RESUMO
BACKGROUND/AIMS: This study aimed to investigate the possible positive effects of arbutin in a trinitrobenzene sulfonic acid (TNBS)- induced experimental colitis model, to compare it with mesalazine, which is used in treating inflammatory bowel disease and to observe the effect of its concomitant use. MATERIALS AND METHODS: Forty Wistar albino species male rats were randomized into 5 groups as control, colitis, colitis+arbutin (Arb), colitis+mesalazine (Mes), and colitis+mesalazine+arbutin (M+A). Proinflammatory cytokines [interleukin (IL)-6, IL-1ß, tumor necrosis factor alpha (TNF-α)] and oxidant/antioxidant parameters [malondialdehyde (MDA), superoxide dismutase inhibition (SOD) inhibition, myeloperoxidase (MPO), and catalase, glutathione peroxidase (GPx)] were processed from the samples. Histopathological evaluation evaluated goblet cell reduction, cellular infiltration, and mucosal loss. RESULTS: When the treatment groups and the TNBS group were compared, statistical significance was achieved in MDA, MPO, SOD inhibition, GPx values, IL-6, IL-1ß and TNF-α levels. Histopathological evaluation revealed a statistically significant decrease in the mucosal loss value in the group where mesalazine and arbutin were used together compared to the TNBS group. CONCLUSION: Our study's results elaborated that using arbutin alone or in combination with mesalazine produced positive effects in colitis-induced rats.
Assuntos
Arbutina , Colite , Modelos Animais de Doenças , Mesalamina , Peroxidase , Ratos Wistar , Ácido Trinitrobenzenossulfônico , Animais , Masculino , Arbutina/farmacologia , Arbutina/uso terapêutico , Ratos , Colite/tratamento farmacológico , Colite/induzido quimicamente , Ácido Trinitrobenzenossulfônico/toxicidade , Mesalamina/farmacologia , Mesalamina/uso terapêutico , Peroxidase/metabolismo , Superóxido Dismutase/metabolismo , Citocinas/metabolismo , Malondialdeído/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Fator de Necrose Tumoral alfa , Distribuição Aleatória , Glutationa Peroxidase/metabolismo , Interleucina-1beta/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêuticoRESUMO
OBJECTIVE: To investigate the protective effect of arbutin against CCl4-induced hepatic fibrosis in mice and explore the underlying mechanisms. METHODS: Twenty-four C57BL/6 mice were randomly divided into control group, model group, and low- and high-dose arbutin treatment (25 and 50 mg/kg, respectively) groups. Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4, and arbutin was administered daily via gavage for 6 weeks. After the treatments, serum biochemical parameters of the mice were tested, and liver tissues were taken for HE staining, Sirius Red staining and immunohistochemical staining. RT-qPCR was used to detect the mRNA levels of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a, and Western blotting was performed to detect α-SMA protein expression in the liver tissues. In the cell experiment, the effect of arbutin treatment for 24 h on THP-1 and RAW264.7 cell migration and recruitment was examined using Transwell migration assay and DAPI staining; The changes in protein levels of Akt, p65, Smad3, p-Akt, p-p65, p-Smad3 and α-SMA in arbutintreated LX-2 cells were detected with Western blotting. RESULTS: Arbutin treatment significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels, alleviated liver tissue damage and collagen deposition, and reduced macrophage infiltration and α-SMA protein expression in the liver of the mouse models (P < 0.05 or 0.001). Arbutin treatment also significantly reduced CCl4-induced elevation of a-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a mRNA levels in mice (P < 0.05). In the cell experiment, arbutin treatment obviously inhibited migration and recruitment of THP-1 and RAW264.7 cells and lowered the phosphorylation levels of Akt, p65 and Smad3 and the protein expression level of α-SMA in LX-2 cells. CONCLUSION: Arbutin ameliorates liver inflammation and fibrosis in mice by inhibiting hepatic stellate cell activation via reducing macrophage recruitment and infiltration and suppressing activation of the Akt/NF-κB and Smad signaling pathways.
