RESUMEN

Although the combination of chemotherapy and radiotherapy has increased the survival rate of patients with nasopharyngeal carcinoma (NPC), certain patients do not respond well to the treatment and have a poor prognosis. Therefore, novel therapeutic drugs and strategies to improve prognosis of patients with NPC are required. As certain plant extracts can suppress the viability of cancer cells, the present study investigated whether oligonol, a polyphenolic compound primarily found in lychee fruit, exerts anticancer activities in NPC cells. MTT, ELISA and immunoblotting were performed to investigate cell survival, cytokeratin-18 fragment release, and the expression of apoptosis and autophagy markers, respectively. Oligonol decreased the viability of NPC-TW01 and NPC/HK1NPC cell lines. Oligonol increased the protein expression of several apoptosis markers, including cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment. Moreover, it also increased expression of autophagy markers Beclin 1 and LC3-II, as well as LC3-II/LC3-I ratio in both NPC cell lines. Furthermore, treatment with autophagy inhibitors 3-methyladenine or LY294002 significantly increased oligonol-induced viability inhibition in NPC-TW01 cells. Combined treatment of oligonol + LY294002 reduced LC3-II expression and the LC3II/LC3I ratio while increasing cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment expression in NPC-TW01 cells. These findings indicated autophagy inhibitors could enhance viability inhibition and apoptotic effects induced by oligonol in NPC cells.

RESUMEN

Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, is well recognized for its antioxidant properties, blood glucose regulation, and fat mass reduction capability. However, its effect on the central nervous system remains unclear. Here, we investigated the effects of oligonol on brain in a high-fat diet (HFD) fed mouse model, and SH-SY5Y neuronal cells and primary cultured cortical neuron under insulin resistance conditions. HFD mice were orally administered oligonol (20 mg/kg) daily, and SH-SY5Y cells and primary cortical neurons were pretreated with 500 ng/mL oligonol under in vitro insulin resistance conditions. Our findings revealed that oligonol administration reduced blood glucose levels and improved spatial memory function in HFD mice. In vitro data demonstrated that oligonol protected neuronal cells and enhanced neural structure against insulin resistance. We confirmed RNA sequencing in the oligonol-pretreated insulin-resistant SH-SY5Y neuronal cells. Our RNA-sequencing data indicated that oligonol contributes to metabolic signaling and neurite outgrowth. In conclusion, our study provides insights into therapeutic potential of oligonol with respect to preventing neuronal cell damage and improving neural structure and cognitive function in HFD mice.

RESUMEN

Liver fibrosis, defined by the aberrant accumulation of extracellular matrix proteins in liver tissue due to chronic inflammation, represents a pressing global health issue. In this study, we investigated the transcriptomic signatures of three independent liver fibrosis models induced by bile duct ligation, carbon tetrachloride, and dimethylnitrosamine (DMN) to unravel the pathological mechanisms underlying hepatic fibrosis. We observed significant changes in gene expression linked to key characteristics of liver fibrosis, with a distinctive correlation to the burn-wound-healing pathway. Building on these transcriptomic insights, we further probed the p53 signaling pathways within the DMN-induced rat liver fibrosis model, utilizing western blot analysis. We observed a pronounced elevation in p53 protein levels and heightened ratios of BAX/BCL2, cleaved/pro-CASPASE-3, and cleaved/full length-PARP in the livers of DMN-exposed rats. Furthermore, we discovered that orally administering oligonol-a polyphenol, derived from lychee, with anti-oxidative properties-effectively countered the overexpressions of pivotal apoptotic genes within these fibrotic models. In conclusion, our findings offer an in-depth understanding of the molecular alterations contributing to liver fibrosis, spotlighting the essential role of the apoptosis pathway tied to the burn-wound-healing process. Most importantly, our research proposes that regulating this pathway, specifically the balance of apoptosis, could serve as a potential therapeutic approach for treating liver fibrosis.

