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1.
J Agric Food Chem ; 69(37): 10856-10868, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34493038

RESUMO

The characterization and quantification of phenolic compounds in bearberry leaves were performed using hyphenated ion mobility spectroscopy (IMS) and a quadrupole time-of-flight mass spectrometer. A higher identification confidence level was obtained by comparing the measured collision cross section (TWCCSN2) with predicted values using a machine learning algorithm. A total of 88 compounds were identified, including 14 arbutin derivatives, 33 hydrolyzable tannins, 6 flavanols, 26 flavonols, 9 saccharide derivatives, and glycosidic compounds. Those most reliably reproduced in all samples were quantified against respective standards. Arbutin (47-107 mg/g), 1,2,3,4,6-pentagalloylglucose (6.6-12.9 mg/g), and quercetin 3-galactoside/quercetin 3-glucoside (2.7-5.7 mg/g) were the most abundant phenolic components in the leaves. Quinic acid and ellagic acid were also detected at relatively high concentrations. The antioxidant activity of the most abundant compounds was evaluated. A critical view of the advantages and limitations of traveling wave IMS and CCS for the discovery of natural products is given.


Assuntos
Arctostaphylos , Arbutina , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Espectrometria de Massas , Folhas de Planta
2.
Biochem Biophys Res Commun ; 577: 52-57, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34507065

RESUMO

Focal ischemia causes irreversible brain damage if cerebral blood flow is not restored promptly. Acute phase excitotoxicity and pro-oxidant and inflammatory events in the sub-chronic phase elicit coagulative necrosis, vascular injury, cerebral oedema, and neurobehavioral deficits. Earlier, in pre-clinical studies arbutin protected behavioral functions and improved therapeutic outcomes in different models of brain and metabolic disorders. Arbutin is natural hydroquinone that might protect against ischemia-reperfusion (I/R) injury. In this study, cerebro-protective effects of arbutin were evaluated in the middle cerebral artery occlusion-reperfusion (MCAo/R) mouse model. Mice were administered arbutin (50, 100 mg/kg, i.p.) for 21 days, and subjected to MCAo/R or sham surgery on day 14. Results showed brain infarction, blood-brain barrier dysfunction, oedema, and neurological deficits 24 h post-MCAo/R injury that were prevented by arbutin. Behavioral evaluations over the sub-chronic phase revealed MCAo/R triggered spatial and working memory deficits. Arbutin protected the memory against MCAo/R injury and decreased hydroxy-2'-deoxyguanosine, protein carbonyls, inflammatory cytokines (tumor necrosis factor-α, myeloperoxidase, matrix metalloproteinase-9, inducible nitric oxide synthase), and enhanced glutathione levels in the ischemia ipsilateral hemisphere. Arbutin decreased brain acetylcholinesterase activity, glutamate, and enhanced GABA levels against MCAo/R. Arbutin can alleviate I/R pathogenesis and protects neurobehavioral functions in the MCAo/R mouse model.


Assuntos
Arbutina/farmacologia , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/fisiologia , Encéfalo/fisiopatologia , Cromatografia Líquida de Alta Pressão , Ácido Glutâmico/metabolismo , Humanos , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Camundongos , Fármacos Neuroprotetores/farmacologia , Neurotransmissores/metabolismo , Permeabilidade/efeitos dos fármacos , Traumatismo por Reperfusão/fisiopatologia , Ácido gama-Aminobutírico/metabolismo
3.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361788

