Effects Of Various Flavonoids Research Articles

Protective Role of Myricetin and Fisetin Against Nephrotoxicity Caused by Lead Acetate Exposure through Up-regulation of Nrf2/HO-1 Signalling Pathway.

The effect of various flavonoids against oxidative stress and inflammation caused by lead exposure has been investigated. However, the protective effects of myricetin (MYC) and fisetin (FST), which are known to have potent antioxidant properties, against nephrotoxicity caused by exposure to lead acetate (LA), the water-soluble form of lead, have not been investigated. Our study investigated the protective role of these flavonoids against LA intoxication-induced nephrotoxicity. In our study, 42 male rats were used. The rats were randomly selected and divided into 6 groups. These groups were: control, LA (100g/kg), LA + MYC (100mg/kg), LA + MYC (200mg/kg), LA + FST (100mg/kg) and LA + FST (200mg/kg). All chemicals were administered daily by gavage for 28 days. According to the experimental protocol, the animals were sacrificed and their kidney tissues were isolated. Serum biochemical parameters, histological examinations, levels of several trace elements, oxidative stress and inflammatory parameters at both biochemical and molecular levels in kidney tissues were examined. After LA administration, tissue lead levels increased and zinc levels decreased. This situation was reversed by MYC and FST treatment. Oxidative stress and inflammatory response were increased in the kidney tissue of LA-treated rats and renal function was impaired. It was observed that both doses of MYC and high dose of FST could prevent nephrotoxicity. Oral administration of both doses of MYC and high dose FST ameliorated the changes in biochemical, oxidative and inflammatory parameters. Restoration of normal renal tissue architecture was also demonstrated by histological studies. MYC and FST were found to have promising biological activity against LA-induced nephrotoxicity, acting by attenuating inflammation and oxidative stress and improving antioxidant status.

Effects of Flavonoids on Skin according to Their Structural Characteristics: A Review

Functional materials with anti-aging properties that prevent aging in the human body in advance have been attracting attention in the pharmaceutical, food, and cosmetic industries, and active research regarding cosmetic ingredients employing flavonoids among such substances is underway. Therefore, this general review assessed previous studies regarding the effect of various flavonoids on the skin according to their structural characteristics. In this study, the antioxidant, whitening, and antiinflammatory effects of flavonoids present in natural extracts were analyzed. Among the flavonoids, the collagen activity enhancing, antioxidant, anti-inflammatory, and whitening effects of apigenin, baicalein, genistein, naringenin, hesperetin, proanthocyanidins, quercetin, and kaempferol were evaluated. In addition, a study conducted to increase the bioavailability of flavonoids by converting them into clathrates using the structural characteristics of β-cyclodextrin, which further analyzed the difference in the effects of glycoside-containing and non-glycoside flavonoids, was reviewed. Another study reported that the 3'-hydroxyl functional group of flavonoids plays an important role in their antioxidant and anti-inflammatory activities; hence, effects consequent to the modification of their molecular structure were expected. Therefore, the studies that suggest that structural modifications can supplement the efficacy of verified flavonoids are considered to be valid. In future, flavonoids may be used as a stable anti-aging material on the basis of this study on their effects on the skin according to their structural characteristics.

In vitro potential of flavonoids from tartary buckwheat on antioxidants activity and starch digestibility

SummaryThe effects of various flavonoids of Tartary buckwheat (rutin‐enhanced flavonoid extract [REFE and quercetin‐enhanced flavonoid extract [QEFE]) and individual flavonoids (rutin, quercetin and kaempferol) on the antioxidant activity, inhibition of α‐glucosidases and α‐amylase and starch digestibility were evaluated. Quercetin possessed the highest antioxidant activity and inhibition of α‐glucosidases and α‐amylase activity followed by kaempferol and rutin. REFE and QEFE have similar antioxidant and inhibition of α‐amylase activities, but QEFE has much higher α‐glucosidases inhibition than REFE. Tartary buckwheat flour has the lowest content of rapidly digestible starch and predicted glycaemic index (pGI) compared to maize flour, wheat flour and rice flour. Addition of rutin and quercetin to wheat flour showed a weak or no effect on digestion inhibition, but they inhibited starch digestion under solid complex conditions. Our results may help explain the benefits of supplementing the diet with food rich in flavonoids.