RESUMEN

Introduction: Oligonol, an oligomerized-polyphenol from Litchi chinensis extract, has been shown to alleviate metabolic syndrome. The aim of this study was to evaluate the effects of oligonol in patients with nonalcoholic fatty liver disease (NAFLD). Methods: Adult patients with NAFLD defined by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) ≥11% were enrolled and then randomly assigned to receive either oligonol or placebo capsules. Primary endpoint was ≥30% reduction in MRI-PDFF at 24 weeks. Secondary outcomes were reductions in bodyweight, waist circumference, alanine transaminase, fasting blood sugar, and lipid profiles at week 24. Results: Forty patients were enrolled (n = 20/group). Primary endpoint was achieved in 20% in the oligonol group and 15% in the placebo group (p = 0.50). The authors found a reduction in MRI-PDFF between weeks 0 and 24 in the oligonol group; however, the change was not different from the placebo group. Secondary outcomes were similar between two groups. Discussion: Oligonol has not shown a significant therapeutic effect in NAFLD. Future studies with a longer duration of therapy might be needed to achieve the primary endpoint. Clinical Trial Registration Number: Thai Clinical Trial Registry identification number: TCTR20200814001.

Asunto(s)

Catequina , Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Fenoles/uso terapéutico , Catequina/uso terapéutico

RESUMEN

BACKGROUND: Oligonol® is a low-molecular-weight polyphenol that has biological effects on metabolism in animals. However, little is known about its roles in muscle function and muscle quality in middle-aged and older adults. METHODS: 120 participants were enrolled for study based on 1:1 randomization. Participants in the intervention group were provided 200 mg oligonol® prepared as capsules, and 200 mg placebo (dextrin) was provided in control group. RESULTS: Data from 103 participants (52 in the intervention group and 51 in the control group) were available for analysis. The mean age of all participants was 64.0 ± 8.2 years, and two-thirds of the participants were females. Baseline demographic characteristics, functional assessment, laboratory data and muscle parameters were similar between groups. Hip circumference decreased (p = 0.009) during the study period, and the 6-m walking speed increased (p = 0.001) in women in the intervention group. In contrast, 6-m walking speed, 6-min walking distance and handgrip strength were significantly improved in men in the intervention group, but increased total body fat percentage (p = 0.038) and decreased mid-thigh cross-muscle area (CMA) (p = 0.007) were observed in the control group. Compared to the control group, the 12-week interval change in the percentage of mid-thigh CMA was maintained in men in the intervention group but was significantly decreased in the control group (p = 0.03, 95% CI:0.002-0.05). CONCLUSIONS: Oligonol supplementation (200 mg per day) significantly improved physical performance and muscle mass in men. Further studies are needed to confirm the potential favorable effects of oligonol® supplementation.

RESUMEN

The aim of this study was to observe the effects of oligonol on submandibular gland dysfunction in ovariectomized rats. We randomly divided female Sprague-Dawley rats into sham-operated, ovariectomized, and oligonol-treated ovariectomized groups. Oligonol was intraperitoneally administered at 30 mg/kg daily for six weeks. Lipogenesis increased after the ovariectomy while fatty acid oxidation increased and intracellular triglyceride levels decreased in response to oligonol treatment. Submandibular gland fibrosis characterized by collagen type I accumulation was observed in the ovariectomized group. However, oligonol markedly reduced fibrosis to a level comparable to that observed in the sham group. Aquaporin 1 and glucose transporter 4 were downregulated in the ovariectomized group. Nevertheless, both factors were significantly upregulated by oligonol treatment. However, aquaporin 5 was significantly downregulated in the oligonol treatment group. Our findings indicate that oligonol protects against damage in postmenopausal rat salivary glands.

Asunto(s)

Catequina/análogos & derivados , Ovariectomía , Fenoles/farmacología , Glándula Submandibular/efectos de los fármacos , Animales , Acuaporina 5/metabolismo , Catequina/administración & dosificación , Catequina/farmacología , Colágeno Tipo I/metabolismo , Ácidos Grasos/metabolismo , Femenino , Fibrosis/patología , Inyecciones Intraperitoneales , Peroxidación de Lípido/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Oxidación-Reducción , Fenoles/administración & dosificación , Ratas , Ratas Sprague-Dawley , Triglicéridos/metabolismo