RESUMO

This research investigated a UPLC-QTOF/ESI-MS-based phytochemical profiling of Combretum indicum leaf extract (CILEx), and explored its in vitro antioxidant and in vivo antidiabetic effects in a Long-Evans rat model. After a one-week intervention, the animals' blood glucose, lipid profile, and pancreatic architectures were evaluated. UPLC-QTOF/ESI-MS fragmentation of CILEx and its eight docking-guided compounds were further dissected to evaluate their roles using bioinformatics-based network pharmacological tools. Results showed a very promising antioxidative effect of CILEx. Both doses of CILEx were found to significantly (p < 0.05) reduce blood glucose, low-density lipoprotein (LDL), and total cholesterol (TC), and increase high-density lipoprotein (HDL). Pancreatic tissue architectures were much improved compared to the diabetic control group. A computational approach revealed that schizonepetoside E, melianol, leucodelphinidin, and arbutin were highly suitable for further therapeutic assessment. Arbutin, in a Gene Ontology and PPI network study, evolved as the most prospective constituent for 203 target proteins of 48 KEGG pathways regulating immune modulation and insulin secretion to control diabetes. The fragmentation mechanisms of the compounds are consistent with the obtained effects for CILEx. Results show that the natural compounds from CILEx could exert potential antidiabetic effects through in vivo and computational study.


Assuntos
Antioxidantes/farmacologia , Combretum/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Arbutina/química , Arbutina/isolamento & purificação , Sítios de Ligação , Glicemia/efeitos dos fármacos , HDL-Colesterol/agonistas , HDL-Colesterol/sangue , LDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/sangue , Biologia Computacional/métodos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Flavonoides/química , Flavonoides/isolamento & purificação , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Insulina/agonistas , Insulina/metabolismo , Masculino , Modelos Moleculares , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Extratos Vegetais/química , Folhas de Planta/química , Ligação Proteica , Conformação Proteica , Ratos , Ratos Long-Evans , Triterpenos/química , Triterpenos/isolamento & purificação
4.
J Biochem Mol Toxicol ; 35(9): e22857, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34338399

RESUMO

Gliomas are a type of brain cancer that occurs in the supporting glial cells of the brain. It is highly malignant and accounts for 80% of brain tumors with high mortality and morbidity. Phytomedicines are potent alternatives for allopathic drugs which cause side effects. They have been used from ancient times by traditional Chinese, Ayurveda, and Siddha medicine. Arubtin is a glycoside phytochemical extracted from plants and belongs to the family of Ericaceae. Arbutin possesses various pharmacological properties such as anti-inflammatory, antioxidant, antitumor, and so on. Hence in the present study, we analyzed the anticancer potency of arbutin against rat C6 glioma cells. Rat C6 glioma cells were procured from American Type Culture Collection and the cells were cultured in Roswell Park Memorial Institute-1640 medium. To assess the cytotoxicity effect of the arbutin against C6 glioma cells, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test was performed with different doses from 10 to 60 µM. Arbutin effectively induced apoptosis in the cells and the IC50 dose was obtained at 30 µM. For further studies, we selected the 30 µM IC50 dose and a higher dose of 40 µM. Reactive oxygen species (ROS) generated were analyzed with DCFDA/H2DCFDA stain and the destruction of mitochondrial membrane permeability which is the initiator of apoptosis was analyzed with a cationic stain Rhodamine 123. Dual staining with acridine orange and ethidium bromide was performed to assess the viable and dead cells. Cell adhesion properties of glioma cells were analyzed with Matrigel assay. The apoptotic, inflammatory, and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling molecules were analyzed with quantitative polymerase chain reaction (qPCR) analysis to confirm the anticancer effect of arbutin. Arbutin generated excessive ROS and disrupted the mitochondrial membrane, which induced apoptosis in cells, it also inhibited the cell adhesion property of C6 glioma cells. qPCR analysis clearly indicates arbutin increases the apoptotic genes and decreased the inflammatory and PI3K/mTOR signaling molecules. Overall, our results authentically confirm that arbutin can be a potent alternative for treating glioma.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Arbutina/farmacologia , Glioma , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Ratos
5.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361723

RESUMO

Genito-urinary tract infections have a high incidence in the general population, being more prevalent among women than men. These diseases are usually treated with antibiotics, but very frequently, they are recurrent and lead to the creation of resistance and are associated with increased morbidity and mortality. For this reason, it is necessary to develop new compounds for their treatment. In this work, our objective is to review the characteristics of the compounds of a new formulation called Itxasol© that is prescribed as an adjuvant for the treatment of UTIs and composed of ß-arbutin, umbelliferon and n-acetyl cysteine. This formulation, based on biomimetic principles, makes Itxasol© a broad-spectrum antibiotic with bactericidal, bacteriostatic and antifungal properties that is capable of destroying the biofilm and stopping its formation. It also acts as an anti-inflammatory agent, without the adverse effects associated with the recurrent use of antibiotics that leads to renal nephrotoxicity and other side effects. All these characteristics make Itxasol© an ideal candidate for the treatment of UTIs since it behaves like an antibiotic and with better characteristics than other adjuvants, such as D-mannose and cranberry extracts.