Effect of plant secondary metabolites on common cutworm, Spodoptera litura (Lepidoptera: Noctuidae)

AbstractThe effect of various flavonoids, lectins and phenyl β‐D‐glucoside on larval survival, weights and the activities of digestive (total serine protease and trypsin) and detoxifying (esterase and glutathione‐S‐transferase) enzymes of Spodoptera litura larvae at 7 days after treatment was studied through diet incorporation assay. Flavonoids (rutin, chlorogenic acid, quinic acid, caffeic acid, naringenin, quercitin, kaempferol, myricetin, catechin, and ferulic acid) were incorporated in artificial diet at 100, 500 and 1000 ppm, lectins: groundnut leaf lectin (GLL), concavalin A (ConA) and phenyl β‐D‐glucoside at 1, 2 and 5 μg/mL. Flavonoids such as rutin, quercitin and kaempferol at 1000 ppm were more toxic to S. litura larvae than quinic acid, caffeic acid, naringenin, myricetin, catechin, and ferulic acid. Larval growth and development were significantly reduced in S. litura larvae fed on a diet with GLL and ConA at 5 μg/mL compared to the larvae fed at 2 and 1 μg/mL concentrations. The larvae fed on flavonoid‐treated diets showed significant reduction in serine protease, trypsin and esterase activities. The flavonoids such as rutin, chlorogenic acid, quinic acid, naringenin, quercitin, kaempferol and myricetin, and lectins, GLL and ConA can be utilized in insect control programs.

Global SUMOylation facilitates the multimodal neuroprotection afforded by quercetin against the deleterious effects of oxygen/glucose deprivation and the restoration of oxygen/glucose.

The putative neuroprotective properties of various flavonoids have long been reported. Among this class of chemicals, quercetin, a major flavone/flavonol naturally occurring in plants, deserves focused attention because of the myriad of beneficial effects observed in various invitro and invivo models of central nervous system damage/degeneration. However, the mechanisms governing the beneficial outcomes mediated by quercetin remain to be elucidated. In an effort to define the underlying molecular mechanisms, our study employed human/rat neuroblastoma cell lines (SHSY5Y and B35, respectively) and E18-derived rat primary cortical neurons upon which the effects of various flavonoids were examined. Of note, increases in the levels of global SUMOylation, a post-translational modification with the Small Ubiquitin-like MOdifier (SUMO) were pronounced. Quercetin treatment increased SUMOylation levels in both SHSY5Y cells and rat cortical neurons in a dose and time-dependent manner, possibly via the direct inactivation of certain SENPs (SUMO-specific isopeptidases). Of particular interest, cells treated with quercetin displayed increased tolerance to oxygen/glucose deprivation exposure, an invitro model of ischemia. SHSY5Y cells treated with quercetin also increased the expression of Nrf2 (via a decrease in the levels of Keap1), heme oxygenase-1 (HO-1), and nitric oxide synthase 1 (NOS1), which provide further protection from oxidative stress. In addition, the increased SUMOylation of HIF-1α was noted and deemed to be significant. We hypothesize that SUMOylated HIF-1α plays a fundamental role in the protection afforded and may underlie some of quercetin's ability to protect cells from oxygen/glucose deprivation-induced cell death, via an up-regulation of HO-1 and NOS1, which ultimately leads to the induction of pro-life NOS1/protein kinase G signaling. Quercetin acts to increase survival in the face of ischemia via an increase of SENP3 expression, the possible inactivation of SENPs 1/2, and via a decrease in KEAP1 levels (thereby increasing Nrf2 stability). These changes may then lead to increase in HIF-1α SUMOylation and HO-1 activation, followed by an up-regulation of NOS1/PKG signaling. Pathways altered via quercetin treatment within our experimental system are represented by blue arrowheads. Solid black arrows represent relationships that have been explored while a dotted arrow represents a relationship that has yet to be confirmed.

