Synergistic Effects Of Flavonoids Research Articles

Synergistic Effect of Flavonoids and Metformin on Protection of the Methylglyoxal-Induced Damage in PC-12 Neuroblastoma Cells: Structure-Activity Relationship and Potential Target.

Methylglyoxal-induced ROS elevation is the primary cause of neuronal damage. Metformin is a traditional hypoglycemic drug that has been reported to be beneficial to the nervous system. In this study, flavonoids were found to enhance the protective effect of metformin when added at a molar concentration of 0.5%. The structure-activity relationship (SAR) analysis indicated that ortho- substitution in the B ring, and the absence of double bonds between the 2 and 3 position combined with the gallate substitution with R configuration at the 3 position in the C ring played crucial roles in the synergistic effects, which could be beneficial for designing a combination of the compounds. Additionally, the mechanism study revealed that a typical flavonoid, EGCG, enhanced ROS scavenging and anti-apoptotic ability via the BCL2/Bax/Cyto C/Caspase-3 pathway, and synergistically inhibited the expression of GSK-3β, BACE-1, and APP in PC-12 cells when used in combination with metformin. The dose of metformin used in the combination was only 1/4 of the conventional dose when used alone. These results suggested that ROS-mediated apoptosis and the pathways related to amyloid plaques (Aβ) formation can be the targets for the synergistic neuroprotective effects of flavonoids and metformin.

Cytotoxic activity of standardized extracts, a fraction, and individual secondary metabolites from fenugreek seeds against SKOV-3, HeLa and MOLT-4 cell lines

Context Trigonella foenum-graecum L. (Fabaceae) has many therapeutic properties and anticancer potential. Objective The cytotoxic activities of standardized extracts and a fraction from fenugreek seeds and their compounds (sapogenins, flavone C-glycosides, alkaloid trigonelline) against human cancer SKOV-3, HeLa and MOLT-4 cells were evaluated. Materials and methods Fenugreek seeds were extracted with 70% methanol (A) or water (B). Furthermore, the seeds were purified with petroleum ether and chloroform and next extracted with methanol to obtain fraction (C). The quantitative analysis of saponins and flavonoids in the extracts was done with HPLC methods. The extracts (5–120 µg/mL) and compounds (1–50 µg/mL) were tested on the cells by MTT assay and RTCA system. The effect of a fraction on ROS production, mitochondrial membrane potential and caspase-3/7 activity in HeLa and SKOV-3 cells was also evaluated by flow cytometry. Results The strongest cytotoxic activity on cancer cells showed the fraction C (IC50 was 3.91 ± 0.03 for HeLa, 3.97 ± 0.07 for SKOV-3, and 7.75 ± 0.37 for MOLT-4) with the highest content of steroidal saponins (163.18 ± 11.03 μg/mg) and flavone C-glycosides (820.18 ± 0.05 μg/mg). The fraction significantly increased ROS production (up to four times higher than in keratinocytes as control) and caspases activity in the cells. The examined flavonoids did not exhibit the cytotoxic activity in contrast to yamogenin, tigogenin, and diosgenin. Conclusions The obtained results complement the data on the cytotoxic activity of Foenugraeci Semen and synergistic effect of flavonoids and saponins complex contained in the plant.

Antibiotics Susceptibility Profile and Synergistic Effects of Flavonoids with Antibiotics against Resistant Staphylococcus aureus from Asymptomatic Individuals