Assuntos
Arbutina , Cirrose Hepática , Macrófagos , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Masculino , Camundongos , Arbutina/farmacologia , Arbutina/uso terapêutico , Tetracloreto de Carbono , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismoRESUMO
BACKGROUND: Doxorubicin is an effective antineoplastic agent but has limited clinical application because of its cumulative toxicities, including cardiotoxicity. Cardiotoxicity causes lipid peroxidation, genetic impairment, oxidative stress, inhibition of autophagy, and disruption of calcium homeostasis. Doxorubicin-induced cardiotoxicity is frequently tried to be mitigated by phytochemicals, which are derived from plants and possess antioxidant, anti-inflammatory, and anti-apoptotic properties. Arbutin, a natural antioxidant found in the leaves of the bearberry plant, has numerous pharmacological benefits, including antioxidant, anti-bacterial, anti-hyperglycemic, anti-inflammatory, and anti-tumor activity. METHODS AND RESULTS: The study involved male Wistar rats divided into three groups: a control group, a group treated with doxorubicin (20 mg/kg) to induce cardiac toxicity, a group treated with arbutin (100 mg/kg) daily for two weeks before doxorubicin administration. After treatment, plasma and heart tissue samples were collected for analysis. The samples were evaluated for oxidative stress parameters, including superoxide dismutase, malondialdehyde, and catalase, as well as for cardiac biomarkers, including CK, CK-MB, and LDH. The heart tissues were also analyzed using molecular (TNF-α, IL-1ß and Caspase 3), histopathological and immunohistochemical methods (8-OHDG, 4 Hydroxynonenal, and dityrosine). The results showed that arbutin treatment was protective against doxorubicin-induced oxidative damage by increasing SOD and CAT activity and decreasing MDA level. Arbutin treatment was similarly able to reverse the inflammatory response caused by doxorubicin by reducing TNF-α and IL-1ß levels and also reverse the apoptosis by decreasing caspase-3 levels. It was able to prevent doxorubicin-induced cardiac damage by reducing cardiac biomarkers CK, CK-MB and LDH levels. In addition to all these results, histopathological analyzes also show that arbutin may be beneficial against the damage caused by doxorubicin on heart tissue. CONCLUSION: The study suggests that arbutin has the potential to be used to mitigate doxorubicin-induced cardiotoxicity in cancer patients.
Assuntos
Antioxidantes , Cardiotoxicidade , Humanos , Ratos , Animais , Antioxidantes/metabolismo , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/prevenção & controle , Cardiotoxicidade/etiologia , Arbutina/farmacologia , Arbutina/metabolismo , Arbutina/uso terapêutico , Miocárdio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ratos Wistar , Doxorrubicina/efeitos adversos , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Apoptose , Biomarcadores/metabolismoRESUMO
Arbutin (ARB) is a glycosylated hydroquinone with potent antioxidant effects. Although cisplatin (CP) is widely used in chemotherapy, its toxicity in healthy tissues, including ovotoxicity, is an insurmountable problem. This study aimed to evaluate the therapeutic effect of ARB against CP-related ovototoxicity by including nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in rats for the first time. Rats treated one dose of CP (5 mg/kg) on the first day, followed by ARB (5 and 10 mg/kg) for three days. Serum reproductive hormone levels were determined using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in ovarian tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of ARB on this situation were also addressed. ARB treatment reduced the levels of markers of OS, inflammation, ERS and apoptosis in ovarian tissue of CP-stimulated animals. ARB regenerated the depleted antioxidant system by triggering Nrf2 pathway in the ovarian tissues of animals stimulated by CP. Histological findings also supported the therapeutic efficacy of ARB. The results indicate that ARB may have therapeutic effects against CP-induced reproductive toxicity with its Nrf2 activator potential. ARB should be tested in more extensive studies as a new generation chemopreventive candidate molecule.