Effects of Flavonoid Compounds on β-amyloid-peptide-induced Neuronal Death in Cultured Mouse Cortical Neurons.

Excessive accumulation of β-amyloid peptide (Aβ) is one of the major mechanisms responsible for neuronal death in Alzheimer's disease. Flavonoids, primarily antioxidants, are a group of polyphenolic compounds synthesized in plant cells. The present study aimed to identify flavonoid compounds that could inhibit Aβ-induced neuronal death by examining the effects of various flavonoids on the neurotoxicity of Aβ fragment 25-35 (Aβ25-35) in mouse cortical cultures. Aβ25-35 induced concentration- and exposure-time-dependent neuronal death. Neuronal death induced by 20 µM Aβ25-35 was significantly inhibited by treatment with either Trolox or ascorbic acid. Among 10 flavonoid compounds tested [apigenin, baicalein, catechin, epicatechin, epigallocatechin gallate (EGCG), kaempferol, luteolin, myricetin, quercetin, and rutin], all except apigenin showed strong 1,1-diphenyl-2-pycrylhydrazyl (DPPH) scavenging activity under cell-free conditions. The flavonoid compounds except apigenin at a concentration of 30 µM also significantly inhibited neuronal death induced by 20 µM Aβ25-35 at the end of 24 hours of exposure. Epicatechin, EGCG, luteolin, and myricetin showed more potent and persistent neuroprotective action than did the other compounds. These results demonstrated that oxidative stress was involved in Aβ-induced neuronal death, and antioxidative flavonoid compounds, especially epicatechin, EGCG, luteolin, and myricetin, could inhibit neuronal death. These findings suggest that these four compounds may be developed as neuroprotective agents against Alzheimer's disease.

Effect of plant secondary metabolites on legume pod borer, Helicoverpa armigera

The effect of various flavonoids, lectins and phenyl β-d-glucoside on larval survival, weights and the activities of digestive (total serine protease and trypsin) and detoxifying [esterase and glutathione-S-transferase] enzymes of Helicoverpa armigera larvae at 5 and 10 days after treatment (DAT) was studied through diet incorporation assay. Flavonoids (quercetin, cinnamic acid, caffeic acid, chlorogenic acid, catechin, trihydroxyflavone, gentisic acid, ferulic acid, protocatechuic acid and umbelliferone) were incorporated in artificial diet at 100, 500 and 1000 ppm, lectins: groundnut leaf lectin (GLL), concavalin (ConA) and phenyl β-d-glucoside at 2.5 and 5 μg mL−1. Flavonoids such as chlorogenic acid, caffeic acid and protocatechuic acid at 1,000 ppm were more toxic to H. armigera larvae at 10 DAT than quercetin, catechin, cinnamic acid, trihydroxyflavone, gentisic acid, ferulic acid and umbelliferone. Larval growth and development were significantly reduced in H. armigera larvae fed on a diet with GLL and ConA at 5 μg mL−1 compared to the larvae fed at 2.5 and 1.25 μg mL−1 concentrations. The enzyme activities of the larvae were significantly reduced in flavonoid-treated diets. The flavonoids such as chlorogenic acid, caffeic acid, gentisic acid, trihydroxyflavone, catechin and protocatechuic acid, and lectins, GLL and ConA can be utilized in insect control programs.

Flavonoids inhibit the respiratory burst of neutrophils in mammals.

