Search

Ulcerative colitis is a gastrointestinal problem with increasing prevalence. In this study, the effect of hesperidin (commonly found in citrus white peel) on colitis was investigated. For this purpose, 28 Wistar albino female rats, 3-- 4 months old and weighing between 250--350 g, were used in the study. Rats were randomly divided into four groups: control (n=7), colitis (n=7), protective effect (n=7), and treatment (n=7) groups. Colitis was induced in rats with acetic acid (except control), and hesperidin was then administered at 150 mg/kg for 1 week before and after colitis. At the end of the study, IFN-γ and IL-6 values in blood, TAS, TOS, and OSI in tissue were evaluated. Intestinal tissues were assessed visually by haematoxylin and eosin staining. Our results showed that the levels of IFN-γ and IL-6 were highest in the colitis group and lowest in the treatment group, with statistical significance. The most histopathological damage was seen in the colitis group, while less prevalent in the treatment and control groups. The results of the study show that hesperidin had limited protective and therapeutic effects on experimental colitis mouse models. [ABSTRACT FROM AUTHOR]

Citrus fruits contain numerous antioxidative biomolecules including phenolic acids, flavonols, flavanones, polymethoxyflavones (PMFs), and their derivatives. Previous in vitro and in vivo studies thoroughly investigated the antioxidant and therapeutic potential of bioflavonoids extracted from different citrus varieties and fruit fractions. Major bioflavonoids such as hesperidin, naringin, naringenin, and PMFs, had restricted their incorporation into food and health products due to their poor solubility, chemical stability and bioavailability. Considering these limitations, modern encapsulation methodologies such as hydrogelation, liposomal interactions, emulsifications, and nanoparticles have been designed to shield bioflavonoids with improved target distribution for therapeutic enhancements. The size, durability, and binding efficiency of bioflavonoid-loaded encapsulates were acquired by the optimized chemical and instrumental parameters such as solubility, gelation, dispersion, extrusion, and drying. Bioflavonoid-enriched encapsulates have been also proven to be effective against cancer, inflammation, neurodegeneration, and various other illnesses. However, in the future, newer natural binding agents with higher binding capacity might accelerate the encapsulating potential, controlled release, and enhanced bioavailability of citrus bioflavonoids. Overall, these modern encapsulation systems are currently leading to a new era of diet-based medicine, as demand for citrus fruit-based nutritional supplements and edibles grows. [ABSTRACT FROM AUTHOR]

The article focuses on the issue concerning the questionable use of antiviral chemotherapeutics for managing orally related primary and recurrent herpetic infections. The author cites that the application of photodynamic inactivation is intended for treating herpes hominis via exposure to heterocyclic dyes and light, but new controlled trials revealed that this medical approach had no significant effect on rate of resolution for the disease. Other medical approaches include idoxuridine therapy for herpetic keratoconjunctivitis, and the application of adenine arabinoside, water-soluble bioflavonoids and ascorbic acid.

Fenugreek (Trigonella foenum-graecum) is used as a spice throughout the world. It is known for its medicinal properties such as antidiabetic, anticarcinogenic, and immunological activities. The present study shows the properties and the nutritional quality of fenugreek seed extract and focuses on screening of active compounds in drug designing for type 2 diabetes and breast cancer. Quantitative analysis was used to calculate the percentages of protein, carbohydrates moisture, fatty acid, galactomannan, oil, and amino acid. Phytochemical analysis revealed the presence of flavonoids, terpenoids, phenols, proteins, saponins, and tannins in fenugreek seed extracts. Molecular docking and molecular dynamics simulation-based computational drug discovery methods were employed to address the role of fenugreek seed constituents against type 2 diabetes and breast cancer. The computational results reveal that the compound galactomannan can be ascribed as potential drug candidate against breast cancer and type 2 diabetes rendered by higher molecular dock scores, stable molecular dynamics (MD) simulations results, and lower binding energy calculations. [ABSTRACT FROM AUTHOR]

Background and purpose Based on ethno-botanical information collected from diabetic patients in Cuba and firstly reported inhibition of PTP1B and DPPIV enzymes activities, Allophylus cominia ( A. cominia ) was identified as possible source of new drugs that could be used for the treatment of type 2 diabetes mellitus (T2-DM). Experimental approach in this study, the activity of the characterised extracts from A. cominia was tested on the glucose uptake using HepG2 and L6 cells, 3T3-L1 fibroblasts and adipocytes as well as their effect on the fat accumulation using 3T3-L1 adipocytes. Key results on 2-NBDG glucose uptake assay using HepG2 and L6 cells, extracts from A. cominia enhanced insulin activity by increasing glucose uptake. On HepG2 cells Insulin EC 50 of 93 ± 21 nM decreased to 13 ± 2 nM in the presence of the flavonoids mixture from A.cominia . In L6 cells, insulin also produced a concentration-dependent increase with an EC 50 of 28.6 ± 0.7 nM; EC 50 decreased to 0.08 ± 0.02 nM and 5 ± 0.9 nM in the presence of 100 μg/ml of flavonoids and pheophytins mixtures, respectively. In 3T3-L1 fibroblasts, insulin had an EC 50 of >1000 nM that decreased to 38 ± 4 nM in the presence of the flavonoids extract. However, in adipocytes, insulin produced a significant concentration-dependent increase and an EC 50 of 30 ± 8 nM was a further confirmation of the insulin responsiveness of the adipocytes to the insulin. At 100 µg/ml, flavonoids and pheophytins extracts decreased fat accumulation in 3T3-L1 adipocytes by two folds in comparison to the control differentiated cells (p < 0.05). The crude extract of A. cominia did not show any enhancement of 2-NBDG uptake by 3T3-L1 adipocytes in the presence or absence of 100 nM insulin. In addition, in fully differentiated adipocytes, both extracts produced significant decrease in lipid droplets in the cells and no lipid accumulation were seen after withdrawal of the extracts from the cell growth medium. However, there was no effect of both extracts on total protein concentration in cells as well as on Glut-4 transporters. Conclusions and implications the pharmacological effects of the extracts from A. cominia observed in experimental diabetic models were shown in this study. A. cominia is potentially a new candidate for the treatment and management of T2-DM. [ABSTRACT FROM AUTHOR]

Tibial dyschondroplasia (TD) is a disease of rapid growing chickens that occurs in many avian species; it is characterized by nonvascular and nonmineralized growth plates, along with tibia bone deformation and lameness. Icariin is widely used to treat bone diseases in humans, but no report is available regarding the effectiveness of icariin against avian TD. Therefore, this study was designed to determine its effect against TD. For this purpose, a total of 180 broiler chicks were distributed into three groups including control, TD, and icariin group. Control group was given a standard normal diet, while TD and icariin groups received normal standard diet containing 50 mg/kg thiram to induce TD from days 3 to 7 after hatch. After the induction of TD, the chicks of icariin group were fed with standard normal diet by adding 10 mg/kg icariin in water. Then morphological and production parameters analysis of tibial bone indicators, physiological index changes, and gene expression were examined. The results showed that icariin administration not only decreased the mortality but also mitigated the lameness and promoted the angiogenesis, which diminished the TD lesion and significantly increased the expression of P2RX7 (P<0.05) in TD affected thiram induced chicks. In conclusion, present findings suggest that icariin has a significant role in promoting the recovery of chicken growth plates affected by TD via regulating the P2RX7. Our findings reveal a new target for clinical treatment and prevention of TD in broiler chickens. [ABSTRACT FROM AUTHOR]