RESUMEN

Oligonol is a low molecular weight polyphenol product derived from lychee fruit by a manufacturing process. We investigated oligonol's anti-fibrotic effect and the underlying mechanism in dimethylnitrosamine (DMN)-induced chronic liver damage in male Sprague-Dawley rats. Oral administration of oligonol (10 and 20 mg/kg body weight) ameliorated the DMN-induced abnormalities in liver histology and serum parameters in rats. Oligonol prevented the DMN-induced elevations of TNF-α, IL-1ß, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase expressions at the mRNA level. NF-κB activation and JNK phosphorylation in DMN-treated rats were ablated by oligonol. Oligonol reduced the enhanced production of hepatic malondialdehyde and reactive oxygen species and recovered protein SH, non-protein SH levels, and catalase activity in the DMN treated liver. Nrf2 translocation into the nucleus was enhanced, and PI3K and phosphorylated Akt levels were increased by administering oligonol. The level of hepatic fibrosis-related factors such as α-smooth muscle actin, transforming growth factor-ß1, and type I collagen was reduced in rats treated with oligonol. Histology and immunohistochemistry analysis showed that the accumulation of collagen and activation of hepatic stellate cells (HSCs) in liver tissue were restored by oligonol treatment. Taken together, oligonol showed antioxidative, hepatoprotective, and anti-fibrotic effects via JNK/NF-κB and PI3K/Akt/Nrf2 signaling pathways in DMN-intoxicated rats. These results suggest that antioxidant oligonol is a potentially useful agent for the protection against chronic liver injury.

RESUMEN

Effective treatment to prevent or arrest the advance of Alzheimer disease (AD) has yet to be discovered. We investigated whether OligonolR, an FDA-approved flavanol-rich extract prepared from lychee fruit and green tea, exerted beneficial effects relevant to AD in a triple transgenic male mouse model of AD (3×Tg-AD). At 9 months of age, untreated 3×Tg-AD mice vs. wild-type (WT) controls displayed cognitive deficits in behavioral assays and, at 12 months, elevated levels of hippocampal amyloid beta-protein (Aß), amyloid precursor protein (APP), tau phosphorylation, and pro-inflammatory cytokines. 3×Tg-AD mice given Oligonol showed fewer cognitive deficits and attenuated pathological indices at 12 months. Oligonol treatment of 3×Tg-AD mice modulated expression of some critical brain proteins that involve multiple pathways relevant to mitochondrial dysfunction, proteasomal failure, endoplasmic reticulum (ER) stress and synaptic impairment. Together, these results demonstrate that continuous Oligonol treatment attenuates AD-like pathology and cognitive impairment of 3×Tg-AD mice and set the stage for clinical trials of this flavanol-rich plant extract in patients with early AD.

Asunto(s)

Enfermedad de Alzheimer/tratamiento farmacológico , Catequina/análogos & derivados , Disfunción Cognitiva/tratamiento farmacológico , Litchi/química , Fenoles/administración & dosificación , Extractos Vegetales/administración & dosificación , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animales , Catequina/administración & dosificación , Modelos Animales de Enfermedad , Flavonoides/administración & dosificación , Frutas/química , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Masculino , Ratones , Ratones Transgénicos , Mutación/genética , Fosforilación/efectos de los fármacos , Té/química , Transgenes/genética , Proteínas tau/genética , Proteínas tau/metabolismo

RESUMEN

There is growing research interest in the hypocholesterolemic effect of various food components such as polyphenols. In this study, we examined the effects of oligonol-a low-molecular weight polyphenol extracted from lychee fruit-on cholesterol metabolism in rats under short-term administration. Administration of oligonol for 3 days significantly increased cecum weight and decreased cecal n-butyric acid concentrations in rats. Oligonol also significantly lowered the levels of hepatic cholesterol and increased the levels of total neutral steroids excreted in the feces. It also increased fecal ß-muricholic acid significantly, whereas the levels of total acidic steroids remained unchanged. Gene expression of hepatic CYP7A1 (cytochrome P450 family 7 subfamily A member 1) significantly increased following the administration of oligonol. This increase could be ascribed to changes in the expression of farnesoid X receptor, small heterodimer partner, and fibroblast growth factor 15 in ileum. Our data suggest that oligonol induces hypocholesterolemic effects through the inhibition of biliary cholesterol absorption from the intestine and the upregulation of cholesterol catabolism in rats even following short-term administration. Therefore, oligonol may be an important food component for reducing cholesterol level.