Assuntos
Acetilcisteína/uso terapêutico , Arbutina/uso terapêutico , Produtos Biológicos/uso terapêutico , Umbeliferonas/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Acetilcisteína/química , Antibacterianos/química , Antibacterianos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antifúngicos/química , Antifúngicos/uso terapêutico , Arbutina/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Produtos Biológicos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/uso terapêutico , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Candida/patogenicidade , Combinação de Medicamentos , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Bactérias Gram-Positivas/patogenicidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Umbeliferonas/química , Infecções Urinárias/microbiologia , Infecções Urinárias/patologia
6.
J Pharm Biomed Anal ; 205: 114294, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34375783

RESUMO

Molecularly imprinted polymers (MIPs) for glycosides, arbutin (ARB) and rutin (RUT), were prepared using methacrylamide (MAM) and 4-vinylpyridine (4-VPY) as functional monomers and divinylbenzene as a crosslinker by modified precipitation polymerization. The template molecule, ARB or RUT, was first dissolved in methanol, followed by precipitation polymerization using a mixture of acetonitrile and toluene as a porogenic solvent. The molar ratios of the template molecule, MAM and 4-VPY were optimized to achieve a high molecular recognition ability for ARB and RUT. The retention and molecular recognition properties of these MIPs were evaluated in HILIC or normal-phase mode. With an increase in the acetonitrile content in the mobile phase, the retention factor of ARB or RUT was increased. Furthermore, the MIPs for ARB and RUT showed the highest imprinting factors of 3.65 and 66.5 for the template molecules, respectively. Hydrogen bonding interactions such as N⋯H-O, C=O⋯H-O and NH⋯O-H between 4-VPY or MAM and hydroxy groups of d-glucose or d-rutinose could function in the recognition of a glycone. Furthermore, hydrogen bonding interactions between functional monomers and the hydroxy group(s) of hydroquinone or quercetin could function in the recognition of an aglycone. These results suggest that the MIPs could recognize both a glycone and aglycone via hydrogen bonding interactions. Furthermore, MIPs for RUT were successfully applied to extract RUT in nutritional supplements.


Assuntos
Impressão Molecular , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Arbutina , Polímeros Molecularmente Impressos , Polimerização , Polímeros , Rutina
7.
Enzyme Microb Technol ; 148: 109818, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34116761

RESUMO

In this study, a novel one-step enzymatic acylation was developed for the synthesis of hydrophobic arbutin ester, by using supercritical carbon dioxide (SC-CO2) as the reaction solvent. Immobilized Novozym 435 from Candida antarctica was identified as the best biocatalyst for producing arbutin palmitate through transesterification between arbutin and palmitic acid ethyl ester in SC-CO2. A transesterification yield of 85.21 % was obtained in batch operation using palmitic acid ethyl ester as the acyl donor, hexane/propylene glycol as the co-solvent and Novozym 435 as the enzyme at 10 MPa and 60 °C for 20 h in SC-CO2. The yield of arbutin palmitate increased with increasing temperature over the range of 40-60 °C in the current study. Operating at an arbutin/palmitic acid ethyl ester molar ratio of 5.0, the conversion of arbutin decreased, probably due to an inhibitory effect of the high concentration of palmitic acid ethyl ester on the enzyme. The 38 % original enzyme activity of Novozym 435 was maintained after being used for 3 cycles (60 h) under optimized conditions.