Aim: This study aims to evaluate the effect of two bioflavonoids (epigallocatechin-3-gallate [EGCG] and catechin) and a protein inhibitor (chlorhexidine [CHX]) on the immediate and delayed microtensile bond strength of self-etch and total-etch adhesive systems to sound dentin.Materials and Methods: The occlusal surfaces of 96 mandibular human third molar teeth specimens were ground after removal of the excess tissues, to expose the middle dentin. The dentin specimens were randomly allocated into four groups, each consisting of 24 teeth (n = 24) according to the application of the enzyme inhibitor. The adhesive system used in this study was Adper easy bond, a self-etch adhesive system, and Adper Single Bond 2, a total-etch adhesive system. Microtensile bond strength testing was conducted using thermocycler 2000, Heto-Holten A/S.Results: All the three enzyme inhibitors increase the bond strength values of the resin-dentin interphase when used during dentin bonding. The EGCG enzyme inhibitor has shown the highest immediate bond strength to dentin when used with both the adhesive systems. [ABSTRACT FROM AUTHOR]

Background: Naringenin (Nar), a common dietary flavonoid abundantly present in fruits, vegetables, and Chinese herbs, is believed to possess strong anti-inflammatory properties and to modulate hepatic apolipoprotein and lipid synthesis. However, there are no reports describing Nar's effects on the hepatitis B virus protein X (HBx) -induced hepatic steatosis, and the detailed molecular mechanisms of the compound's effects are still unclear. Methods: Nar was administered by oral gavage to HBx-transgenic mice from 4 to 6 weeks of age. Mice were sacrificed after 14 days of once-daily naringenin administration. Liver tissues and sera were collected for histopathology and biochemical analysis. Results: Nar counteracted hepatic lipid accumulation and liver dysfunction in HBx-transgenic mice. In addition, Nar significantly decreased expression of adipogenic and lipogenic genes in mice, suggesting that the compound may have therapeutic effects in the early stages of HBx-mediated hepatic steatosis. These results indicated that naringenin inhibits HBx-induced expression of hepatic adipogenic and lipogenic genes through suppression of HBx-induced gene expression, including decreases in the transcriptional activity of SREBP1c, LXRα, and PPARγ in HBx-trangenic mice and HBx-transfected HepG2 cells. Conclusions: Results from this study suggested that Nar may serve as a therapeutic agent for preventing HBxinfected hepatic steatosis in humans. [ABSTRACT FROM AUTHOR]

Crosstalk between adipocytes and macrophages has been suggested to play a crucial role in metabolic disorders such as obesity, insulin resistance, and type 2 diabetes. The objective of this study was to evaluate the effect of nobiletin on the interaction between adipocytes and macrophages. The results showed that nobiletin significantly and dose-dependently inhibited the secretion of inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor (TNF- α), and monocyte chemoattractant protein (MCP)-1, in a coculture of adipocytes and macrophages. The expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPAR γ) and CCAAT/enhancer-binding protein α (C/EBP α), in differentiated 3T3-L1 cells cocultured in transwell system was blocked by nobiletin. Nobiletin also downregulated the expression of inducible NO synthase in cocultured differentiated RAW264.7 cells. Furthermore, heme oxygenase-1 (HO-1) was significantly induced by nobiletin treatment in both cell types, and small interfering (si) RNA-mediated knockdown of HO-1 significantly recovered the inhibitory effects of nobiletin on the NO production in cocultured cells. These results suggest that nobiletin exerts anti-inflammatory effects on the crosstalk between adipocytes and macrophages by inducing HO-1. Nobiletin may have potential for the prevention of obesity-related metabolic diseases. [ABSTRACT FROM AUTHOR]

The toxic liver impairment caused by free radical injury or excessive reactive oxigen species (ROS) formation could be effectivelly attenuated by natural antioxidants. The present study aimed to explore and compare the hepatoprotective and antioxidant effects of free and encapsulated quercetin in in vitro and in vivo models of hepatotoxicity. Thus, quercetin was encapsulated in chitosan/alginate nanoparticles by gelation method. Both empty and quercetin-loaded nanoparticles revealed good safety profile in vitro, determined by the lack of cytotoxicity in human hepatoma HepG2 cells. The pretreatment of HepG2 cells with encapsulated quercetin (10 μg/ml) significantly attenuated the decrease in cell viability in H 2 О 2 -induced oxidative stress (0.1 mM H 2 О 2 ) , thus showing an effective in vitro protection. In vivo evaluation of the antioxidant and hepatoprotective potential of free and encapsulated quercetin was performed in a model of paracetamol − induced liver injury in male Wistar rats. The oral pretreatment with encapsulated quercetin (0.18 mg/kg b.w., 7 days) significantly diminished the increased levels of serum transaminases ALT and AST, attenuated the lipid peroxidation and restored the levels of gluthation (a marker of cell antioxidant defence system). The protective effects of quercetin encapsulated in chitosan-based nanoformulation were superior to those of free quercetin. The results of the study suggest that the encapsulation of quercetin in chitosan/alginate nanoformulations might represent an effective therapeutic approach against oxidative stress induced liver injury. [ABSTRACT FROM AUTHOR]

Troxerutin is a bioflavonoid, which can be used to treat venous disorders, thrombosis and cerebrovascular diseases. Recent studies have demonstrated that it may also be used to prevent edemas. However, it is not known whether troxerutin protects against the cardiomyopathic complications of diabetes. In the present study, a rat model of type 2 diabetes was used to investigate the potential for troxerutin to protect against diabetic cardiomyopathy, through changes to nuclear factor‑κB (NF‑κB) expression. Troxerutin administration significantly reduced heart rate, blood pressure, blood glucose and plasma triglyceride levels across all measured time points. Furthermore, troxerutin significantly reduced reactive oxygen species levels, NF‑κB protein expression, and suppressed the phosphorylated forms of AKT, insulin receptor substrate 1 (IRS1) and c‑Jun N‑terminal kinase (JNK). These results suggested that troxerutin protects against cardiomyopathy via alterations in NF‑κB, AKT and IRS1 signaling, in a rat model of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Osteosarcoma chemotherapy has improved survival rates, however, chemoresistance and drug toxicity still limit therapy. Drug combinations may overcome these limitations by allowing fewer chemoresistant cells to survive. The aim of this study was to evaluate the cytotoxic potential of hesperetin to osteosarcoma and to analyze the cell cycle effects of combinations of hesperetin with chemotherapeutic agents. For this, the U2OS human osteosarcoma cell line was exposed to hesperetin or hesperetin combined with etoposide or doxorubicin in defined proportions. Hesperetin was less cytotoxic compared to chemotherapeutic agents, as shown by cell growth, viability and clonogenic assays. Notwithstanding, hesperetin combined with etoposide showed additive effects on the inhibition of cell growth. Furthermore, hesperetin induced G2-phase arrest, associated with decreased gene expression of cyclins B1 and E1 and cyclin-dependent kinases 1 and 2. The combination with higher additive effect resulted in higher percentage of cells in G2-phase, showing that G2-phase arrest is associated with cytotoxicity. Moreover, hesperetin induced cytostatic effects. In conclusion, our results suggest that G2-phase arrest is an important step for hesperetin-induced cytotoxicity in U2OS cells. Hesperetin shows potential cytotoxicity when combined with etoposide, which may have implications on therapeutic developments for osteosarcoma. [ABSTRACT FROM AUTHOR]