Staphylococcus aureus exhibits resistance to most of the commonly used antibiotics. Although antibiotics suceptibility studies have been performed on the pathogen isolated from the patient samples, only limited information is available about that of S. aureus isolated from asymptomatic individuals. In this study, S. aureus was isolated from the skin microbiota of the asymptomatic individuals, and susceptibility of the pathogen against different antibiotics and plant flavonoids was compared to drug-sensitive strain. The minimum inhibitory concentration (MIC) value and IC50 of the pathogen were calculated against the antibiotics and flavonoids. The susceptibility pattern of the isolated strain showed higher resistance against erythromycin (100 μg mL-1) and vancomycin (25 μg mL-1). Based on the fractional inhibitory concentration index (FICI) values, the combinatory effects of antibiotics and flavonoids were categorized into synergistic, additive, and indifferent. The combination of rutin and erythromycin showed a synergistic effect with the concentrations of 31.25 μg mL-1 and 1.562 μg mL-1 against drug-sensitive strains of S. aureus. Similarly, the same combination showed synergistic effects against isolated strains at the concentration of 625 μg mL-1 and 12.5 μg mL-1.We observed an increase in drug resistance in the isolated strain of S. aureus in comparison to the drug-sensitive strain. To the best of our knowledge, this was the first study reporting increase in antimicrobial resistance of S. aureus present on asymptomatic individuals than the sensitive strain.

Prospect of Plant-based Flavonoids to Overcome Antibacterial Resistance: A Mini-Review

Although antibiotic has been frequently used for the treatment of infection, it has led to the emergence of resistant problem. Plant-derived compounds are alternative source for discovering novel therapeutics. Flavonoid is widely distributed and present in plant kingdom. This compound possessed several pharmacological properties including antibacterial. This review aims to present some information about the potency of flavonoids as antibacterial compound including their mechanism of antibacterial action as well as the relationship between their activity and flavonoid structure. The synergistic effect of flavonoids when used in combination with antibiotics against resistant bacterial is also described. Published literatures were collected from data bases such as PubMed, Google Scholar, Science Direct and Scopus. Scientific papers were selected based on information of antibacterial activity of flavonoid compounds. The information may provide an insight on the potency of flavonoid compounds to overcome resistant problem.

Spectroscopic Studies on Dual Role of Natural Flavonoids in Detoxification of Lead Poisoning: Bench-to-Bedside Preclinical Trial.

Ubiquitousness in the target organs and associated oxidative stress are the most common manifestations of heavy-metal poisoning in living bodies. While chelation of toxic heavy metals is important as therapeutic strategy, scavenging of increased reactive oxygen species, reactive nitrogen species and free radicals are equally important. Here, we have studied the lead (Pb) chelating efficacy of a model flavonoid morin using steady-state and picosecond-resolved optical spectroscopy. The efficacy of morin in presence of other flavonoid (naringin) and polyphenol (ellagic acid) leading to synergistic combination has also been confirmed from the spectroscopic studies. Our studies further reveal that antioxidant activity (2,2-diphenyl-1-picrylhydrazyl assay) of the Pb–morin complex is sustainable compared to that of Pb-free morin. The metal–morin chelate is also found to be significantly soluble compared to that of morin in aqueous media. Heavy-metal chelation and sustainable antioxidant activity of the soluble chelate complex are found to accelerate the Pb-detoxification in the chemical bench (in vitro). Considering the synergistic effect of flavonoids in Pb-detoxification and their omnipresence in medicinal plants, we have prepared a mixture (SKP17LIV01) of flavonoids and polyphenols of plant origin. The mixture has been characterized using high-resolution liquid chromatography assisted mass spectrometry. The mixture (SKP17LIV01) containing 34 flavonoids and 76 other polyphenols have been used to investigate the Pb detoxification in mouse model. The biochemical and histopathological studies on the mouse model confirm the dual action in preclinical studies.

Is a flavonoid-rich diet with steamer cooking safe during calcineurin inhibitors therapy?