Assuntos
Dióxido de Carbono , Ésteres , Arbutina , Basidiomycota , Enzimas Imobilizadas/metabolismo , Esterificação
8.
Adv Clin Exp Med ; 30(5): 535-544, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33974755

RESUMO

BACKGROUND: SIRT1 plays a protective role against diabetic retinopathy as it regulates inflammation, apoptosis and autophagy of cells. OBJECTIVES: This study was designed to investigate the effects of arbutin and to identify a potential mechanism of action. Adult human retinal pigment epithelial (ARPE-19) cells were exposed to high glucose (HG) or treated with different concentrations of arbutin. MATERIAL AND METHODS: The protein levels of pro-inflammatory cytokines, like tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß), IL-6, and p65 were assessed using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB p65 and cyclooxygenase-2 (COX-2) was detected with western blot assay. Cell apoptosis was analyzed with TUNEL assay, and expression levels of Bcl2, BAX, cleaved caspase-3, cleaved PARP, LC3II, LC3I, and beclin1 were detected with western blot assay. Autophagy levels were detected using LC3II immunofluorescence staining. RESULTS: Arbutin treatment markedly enhanced viability and autophagy mediators, decreased pro-inflammatory proteins and reduced apoptosis in ARPE cells under HG exposure, while increasing SIRT1 protein level. This could be blocked by Sirtinol treatment. Additionally, 3MA treatment significantly reduced the efficacy of arbutin against inflammatory markers and apoptosis in ARPE cells exposed to HG. CONCLUSIONS: Arbutin suppressed inflammation and apoptosis of ARPE cells induced by HG by promoting autophagy via SIRT1. A potential target, SIRT1, was identified for the treatment of DR, and new effects of and action mechanisms for arbutin were found and confirmed.


Assuntos
MicroRNAs , Sirtuína 1 , Apoptose , Arbutina , Autofagia , Humanos , Inflamação/tratamento farmacológico , NF-kappa B
9.
Eur J Pharmacol ; 901: 174078, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33839087

RESUMO

The abnormal dietary life style leads to hyperlipidemia and insulin resistance with ectopic lipid accumulation and elevated levels of hepatic glucose development which are the underlying pathological characteristics of fatty liver diseases. The pharmacological inhibition of fatty acid synthase of de novo lipogenesis may regulate the dysfunctional lipid biotransformation and reverse the pathological state of diabetic liver injury. The three pharmacological interventions (PTS; Pterostilbene, ARB; Arbutin, PUR; Purpurin) were administered to manage the condition of diabetic liver injury against the high fat diet (HFD) + Streptozotocin (STZ) 30 mg/kg b.wt. rodent animal model to observe the effect of abnormal fatty acid synthesis. The qRT-PCR was used to evaluate the fatty acid synthase (FASN) expression which is independently allied with diabetes associated fatty liver disorders. To determine the therapeutic potential of three selected drugs, the biochemical parameters and histopathological considerations were utilized. Three subsequent dosage of PTS, ARB and PUR administered (i.e., 30,60 & 120 mg/kg/p.o.) for five weeks significantly alter the serum parameters, oxidative burden in HFD-STZ which, in turn, resulted in diabetic liver injury. It was also revealed that increased mRNA expression of fatty acid synthase (FASN), which is known to promote abnormal fatty acid synthesis through different molecular signaling pathways, was associated with the development of diabetes associated liver injury, this expression was observed to be significantly suppressed by PTS, ARB and PUR treatment. Moreover, the studies of histopathology showed that there was substantial structural improvement after PTS, ARB and PUR treatment. All three selected drugs have been shown to be effective for Diabetic liver injury (DLI) care but PTS shows impressive results compared to other selected drugs.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Ácido Graxo Sintase Tipo I/antagonistas & inibidores , Hepatopatias/prevenção & controle , Animais , Antraquinonas/uso terapêutico , Antioxidantes/metabolismo , Arbutina/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Dieta Hiperlipídica , Ácido Graxo Sintase Tipo I/biossíntese , Ácido Graxo Sintase Tipo I/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Hepatopatias/etiologia , Masculino , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Estilbenos/uso terapêutico
10.
J Agric Food Chem ; 69(14): 4243-4252, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33821640