Background and Purpose: Liver diseases are mostly accompanied by inflammation and hepatocyte death. Therapeutic approaches targeting both hepatocyte injury and inflammation are not available. Natural compounds are considered as potential treatment for inflammatory liver diseases. Hesperetin, a flavonoid component of citrus fruits, has been reported to have anti-inflammatory properties. The aim of this study was to evaluate the cytoprotective and anti-inflammatory properties of hesperetin both in vitro and in models of fulminant hepatitis.Experimental Approach: Apoptotic cell death and inflammation were induced in primary cultures of rat hepatocytes by bile acids and cytokine mixture respectively. Apoptosis was quantified by caspase-3 activity and necrosis by LDH release. The concanavalin A (ConA) and D-galactosamine/LPS (D-GalN/LPS) were used as models of fulminant hepatitis. Liver injury was assessed by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver histology and TUNEL assay and inflammation by inducible NOS (iNOS) expression.Key Results: Hesperetin blocked bile acid-induced apoptosis and cytokine-induced inflammation in rat hepatocytes. Moreover, hesperetin improved liver histology and protected against hepatocyte injury in ConA- and D-GalN/LPS-induced fulminant hepatitis, as assessed by TUNEL assay and serum AST and ALT levels. Hesperetin also reduced expression of the inflammatory marker iNOS and the expression and serum levels of TNFα and IFN-γ, the main mediators of cell toxicity in fulminant hepatitis.Conclusion and Implications: Hesperetin has anti-inflammatory and cytoprotective actions in models of acute liver toxicity. Hesperetin therefore has therapeutic potential for the treatment of inflammatory liver diseases accompanied by extensive hepatocyte injury, such as fulminant hepatitis. [ABSTRACT FROM AUTHOR]

We have previously shown that pycnogenol (PYC) increases antioxidants, decreases oxidative stress, suppresses neuroinflammation and enhances synaptic plasticity following traumatic brain injury (TBI). Here, we investigate the effects of PYC on cognitive function following a controlled cortical impact (CCI). Adult Sprague-Dawley rats received a CCI injury followed by an intraperitoneal injection of PYC (50 or 100 mg/kg). Seven days post trauma, subjects were evaluated in a Morris water maze (MWM) and evaluated for changes in lesion volume. Some animals were evaluated at 48 h for hippocampal Fluoro-jade B (FJB) staining. The highest dose of PYC therapy significantly reduced lesion volume, with no improvement in MWM compared to vehicle controls. PYC failed to reduce the total number of FJB positive neurons in the hippocampus. These results suggest that the reduction of oxidative stress and neuroinflammation are not the key components of the secondary injury that contribute to cognitive deficits following TBI. [ABSTRACT FROM AUTHOR]

We have earlier reported antidepressant-like effect of Cnestis ferruginea and its bioflavonoid constituent, amentoflavone in behavioural paradigms but its effects on neurochemical and neuroendocrine systems are yet to be elucidated. This study sought to investigate the effect of subchronic treatment of C. ferruginea (CF) on monoamines system, hypothalamo-pituitary adrenal axis and nitrosative/oxidative stresses. Male albino rats (150–200 g) randomly divided into seven groups; Group I: vehicle treated (0.2% v / v Tween 80 in normal saline (10 ml/kg; p.o .; unstressed), Group II: vehicle treated + restraint stress, Group III: imipramine (20 mg/kg; p.o .), Group IV–VI: CF (12.5, 50, or 100 mg/kg; p.o., respectively), Group VII: CF 6.25 + imipramine 5 mg/kg. One hour post-treatment, animals were subjected to 20 min restraint stress and 6 min, forced swim test (FST) for a period of 14 days. CF (12.5, 50 and 100 mg/kg) produced significant reduction in immobility time and an increase in climbing behaviour. CF attenuated repeated restraint stress × FST-induced serum corticosterone [F(6,28) = 5.45,P < 0.01]. Exposure of rats to FST + restraint stress paradigms produced significant (P < 0.05) increase in malondialdehyde and nitrite level, also reduced the glutathione level and superoxide dismutase activity which was reversed by subchronic treatment of rats with CF. Restraint stress × FST significantly decreased NA, DA and 5-HT concentrations, with increased DA and 5-HT turnover ratios in discrete brain regions which was ameliorated by CF or imipramine subchronic treatment. These results suggest that the antidepressant-like effect of C. ferruginea involved enhancement of monoamines and antioxidant as well as normalization of neuroendocrine systems. [ABSTRACT FROM AUTHOR]

1. Acetaminophen (APAP) overdose leads to severe hepatotoxicity. 3,4-dihydroxyphenylacetic acid (DOPAC) is a scarcely studied microbiota-derived metabolite of quercetin. The aim of this study was to determine the protective effect of DOPAC against APAP-induced liver injury. 2. Mice were treated intragastrically with DOPAC (10, 20 or 50 mg/kg) for 3 days before APAP (300 mg/kg) injection. APAP alone caused increase in serum aminotransferase levels and changes in hepatic histopathology. APAP also promoted oxidative stress by increasing lipid peroxidation and decreasing anti-oxidant enzyme activities. These events led to hepatocellular necrosis and reduced liver function. DOPAC increased nuclear factor erythroid 2-related factor 2 (Nrf-2) translocation to the nucleus and enhanced the expression of phase II enzymes and anti-oxidant enzymes, and thereby reduced APAP hepatotoxicity and enhanced anti-oxidant ability. 3. Our data provide evidence that DOPAC protected the liver against APAP-induced injury, which is involved in Nrf-2 activation, implying that DOPAC can be considered as a potential natural hepatoprotective agent. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a serious health problem throughout the world. 5-Flurouracil, the first-line chemotherapy of colorectal cancer often produces more toxicity to neighboring cells; however, it is still used for CRC treatment. To overcome this, umbelliferone (UMB), a less toxic bioflavonoid has been used to test its anticancer effects on animal model. The objective of the present study is to evaluate the anticancer activity of UMB on 1,2-dimethylhydrazine (DMH)-induced rat colon tumorigenesis to determine the development of aberrant crypt foci (ACF), agyrophylic nucleolar organizer regions (AgNORs), mast cell recruitment, pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and also study the expressions of inducible nitric oxide synthase, cyclooxygenase (COX)-2, and apoptotic markers. DMH-induced rats showed increased ACF number (incidence), multiplicity and its distribution, counts of AgNORs, mast cells, inflammatory markers and apoptotic proteins. Interestingly, UMB supplementation to DMH-induced rats (group 4) significantly (p < 0.05) suppressed ACF development, AgNORs, mast cells, and inflammatory markers and increased the apoptotic markers as compared to DMH-induced rats (group 2). We concluded that UMB is a potential anticancer agent that can be used for the prevention and treatment of CRC. [ABSTRACT FROM AUTHOR]