Neutrophils represent the front-line defence cells in protecting organisms against infection and play an irreplaceable role in the proper performance of the immune system. As early as within the first minutes of stimulation, neutrophilic NADPH oxidase is activated, and cells release large quantities of highly toxic reactive oxygen species (ROS). These oxidants can be highly toxic not only for infectious agents but also for neighboring host tissues. Since flavonoids exhibit antioxidant and anti-inflammatory effects, they are subjects of interest for pharmacological modulation of ROS production. The present paper summarizes contemporary knowledge on the effects of various flavonoids on the respiratory burst of mammalian neutrophils. It can be summarized that the inhibitory effects of flavonoids on the respiratory burst of phagocytes are mediated via inhibition of enzymes involved in cell signaling as well as via modulation of redox status. However, the effects of flavonoids are even more complex, and several sites of action, depending upon the flavonoid structure and way of application, are included.

Effects of various flavonoids isolated from Scutellaria baicalensis roots on skin damage in acute UVB-irradiated hairless mice

Solar ultraviolet (UV) radiation causes skin damage including increasing skin thickness, edema and flush. Scutellaria baicalensis roots have been traditionally used as a remedy for allergic inflammatory diseases in China and Japan. In this study, we examined the effects of four flavonoids isolated from these roots, namely 2',5, 5',7-tetrahydroxy-6',8-dimethoxyflavone (1), skullcapflavone II (2), 2(S)-2',5,6',7-tetrahydroxyflavanone (3) and 2(R), 3(R)-2',3,5,6',7-pentahydroxyflavanone (4), on acute UVB irradiation-induced skin damage in hairless mice. The four flavonoids were orally administered twice daily, at doses of 10 and 50 mg/kg, for 14 consecutive days. The UVB irradiation was performed at a dose of 200 mJ cm(-2) on days 7 and 8 after beginning oral administration of the four flavonoids. Compounds 1 and 4 prevented increases in skin thickness, levels of matrix metalloproteinases (MMP)-2 and MMP-9, and vascular endothelial growth factor (VEGF) induced by UVB irradiation. The other two flavonoids 2 and 3 had no effect. Compounds 1 and 4 isolated from Scutellaria baicalensis roots may be useful for preventing skin inflammation induced by acute UVB irradiation.

Neuroprotective effects of various flavonoids alone and in combination on lipopolysaccharide‐induced neurotoxicity in PC‐12 cells

Pro‐inflammatory cytokines have been detected in Alzheimer's disease (AD) brain suggesting that neuroinflammation also plays a role in the pathogenesis of AD. PC‐12 cells in culture respond to LPS stimuli by upregulating the levels of cytokines TNF‐alpha, IL‐1beta, nitric oxide (NO), and caspase activation thereby causing neuronal cell death. The present study investigated the neuroprotective effects of flavonoids such as fisetin, diosmetin and robinetin when administered alone and in combination, on the proinflammatory responses and apoptosis induced in LPS‐stimulated PC‐12 cells. Our studies showed that all the flavonoids alone and in combination markedly suppressed the production of TNF‐alpha, interleukin (IL)‐1beta, and nitric oxide (NO) in a dose –dependent manner, respectively. In parallel, cell apoptosis triggered by LPS and characterized with caspase‐3 activity, pro‐apoptotic gene Bad and anti‐apoptotic gene Bcl‐2 expressions were also significantly inhibited by these flavonoids. The results indicate that the inhibitory activity of flavonoids was greater when taken in combinations compared to those when taken alone. The present study suggests that flavonoids alone and in combination, might offer therapeutic opportunities to delay the progression of neuroinflammatory diseases such as AD.