Dietary therapy is recommended for decreasing the symptoms of the metabolic syndrome and the risk of type 2 diabetes and cardiovascular diseases in subjects on calcineurin inhibitors. However, food-drug interactions may occur particularly with patients on such immunosuppressive therapy. This article comments on the benefit/risk assessment of a flavonoid-rich diet and steam-cooking of such food during calcineurin inhibitors therapy. Patients are commonly advised against consuming citrus fruits and juices, grape juice and green tea. High vegetable intake may however increase the risk of food-diet interactions by inhibiting drug metabolic enzymes and transporters. Vegetable glucosinolates are potential interactants and may lead to adverse effects of drugs with narrow therapeutic indices and in the presence of genetic polymorphism. Examples of food components with potential drug interactants include all members of the Brassicaceae family. The potential additive and synergistic effects of flavonoids with other molecules in interfering with drug bioavailability need to be taken into account. The risk is highest with drugs with a narrow therapeutic index and in subjects with genetic polymorphisms of proteins involved in the disposition of those drugs.

Sensitisation of ovarian cancer cells to cisplatin by flavonoids from Scutellaria barbata

Combination of natural components with anticancer drugs is a new strategy for cancer chemotherapy to increase antitumour responses. In this study, we investigated the sensitisation effects of nine flavonoids from Scutellaria barbata to cisplatin (CDDP) on human ovarian cancer cells. The combinations of three flavonoids with CDDP showed the synergistic effects. The intracellular reactive oxygen species and the antioxidant activity were measured. The data suggest that the synergistic effects of flavonoids with CDDP on ovarian cancer cells did not directly correlate with their redox properties, but could be associated with the positions of hydroxyl group and methoxy group of flavonoids.

Bioactivity comparison of extracts from various parts of common and tartary buckwheats: evaluation of the antioxidant- and angiotensin-converting enzyme inhibitory activities

BackgroundBuckwheat flour and buckwheat sprouts possess antioxidant properties, and previous studies have reported on buckwheat flour displaying an inhibitory activity for angiotensin-I converting enzyme (ACE). Information is lacking on the bioactivity of other parts of the buckwheat, such as the seed hulls and plant stalks. This study investigates the ACE inhibitory activity and antioxidant activity of various parts of 2 types of buckwheat, namely, common buckwheat (Fagopyrum esculentum Moench) and tartary buckwheat (Fagopyrum tataricum Gaertn).ResultsThe extract of common hulls extracted using 50% (v/v)-ethanol solvent presented a remarkable inhibitory activity. The value of IC50 is 30 μg ml-1. The extracts of both common and tartary hulls extracted using 50% (v/v)-ethanol solvent demonstrated an antioxidant activity that is superior to that of other extracts.ConclusionThis study determined that the ethanolic extract of the hulls of common buckwheat presented more favorable antioxidant and ACE inhibitory abilities. However, the correlation of antioxidant activity and ACE inhibitory activity for all 18 types of extracts is low. The ACE inhibitory activity could have been caused by a synergistic effect of flavonoids or from other unidentified components in the extracts. The ethanolic extract of common hulls demonstrated remarkable ACE inhibitory activity and is worthy of further animal study.

Targeting intestinal digestive enzymes by natural products: synergistic effect of flavonoids

Diabetes is a common metabolic disorder that is caused by either inherited and/or acquired deficiency in insulin secretion or due to decreased responsiveness to insulin. One of the common approaches in the treatment of diabetes is decreasing postprandial hyperglycemia by inhibiting key enzymes for the hydrolysis of carbohydrates in the small intestine. In our laboratories, the effects of various natural products on key digestive enzymes, α-glucosidase and α -amylase, are routinely assessed [1]. It was found that some flavonoids including kaempferol-3-O-rutinoside (KR, Fig.1) are potent inhibitors of these enzymes. A synergistic enzyme inhibitory effect; e.g, between KR and flavonoid aglycones, was observed for some flavonoids. The structure activity relationship established from the study and potential therapeutic implications are discussed.