Background: Several tinnitus sufferers suggest that manganese has been helpful with their tinnitus. Purpose: We tested this in a controlled experiment where participants were committed to taking manganese and Lipoflavonoid Plus® to treat their tinnitus. Research Design: Randomized controlled trial. Study Sample: 40 participants were randomized to receive both manganese and Lipoflavonoid Plus® for 6 months, or Lipoflavonoid Plus® only (as the control). Data Collection and Analysis: Pre- and postmeasures were obtained with the Tinnitus Handicap Questionnaire, Tinnitus Primary Functions Questionnaire, and tinnitus loudness and annoyance ratings. An audiologist performed the audiogram, the tinnitus loudness match, and minimal masking level. Results: Twelve participants were dropped out of the study because of the side effects or were lost to follow-up. In the manganese group, 1 participant (out of 12) showed a decrease in the questionnaires, and another showed a decrease in the loudness and annoyance ratings. No participants from the control group (total 16) showed a decrease in the questionnaires ratings. Two participants in the control group reported a loudness decrement and one reported an annoyance decrement. Conclusions: We were not able to conclude that either manganese or Lipoflavonoid Plus® is an effective treatment for tinnitus. [ABSTRACT FROM AUTHOR]

Acacetin, a O -methylated bioflavonoid isolated from the traditional Chinese medicine Xuelianhua ( Saussurea tridactyla ), is a promising orally effective atrium-selective antiarrhythmic agent for the treatment of atrial fibrillation (AF). Here we describe an efficient two-component method for the synthesis of acacetin and its derivatives. [ABSTRACT FROM AUTHOR]

The objective of this study is to check the regulation of crystal matrix proteins and inflammatory mediators by citrus bioflavonoids (CB) and Lemon peel (LP) extract in hyperoxaluric rats. The animals were divided into six groups with 6 animals each. Group 1: Control, Group 2: Urolithic (Ethylene glycol (EG)-0.75%); Group 3 & 5: Preventive study (EG + CB (20 mg/kg body weight) and LP (100 mg/kg body weight) extract administration from 0th-7th week) respectively; Group 4 & 6: Curative study (EG + CB and LP extract administration from 4th–7th week) respectively by oral administration. Urinary lithogenic factors (Calcium, oxalate, phosphate and citrate) were normalized in CB & LP supplemented rats, while serum parameters revealed the nephroprotective nature of the intervening agents compared to urolithic rats (p < 0.001). Immunoblotting studies showed significantly increased expression of THP, osteopontin and transferrin in kidneys of urolithic rats (p < 0.001), while preventive and curative study showed near normal expression of these proteins. Expression of NF-κB, TNF-α and IL-6 were raised significantly (p < 0.001), while a very minimal increase in MCP-1 expression was observed in urolithic rats compared to control. Hence, supplementation of CB and LP reduced the crystal promoting factors and provides protection from crystal induced renal damage. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The water-soluble total flavonoids (WSTF) were extracted from Isodon lophanthoides var. gerardianus (Benth.) H. Hara, a common folk herbal medicine in China, which has been recorded by the “Chinese Pharmacopoeia” in 2015 and used for prevention and clinical treatment of common diseases of liver and gall for many years. Objective of the study The aim of this study is to evaluate the effects of WSTF on apoptosis in HepG2 cell and investigate the relevant mechanisms underlying. Materials and methods C ytotoxicity was evaluated in HepG2 cells (human hepatoma cell lines) using MTT assay. The influence of the WSTF on the intracellular reactive oxygen species (iROS) and the mitochondrial membrane potential were also determinated. We used flow cytometry analysis to detect the effects of WSTF on apoptosis, cell cycle. Then we applied RT-PCR for genetic expression of main effectors and western blot analysis for activation of main effectors involved in the potential apoptosis signaling pathways. Results WSTF inhibited cell growth in HepG2 cells. Moreover, WSTF stimulates to increase amount of iROS, mitochondrial membrane potential, and the apoptotic relevant factors (cytochrome c, caspase-3) in HepG2 cells. WSTF could significantly induce apoptosis through downregulating apoptosis-antagonizing protein (Bcl-2, Survivin, mcl-1) and upregulating apoptosis-promoting proteins (Bax) and cell cycle G0/G1 arrest in HepG2 cells. Conclusion The results indicate that WSTF induces cell apoptosis through mitochondrial pathway in the HepG2 cells. Therefore, these studies suggest that WSTF could be used as a chemotherapeutic agent to treat hepatoma. [ABSTRACT FROM AUTHOR]

Antioxidants are substances that may protect cells from the damage caused by unstable molecules such as free radicals. Flavonoids are phenolic substances widely found in fruits and vegetables. The previous studies showed that the ingestion of flavonoids reduces the risk of cardiovascular diseases, metabolic disorders, and certain types of cancer. These effects are due to the physiological activity of flavonoids in the reduction of oxidative stress, inhibiting low-density lipoproteins oxidation and platelet aggregation, and acting as vasodilators in blood vessels. Free radicals are constantly generated resulting in extensive damage to tissues leading to various disease conditions such as cancer, Alzheimer's, renal diseases, cardiac abnormalities, etc., Medicinal plants with antioxidant properties play a vital functions in exhibiting beneficial effects and employed as an alternative source of medicine to mitigate the disease associated with oxidative stress. Flavonoids have existed over one billion years and possess wide spectrum of biological activities that might be able to influence processes which are dysregulated in a disease. Quercetin, a plant pigment is a potent antioxidant flavonoid and more specifically a flavonol, found mostly in onions, grapes, berries, cherries, broccoli, and citrus fruits. It is a versatile antioxidant known to possess protective abilities against tissue injury induced by various drug toxicities. [ABSTRACT FROM AUTHOR]

The global prevalence of diabetes is increasing at an alarming rate. The serious side effect of current pharmacotherapy limits its use in the general population, with increased dependence on herbal and polyherbal formulations. Thus the present study was undertaken to evaluate the anti-diabetic effect of silibinin, a bioflavonoid in streptozotocin induced diabetes in rats. Sprague Dawley rats (200-250 g) were randomly divided into six groups (n=6) and were treated orally for 28 days. Group I received 1% (W/V) CMC and was considered as normal control. Diabetic non-treated rats received STZ (55 mg/kg) i.p. Group III, IV and V received silibinin at dose of 20, 40 and 80 mg/kg respectively along with STZ. Group VI received standard treatment of glibenclamide. At the end of treatment the effect on body weight, blood glucose, HbA1c, insulin, lipid profile levels and glucose homeostasis indices were determined. Histopathological changes and oxidative stress parameters in the pancreas were investigated. Diabetic rats treated with silibinin at a dose of 40 mg/kg and 80mg/kg, significantly restored body weight, blood glucose, HbA1c, insulin, lipid profile levels and glucose homeostasis indices as compared to nontreated diabetic rats. Significant effect on the restoration of antioxidant defence such as decreased MDA concentration and increased GSH concentration as well as increased activities of SOD and CAT was also observed in diabetic rats treated with silibinin (40 and 80 mg/kg). Further a high dose of silibinin treated diabetic rats restore the normal histological structure of the pancreas. Thus it can be concluded that silibinin possesses a potent antidiabetic activity and prevented oxidative stress-induced damage to the pancreas in diabetes. [ABSTRACT FROM AUTHOR]

