been identified as attractive therapeutic targets for obesity and hypercholesteremia, respectively. Obesity and hypercholesteremia usually co-exist, however no dual-inhibitors against PTL and NPC1L1 were reported for the treatment of obesity patients with hypercholesteremia so far. In this work, molecular hybridization-based one-step modification screening identified a potent dual-inhibitor against PTL and NPC1L1. Compound P1-11 has IC50 values of 2.1 µM against PTL through covalent binding, as well as significantly reduces cholesterol absorption in a non-competitive inhibitory manner. Molecule docking and molecular dynamics studies revealed the reason of its activity to both PTL and NPC1L1. Moreover, the gene and protein expression levels of PTL and NPC1L1 were also determined respectively after the treatment of P1-11. Development of dual-inhibitors against PTL and NPC1L1 could provide novel treatment options for obesity patients with hypercholesteremia. The results of current research would great support the development of dual-inhibitors against PTL and NPC1L1.


Assuntos
Anticolesterolemiantes/química , Lipase/antagonistas & inibidores , Proteínas de Membrana Transportadoras/metabolismo , Pâncreas/enzimologia , Anticolesterolemiantes/metabolismo , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Sítios de Ligação , Linhagem Celular Tumoral , Desenho de Fármacos , Ezetimiba/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/patologia , Lipase/metabolismo , Proteínas de Membrana Transportadoras/sangue , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Orlistate/química
17.
Food Chem ; 355: 129414, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773461

RESUMO

A screening of inhibitory activity of α-amylase, as well as pancreatic lipase (PL), under the influence of aqueous and ethanolic preparations from 12 plant materials was performed. The most active aqueous extracts from the fruits of Chaenomeles japonica (CJ) and Hippophaë rhamnoides (HR) were selected for artificial gastrointestinal digestion (GID). The aim of this study was to evaluate the inhibitory effect of the fractions obtained after GID on PL and α-amylase activities using a fluorescence assay. The changes in the composition of crude extracts in GID aliquots were followed by analysis with HPLC-DAD-MSn method in order to indicate active constituents. The main constituents of CJ and HR extracts were procyanidins and isorhamnetin derivatives, respectively. The most abundant compounds of extracts were found in all compartments of the digestion model correlated with relevant lipase/α-amylase inhibitory activity. What is more, the gastric and intestinal fractions inhibited enzymatic activity by at least 40%.


Assuntos
Hippophae/química , Lipase/antagonistas & inibidores , Extratos Vegetais/química , Rosaceae/química , alfa-Amilases/antagonistas & inibidores , Cromatografia Líquida de Alta Pressão , Digestão , Frutas/química , Frutas/metabolismo , Hippophae/metabolismo , Humanos , Lipase/metabolismo , Espectrometria de Massas , Extratos Vegetais/análise , Extratos Vegetais/metabolismo , Proantocianidinas/análise , Proantocianidinas/química , Proantocianidinas/metabolismo , Rosaceae/metabolismo , alfa-Amilases/metabolismo
18.
Int J Biol Macromol ; 175: 270-280, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33561462

RESUMO

The burden of obesity is increasing all over the world. Except for Orlistat, no effective anti-obesity drug is currently available. Therefore, a search for the new anti-obesity compound is need of time. This study demonstrates macromolecular interaction and inhibitory effect of pentacyclic triterpenoids (PTT) on pancreatic lipase (PL). In the present study PTTs from endophytic Colletotrichum gigasporum were found to show significant inhibitory activity against PL with IC50 of 16.62 ± 1.43 µg/mL. The PTT isolated through bioassay-guided isolation showed a dose-dependent (R2 = 0.915) inhibition against porcine PL and the results were comparable with the standard (Orlistat). Based on inhibition kinetic data, the gradual increase in Km (app) with increasing PTT concentration indicated that the mode of interaction of PTT with PL was a competitive type, and it directly competed with the substrate (pNPB) for the active site of PL. In vivo studies in Wistar rats at the oral dose (100 mg/kg body weight) of PTT significantly decreased (p < 0.05) incremental plasma triglyceride levels as compared to group B and TG absorption was down-regulated up to 49.18% vis a vis group D animals. The isolated PTT was identified as lupeol based on chromatographic and spectral data. The endophytic isolate was identified as Colletotrichum gigasporum based on morphology and ITS gene sequencing. The present study indicated that PTT had the potential to be used as a natural PL inhibitor in the treatment of obesity and the isolated endophyte can be a valuable bioresource for it.