Asunto(s)

Catequina/análogos & derivados , Colesterol/metabolismo , Litchi/química , Fenoles/aislamiento & purificación , Fenoles/farmacología , Animales , Butiratos/metabolismo , Catequina/administración & dosificación , Catequina/aislamiento & purificación , Catequina/farmacología , Colesterol 7-alfa-Hidroxilasa/genética , Colesterol 7-alfa-Hidroxilasa/metabolismo , Expresión Génica/efectos de los fármacos , Íleon/metabolismo , Hígado/metabolismo , Masculino , Peso Molecular , Fenoles/administración & dosificación , Polifenoles , Ratas Wistar , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Tiempo

RESUMEN

SCOPE: Oligonol has been shown to moderate mitochondrial biogenesis, protein synthesis, and protein degradation in diabetic mice in a previous study. It is therefore hypothesized that oligonol alleviated sarcopenia by regulating pathways involved in protein turnover and mitochondrial quality. METHODS AND RESULTS: The 32-week-old senescence-accelerated mouse prone 8 (SAMP8) mice are fed with chow diet containing 200 mg kg-1 oligonol for 8 weeks. Oligonol supplementation increased skeletal muscle mass, cross-sectional areas, and grip strength in SAMP8 mice. Oligonol increased phosphorylation of AKT/mTOR/p70sk6, inhibited nuclear localization of FoxO3a and NFκB, and decreased transcription of MuRF-1 and MAFbx in skeletal muscle of SAMP8 mice. Downregulation of mitochondrial biogenesis genes (PGC-1α and Tfam) and mitochondrial fusion genes (Mfn2 and Opa1), loss of PINK1, overexpression of Atg13, LC3-II, and p62, and abundant accumulation of autophagosomes and lysosomes in skeletal muscle of SAMP8 mice are limited by oligonol. Furthermore, oligonol reduced expression of released cytochrome c and cleaved caspase-9 in skeletal muscle of SAMP8 mice. CONCLUSION: Regulating pathways involved in protein synthesis and degradation, mitochondrial biogenesis, mitochondrial fusion/fission, autophagy, and mitochondria-dependent apoptosis by oligonol contribute to positive protein turnover and mitochondrial quality, thus increasing muscle mass and strength in SAMP8 mice.

Asunto(s)

Catequina/análogos & derivados , Mitocondrias Musculares/efectos de los fármacos , Proteínas Musculares/metabolismo , Fenoles/farmacología , Sarcopenia/tratamiento farmacológico , Envejecimiento/fisiología , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Catequina/farmacología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteína Forkhead Box O3/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas del Grupo de Alta Movilidad/genética , Proteínas del Grupo de Alta Movilidad/metabolismo , Ratones Endogámicos , Mitocondrias Musculares/metabolismo , Dinámicas Mitocondriales/efectos de los fármacos , Proteínas Musculares/genética , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Ligasas SKP Cullina F-box/genética , Proteínas Ligasas SKP Cullina F-box/metabolismo , Sarcopenia/metabolismo , Sarcopenia/patología

RESUMEN

This study investigated the effects of oligonol, a low-molecular-polyphenol derived from lychee peel, against diabetes-induced pancreatic damage via oxidative stress-induced inflammation. Oligonol was orally administered at 10 or 20 mg/kg body weight/day for 10 days to streptozotocin-induced diabetic rats, and the rats were compared with nondiabetic and diabetic control rats. The diabetic rats showed loss of body weight and increased pancreatic weight, and the oral administration of oligonol attenuated these parameters. Moreover, the administration of oligonol caused a significant decrease in the serum glucose level and a significant increase in the serum and pancreatic insulin and C-peptide levels in the diabetic rats. Oligonol also significantly reduced the enhanced levels of reactive oxygen species and 2-thiobarbituric acid reactive substance, which are oxidative stress biomarkers, in the serum and pancreas. Oligonol treatment reduced the overexpression of phospho-p38, phospho-ERK1/2, phospho-inhibitor of nuclear factor-kappa B (NF-κB), NF-κBp65, and NF-κBp65-induced inflammatory protein such as cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. Furthermore, oligonol treatment led to significantly attenuated histological damage in the pancreas. On the basis of these results, we conclude that a plausible mechanism of oligonol's antidiabetic action may be its antioxidative stress-related anti-inflammatory action.