Objective: The migration and invasion features, which were associated with inflammatory response, acted as vital roles in the development of colon cancer. Quercetin, a bioflavonoid compound, was widely spread in vegetables and fruits. Although quercetin exerts antioxidant and anticancer activities, the molecular signaling pathways in human colon cancer cells remain unclear. Hence, the present study was conducted to investigate the suppression of quercetin on migratory and invasive activity of colon cancer and the underlying mechanism. Materials and Methods: The effect of quercetin on cell viability, migration, and invasion of Caco-2 cells was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound-healing assay, and transwell chambers assay, respectively. The protein expressions of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) p65, mitochondrial membrane potential-2 (MMP-2), and MMP-9 were detected by Western blot assay. The inflammatory factors, such as tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (Cox-2), and interleukin-6 (IL-6), in cell supernatant were detected by enzyme-linked immunosorbent assay. Results: The concentration of quercetin <20 μM was chosen for further experiments. Quercetin (5 μM) could remarkably suppress the migratory and invasive capacity of Caco-2 cells. The expressions of metastasis-related proteins of MMP-2, MMP-9 were decreased, whereas the expression of E-cadherin protein was increased by quercetin in a dose-dependent manner. Interestingly, the anti-TLR4 (2 μg) antibody or pyrrolidine dithiocarbamate (PDTC; 1 μM) could affect the inhibition of quercetin on cell migration and invasion, as well as the protein expressions of MMP-2, MMP-9, E-cadherin, TLR4, and NF-κB p65. In addition, quercetin could reduce the inflammation factors production of TNF-α, Cox-2, and IL-6. Conclusion: The findings suggested for the 1st time that quercetin might exert its anticolon cancer activity via the TLR4- and/or NF-κB-mediated signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: Citrus is considered as a medically important plant from ancient times and the bioflavonoids of different variety of citrus fruits were well explored for their biological activities. The study aim was to explore the effect of citrus bioflavonoids (CB) to prevent and cure hyperoxaluria induced urolithiasis. Methods: Twenty four Wistar rats were segregated into 4 Groups. Group 1: Control; Group 2: Urolithic (EG-0.75%); Group 3: Preventive study (EG+CB, day 1-50); Group 4: Curative study (EG+CB, day 30-50). Animals received CB orally (20mg/kg body weight) after performing a toxicity study. Results: Urinary risk factors and serum renal function parameters were significantly reduced by CB administration in both preventive and curative study (p<0.001). Hematoxylin & Eosin and von Kossa staining demonstrated that renal protection was offered by CB against EG insult. Immunohistochemical analyses revealed over expression and abnormal localization of THP and NF-?B in urolithic rats, while it was effectively regulated by CB supplementation. Conclusion: CB prevented and significantly controlled lithogenic factors and CaOx deposition in rats. We propose CB as a potential therapy in management of urolithiasis. [ABSTRACT FROM AUTHOR]

As part of an ongoing search for new antidiabetic agents from medicinal plants, the methanol extract of the aerial parts of Selaginella tamariscina was found to possess stimulatory effect on glucose uptake in 3T3-L1 adipocyte cells. Thus, bioassay-guided isolation of this active extract yielded two new compounds ( 1 and 2 ) along with five known biflavonoids ( 3 – 7 ). Their structures were elucidated by extensive analysis of spectroscopic and physicochemical data. The absolute configuration of compound 2 was determined by specific rotation and CD data analysis. All isolates exhibited potent inhibitory effects on PTP1B enzyme with IC 50 values ranging from 4.5 ± 0.1 to 13.2 ± 0.8 μM. Furthermore, the isolates ( 1 – 7 ) showed significant stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. Of these, compounds ( 1 , 6 , and 7 ) which exhibited mixed-competitive inhibition modes against PTP1B, showed potent stimulatory effects on 2-NBDG uptake. This result indicated the potential of these biflavonoids as lead molecules for development of antidiabetic agents and the beneficial use of S. tamariscina against hyperglycemia. [ABSTRACT FROM AUTHOR]

Purpose The goal of the present study was to develop a poly (ethylene oxide) N10 (PEO N10) based melt-cast matrix system for efficient and prolonged delivery of hesperetin (HT), a promising bioflavonoid, to the posterior segment of the eye through the topical route. Methods HT film was prepared by melt-cast method using PEO N10 and cut into 4 mm × 2 mm segments, each weighing 8 mg. This film was evaluated with respect to in vitro release rates and also transmembrane delivery across Spectra/Por® membrane (MWCO: 10,000 Daltons) and isolated rabbit corneas. Ocular tissue concentrations were also determined postapplication of the film in ex vivo and in vivo models. Results HT release from the film was determined to be about 95.3% within 2 h. In vitro transcorneal flux was observed to be 0.58 ± 0.05 μg/min/cm 2 across the isolated rabbit cornea. High levels of HT were detected in the retina-choroid (RC) and vitreous humor (VH) in the ex vivo model following topical application of the film. Significant levels of HT were observed in both anterior and posterior segment ocular tissues 1 h post topical application of the 10 and 20%w/w HT films on the rabbit eye. Moreover, HT was detected in the VH and RC even after 6 h following topical application of the film in vivo . Conclusion The results from this study suggest that the melt-cast films can serve as a viable platform for sustained topical delivery of bioflavonoids, and other therapeutic agents, into the back-of-the eye tissues. [ABSTRACT FROM AUTHOR]

Preclinical in vitro and in vivo studies demonstrate potent effects of pomegranate preparations in cancer cell lines and animal models with chemically induced cancers. We have carried out one systematic review of the effectiveness of pomegranate products in the treatment of cancer and another on their safety. The PubMed search provided 162 references for pomegranate and cancer and 122 references for pomegranate and safety/toxicity. We identified 4 clinical studies investigating 3 pomegranate products, of which one was inappropriate because of the low polyphenol content. The evidence of clinical effectiveness was poor because the quality of the studies was poor. Although there is no concern over safety with the doses used in the clinical studies, pomegranate preparations may be harmful by inducing synthetic drug metabolism through activation of liver enzymes. We have analysed various pomegranate products for their content of anthocyanins, punicalagin, and ellagic acid in order to compare them with the benchmark doses from published data. If the amount of coactive constituents is not declared, patients risk not benefiting from the putative pomegranate effects. Moreover, pomegranate end products are affected by many determinants. Their declaration should be incorporated into the regulatory guidance and controlled before pomegranate products enter the market. [ABSTRACT FROM AUTHOR]

Phenytoin, an anticonvulsant agent used for the treatment of epilepsy has been reported to exhibit toxic side effects on the liver and testes. The present study investigated the protective effects of kolaviron (KV, a bioflavonoid from Garcinia kola seeds) against hepatic and testicular damage in rats exposed to phenytoin. The study consisted of four groups of six rats per group. Group I rats received 2 mL/kg of corn alone while group II received 75 mg/kg of phenytoin (PHT) alone. Groups III and IV were co-treated with kolaviron (200 mg/kg KV) and vitamin E (500 mg/kg VTE), respectively, for 14 days. The antioxidant status, hepatic and reproductive functional parameters were subsequently determined. PHT treatment significantly ( p < 0.05) increased superoxide dismutase (SOD) and catalase (CAT) activities, elevated lipid peroxidation (LPO) and hydrogen peroxide (H2O2) levels along with significant reduction in the hepatic and testicular levels of glutathione (GSH). Moreover, PHT exposure elicited significant increases in alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels. The significant reduction in seminal epithelium thickness and the diameter of seminiferous tubules was accompanied with marked decrease in sperm motility, sperm count, and viability in PHT-treated rats. However, antioxidant status and the functional indices of liver and testes were restored to near control levels in rats co-treated with KV and VTE. In conclusion, KV and VTE protect the liver and testes against functional impairment due to PHT treatment. [ABSTRACT FROM AUTHOR]