No impact of oral quercetin on plasma glucose in patients with type 2 diabetes

Background Quercetin has been detected in a wide range of plant food products. It is believed that gut luminal concentrations of quercetin may be as much as 50-fold greater than those commonly attained in plasma. In vitro observations describe significant effects of various flavonoids, including quercetin, on several nutrient transporters that are active in human gut (SLGT1, GLUT2, GLUT5). This study was designed to assess the effect of orally administered quercetin on plasma glucose in patients (n=20) with type 2 diabetes. Methods A single-blind, placebo-controlled, within subject, repeated measures design was employed. Plasma glucose concentrations (0–4 hrs) during 75 gm oral glucose tolerance test were documented on two occasions; after concurrent consumption of oral quercetin placebo beverage at baseline and following the last of 5 consecutive days of oral quercetin (1500 mg) beverage. Glucose exposure estimates included; total (AUC0–4, hr*mg/dL) & incremental (iAUC0–4, hr*mg/dL) area-under-glucose-concentration time curve, partial areas, and individual glucose concentrations at key time points after glucose ingestion. Paired t-test and Wilcoxon match-pairs signed-ranks test were employed with p ≤ 0.05. Results No differences in plasma total or incremental glucose AUC (mean ± SD) were detected between placebo and quercetin exposure. AUC0–4 SD iAUC0–4 SD Placebo 871.9 269.6 309.5 158.9 quercetin 843.4 234.9 308.5 152.2 p-value 0.335 0.964 Additionally, no differences were detected in any of the other plasma glucose exposure estimates or concentrations. Conclusions Concurrent oral administration of quercetin (1500 mg) with glucose does not impact ultimate absorption of glucose in human patients with type 2 diabetes when absorption is assessed by measurement of changes in plasma glucose concentrations. Research was developed and funded by PepsiCo Global R&D.

Antimicrobial effects of various flavonoids on Escherichia coli O157:H7 cell growth and lipopolysaccharide production

Flavonoids have biofunctional effects as antioxidant and antimicrobial agents. The objective of this study was to evaluate the bactericidal activity and antilipopolysaccharide (LPS) effects of flavonoids on Escherichia coli O157:H7. The effects of flavonoids on the growth of E. coli O157:H7 were bacteriostatic rather than bactericidal at concentrations below 200 μM, and there was no significant difference among the flavonoids tested (p<0.05). LPS production in E. coli O157:H7 treated with 200 μM quercetin and naringenin decreased by 34.06±1.03 and 19.90±1.51%, respectively, relative to the control (no flavonoid). Luteolin, genkwanin, hesperetin, and apigenin caused decreases in LPS production of 69.85±1.03, 61.18±1.15, 60.74±1.10, and 58.93±0.98%, respectively, relative to the control. Based on these results, luteolin had the greater inhibitory effect on LPS production by E. coli O157:H7 than other flavonoids tested in this study.

Inhibitory effects of flavonoids on aldehyde oxidase activity

Flavonoids are an important group of natural compounds that can interfere with the activity of some enzymes. In this study, effects of various flavonoids on aldehyde oxidase (AO) activity were evaluated in vitro. AO was partially purified from guinea pig liver. The effects of 12 flavonoids from three subclasses of flavon-3-ol, flavan-3-ol and flavanone on the oxidation of vanillin and phenanthridine as substrates of AO and xanthine as a substrate of xanthine oxidase (XO) were investigated spectrophotometrically. Among the 12 flavonoids, myricetin and quercetin were the most potent inhibitors of both AO and XO. In general, the oxidation of vanillin was more inhibited by flavonoids than that of phenanthridine. Almost all of the flavonoids inhibited AO activity more potently than XO, which was more evident with non-planner flavanols. A planner structure seems to be essential for a potent inhibitory effect and any substitution by sugar moieties reduces the inhibitory effects. This study could provide a new insight into AO natural inhibitors with potential to lead to some food-drug interactions.

Protection of quercetin against ethanol-induced human hepatotoxicity is regulated is regulated via HO–1/CO system through MAPK/Nrf2 pathway

Aims: Flavonoids, including quercetin, have been reported to have potent hepatoprotective effects against oxidative stress. The protecting effects have been associated with HO–1 induction. Although a number of studies have demonstrated protecting effects of various flavonoids, the exact signalling pathway of quercetin involved in HO–1 induction during oxidative stress in liver damage is still not fully understood. Thus, we have initiated the following study to investigate the role of HO–1 induction as well as its transcriptional regulation and the effects of carbon monoxide (CO), free iron and bilirubin,–all of them catalytic by-products of HO–1.