Asunto(s)

Catequina/análogos & derivados , Diabetes Mellitus Experimental/complicaciones , Litchi/química , Páncreas/efectos de los fármacos , Enfermedades Pancreáticas/prevención & control , Fenoles/farmacología , Animales , Antioxidantes/farmacología , Catequina/aislamiento & purificación , Catequina/farmacología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Frutas/química , Hipoglucemiantes/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Páncreas/patología , Enfermedades Pancreáticas/complicaciones , Enfermedades Pancreáticas/patología , Fenoles/aislamiento & purificación , Extractos Vegetales/farmacología , Polifenoles/farmacología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos

RESUMEN

BACKGROUND: Obesity is a global health problem, increasing susceptibility to Type 2 Diabetes (T2DM) and Cardiovascular Disease (CVD). Varieties of products have been proposed for treatment with varying degrees of success. Recent studies, suggested Oligonol; an optimized phenolic product mixture from Lychee Fruit Polyphenols (LFP); as such treatment in Japanese population. OBJECTIVES: We aimed to investigate the effect of oligonol on weight, insulin resistance by (HOMA-IR), lipids profile, leptin, Adiponectin, and resistin in healthy overweight and obese Saudi females. SUBJECTS AND METHODS: 60 Saudi healthy overweight and obese females were enrolled in a double blind case/control study to take either Oligonol or placebo for 12 weeks without dietary or lifestyle re-strictions. Weight, height, Waist Circumference (WC), hip circumference (HC), and blood pressure were measured, and fasting blood samples of participants were taken before, and at the end of study. Total cholesterol, HDL-cholesterol, triglycerides, glucose, insulin, leptin, adiponectin, and resistin were meas-ured. LDL- cholesterol, HOMA-IR were calculated by equation. RESULTS: 47 subjects completed the study, 25 in placebo group, and 22 in Oligonol group. No ill effects were noted in any participant. Oligonol reduced means of serum triglycerides (P=0.008), and resistin (P=0.045) significantly. In addition, no weight gain was noted in oligonol group, unlike placebo group which exhibited significant increase in mean weight (P= 0.036), WC (P=0.027), HC (P= 0.047), and leptin (P <0.001). CONCLUSION: Oligonol could be suggested as future hypolipidemic and weight controlling agent for overweight and obese Saudi females.

RESUMEN

Oligonol, a polyphenol derived from lychee fruit, is produced by an oligomerization process that converts high-molecular-weight polyphenol polymers into low-molecular-weight oligomers. Evidence suggests that oligonol exerts its beneficial effects based on antioxidant and anti-inflammatory properties. This study was the first to investigate the antioxidative and anti-inflammatory effects of oligonol on gastroesophageal inflammatory models: surgically induced acute reflux esophagitis (RE) and gastric ulcer (GU) induced by HCl/ethanol. In the in vitro study, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) radical scavenging assays were performed to determine the antioxidant activity of oligonol. The experimental groups were each composed of normal, vehicle, and oligonol groups. RE rats and GU mice were treated orally with oligonol (100 mg/kg bw) or distilled water as a vehicle (n = 8 for each group). Oligonol exhibited potent free radical-scavenging capacities for DPPH and ABTS radicals, activities that were similar to those of ascorbic acid. The in vivo study revealed that oligonol consumption significantly prevented RE and GU formation and decreased the gross mucosal injury from oxidative stress. Oligonol decreased the reactive oxygen species levels and elevated levels of both inflammatory mediators and cytokines (p-IκB, NF-κBp65, COX-2, iNOS, TNF-α, and IL-1ß) in the RE and GU models. Oligonol had a protective effect against oxidative stress by regulating antioxidant enzyme (superoxide dismutase, catalase, and GPx-1/2) activities in GU mice. Oligonol has potential as a preventive and therapeutic agent for gastroesophageal inflammatory diseases, including RE and GU.