Aims The present study has been designed to investigate the ameliorative potential of vitamin P, and digoxin in ischemic–reperfusion (I/R)-induced renal injury in isolated rat kidney preparations by using the Langendorff apparatus. Main methods Vitamin P (50 and 100 mg/kg; p.o.) was administered to rats for 5 consecutive days. On the 6th day, isolated kidneys were subjected to 30 min of ischemia followed by 120 min of reperfusion by constant flow (8 ml/min). The total renal effluent was collected at various time intervals (i.e., basal, 0, 15, 30, 45 and 60 min). In addition, urea, creatinine, and creatine kinase (CK) activity were evaluated in the renal effluent, and TBARS, GSH, and Na + –K + -ATPase activity were evaluated in tissue. Key findings I/R of renal tissue produced a rise in the activity of CK and the levels of urea and creatinine in the renal effluent, as well as in the activity of Na + –K + -ATPase and levels of TBARS in the tissue. Additionally, it decreased GSH levels when compared with the sham control group. Digoxin served as positive control in the present work. Treatment with vitamin P (100 mg/kg), and digoxin (500 μg/kg) produced a significant (P < 0.05) ameliorative effect against the I/R induced changes in biomarkers. Significance The renoprotective effect of vitamin P is caused by its inhibition of Na + –K + -ATPase activity, which subsequently results in free radical scavenging and anti-infarct properties. Therefore, this vitamin can be useful in the management of renovascular disorders. [ABSTRACT FROM AUTHOR]

Aims. In this work we studied cytodifferentiation effects of newly characterized prenyl flavonoid 4′-O-methylkuwanon E (4ME) isolated from white mulberry (Morus alba L.). Main Methods. Cell growth and viability were measured by dye exclusion assay; cell cycle and surface antigen CD11b were monitored by flow cytometry. For the cytodifferentiation of cells the NBT reduction assay was employed. Regulatory proteins were assessed by western blotting. Key Findings. 4ME induced dose-dependent growth inhibition of THP-1 cells, which was not accompanied by toxic effect. Inhibition of cells proliferation caused by 4ME was associated with the accumulation in G1 phase and with downregulation of hyperphosphorylated pRb. Treatment with 4ME led to significant induction of NBT-reducing activity of PMA stimulated THP-1 cells and upregulation expression of differentiation-associated surface antigen CD11b. Our results suggest that monocytic differentiation induced by 4ME is connected with up-regulation of p38 kinase activity. Significance. Our study provides the first evidence that 4ME induces the differentiation of THP-1 human monocytic leukemia cells and thus is a potential cytodifferentiating anticancer agent. [ABSTRACT FROM AUTHOR]

Dihydroquercetin monosuccinate is a synthetic derivative of native antioxidant dihydroquercetin, which has a wide spectrum of pharmacological properties. Being more soluble in water than its precursor, the novel synthetic derivative of the bioflavonoid maintains a high antioxidant activity, which is confirmed by the TEAC method and the voltammetry data. The redox transformations of dihydriquercetin monosuccinate on a graphite electrode are more complicated as compared to the parent flavonoid. [ABSTRACT FROM AUTHOR]

Hesperidin (HDN) is a citrus bioflavonoid, which widely exists in many plants. Previous researches have proved that HDN has several functions such as anti-oxidant, anti-tumor, anti-inflammatory, immune regulation and so on. In the present study, we explored the protective effects of HDN on concanavalin A (Con A)-induced hepatic injury. Acute hepatic injury model was established successfully by intravenous administration of Con A (15mg/kg) in male C57BL/6 mice, and HDN was pretreated for 10days before Con A challenge. It was found that the hepatic injury was notably improved in HDN pretreated mice. Furthermore, hepatic oxidative stress and the production of proinflammatory cytokines including TNF-α and IFN-&#947 were decreased by HDN pretreatment. More importantly, compared with Con A-treated mice, the expression and releasing of HMGB1 and T-cell activation were markedly reduced in HDN pretreated mice. Thus, these results suggest that HDN protects mice from Con A-induced hepatic injury by suppressing hepatocyte oxidative stress, producing cytokines, expressing and releasing HMGB1 and activating T cells. [ABSTRACT FROM AUTHOR]

Background and Objectives The aim of this quasi-experimental study is to investigate the effect of 6 weeks of progressive endurance training and Silymarin supplementation intake on hematological parameters in sedentary men (age: 25 ± 5 years, weight 86 ± 21, height 178 ±13 BMI 27 ± 5). Materials and Methods To this end, twenty-one students from Shahrood University of Technology who were willing to participate in the study were chosen for the study. The subjects were then randomly divided into supplemental groups (n=11) and placebo groups (n=10). Both groups received progressive endurance training. The control group received placebo while the experimental or supplemental group received Silymarin. Blood samples were collected before and after 6 weeks of exercise training and supplementation intake. Hematological parameters such as RBC, MON, RBC, HCT, PLT were measured. Data were then analyzed using repeated measure (2×2). Results Hematological parameters such as RBC, MON, RBC, HCT, PLT were measured. Data were analyzed using repeated measure (2×2). Conclusions The results of this study showed that Silymarin supplementation and progressive endurance training not only increases hemoglobin factor but also reduces monocytes, erythrocytes, and hematocrit factors significantly (P⩽0.05). [ABSTRACT FROM AUTHOR]

Background Acacetin is a bioflavonoid with pharmacological properties such as antinociceptive/anti-inflammatory activities. However, scientific evidence of its spectrum activity and mechanisms of action is unknown. Methods Acacetin administered via i.p. was assessed using several nociceptive experimental models such as the writhing test, the formalin test and carrageenan paw oedema in the thermal plantar tests ( Hargreaves method) in mice, as well as the pain-induced functional impairment model in rat ( PIFIR model). Results Acacetin produced a significant and dose-dependent inhibition of the writhes with an ED50 = 20 mg/kg. Furthermore, acacetin inhibited licking and shaking associated with nociceptive behaviour mainly in the inflammatory phase of the formalin test. No significant differences were observed in the plantar test in mice, but a minor response was obtained in the PIFIR model. Animals receiving pre-treatment of WAY100635 (0.1 mg/kg, s.c.), flumazenil (3 mg/kg, i.p.) or naloxone (1 mg/kg, i.p.) partially reduced the antinociceptive response of acacetin in the writhing test. Presence of the inhibitors in the NO-cGMP-K+ channel pathway did not modify the antinociceptive effect of acacetin in the writhing or the formalin test. Conclusions Our data showed that systemic administration of acacetin decreased visceral and inflammatory nociception and prevented the formalin-induced oedema. In the mechanism of the acacetin antinociceptive effect, 5- HT1A, GABA/ BDZs and opioid receptors but not the NO-cGMP-K+ channel pathway seem to be involved. The data presented prove acacetin to be potentially useful in the therapy of pain-related diseases. [ABSTRACT FROM AUTHOR]