Assuntos
Cisplatino , Fator 2 Relacionado a NF-E2 , Ratos , Animais , Cisplatino/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Arbutina/farmacologia , Arbutina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antioxidantes/metabolismo , Estresse Oxidativo , Estresse do Retículo Endoplasmático , Inflamação/metabolismo , ApoptoseRESUMO
Arbutin is a glycosylated hydroquinone with antioxidant and anti-hyperglycemia effects. However, its beneficial effects in type 2 diabetes (T2D) were not clarified. This study evaluated the effect of arbutin on hyperglycemia, dyslipidemia, insulin resistance, oxidative stress, and inflammatory response in T2D. Rats induced by high fat diet and streptozotocin were treated with arbutin (25 and 50 mg/kg) for 4 weeks. Diabetic rats exhibited glucose intolerance, elevated HbA1c%, reduced insulin, and high HOMA-IR. Liver glycogen and hexokinase activity were decreased in T2D rats while glucose-6-phosphatase (G6Pase), fructose-1,6- biphosphatase (FBPase), and glycogen phosphorylase were upregulated. Circulating and hepatic cholesterol and triglycerides and serum transaminases were elevated in T2D rats. Arbutin ameliorated hyperglycemia, dyslipidemia, insulin deficiency and resistance, and liver glycogen and alleviated the activity of carbohydrate-metabolizing enzymes. Both doses of arbutin decreased serum transaminases and resistin, and liver lipids, TNF-α, IL-6, malondialdehyde and nitric oxide, downregulated liver resistin and fatty acid synthase, and increased serum and liver adiponectin, and liver reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). These effects were associated with the upregulation of hepatic PPARγ. Arbutin inhibited α-glucosidase in vitro and in silico investigations revealed the ability of arbutin to bind PPARγ, hexokinase, and α-glucosidase. In conclusion, arbutin effectively ameliorated glucose intolerance, insulin resistance, dyslipidemia, inflammation, and oxidative stress, and modulated carbohydrate-metabolizing enzymes, antioxidants, adipokines and PPARγ in T2D in rats.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Dislipidemias , Intolerância à Glucose , Resistência à Insulina , Ratos , Animais , PPAR gama/metabolismo , Dieta Hiperlipídica/efeitos adversos , Diabetes Mellitus Tipo 2/metabolismo , Resistina/metabolismo , Resistina/farmacologia , Resistina/uso terapêutico , Estreptozocina/farmacologia , Arbutina/farmacologia , Arbutina/uso terapêutico , Adipocinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hexoquinase/metabolismo , Glicogênio Hepático/metabolismo , alfa-Glucosidases/metabolismo , Glicemia/metabolismo , Estresse Oxidativo , Insulina/metabolismo , Dislipidemias/tratamento farmacológico , Dislipidemias/metabolismoRESUMO
Arbutin, a hydroquinone glucoside, has been detected in ca. 50 plant families, especially in the plants of the Asteraceae, Ericaceae, Proteaceae and Rosaceae families. It is one of the most widely used natural skin-whitening agents. In addition to its skin whitening property, arbutin possesses other therapeutically relevant biological properties, e.g., antioxidant, antimicrobial and anti-inflammatory, as well as anticancer potential. This review presents, for the first time, a comprehensive overview of the distribution of arbutin in the plant kingdom and critically appraises its therapeutic potential as an anticancer agent based on the literature published until the end of August 2022, accessed via several databases, e.g., Web of Science, Science Direct, Dictionary of Natural Products, PubMed and Google Scholar. The keywords used in the search were arbutin, cancer, anticancer, distribution and hydroquinone. Published outputs suggest that arbutin has potential anticancer properties against bladder, bone, brain, breast, cervix, colon, liver, prostate and skin cancers and a low level of acute or chronic toxicity.
Assuntos
Antineoplásicos , Arbutina , Feminino , Humanos , Arbutina/farmacologia , Arbutina/uso terapêutico , Hidroquinonas , Glucosídeos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
Urinary tract infections (UTIs) represent a health problem of the first magnitude since they affect large segments of the population, cause increased mortality and comorbidity, and have a high incidence of relapse. Therefore, UTIs cause a major socioeconomic concern. Current antibiotic treatments have various limitations such as the appearance of resistance to antibiotics, nephrotoxicity, and side effects such as gastrointestinal problems including microbiota alterations that contribute to increasing antibiotic resistance. In this context, Itxasol© has emerged, approved as an adjuvant for the treatment of UTIs. Designed with biomimetic principles, it is composed of arbutin, umbelliferon, and N-acetyl cysteine. In this work, we review the activities of these three compounds concerning the changes they produce in the expression of bacterial genes and those related to inflammation as well as assess how they are capable of affecting the DNA of bacteria and fungi.