Asunto(s)

Catequina/análogos & derivados , Esofagitis Péptica/tratamiento farmacológico , Litchi/química , Fenoles/administración & dosificación , Extractos Vegetales/administración & dosificación , Úlcera Gástrica/tratamiento farmacológico , Animales , Antioxidantes/administración & dosificación , Catequina/administración & dosificación , Catequina/química , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Esofagitis Péptica/genética , Esofagitis Péptica/metabolismo , Etanol/efectos adversos , Frutas/química , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo/efectos de los fármacos , Fenoles/química , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/genética , Úlcera Gástrica/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Insulin resistance and protein tyrosine phosphatase 1B (PTP1B) overexpression are strongly associated with type 2 diabetes mellitus (T2DM), which is characterized by defects in insulin signaling and glucose intolerance. In a previous study, we demonstrated oligonol inhibits PTP1B and α-glucosidase related to T2DM. In this study, we examined the molecular mechanisms underlying the anti-diabetic effects of oligonol in insulin-resistant HepG2 cells. Glucose uptake was assessed using a fluorescent glucose tracer, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose, and the signaling pathway was investigated by western blotting. Oligonol significantly increased insulin-provoked glucose uptake and decreased PTP1B expression, followed by modulation of ERK phosphorylation. In addition, oligonol activated insulin receptor substrate 1 by reducing phosphorylation at serine 307 and increasing that at tyrosine 895, and enhanced the phosphorylations of Akt and phosphatidylinositol 3-kinase. Interestingly, it also reduced the expression of two key enzymes of gluconeogenesis (glucose 6-phosphatase and phosphoenolpyruvate carboxykinase), attenuated oxidative stress by scavenging/inhibiting peroxynitrite, and reactive oxygen species (ROS) generation, and augmented the expression of nuclear factor kappa B. These findings suggest oligonol improved the insulin sensitivity of insulin-resistant HepG2 cells by attenuating the insulin signaling blockade and modulating glucose uptake and production. Furthermore, oligonol attenuated ROS-related inflammation and prevented oxidative damage in our in vitro model of type 2 diabetes. These result indicate oligonol has promising potential as a treatment for T2DM.

Asunto(s)

Catequina/análogos & derivados , Resistencia a la Insulina , Insulina/metabolismo , Fenoles/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Catequina/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Gluconeogénesis , Glucosa/metabolismo , Células Hep G2 , Humanos , Hipoglucemiantes/farmacología , Inflamación/tratamiento farmacológico , Inflamación/patología , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos

RESUMEN

Monocytes produce high levels of inflammatory cytokines including IL-6 and TNF-α that are involved in autoimmunity, inflammatory diseases, cardiovascular disease and obesity. Therapies targeting IL-6 and TNF-α have been utilized in treating chronic inflammatory diseases. Oligonol is a lychee fruit-derived low-molecular form of polyphenol mixture, typically catechin-type monomers and oligomers of proanthocyanidins, which are produced by an oligomerization process. Although previous studies reported anti-inflammatory properties of Oligonol, it is unknown whether and how Oligonol suppresses IL-6 and TNF-α production in human monocytes. The results of our study demonstrate that Oligonol (25µg/ml) decreases the production of IL-6 and TNF-α from human primary monocytes as measured by flow cytometry and ELISA. Such an anti-cytokine effect was likely mediated by the suppression of NF-κB activation without inducing cell death. Our findings raise the possibility of exploring the benefits of Oligonol in controlling inflammatory conditions, especially those associated with monocytes, in humans.

Asunto(s)

Antiinflamatorios/uso terapéutico , Catequina/análogos & derivados , Inflamación/tratamiento farmacológico , Litchi/inmunología , Monocitos/efectos de los fármacos , Fenoles/uso terapéutico , Extractos Vegetales/uso terapéutico , Catequina/uso terapéutico , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/inmunología , Interleucina-6/genética , Interleucina-6/metabolismo , Monocitos/inmunología , FN-kappa B/metabolismo , Extractos Vegetales/química , Polifenoles/química , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