Dietary Flavones and Flavonoles Are Inhibitors of Poly(ADP-ribose)polymerase-1 in Pulmonary Epithelial Cells ,

The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1), which was initially known to be highly activated by oxidative stress-induced DNA strand breaks, has been shown to be involved in the pathophysiology of acute and chronic inflammatory diseases. PARP-1 deficiency in mice led to the discovery of its coactivating function in the nuclear factor-kappa B-mediated gene expression and in addition, pharmaceutical inhibition of PARP-1 was shown to reduce the production of inflammatory mediators. In this study, the in vitro PARP-1-inhibiting effect of various flavonoids was investigated. The flavonoids myricetin, tricetin, gossypetin, delphinidin, quercetin, and fisetin were identified as significant inhibitors of the purified enzyme. Further evaluation of these compounds in N-methyl-N´-nitro-N-nitrosoguanidine-treated human pulmonary epithelial cells showed that the formation of the poly(ADP-ribose) polymers, as well as the decreased NAD+ levels, was reduced by quercetin, fisetin, and tricetin. Finally, IL-8 production of LPS-stimulated human pulmonary epithelial cells could be significantly reduced by these flavonoids. The results of this study indicate that specific flavonoids have PARP-1-inhibiting activity in addition to the earlier described antioxidant effects. PARP-1 inhibition and preservation of cellular NAD+ and energy production could play a role in the antiinflammatory activity of these specific flavonoids. In addition, these results indicate additional mechanisms by which flavonoids can exert antiinflammatory activity. Furthermore, these results indicate possibilities to use food-derived flavonoids in the treatment of chronic inflammatory diseases.

Effect of Flavonoids on Human Health: Old Subjects but New Challenges

Flavonoids are highly diversified plant pigments that are present in a wide range of fruits, vegetables, nuts, and beverages. They are regularly consumed in the human diet and have various biological activities including anti-inflammatory, anti-cancer, and anti-viral properties. The flavonoids maybe one of the safest non-immunogenic drugs because they are small organic compounds which have been normally absorbed by the human body for long time. During the past decades, the patents on their health effects have inflated very much and the yearly number of the patents is on an increasing trend. This review summarizes the current patents on the health effects of various flavonoids, and suggests the possible expectation that a wide variety of diseases are successful treated with newly-developed specific flavonoids or their derivatives in the near future. In recent patents, specific flavonoids were described to function as anti-oxidants, enzyme inhibitors, hormones, or immune modulators. Moreover, the recent patents also tried to provide the molecular mechanism of the flavonoid compounds on treating or preventing various human diseases. Recent mechanistic studies in molecular level make it possible that specific flavonoids are identified to have a wide range of biological properties that can contribute to the beneficial effects on human health.

Effects of flavonoid on calcium content in femoral tissue culture and parathyroid hormone-stimulated osteoclastogenesis in bone marrow culture in vitro

The effect of various flavonoids, which are present in food and plants, on bone calcium content and osteoclastogenesis were investigated to compare action of flavonoid on bone formation and bone resorption in vitro. Rat femoral-diaphyseal (cortical bone) and -metaphyseal (trabecular bone) tissues were cultured for 48 h in Dulbecco's modified Eagle's medium (high glucose) supplemented with antibiotics and bovine serum albumin. Amoung quercetin, myricetin, kaempferol, isorhamnetin, curcumin, hesperidin, or astaxanthin in the range of 10(-7)-10(-5)M, culture with quercetin (10(-6) or 10(-5)M) caused a significant increase in diaphyseal calcium content. Such an effect was not seen in other compounds. Mouse bone marrow cells were cultured for 7 days in the presence of parathyroid hormone (PTH; 10(-7)M), a bone-resorbing factor, in vitro. Culture with PTH caused a significant increase in osteoclast-like cell formation. This increase was significantly inhibited in the presence of quercetin, myricetin, kaempferol, isorhamnetin, or curcumin in the range of 10(-8)-10(-6)M. Such an effect was not seen in the case of hesperidin or astaxanthin. In addition, culture with PTH (10(-7)M) caused a significant decrease in diaphyseal calcium content. This decrease was completely prevented in the presence of quercetin, myricetin, kaempferal, or isorhamnetin of 10(-6)M. This study demonstrates that various flavonoids have a potent inhibitory effect on osteoclastogenesis and bone resorption rather than bone formation in vitro. Among various flavonoids, quercetin had a stimulatory effect on bone formation and an inhibitory effect on bone resorption in vitro.