Assuntos
Colletotrichum/metabolismo , Lipase/antagonistas & inibidores , Triterpenos Pentacíclicos/farmacologia , Animais , Fármacos Antiobesidade/farmacologia , Domínio Catalítico , Endófitos , Inibidores Enzimáticos/farmacologia , Humanos , Concentração Inibidora 50 , Cinética , Lipase/química , Lipase/metabolismo , Masculino , Estrutura Molecular , Obesidade/tratamento farmacológico , Orlistate/farmacologia , Pâncreas/metabolismo , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/metabolismo , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Suínos , Triterpenos/farmacologia
19.
Food Chem ; 348: 129087, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33516997

RESUMO

The present study was aimed to evaluate the functional efficacy of plant extracts as a source of pancreatic lipase inhibitor and antioxidant in goat meat nuggets to address the fat paradox issue of red meat. The PPLIA, antioxidant potential, and resistance against fat digestion were in the order ofPhyllanthus emblica > Eucalyptus globulus > Tinospora cordifolia.PPL inhibition activities of water and ethanolic extracts fromPhyllanthus emblicausing DNPB and Triolein as substrate were 63.76, 67.94 and 56.17 and 64.36 percent respectively whereas, TPC, DPPH RSA, FRPA were 40.82 and 59.52 (mgGAE/g), 54.89 and 59.84 (percent), 1.26 and 1.61 (OD) respectively. The average diameter of fat globules in digest was maximum (8.91 µm) withPhyllanthus emblicafruits extracts whereas; TBARs (0.347 mg MDA/Kg) and FFA (4.47 µg/g) values were lowest. This study showed that extracts from plants can act as a promising natural alternative in the development of healthy meat products.


Assuntos
Antioxidantes/análise , Eucalyptus/química , Lipase/antagonistas & inibidores , Phyllanthus emblica/química , Extratos Vegetais/análise , Carne Vermelha/análise , Tinospora/química , Animais , Antioxidantes/farmacologia , Cabras , Pâncreas/enzimologia , Extratos Vegetais/farmacologia
20.
Life Sci ; 271: 119115, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33515565

RESUMO

Human pancreatic lipase (triacylglycerol acyl hydrolase EC3.1.1.3) is the most widely studied member of the human lipase superfamily related to carboxyl esterase. It is secreted from the acinar cell of pancreas and has strong preference for triacylglycerides over cholesterol esters, phospholipids, and galactolipids. Apart from the hydrolysis of triacylglycerides, pancreatic lipase may cause the hydrolysis of retinyl esters in vivo. So, it is very much evidenced that pancreatic lipase with its cofactor colipase has prominent role in efficient digestion of dietary fat. Hence, the modulation of human pancreatic lipase may represent a new insight in the discovery of a number of therapeutics that can inhibit the absorption of fat in body and can be used in obesity and other related metabolic disorders. Even, the only Food and drug administration (FDA) approved antiobesity drug, orlistat, is also an inhibitor of pancreatic lipase. This review summarizes studies about structure, mechanistic approach of pancreatic lipase enzyme while emphasizing on the various synthetic pancreatic lipase inhibitors with their structure activity relationship (SAR).


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Lipase/antagonistas & inibidores , Lipase/química , Pâncreas/enzimologia , Animais , Fármacos Antiobesidade/farmacologia , Gorduras na Dieta/antagonistas & inibidores , Gorduras na Dieta/metabolismo , Humanos , Lipase/metabolismo , Pâncreas/efeitos dos fármacos , Estrutura Secundária de Proteína , Relação Estrutura-Atividade
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