BACKGROUND/OBJECTIVES: Oligonol, mainly found in lychee fruit, is an antioxidant polyphenolic compound which has been shown to have anti-inflammatory and anti-cancer properties. The detailed mechanisms by which oligonol may act as an anti-aging molecule have not been determined. MATERIALS/METHODS: In this study, we evaluated the ability of oligonol to modulate sirtuin (SIRT) expression in human lung epithelial (A549) cells. Oligonol was added to A549 cells and reactive oxygen species production, mitochondrial superoxide formation, and p21 protein levels were measured. Signaling pathways activated upon oligonol treatment were also determined by western blotting. Furthermore, the anti-aging effect of oligonol was evaluated ex vivo in mouse splenocytes and in vivo in Caenorhabditis elegans. RESULTS: Oligonol specifically induced the expression of SIRT1, whose activity is linked to gene expression, metabolic control, and healthy aging. In response to influenza virus infection of A549 cells, oligonol treatment significantly up-regulated SIRT1 expression and down-regulated viral hemagglutinin expression. Oligonol treatment also resulted in the activation of autophagy pathways and the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, oligonol-treated spleen lymphocytes from old mice showed increased cell proliferation, and mRNA levels of SIRT1 in the lungs of old mice were significantly lower than those in the lungs of young mice. Additionally, in vivo lethality assay revealed that oligonol extended the lifespan of C. elegans infected with lethal Vibrio cholerae. CONCLUSIONS: These data demonstrated that oligonol may act as an anti-aging molecule by modulating SIRT1/autophagy/AMPK pathways.

RESUMEN

Oligonol is a low-molecular-weight form of polyphenol that is derived from lychee fruit extract and contains catechin-type monomers and oligomers of proanthocyanidins. This study investigates the anti-diabetic activities of oligonol via α-glucosidase and human recombinant protein tyrosine phosphatase 1B (PTP1B) assays, as well as its anti-Alzheimer activities by evaluating the ability of this compound to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1). Oligonol exhibited potent concentration-dependent anti-diabetic activities by inhibiting α-glucosidase and PTP1B with IC50 values of 23.14 µg/mL and 1.02 µg/mL, respectively. Moreover, a kinetics study revealed that oligonol inhibited α-glucosidase (K i = 22.36) and PTP1B (K i = 8.51) with characteristics typical of a mixed inhibitor. Oligonol also displayed potent concentration-dependent inhibitory activity against AChE and BChE with IC50 values of 4.34 µg/mL and 2.07 µg/mL, respectively. However, oligonol exhibited only marginal concentration-dependent BACE1 inhibitory activity with an IC50 value of 130.45 µg/mL. A kinetics study revealed mixed-type inhibition against AChE (K i = 4.65) and BACE1 (K i = 58.80), and noncompetitive-type inhibition against BChE (K i = 9.80). Furthermore, oligonol exhibited dose-dependent inhibitory activity against peroxynitrite (ONOO(-))-mediated protein tyrosine nitration. These results indicate that oligonol has strong preventative potential in diabetes mellitus and in Alzheimer's disease.

Asunto(s)

Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Catequina/análogos & derivados , Inhibidores de la Colinesterasa/farmacología , Inhibidores de Glicósido Hidrolasas/farmacología , Fenoles/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Enfermedad de Alzheimer/enzimología , Catequina/farmacología , Diabetes Mellitus/enzimología , Humanos , Cinética , Ácido Peroxinitroso/antagonistas & inhibidores

RESUMEN

BACKGROUND/OBJECTIVES: Oligonol, mainly found in lychee fruit, is an antioxidant polyphenolic compound which has been shown to have anti-inflammatory and anti-cancer properties. The detailed mechanisms by which oligonol may act as an anti-aging molecule have not been determined. MATERIALS/METHODS: In this study, we evaluated the ability of oligonol to modulate sirtuin (SIRT) expression in human lung epithelial (A549) cells. Oligonol was added to A549 cells and reactive oxygen species production, mitochondrial superoxide formation, and p21 protein levels were measured. Signaling pathways activated upon oligonol treatment were also determined by western blotting. Furthermore, the anti-aging effect of oligonol was evaluated ex vivo in mouse splenocytes and in vivo in Caenorhabditis elegans. RESULTS: Oligonol specifically induced the expression of SIRT1, whose activity is linked to gene expression, metabolic control, and healthy aging. In response to influenza virus infection of A549 cells, oligonol treatment significantly up-regulated SIRT1 expression and down-regulated viral hemagglutinin expression. Oligonol treatment also resulted in the activation of autophagy pathways and the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, oligonol-treated spleen lymphocytes from old mice showed increased cell proliferation, and mRNA levels of SIRT1 in the lungs of old mice were significantly lower than those in the lungs of young mice. Additionally, in vivo lethality assay revealed that oligonol extended the lifespan of C. elegans infected with lethal Vibrio cholerae. CONCLUSIONS: These data demonstrated that oligonol may act as an anti-aging molecule by modulating SIRT1/autophagy/AMPK pathways.