Highlights: [•] Hesperidin pretreatment protects cultured primary neurons against oxygen–glucose deprivation. [•] Hesperidin pretreatment also reduced hypoxia–ischemia causing brain tissue injury in neonatal rats. [•] Hesperidin suppressed reactive oxygen species from increasing. [Copyright &y& Elsevier]

Highlights: [•] Neuroprotective effect of the sesamol and naringenin on rotenone-induced model of PD. [•] Bioflavonoids improve body weight and motor impairment of rotenone-induced PD model. [•] Antioxidant property of flavonoids protects neurons and muscles against degeneration. [•] Sesamol and naringenin restore level of protective proteins parkin, DJ1, TH and CHIP. [•] Sesamol and naringenin reduced caspase activation, ubiquitin expression in PD model. [Copyright &y& Elsevier]

Introduction: Nowadays the number of patients that complements its drug treatment through the use of alternative medicine with analgesic purpose grows exponentially; although the presence of supra-additive or additive effect can be positive, the undesirable effects might also be promoted and stays away from the therapeutic utility. Objective: The antinociceptive effects of the bioflavonoid hesperidin and the non-steroidal anti-inflammatory drug ketorolac administrated in combination were determined in an experimental model of gouty arthritis. Material and methods: Nociception was induced by the intra-articular injection of uric acid at 20% to induce dysfunction. When the functionality was zero animals received pharmacologic treatment and then the recovery of functionality was assessed as an expression of antinociception. The data were interpreted using the «surface of synergistic interaction» analysis to establish the nature of the interaction. Results: Between the tested combinations, hesperidin (562.3 mg/kg) and ketorolac (0.56 mg/kg) produced an antinociceptive effect individually of 43.9 ± 18.8 area units (au) and 100.8 ± 18.7 area units, respectively. Moreover, the antinociceptive effect of the combination of these doses was significantly higher than expected from the sum of individual effects manifesting a supra-additive effect with 228.3 ± 30.8 area units. Gastric damage that is commonly produced during administration of NSAIDs was significantly reduced in presence of the bioflavonoid. Discussion: This is the first study to demonstrate that the combination of hesperidin + ketorolac potentiates the antinociceptive effects and reduce adverse effects. Conclusions: The combination of hesperidin + ketorolac preferentially promotes additive and supra-additive antinociceptive responses suggesting its therapeutic potential in treatment of gouty arthritis pain. [ABSTRACT FROM AUTHOR]

Warfarin can stimulate vascular calcification in vitro via activation of α-catenin signaling and/or inhibition of matrix Gla protein (MGP) carboxylation. Calcification was induced in vascular smooth muscle cells (VSMCs) with therapeutic levels of warfarin in normal calcium and clinically acceptable phosphate levels. Although TGF/BMP and PKA pathways are activated in calcifying VSMCs, pharmacologic analysis reveals that their activation is not contributory. However, α-catenin activity is important because inhibition of α-catenin with shRNA or bioflavonoid quercetin prevents calcification in primary human VSMCs, rodent aortic rings, and rat A10VSMCline. In the presence of quercetin, reactivation of α-catenin using the glycogen synthase kinase-3α (GSK-3α) inhibitor LiCl restores calcium accumulation, confirming that quercetin mechanism of action hinges on inhibition of the α-catenin pathway. Calcification in VSMCs induced by 10 μM warfarin does not associate with reduced levels of carboxylated MGP, and inhibitory effects of quercetin do not involve induction of MGP carboxylation. Further, down-regulation of MGP by shRNA does not alter the effect of quercetin. These results suggest a new α-catenin-targeting strategy to prevent vascular calcification induced by warfarin and identify quercetin as a potential therapeutic in this pathology [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation plays a crucial role in hyperglycemia-induced liver injury. Kolaviron (KV), a natural biflavonoid from Garcinia kola seeds have been shown to possess antiinflammatory properties which has not been explored in diabetes. To our knowledge, this is the first study to investigate the effect of KV on pro-inflammatory proteins in the liver of diabetic rats. Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg) in male Wistar rats. Kolaviron (100 mg/kg) was administered orally five times a week for six weeks. The concentrations of cytokines and chemokines were measured using Bio-plex ProTM magnetic bead-based assays (Bio-Rad Laboratories, Hercules, USA). Plasma glucose and serum biomarkers of liver dysfunction were analyzed with diagnostic kits in an automated clinical chemistry analyzer. Insulin concentration was estimated by radioimmunoassay (RIA) Result: Kolaviron (100mg/kg) treatment significantly ameliorated hyperglycemia and liver dysfunction. Serum levels of hepatic marker enzymes were significantly reduced in kolaviron treated diabetic rats. Kolaviron prevented diabetes induced increase in the hepatic levels of proinflammatory cytokines interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF-α) and monocyte chemotactic protein (MCP-1). Conclusion: The results of this study demonstrate that the hepatoprotective effects of kolaviron in diabetic rats may be partly associated with its modulating effect on inflammatory responses. [ABSTRACT FROM AUTHOR]

Background: Morin, a bioflavonoid with antioxidant properties, is a constituent of many herbs and fruits that are used as herbal medicines. It exhibits many biological activities and possibly even has protective effects against chronic diseases. The present study was conducted to determine the protective effect of morin against gentamicin-induced nephrotoxicity in young male rats. Material and Methods: Young male rats (n=24) were divided into four groups as follow; (1): control group, (2): gentamicin (GM) group; rats injected intraperitioneally (i.p.) with GM at a dose of 100 mg /kg body weight (b.w.) for five consecutive days to induced nephrotoxicity, (3): morin group; rats administered morin daily at a dose of 30 mg/ kg b. w. via gavage, and (4) GM group pretreated with morin; rats were orally received morin at the same dose and route in group (3) up to two weeks followed by injected i.p. with GM as in group (2). Separated serum samples were used for determination of protein metabolism parameters, kidney functions, malondialdehyde (MDA), and ionic sodium (Na+) and potassium (K+). Results: GM injection induced marked nephrotoxicity as evidenced by significant elevation in serum levels of albumin, creatinine, urea, uric acid, MDA and K+, with significant reduction in serum levels of total protein, Na+ and albumin/creatinine ratio (ACR). Pretreatment with morin protected the rats from GMinduced nephrotoxicity as evidenced by significant improvement of these investigated parameters. Histological examination of renal tissues showed marked glomerular thickening, vacuolations of the wall of blood vessels associated with necrobiotic changes in GM injected group, meanwhile there were amelioration in rats group received morin pre-GM injection. Conclusion: Morin exert potential antioxidant activity and offer nephroprotective effect against GMinduced nephrotoxicity in young rats. [ABSTRACT FROM AUTHOR]

Abstract: The present study examines the preventive role of hesperidin (HDN) on plasma, cardiac and hepatic lipids in isoproterenol (ISO)-induced rats. Myocardial injury was induced by subcutaneous injection of isoproterenol hydrochloride (85mg/kg BW) twice at an interval of 24h, for two consecutive days. HDN was administered by post-orally at a dose of 200mg/kg BW. The results showed increased levels of plasma cholesterol, low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA) and phospholipids (PL) and decreased level of high density lipoprotein-cholesterol (HDL-C) in ISO-induced rats. ISO rats also showed an increase in cholesterol, TG and FFA and decrease in PL levels in the heart and liver tissues. HDN treatment brought the above parameters towards normal level. This experiment shows that HDN possesses hypolipidemic effect in ISO-induced rats. [Copyright &y& Elsevier]