Assuntos
Antibacterianos/farmacologia , Bactérias/genética , Proteínas de Bactérias/genética , Infecções Urinárias/microbiologia , Acetilcisteína/farmacologia , Acetilcisteína/uso terapêutico , Antibacterianos/uso terapêutico , Arbutina/farmacologia , Arbutina/uso terapêutico , Bactérias/efeitos dos fármacos , Combinação de Medicamentos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Mimetismo Molecular , Umbeliferonas/farmacologia , Umbeliferonas/uso terapêutico , Infecções Urinárias/tratamento farmacológicoRESUMO
Accumulating evidence has revealed the anti-inflammatory effects of arbutin against various diseases. However, the effects of arbutin are not clarified in ulcerative colitis. This study was intended to investigate the protective effects and mechanisms of arbutin on DSS-induced colitis. Hematoxylin eosin staining was performed to determine the pathological damage of intestinal tissue in mice. Inflammatory factors levels in intestinal tissue were detected by enzyme linked immunosorbent assay (ELISA) assay. TUNEL staining showed the apoptosis levels of cells. Intestinal permeability was analyzed using the application of Fluorescein isothiocyanate Dextran (FD) 4. The levels of Zona Occludens 1 (ZO-1), occluding and claudin-1, and the related proteins in MAPK/ELK1 pathway were analyzed by Western blot. DSS promotes pathological injury, the levels of pro-inflammatory factors containing tumor necrosis factor alpha (TNF-α), Interleukin- 6 (IL-6) and myeloperoxidase (MPO), and cell apoptosis in the mouse colon. Additionally, intestinal permeability was increased and the levels of tight function-related proteins were increased following DSS induction. Its effects could be greatly improved by arbutin. Arbutin exerted effects by eliciting anti-inflammatory effects and maintaining normal intestinal mucosal barrier function, the action mechanism of which could be associated with MAPK/ELK1 pathway.
Assuntos
Arbutina/uso terapêutico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Arbutina/administração & dosagem , Arbutina/farmacologia , Peso Corporal/efeitos dos fármacos , Colite Ulcerativa/patologia , Sulfato de Dextrana , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Inflamação/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Masculino , Camundongos Endogâmicos BALB C , Proteínas de Junções Íntimas/metabolismoRESUMO
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/patologiaRESUMO
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 terapêuticoRESUMO
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/etiologiaRESUMO
Arbutin, a glycoside extracted from the plant Arctostaphylos uva-ursi, has been previously reported to possess antioxidant, anti-inflammatory and anticancer effects. Here, we investigated whether arbutin affects the proliferation of the cells of the osteosarcoma (OS) cell lines MG-63 and SW1353. Arbutin suppressed OS cell viability in a dose- and time-dependent manner, as shown by Cell Counting Kit-8 assay. Furthermore, arbutin exposure decreased the protein levels of MTHFD1L, CCND1 and phosphorylated-protein kinase B (AKT)/phosphorylated-mammalian target of rapamycin (mTOR). Potential upstream miRNAs of MTHFD1L were predicted using TargetScan, PICTAR5, miRanda and miRWalk. We performed luciferase activity assays to show that miR-338-3p directly targets and negatively regulates the expression of MTHFD1L. Knockdown of miR-338-3p promoted cell invasion, migration and proliferation in arbutin-treated OS cells via MTHFD1L. In summary, our data suggest that arbutin inhibits OS cell proliferation, migration and invasion via miR-338-3p/MTHFD1L and by inactivating the AKT/mTOR pathway.
Assuntos
Arbutina/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Aminoidrolases/genética , Arbutina/uso terapêutico , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Formiato-Tetra-Hidrofolato Ligase/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Complexos Multienzimáticos/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Neuroinflammation, glial activation, and oxidative injury are the main pathological mechanisms of demyelination in multiple sclerosis (MS). Arbutin, a natural polyphenol compound, possesses antioxidant, anti-inflammatory, and neuroprotective properties whose therapeutic potential has not been studied in the experimental animal models of MS. In the present study, the efficiency of arbutin on lysolecthin (LPC)-induced local demyelination model was investigated. Demyelination was induced by micro-injection of 2 µl LPC (1%) into the rat optic chiasm and the treated group received daily injection of arbutin (50 mg/kg, i.p) during 2 weeks. Visual-evoked potential (VEP) recordings were used to functionally assess the visual pathway. Gene expression analysis was done to evaluate the arbutin effect on the inflammatory, stress oxidative-related mediators, and myelin markers. The myelin-specific staining was performed to assess demyelination and GFAP staining as an astrocyte marker. We found that arbutin significantly reduced P1-latency of VEPs waves and demyelination at 7 and 14 days post-demyelination. Arbutin decreased inflammatory cytokines (IL-1B, IL-17, TNF-α) and iNOS mRNA expression level. In addition, the expression level of anti-inflammatory cytokine (IL-10) and antioxidant mediators (Nrf-2 and HO-1) was enhanced by arbutin treatment. Arbutin increased MBP and Olig2 expression levels in demyelination context. Finally, arbutin attenuated GFAP as an astrocyte marker. Finally, this study demonstrates that arbutin improves functional recovery and myelin repair in the demyelinated optic chiasm through attenuation of inflammation, astrocyte activation, and oxidative stress. These findings might open new promising avenues for treating demyelinating disorders such as multiple sclerosis. Graphical abstract.