RESUMO

Tyrosinase is a key enzyme responsible for enzymatic browning of fruits and vegetables and skin disorders due to overproduction of melanin. Arbutin is an inhibitor of tyrosinase; however, its high polarity and weak transdermal absorption capacity limit its applications. In this paper, a green solvent system was developed to successfully synthesize arbutin esters with improved liposolubilities (Clog P values = 0.27-5.03). Among the obtained esters, arbutin undecenoate (AU) showed the strongest tyrosinase-inhibiting activity (15.6%), which was 9.0 times higher than that of arbutin. An enzyme kinetics study indicated that AU was a competitive inhibitor with reversible inhibition. The esters inhibited tyrosinase by making the secondary structure of tyrosinase looser and less stable; moreover, the interactions between tyrosinase and AU driven by metal interactions and hydrogen bonds also offered a mechanism for inhibition of AU on tyrosinase. In addition, AU (100 µM) reduced the melanin content of B16 mouse melanoma cells to 61.3% of the control group.


Assuntos
Arbutina , Ésteres , Animais , Arbutina/farmacologia , Catálise , Melaninas , Camundongos , Monofenol Mono-Oxigenase
11.
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
12.
Phytochemistry ; 187: 112782, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33915418

RESUMO

Six undescribed compounds (1-6) were isolated from the leaves of Viburnum erosum along with four known compounds 7-10. The structures were determined by NMR and MS spectroscopic analyses, and their absolute configurations were established by chemical and spectroscopic methods. Compounds 1-6 were α-glucosidic hydroquinone derivatives with different linear monoterpenoid structures. Compounds 1-10 were also evaluated for their tyrosinase inhibitory activities, and 10 showed potent inhibition of tyrosinase enzyme with IC50 value of 37.9 µM compared to 47.6 µM of the positive control (ß-arbutin).


Assuntos
Viburnum , Arbutina/farmacologia , Glucosídeos , Hidroquinonas/farmacologia , Monofenol Mono-Oxigenase
13.
Phytother Res ; 35(8): 4136-4154, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33724594

RESUMO

Cosmetic dermatology preparations such as bleaching agents are ingredients with skin-related biological activities for increasing and improving skin beauty. The possibility of controlling skin hyperpigmentation disorders is one of the most important research goals in cosmetic preparations. Recently, cosmetics containing herbal and botanical ingredients have attracted many interests for consumers of cosmetic products because these preparations are found safer than other preparations with synthetic components. However, high-quality trial studies in larger samples are needed to confirm safety and clinical efficacy of phytotherapeutic agents with high therapeutic index. Arbutin (p-hydroxyphenyl-ß-d-glucopyranoside) is a bioactive hydrophilic polyphenol with two isomers including alpha-arbutin (4-hydroxyphenyl-α-glucopyranoside) and ß-arbutin (4-hydroxyphenyl-ß-glucopyranoside). It is used as a medicinal plant in phytopharmacy. Studies have shown that alpha-arbutin is 10 times more effective than natural arbutin. A comparison of IC50 values showed that α-arbutin (with concentration 2.0 mM) has a more potent inhibitory activity on human tyrosinase against natural arbutin (with higher concentration than 30 mM). A review of recent studies showed that arbutin could be beneficial in treatment of various diseases such as hyperpigmentation disorders, types of cancers, central nervous system disorders, osteoporosis, diabetes, etc. This study was designed to describe the therapeutic efficiencies of arbutin.


Assuntos
Arbutina , Cosméticos , Hiperpigmentação , Arbutina/farmacologia , Humanos , Hiperpigmentação/tratamento farmacológico , Monofenol Mono-Oxigenase/antagonistas & inibidores , Pele
14.
Exp Biol Med (Maywood) ; 246(14): 1650-1659, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33757338