Objective: The role of oxidant damage on the development of end-organ injuries caused by diabetic rat is well known. The aim of this study is to examine the effect of quercetin, which is a strong antioxidant bioflavonoid, on oxidant damage and antioxidant capacity in various organs in the case of medium-term or long-term diabetic rat. Material and Methods: Forty-eight male Wistar rats were divided into five groups, namely, control group, diabetic group of 8-weeks, diabetic group of 16-weeks, quercetin treated diabetic group of 8-weeks, and quercetin treated diabetic group of 16-weeks. At the end of the experiment, malondialdehyde levels, superoxide dismutase, catalase, and glutathione peroxidase activities were measured in the lung, aorta, heart, spleen, liver, and kidney tissues. Results: MDA levels were elevated in all tissues except in the lung in non-treated diabetic groups. Quercetin treatment increased the antioxidant enzyme capacities and considerably reduced oxidant damage. Conclusion: We suggest that quercetin has a protective effect on the aorta, heart, brain, liver, and kidneys from oxidant damage in the case of medium-term or long-term diabetic rat. It can be argued that quercetin is effective by increasing the antioxidant defence capacity in this process. [ABSTRACT FROM AUTHOR]

Background: Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. Methodology/Principal Findings: We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3'- sulfate, Q3'S) in spontaneously hypertensive rats (SHR). Q3GA and I3GA (1 mg/kg i.v.), but not Q3'S, progressively reduced mean blood pressure (MBP), measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml). In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg) induced a progressive decrease in MBP, which was also suppressed by SAL. Conclusions: Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect. [ABSTRACT FROM AUTHOR]

Background: French maritime pine bark extract (PBE) has gained popularity as a dietary supplement in the treatment of various diseases due to its polyphenol-rich ingredients. Oligometric proanthocyanidins (OPCs), a class of bioflavonoid complexes, are enriched in French maritime PBE and have antioxidant and anti-inflammatory activity. Previous studies have suggested that French maritime PBE helps reduce ultraviolet radiation damage to the skin and may protect human facial skin from symptoms of photoaging. To evaluate the clinical efficacy of French maritime PBE in the improvement of photodamaged facial skin, we conducted a randomized trial of oral supplementation with PBE. Methods: One hundred and twelve women with mild to moderate photoaging of the skin were randomized to either a 12-week open trial regimen of 100 mg PBE supplementation once daily or to a parallel-group trial regimen of 40 mg PBE supplementation once daily. Results: A significant decrease in clinical grading of skin photoaging scores was observed in both time courses of 100 mg daily and 40 mg daily PBE supplementation regimens. A significant reduction in the pigmentation of age spots was also demonstrated utilizing skin color measurements. Conclusion: Clinically significant improvement in photodamaged skin could be achieved with PBE. Our findings confirm the efficacy and safety of PBE [ABSTRACT FROM AUTHOR]

Abstract: Naringenin (NAR) is a naturally occurring plant bioflavonoid present in citrus fruits and possesses a wide range of biological application including anticancer effects. However, its prominent application in cancer is limited due to its suboptimal pharmacokinetics and poor bioavailability at the tumor sites. The aim of the present study was to develop naringenin-loaded nanoparticles (NARNPs) and to evaluate the anticancer potency of the prepared NARNPs in human cervical (HeLa) cancer cells. NARNPs were prepared by nanoprecipitation technique and characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimeter (DSC), and X-ray diffraction (XRD). The in vitro drug release by UV spectroscopy showed there was a sustained drug delivery pattern of NARNPs. MTT-based colorimetric assay revealed higher cytotoxic efficacy of NARNPs than free NAR in HeLa cells. Further, NARNPs treatment significantly (P <0.05) increased intracellular ROS levels, lipid peroxidation status (TBARS) and decreased GSH levels when compared to free NAR treatment in HeLa cells. It has been also noticed that there was a significant alteration of mitochondrial membrane potential and the presence of apoptotic indices (membrane blebbing, nuclear fragmentation) in NARNPs treated cancer cells. Taken together, the present study demonstrates the anticancer potential of prepared NARNPs than free NAR in cervical cancer cells in vitro. [Copyright &y& Elsevier]

Aim: The aim of this study was to investigate the protective effects of bioflavonoid compounds i.e. rutin and naringin on gentamycin induced testicular oxidative stress in rats.Method: A total of 42 male wistar albino rats were divided in to 7 groups, each contains 6 rats. Gentamycin, 5 mg/kg, I.P was administered to the rats from day 1 to day 10. Rutin and naringin were given in different doses (5mg/kg, 10/kg) for a period of 35 days from day 1 to day 35 to the gentamycin treated animals. A sham control group animals with water, control group animals with gentamycin and vehicle control group animals with 0.1% sod CMC were also maintained until completion of 35 days. On 36th day bilateral orchiectomies were performed for all the animals. The testicular tissue was evaluated for various sperm parameters, biochemical estimations and histological changes.Result: Animals treated with 5mg/kg and 10mg/kg of rutin and naringin (Groups 4, 5, 6, 7) have shown significant and dose dependent reduction in MDA levels and increase in levels of antioxidant enzymes, SOD and Catalase when compared to control group animals (Group 2). Sperm count, motility, viability were also protected and normalized with rutin and naringin. Specimens from group 2 had a histological injury with disordered germinal cells. Drug treated groups shown improved testicular architecture. Rutin was more effective in all the parameters when compared to Naringin. Both the bioflavonoids were effective in reducing the gentamycin induced testicular oxidative stress.Conclusion: Rutin and Naringin pretreatment have shown protective and beneficial effect on gentamycin induced oxidative stress in rats. [ABSTRACT FROM AUTHOR]

Background: Flavonoids have been subjected to considerable investigations due to their antioxidant and anti-inflammatory properties. Yet the effects of flavonoids on the ileum and spleen against hepatic ischemia-reperfusion injury have so far not been addressed.Aims: We aimed to investigate whether micronized purified flavonoid fraction (MPFF) protects the ileum and spleen against hepatic ischemia-reperfusion injury.Methods: Rats were subjected to hepatic ischemia by clamping the hilar area of the rats for 60 min, followed by 60 min of reperfusion. Rats in the treatment group were treated with MPFF (80 mg/kg/day) by gavage for 3 days before surgery, 30 min prior to ischemia and just before the reperfusion. After the reperfusion period, all rats were sacrificed. Ileal and splenic tissues were taken for histological evaluation and determination of the total antioxidant capacity (TAC), catalase, total oxidant status (TOS), oxidative stress index (OSI) and myeloperoxidase (MPO) levels.Results: TAC levels in the splenic tissue and intestinal tissue were significantly higher in the treatment group than in the control group (P < 0.01 for both). TOS, OSI, and MPO in splenic tissue (P < 0.01, P < 0.05, and P < 0.05, respectively) and intestinal tissue (P < 0.01, P < 0.01, and P < 0.001, respectively) were significantly lower in the treatment group than in the control group. Histological tissue damage of intestinal tissue was milder in the treatment group than in the control group.Conclusion: The results of this study indicated that MPFF pretreatment significantly limited the injury to the small intestine and spleen induced by hepatic ischemia-reperfusion in rats. [ABSTRACT FROM AUTHOR]