Synergistic Effects of Flavonoids on Cell Proliferation in Hepa‐1c1c7 and LNCaP Cancer Cell Lines

ABSTRACT: Fruits and vegetables contain a variety of phytochemicals, including flavonoids, which have antioxidant and anticancer properties. The purpose of this study was to evaluate the antiproliferative effects and synergistic interactions of a variety of flavonoids in Hepa‐1c1c7, a mouse liver cancer cell line, and LNCaP, a human prostate cancer cell line. Aglycone flavonoids, such as quercetin, kaempferol, and naringenin (at 12.5 to 50 μM), inhibited cancer cell proliferation in both cell lines in a dose dependent manner without cytotoxicity. In contrast, glycone flavonoids (rutin, quercetrin, and naringin) did not inhibit cell growth. Significant synergistic antiproliferative effects were demonstrated in both cancer cell lines when flavonoids were provided in combination treatments. These results suggest that combinations of flavonoids, which are naturally present in whole fruits and vegetables, are more effective in cancer cell growth inhibition than the individual flavonoids.

Synergistic effects of flavonoids and ascorbate on enhancement in DNA degradation induced by a bleomycin–Fe complex

Flavonoids were examined for synergistic effects with ascorbate on enhancement of DNA degradation induced by a bleomycin(BLM)–Fe complex. The synergistic effects of flavonoids and ascorbate on DNA degradation induced by the BLM–Fe complex were observed to be greater with flavonoids such as isorhamnetin, kaempferol and morin, which accelerated oxidation more markedly in the presence, than in the absence of BLM. Conversely, myricetin and fisetin, which showed oxidation barely accelerated by the addition of BLM, inhibited DNA degradation promoted by ascorbate. Consequently, there was a good correlation between oxidation of flavonoids accelerated by BLM and the extent of DNA degradation promoted synergistically with ascorbate. Our previous studies indicated that oxidation of flavonoids accelerated by BLM and DNA degradation promoted by flavonoids were not correlated with Fe(III)-reducing activity of flavonoids. Those results suggest that Fe(III)-reducing activity of flavonoids is not the only factor determining DNA degradation-promoting activity induced by the BLM–Fe complex. On the other hand, in a Fenton reaction, degradation of 2-deoxy-d-ribose promoted by flavonoids was correlated to the Fe(III)-reducing activity of flavonoids. However, there was not a synergistic interaction between flavonoids and ascorbate in the degradation of 2-deoxy-d-ribose. Therefore, it is suggested that the synergistic DNA degradation caused by flavonoids and ascorbate in the BLM–Fe redox cycle arose from the difference in the reductive processes in which flavonoids and ascorbate mainly act.

Flavonoids quercetin, myricetin, kaemferol and (+)-catechin as antioxidants in methyl linoleate

The antioxidant effect of the flavonoids quercetin, myricetin, kaemferol, (+)-catechin and rutin on methyl linoleate oxidation was investigated. In addition, the synergistic effects of flavonoids and α-tocopherol were studied. Oxidation was monitored by conjugated diene measurement and by determining the formation of hydroperoxide isomers by HPLC. The antioxidant activity of flavonoids in non-polar methyl linoleate differ from that previously reported in water-containing systems, such as LDL and liposome systems. The activity of antioxidants (10–1000 μM) measured by hydroperoxide formation decreased in the order: myricetin>quercetin>α-tocopherol>(+)-catechin >kaemferol=rutin. The antioxidant activity of flavonoids increased as the number of phenolic hydroxyl groups increased. In addition to the number of hydroxyl groups, other structural features such as the 2,3 double bond in the C-ring and a glycoside moiety in the molecule had an effect on the antioxidant activity. Myricetin and rutin, especially had a synergistic effect with α-tocopherol. Myricetin, quercetin and rutin protected α-tocopherol from decomposition, myricetin being the most protective. The relative hydrogen-donating activity measured by the ratio of cis,trans- to trans,transhydroperoxide isomers formed during oxidation decreased in the order: α-tocopherol >myricetin>quercetin. Hydroperoxide isomeric distribution of the samples containing kaemferol or rutin did not differ from the control. Thus, although α-tocopherol was the most effective hydrogendonor, myricetin and quercetin were more effective antioxidants in inhibiting the hydroperoxide formation in methyl linoleate. © 1999 Society of Chemical Industry