Assuntos
Arbutina/farmacologia , Astrócitos/efeitos dos fármacos , Doenças Desmielinizantes/tratamento farmacológico , Potenciais Evocados Visuais/efeitos dos fármacos , Microglia/efeitos dos fármacos , Quiasma Óptico/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Animais , Arbutina/uso terapêutico , Astrócitos/metabolismo , Citocinas/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/metabolismo , Modelos Animais de Doenças , Lisofosfatidilcolinas , Masculino , Microglia/metabolismo , Quiasma Óptico/metabolismo , Ratos , Ratos WistarRESUMO
Parkinson's disease (PD), the most common neurodegenerative movement disorder, is characterized by the progressive loss of dopaminergic neurons in substantia nigra. The underlying mechanisms of PD pathogenesis have not been fully illustrated and currently PD remains incurable. Accumulating evidences suggest that mitochondrial dysfunction plays pivotal role in the dopaminergic neuronal death. Therefore, discovery of novel and safe agent for rescuing mitochondrial dysfunction would benefit PD treatment. Here we demonstrated for the first time that α-Arbutin (Arb), a natural polyphenol extracted from Ericaceae species, displayed significant protective effect on the rotenone (Rot)-induced mitochondrial dysfunction and apoptosis of human neuroblastoma cell (SH-SY5Y). We further found that the neuroprotective effect of Arb was associated with ameliorating oxidative stress, stabilizing of mitochondrial membrane potential, and enhancing adenosine triphosphate production. To investigate the underlying mechanism, we checked the AMP-activated protein kinase and autophagy pathway and we found that both were involved in the neuroprotection of Arb. Moreover, we explored the protective effect of Arb in drosophila PD model and found that Arb rescued parkin deficiency-induced motor function disability and mitochondrial abnormality of drosophila. Taken together, our study demonstrated that Arb got excellent neuroprotective effect on PD models both in vitro and in vivo and Arb might serve as a potent therapeutic agent for the treatment of PD.
Assuntos
Antioxidantes/uso terapêutico , Arbutina/uso terapêutico , Ericaceae/química , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Fitoterapia , Extratos Vegetais/química , Trifosfato de Adenosina/biossíntese , Adenilato Quinase/metabolismo , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Arbutina/isolamento & purificação , Arbutina/farmacologia , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas de Drosophila/deficiência , Proteínas de Drosophila/genética , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/fisiologia , Neuroblastoma/patologia , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/metabolismo , Transtornos Parkinsonianos/tratamento farmacológico , Rotenona/toxicidade , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/genéticaRESUMO
Chinese yam (CY), used as both a traditional Chinese medicine and a nutritious food, is an excellent candidate for treating septic cardiomyopathy (SCM). Adenosine, arbutin and allantoin are the major active components in the aqueous extract of CY. The aim of the present study was to interpret the roles of CY, adenosine, arbutin and allantoin in SCM treatment. Firstly, significant physiological indexes were examined to assess the model and treatment effects of CY, adenosine, arbutin and allantoin. Then, a metabolomic approach was utilized to reveal the metabolic disorders in SCM concerning the intervention of CY/adenosine/arbutin/allantoin. The integrated results demonstrated that adenosine, arbutin and allantoin are responsible for the efficacy of CY on SCM treatment by regulating amino acid, arachidonic acid, sphingolipid, glycerophospholipid and glycol metabolism. Moreover, adenosine and/or arbutin could be used as a substitute for CY in treating SCM, and allantoin efficacy was slightly weaker. This integrated metabolomic approach performed excellently in understanding the herbal function and the roles of its components.