Effects of various flavonoids on xanthine oxidase activities in vitro and on plasma uric acid levels in oxonate-induced rats

Xanthine oxidase (XO) is the key enzyme that catalyzes the oxidation of xanthine and hypoxanthine into uric acid, and plays an important role in producing hyperuricemia and gout [1]. It has been shown in the literature that flavonoids showed potent XO inhibitory activities in vitro [2]. However, less information about the in vivo hypouricemic activities of flavonoids are available. In the present study it was therefore of interest to investigate if the in vitro XO inhibitory activities of various flavonoids can be correlated with hypouricemic effects in vivo. Eight flavonoids including flavones, flavonols, and flavanones were used to inhibit the XO activity in vitro. The aglycones luteolin, apigenin, kaempferol and quercetin were shown to have potent xanthine oxidase inhibitory activities with IC50 values less than 5µM. Glycosides such as luteolin-7-O-glucoside and rutin showed weaker activities with IC50 value greater than 20µM. Eriodictyol and naringenin showed low activities with IC50 value greater than 50µM. All compounds were administered orally to oxonate-induced hyperuricemic rats at doses of 50 and 100mg/kg. None of the tested flavonoids elicited any hypouricemia in vivo after oral administration. This lack of effect might be due to the low intestinal absorption of the flavonoids or the first pass effect through the liver.

Structure–activity relations of inhibitory effects of various flavonoids on lipopolysaccharide-induced prostaglandin E2 production in rat peritoneal macrophages: Comparison between subclasses of flavonoids

A study of the structure-activity relations of the inhibitory effect of flavonoids on lipopolysaccharide (LPS)-induced prostaglandin production was carried out via a comparative examination of 39 flavonoids and related compounds. A comparison of the subclasses showed that flavones were most effective, followed by flavanones. Flavonols were less effective than those two groups. These results suggest that the C2-C3 double-bond and 4-oxo functional group of the C-ring are important factors for the high inhibition activities. Flavonoids showed the strongest inhibitory effect on the expression of Cox-2 protein. These results help to explain part of the reason for the pharmacological efficacy of flavonoids as anti-inflammatory compounds.

The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and interferon-gamma production by murine and human autoimmune T cells

Plant-derived flavonoids are inhibitors of various intracellular processes, notably phosphorylation pathways, and potential inhibitors of cellular autoimmunity. In this study, the inhibiting effects of various flavonoids on antigen-specific proliferation and interferon-gamma (IFN-γ) production by human and murine autoreactive T cells were evaluated in vitro. T-cell responses were evaluated for the human autoantigen alpha B-crystallin, a candidate autoantigen in multiple sclerosis, and for the murine encephalitogen proteolipid protein peptide PLP (139–151). The flavones apigenin and luteolin were found to be strong inhibitors of both murine and human T-cell responses while fisitin, quercitin, morin and hesperitin, members of the subclasses of flavonoles and flavanones, were ineffective. Antigen-specific IFN-γ production was reduced more effectively by flavones than T-cell proliferation, suggesting that the intracellular pathway for IFN-γ production in T cells is particularly sensitive to flavone inhibition. These results indicate that flavones but not flavanoles or flavanones are effective inhibitors of the potentially pathogenic function of autoreactive T cells. The effects of flavones were the same for human and murine autoreactive T cells, stressing the usefulness of animal models of autoimmunity for further studies on the effects of flavonones on autoimmune diseases.