RESUMO

Chronic long-term glucocorticoid use causes osteoporosis partly by interrupting osteoblast homeostasis and exacerbating bone loss. Arbutin, a natural hydroquinone glycoside, has been reported to have biological activities related to the differentiation of osteoblasts and osteoclasts. However, the role and underlying mechanism of arbutin in glucocorticoid-induced osteoporosis are elusive. In this study, we demonstrated that arbutin administration ameliorated osteoporotic disorders in glucocorticoid dexamethasone (Dex)-induced mouse model, including attenuating the loss of bone mass and trabecular microstructure, promoting bone formation, suppressing bone resorption, and activating autophagy in bone tissues. Furthermore, Dex-stimulated mouse osteoblastic MC3T3-E1 cells were treated with arbutin. Arbutin treatment rescued Dex-induced repression of osteoblast differentiation and mineralization, the downregulation of osteogenic gene expression, reduced autophagic marker expression, and decreased autophagic puncta formation. The application of autophagy inhibitor 3-MA decreased autophagy, differentiation, and mineralization of MC3T3-E1 cells triggered by arbutin. Taken together, our findings suggest that arbutin treatment fends off glucocorticoid-induced osteoporosis, partly through promoting differentiation and mineralization of osteoblasts by autophagy activation.


Assuntos
Arbutina/uso terapêutico , Autofagia , Osteoblastos/metabolismo , Osteoporose/tratamento farmacológico , Animais , Arbutina/farmacologia , Linhagem Celular , Dexametasona/toxicidade , Glucocorticoides/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/efeitos dos fármacos , Osteoporose/etiologia
15.
Biochem Biophys Res Commun ; 547: 75-81, 2021 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-33610043

RESUMO

Excessive melanin formation has been linked to various skin disorders such as hyperpigmentation and skin cancer. Tyrosinase is the most prominent target for inhibitors of melanin production. In this study, we investigated whether arbutin and its prodrug, arbutin undecylenic acid ester, might inhibit phenoloxidase (PO), a tyrosinase-like enzyme. Molecular docking simulation results suggested that arbutin and arbutin undecylenic acid ester can bind to the substrate-binding pocket of PO. Arbutin undecylenic acid ester with an IC50 6.34 mM was effective to inhibit PO compared to arbutin (IC50 29.42 mM). In addition, arbutin undecylenic acid ester showed low cytotoxicity in Drosophila S2 cells and the compound inhibited the melanization reaction. Therefore, the results of this study have demonstrated that arbutin undecylenic acid ester as a potential inhibitor of PO. We successfully designed a new platform utilizing Drosophila melanogaster and Bombyx mori as animal models propounding fast, cheap, and high effectiveness in method to screen tyrosinase inhibitors.


Assuntos
Arbutina/análogos & derivados , Arbutina/química , Arbutina/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/química , Ácidos Undecilênicos/química , Ácidos Undecilênicos/farmacologia , Animais , Bombyx , Drosophila melanogaster , Hiperpigmentação/tratamento farmacológico , Hiperpigmentação/metabolismo , Melaninas/biossíntese , Simulação de Acoplamento Molecular
16.
Colloids Surf B Biointerfaces ; 201: 111616, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33618082

RESUMO

The present work designed to improve the skin delivery of arbutin niosome (arbusome) was prepared via an ultrasonic technique. The arbusome formulations were optimized by investigating the effects of the cholesterol:surfactants ratio. To characterize the morphology and solid-state of arbutin in arbusome, differential scanning calorimetry, photon correlation spectroscopy, powder x-ray diffractometer, scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared spectroscopy were utilized. The findings indicated that adding cholesterol incremented the arbusome's particle size. Further studies proved that the zeta potential and the size of nanoparticles can be modulated by the alterations in the ratio of cholesterol: surfactant. When the cholesterol concentration was high in the formulation, the highest entrapment efficiency was found to be approximately 44 %. Solid-state analysis showed that arbutin in the niosome was in the amorphous state. The skin permeation test indicated the greater quantities of the arbutin in skin layers and the receptor chamber for arbusome gel compared to arbutin simple gel. Furthermore, in vitro cytotoxicity test indicated no cytotoxicity for the improved formulation of niosome containing arbutin. The cell viability (HFF cell line) for niosomal formulation of arbutin was reported to be about 86 %. The formulations were examined in terms of skin irritation on Wistar rats, and non-irritancy of arbutin niosomal gels was indicated. The findings of this work discovered that the manufactured arbusome could be utilized as possible nano-vehicle for the arbutin topical delivery and might open new approaches for the treatment of hyperpigmentation complaints.