Assuntos
Cardiomiopatias/terapia , Suplementos Nutricionais , Dioscorea/química , Modelos Animais de Doenças , Extratos Vegetais/uso terapêutico , Tubérculos/química , Sepse/terapia , Adenosina/análise , Adenosina/uso terapêutico , Alantoína/análise , Alantoína/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/uso terapêutico , Arbutina/análise , Arbutina/uso terapêutico , Biomarcadores/sangue , Cardiomiopatias/sangue , Cardiomiopatias/imunologia , Cardiomiopatias/metabolismo , Cardiotônicos/análise , Cardiotônicos/química , Cardiotônicos/uso terapêutico , China , Suplementos Nutricionais/análise , Dioscorea/crescimento & desenvolvimento , Metabolismo Energético , Feminino , Fatores Imunológicos/análise , Fatores Imunológicos/química , Fatores Imunológicos/uso terapêutico , Masculino , Metabolômica/métodos , Extratos Vegetais/química , Tubérculos/crescimento & desenvolvimento , Análise de Componente Principal , Distribuição Aleatória , Ratos Wistar , Sepse/sangue , Sepse/imunologia , Sepse/metabolismoRESUMO
Kidney stone disease involves the aggregation of stone-forming salts consequent to solute supersaturation in urine. The development of novel therapeutic agents for this predominantly metabolic and biochemical disorder have been hampered by the lack of a practical pre-clinical model amenable to drug screening. Here, Drosophila melanogaster, an emerging model for kidney stone disease research, was adapted as a high-throughput functional drug screening platform independent of the multifactorial nature of mammalian nephrolithiasis. Through functional screening, the therapeutic potential of a novel compound commonly known as arbutin that specifically binds to oxalate, a key component of kidney calculi, was identified. Through isothermal titration calorimetry, high-performance liquid chromatography and atomic force microscopy, arbutin was determined to interact with calcium and oxalate in both free and bound states, disrupting crystal lattice structure, growth and crystallization. When used to treat patient urine samples, arbutin significantly abrogated calculus formation in vivo and outperformed potassium citrate in low pH urine conditions, owing to its oxalate-centric mode of action. The discovery of this novel antilithogenic compound via D. melanogaster, independent of a mammalian model, brings greater recognition to this platform, for which metabolic features are primary outcomes, underscoring the power of D. melanogaster as a high-throughput drug screening platform in similar disorders. This is the first description of the use of D. melanogaster as the model system for a high-throughput chemical library screen. This article has an associated First Person interview with the first authors of the paper.
Assuntos
Drosophila melanogaster/metabolismo , Ensaios de Triagem em Larga Escala/métodos , Cálculos Renais/tratamento farmacológico , Modelos Biológicos , Animais , Arbutina/análise , Arbutina/farmacologia , Arbutina/uso terapêutico , Birrefringência , Cálcio/metabolismo , Oxalato de Cálcio , Difosfonatos , Avaliação Pré-Clínica de Medicamentos , Fezes , Células HEK293 , Humanos , Íons , NanopartículasRESUMO
As Dermatologists caring for patients with hyperpigmentation problems, we are always looking for more alternative therapies. Hydroquinone (HQ) is still the standard of care. However, traditional depigmenting agents such as HQ and corticosteroids, although highly effective, can raise safety concerns including exogenous ochronosis, atrophy, carcinogenesis and local and systemic untoward effects with long term use. Therefore, we need to investigate non-prescription natural alternatives. This manuscript presents many of the natural ingredients found in cosmeceuticals for the treatment of hyperpigmentation and their mechanisms of action. It will also describe the melanocyte activation pathways and how each of these ingredients interferes with it.
Assuntos
Cosmecêuticos/uso terapêutico , Hiperpigmentação/tratamento farmacológico , Arbutina/uso terapêutico , Cosmecêuticos/análise , Humanos , Hidroquinonas/uso terapêutico , Melanócitos/efeitos dos fármacos , Melanócitos/fisiologia , Extratos Vegetais/uso terapêutico , Glycine max , Vitamina A/uso terapêuticoRESUMO
BACKGROUND: Arbutin is one of the most effective lightening substances. Serratula quinquefolia is a new source of its ß-anomer. The HPLC method showed that the solid content of this compound in the dried plant raw material accounts for 6.86%. The leaves of Serratula quinquefolia do not contain hydroquinone. AIMS: To assess the efficacy of the aqueous extract from' leaf of five-leaf serratula as a skin-lightening agent. PATIENTS/METHODS: We did a randomized, placebo-controlled, double-blind trial. The study involved 102 women aged 26-55, with two kinds of hyperpigmentary diseases: melasma and lentigo solaris. Patients were randomly assigned to one of the treatment groups: a study group (N = 54) or a control group (N = 48). The study group applied the cream with the aqueous extract from leaf of five-leaf serratula containing 2.51% of arbutin. The cream was applied twice a day on the discolored side for 8 weeks. RESULTS: The experimental data showed that the cream with the extract causes decreased level of melanin in the skin pigmentation spot. Clinical effect in the form of lightening and evening skin tone on the discolored side was observed in 75.86% of the female patients with melasma and 56.00 % of the female patients with lentigo solaris. CONCLUSIONS: The cream with the aqueous extract from leaf of five-leaf serratula proved to be an effective and safe preparation for lightening skin discolorations (66.67 % of the female patients in the study group).