Asunto(s)

Animales , Humanos , Ratones , Envejecimiento , Proteínas Quinasas Activadas por AMP , Autofagia , Western Blotting , Caenorhabditis elegans , Proliferación Celular , Frutas , Expresión Génica , Hemaglutininas Virales , Litchi , Pulmón , Linfocitos , Orthomyxoviridae , Fosforilación , Especies Reactivas de Oxígeno , ARN Mensajero , Bazo , Superóxidos , Vibrio cholerae

RESUMEN

BACKGROUND: Chronic Nonbacterial Prostatitis (CNBP) is a condition that frequently causes long-term pain and a significant decrease in the quality of life. OBJECTIVES: The present study aimed to examine the analgesic effects of oligonol, acupuncture, quantum light therapy and their combinations on estrogen-induced CNBP in rats. MATERIALS AND METHODS: This experimental study was conducted in Edirne, Turkey, using a simple randomized allocation. A total of 90 adult male Wistar rats were randomized into 9 groups of 10 rats each: Group I, control; Group II, CNBP, Group III, oligonol only, Group IV, acupuncture only; Group V, quantum only; Group VI, oligonol + quantum; Group VII, acupuncture + oligonol; Group VIII, quantum + acupuncture; Group IX, acupuncture + quantum + oligonol. Oligonol treatment was given at a dose of 60 mg/day for 6 weeks. Conceptual vessels (CV) 3 and 4, and bilaterally urinary bladder (Bl) 32 and 34 points were targeted with 1-hour acupuncture stimulation. The quantum light therapy was applied in 5-minute sessions for 6 weeks (3-times/a week). For pain measurements, mechanical pressure was applied to a point 2 cm distal to the root of the tail to elicit pain and consequent parameters (peak force, latency time of response and total length of measurement) were assessed. RESULTS: Analgesic effects were observed with all treatment regimens; however, the most prominent median analgesic effect was shown in the quantum light therapy in combination with acupuncture for estrogen-induced CNBP (PF1 = 663.9, PF2 = 403.4) (P = 0.012). Furthermore, we observed that monotherapy with quantum light showed a better analgesic efficacy as compared to oligonol and acupuncture monotherapies (PF1 = 1044.6, PF2 = 661.2) (P = 0.018, P = 0.008, P = 0.018; respectively). CONCLUSIONS: All treatment modalities showed a significant analgesic effect on CNBP in rats, being most prominent with the quantum light therapy.

RESUMEN

BACKGROUND/OBJECTIVES: Natural products or active components with a protective effect against oxidative stress have attracted significant attention for prevention and treatment of degenerative disease. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from Litchi chinensis Sonn. We investigated the protective effect and its related mechanism of oligonol against oxidative stress. MATERIALS/METHODS: Oxidative stress in C6 glial cells was induced by hydrogen peroxide (H2O2) and the protective effects of oligonol on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) synthesis, and mRNA expression related to oxidative stress were determined. RESULTS: Treatment with oligonol inhibited NO and ROS formation under cellular oxidative stress in C6 glial cells. In addition, it recovered cell viability in a dose dependent-manner. Treatment with oligonol also resulted in down-regulated mRNA expression related to oxidative stress, nuclear factor kappa-B (NF-κB) p65, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), compared with the control group treated with H2O2. In particular, expression of NF-κB p65, COX-2, and iNOS was effectively reduced to the normal level by treatment with 10 µg/mL and 25 µg/mL of oligonol. CONCLUSIONS: These results indicate that oligonol has protective activity against oxidative stress-induced inflammation. Oligonol might be a promising agent for treatment of degenerative diseases through inhibition of ROS formation and NF-κB pathway gene expression.