Assuntos
Hiperpigmentação , Nanopartículas , Animais , Arbutina/farmacologia , Lipídeos , Lipossomos , Nanotecnologia , Tamanho da Partícula , Ratos , Ratos Wistar , Pele
17.
Phytomedicine ; 82: 153466, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33494001

RESUMO

BACKGROUND: Arbutin (Ar) has anti-oxidative and anti-inflammatory activities. However, the effects of Ar on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) are not clear. PURPOSE: This study aimed to investigate the effects of Ar on LPS-induced AKI in rats. METHODS: The possible data regarding the effects of Ar on AKI were collected by network pharmacology research. Histological changes in the kidney and the levels of blood urea nitrogen, serum creatinine, and kidney injury molecule 1 were measured to assess the effects of Ar on renal function in LPS-induced AKI. The levels of inflammatory were detected by live small-animal imaging, cytometric bead array and enzyme linked immunosorbent assay. The levels of reactive oxygen species and apoptosis of primary kidney cells were detected by flow cytometry. The oxidative stress-related markers were detected by the cuvette assay. The TLR4/NF-κB and PI3K/Akt/Nrf2 levels and apoptosis were detected by Western blot analysis. The effects of GDC-0068 (GDC, Akt inhibitor) on Ar interposed on LPS-induced NRK-52e cell apoptosis were investigated by flow cytometry. RESULTS: The data collected by network pharmacology suggested that Ar might inhibit AKI by exerting an anti-inflammatory effect and regulating the Akt signaling pathway. The experimental results showed that Ar markedly improved renal function, and attenuated inflammation and cell apoptosis via regulating PI3K/Akt/Nrf2 pathway following LPS challenge in vivo, which blocked by GDC effectively in vitro. CONCLUSION: In a word, this study demonstrated that Ar attenuated LPS-induced AKI by inhibiting inflammation and apoptosis via the PI3K/Akt/Nrf2 pathway.


Assuntos
Injúria Renal Aguda/prevenção & controle , Apoptose/efeitos dos fármacos , Arbutina/farmacologia , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Injúria Renal Aguda/induzido quimicamente , Animais , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Rim/efeitos dos fármacos , Masculino , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Int J Pharm Compd ; 25(1): 62-72, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33503011

RESUMO

Concentrated 7% w/w a-arbutin cream was formulated and evaluated using O/W and W/O emulsion bases as an extemporaneous preparation for melasma treatment. Cream bases were formulated with two pH values, 4.0 and 5.5, using a hot process. The stability of the creams was studied for 60 days under three storage conditions (i.e., 2°C to 8°C, 30°C, 40°C). Cream characteristics and all aspects of product stability including physical, chemical, and microbial were investigated. Stability was defined as no dramatic change in color, viscosity, pH, and no visible microbial growth. For stability, at least 90% of the initial a-arbutin concentration quantified by stability-indicating high-performance liquid chromatography must be obtained. It was found that pH had no influence on the a-arbutin or formulations' stability. All formulations had a-arbutin remaining higher than 90% (approximately 92%) after being stored for 60 days in all storage conditions with no significant changes in pH or viscosity. All samples complied with the microbial limits test for nonsterile pharmaceutical preparation for cutaneous products. However, a color change was detected in O/W and W/O emulsions, especially at 40°C storage condition within 28 and 14 days, respectively. Drug crystals were observed in W/O emulsion stored at 2°C to 8°C. Concerning the in vitro drug release, a-arbutin was released from O/W emulsion but not from W/O emulsion. From the above results, the O/W emulsion that was developed in this study can be used as a cream base for concentrated a-arbutin as an extemporaneous preparation. The developed a-arbutin cream prepared using O/W emulsions can be used as an extemporaneous preparation with a beyond-use date of 60 days when stored at room temperature (30°C) and in the refrigerator (2°C to 8°C).