Assuntos
Arbutina/uso terapêutico , Asteraceae , Lentigo/tratamento farmacológico , Melanose/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Preparações Clareadoras de Pele/uso terapêutico , Adulto , Arbutina/análise , Método Duplo-Cego , Feminino , Humanos , Lentigo/metabolismo , Melaninas/metabolismo , Melanose/metabolismo , Pessoa de Meia-Idade , Folhas de Planta/química , Creme para a Pele/uso terapêuticoRESUMO
Turnera diffusa Willd, commonly known as Damiana, is employed in traditional medicine as a stimulant, aphrodisiac, and diuretic. Its leaves and stems are used for flavoring and infusion. Damiana is considered to be safe for medicinal use by the FDA. Pharmacological studies have established the hypoglycemic, antiaromatase, prosexual, estrogenic, antibacterial, and antioxidant activity of T. diffusa. The aim of the present study was to evaluate the possible cytotoxic effect of extracts and organic fractions of this plant on five tumor cell lines (SiHa, C-33, Hep G2, MDA-MB-231, and T-47D) and normal human fibroblasts. The results show that the methanolic extract (TdM) displayed greater activity on MDA-MB-231 breast cancer cells (with an IC50 of 30.67 µg/mL) than on the other cancer cell lines. Four organic fractions of this extract exhibited activity on this cancer cell line. In the most active fraction (F4), two active compounds were isolated, arbutin (1) and apigenin (2). This is the first report of a cytotoxic effect by T. diffusa on cancer cells. The IC50 values suggest that the methanolic extract of T. diffusa has potential as an anticancer therapy.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Apigenina/uso terapêutico , Arbutina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Turnera/química , Antineoplásicos Fitogênicos/farmacologia , Apigenina/análise , Apigenina/farmacologia , Arbutina/análise , Arbutina/farmacologia , Linhagem Celular Tumoral , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Extratos Vegetais/farmacologiaRESUMO
BACKGROUND: Bacterial prostatitis (BP) is a common condition accounting responsible for about 5-10% of all prostatitis cases; chronic bacterial prostatitis (CBP) classified as type II, are less common but is a condition that significantly hampers the quality of life, (QoL) because not only is it a physical condition but also a psychological distress. Commonly patients are treated with antibiotics alone, and in particular fluoroquinolones are suggested by the European Urology guidelines. This approach, although recommended, may not be enough. Thus, a multimodal approach to the prolonged antibiotic therapy may be helpful. METHODS: 210 patients affected by chronic bacterial prostatitis were enrolled in the study. All patients were positive to Meares-Stamey test and symptoms duration was > 3 months. The purpose of the study was to evaluate the efficacy of a long lasting therapy with a fluoroquinolone in association with a nutraceutical supplement (prulifloxacin 600 mg for 21 days and an association of Serenoa repens 320 mg, Lactobacillus Sporogens 200 mg, Arbutin 100 mg for 30 days). Patients were randomized in two groups (A and B) receiving respectively antibiotic alone and an association of antibiotic plus supplement. RESULTS: Biological recurrence at 2 months in Group A was observed in 21 patients (27.6%) and in Group B in 6 patients (7.8%). Uropathogens found at the first follow-up were for the majority Gram - (E. coli and Enterobacter spp.). A statistically significant difference was found at the time of the follow-up between Group A and B in the NIH-CPSI questionnaire score, symptoms evidence and serum PSA. CONCLUSIONS: Broad band, short-lasting antibiotic therapy in association with a nutritional supplement (serenoa repens, lactobacillus sporogens and arbutin) show better control and recurrence rate on patients affected by chronic bacterial prostatitits in comparison with antibiotic treatment alone. TRIAL REGISTRATION: NCT02130713. Date of trial Registration: 30/04/2014.