Assuntos
Arbutina , Melanose , Estabilidade de Medicamentos , Emulsões , Humanos , Temperatura , Viscosidade
19.
Phytomedicine ; 85: 153310, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32948420

RESUMO

BACKGROUND: SARS-CoV-2, an emerging strain of coronavirus, has affected millions of people from all the continents of world and received worldwide attention. This emerging health crisis calls for the urgent development of specific therapeutics against COVID-19 to potentially reduce the burden of this emerging pandemic. PURPOSE: This study aims to evaluate the anti-viral efficacy of natural bioactive entities against COVID-19 via molecular docking and molecular dynamics simulation. METHODS: A library of 27 caffeic-acid derivatives was screened against 5 proteins of SARS-CoV-2 by using Molegro Virtual Docker 7 to obtain the binding energies and interactions between compounds and SARS-CoV-2 proteins. ADME properties and toxicity profiles were investigated via www.swissadme.ch web tools and Toxtree respectively. Molecular dynamics simulation was performed to determine the stability of the lead-protein interactions. RESULTS: Our obtained results has uncovered khainaoside C, 6-O-Caffeoylarbutin, khainaoside B, khainaoside C and vitexfolin A as potent modulators of COVID-19 possessing more binding energies than nelfinavir against COVID-19 Mpro, Nsp15, SARS-CoV-2 spike S2 subunit, spike open state and closed state structure respectively. While Calceolarioside B was identified as pan inhibitor, showing strong molecular interactions with all proteins except SARS-CoV-2 spike glycoprotein closed state. The results are supported by 20 ns molecular dynamics simulations of the best complexes. CONCLUSION: This study will hopefully pave a way for development of phytonutrients-based antiviral therapeutic for treatment or prevention of COVID-19 and further studies are recommended to evaluate the antiviral effects of these phytochemicals against SARS-CoV-2 in in vitro and in vivo models.


Assuntos
Antivirais/farmacologia , Ácidos Cafeicos/farmacologia , Alimento Funcional , SARS-CoV-2/efeitos dos fármacos , Arbutina/análogos & derivados , Arbutina/farmacologia , Sítios de Ligação , Glucosídeos/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores
20.
Hum Exp Toxicol ; 40(1): 100-112, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32757845

RESUMO

The present study demonstrated the protective effects of arbutin (ARB) on hyperlipidemia, mitochondrial, and lysosomal membrane damage and on the DNA damage in rats with isoproterenol (ISO)-induced myocardial infarction (MI). Rats were pretreated with ARB (25 and 50 mg/kg body weight (bw)) for 21 days. After pretreatment with ARB, MI was induced by subcutaneous injection of ISO (60 mg/kg bw) for two consecutive days at an interval of 24 h. The levels of TC, TG, and FFA were increased and decreased the level of PL in the heart tissue of ISO-induced MI rats. Very-low-density lipoprotein cholesterol and low-density lipoprotein cholesterol were increased while high-density lipoprotein cholesterol was decreased in the plasma of ISO-administered rats. A heart mitochondrial fraction of the ISO rats showed a significant decrease in the activities of mitochondrial enzymes isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase. The activities of lysosomal enzymes (ß-glucosidase, ß-glucuronidase, α-galactosidase, ß-galactosidase, cathepsin-B, and cathepsin-D) were increased significantly in the heart tissue homogenate of disease control rats. In ISO-induced MI, rat's significant increase in the percentage of tail DNA and tail length, and a decrease in the level of head DNA were also observed. ARB administration to MI rats brought all these parameters to near normality, showing the protective effect of ARB against MI in rats. The results of this study demonstrated that the 50 mg/kg bw of ARB shows higher protection than 25 mg/kg bw against ISO-induced damage.


Assuntos
Arbutina/metabolismo , Isoproterenol/toxicidade , Substâncias Protetoras/metabolismo , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Animais , Catepsina B , Coração , Lisossomos/fisiologia , Masculino , Mitocôndrias Cardíacas , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/enzimologia , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico
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