Related Flavonoids Research Articles

Inhibition of angiotensin convertin enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3- O-sambubiosides from Hibiscus sabdariffa

Ethnopharmacological relevance The beverages of Hibiscus sabdariffa calyces are widely used in Mexico as diuretic, for treating gastrointestinal disorders, liver diseases, fever, hypercholesterolemia and hypertension. Different works have demonstrated that Hibiscus sabdariffa extracts reduce blood pressure in humans, and recently, we demonstrated that this effect is due to angiotensin converting enzyme (ACE) inhibitor activity. Aim of the study The aim of the current study was to isolate and characterizer the constituents responsible of the ACE activity of the aqueous extract of Hibiscus sabdariffa. Materials and methods Bioassay-guided fractionation of the aqueous extract of dried calyces of Hibiscus sabdariffa using preparative reversed-phase HPLC, and the in vitro ACE Inhibition assay, as biological monitor model, were used for the isolation. The isolated compounds were characterized by spectroscopic methods. Results The anthocyanins delphinidin-3- O-sambubioside ( 1) and cyanidin-3- O-sambubioside ( 2) were isolated by bioassay-guided purification. These compounds showed IC 50 values (84.5 and 68.4 μg/mL, respectively), which are similar to those obtained by related flavonoid glycosides. Kinetic determinations suggested that these compounds inhibit the enzyme activity by competing with the substrate for the active site. Conclusions The competitive ACE inhibitor activity of the anthocyanins 1 and 2 is reported for the first time. This activity is in good agreement with the folk medicinal use of Hibiscus sabdariffa calyces as antihypertensive.

Distribution of rutin in fava d'anta (Dimorphandra mollis) seedlings under stress

Fava d'anta is a tree rich in the flavonoid rutin; it is found mainly in the Brazilian savannah, which is called the cerrado and has a defined drought season. The distribution of rutin in fava d'anta seedlings was studied at different developmental stages and in an adult tree. In addition, the effects of flooding, drought and salinity on the content of this flavonoid in seedlings were investigated. Rutin was found in all of the analyzed fava d'anta plant parts, and its content was always higher than quercetin, a related flavonoid. Young leaves showed the highest rutin content. In general, the stresses caused an increase in both of the flavonoids in the seedling leaves, with some variation depending on the leaf age. Seedlings under stress showed a similar growth to the control seedlings, suggesting that rutin may have a role in protecting the tissues against oxidative damage during drought periods in its natural habitat.

Micromorphological investigation on the leaves of the rock samphire (Crithmum maritimum L.): Occurrence of hesperidin and diosmin crystals

A micromorphological study was carried out on Crithmum maritimum L. (rock samphire), a halophyte belonging to the Apiaceae and used in folk medicine. The study led to the finding of relevant amounts of two closely related flavonoids, namely diosmin and hesperidin, which attract increasing interest for their biological properties. Anatomical investigations of leaf tissue showed the presence of needle‐shaped crystals forming plumose clusters, mainly located close to, or within, vascular bundles. Scanning electron microscopy (SEM) analysis provided a more detailed morphological characterization of crystals, while the absence of mineral elements in their composition was assessed by SEM‐EDX. High performance liquid chromatography (HPLC) analysis of leaf tissue was conducted to detect hesperidin and diosmin and to quantify their amounts. SEM analysis of two Rutaceae plants rich in hesperidin and diosmin, i.e., Citrus limon and Barosma betulina, revealed the same plumose crystals found in C. maritimum, while in these plants the two flavonoids were also quantified by HPLC. The data clearly indicate the occurrence of hesperidin and diosmin crystals in C. maritimum leaves, thus providing a scientific basis for an exploitation of this plant in saline agriculture, as a crop or source of bioactive phytocompounds.

Abyssinones and related flavonoids as potential steroidogenesis modulators.

Abyssinones and related flavonoids were screened against 3 enzymes (3betaHSD, 17betaHSD and Aromatase) of steroidogenesis pathway. The virtual screening experiment shows high affinity for flavonones than their respective chalcones. A 4' -OH blocked prenylated flavonone 2b (2-(2', 2'-dimethyl chroman-6'-yl)-7-hydroxy chroman-4-one) had consistent binding affinity to all the three enzymes used in this study showing higher binding affinity to aromatase. A good correlation was observed between cytotoxic data (MCF-7, breast cancer cell line) and docking results indicating flavonone as a better steroidogenesis modulator in hormone dependent cancer.

Antifeedant activity of ethanolic extract from Flourensia oolepis and isolation of pinocembrin as its active principle compound

The ethanolic extract from Flourensia oolepis aerial parts showed strong antifeedant activity against the pest larvae, Epilachna paenulata, with an antifeedant index (AI%) of 99.1% at 100 μg/cm 2. Based on chromatographic fractionation of the extract, guided by bioassays on E. paenulata, the flavanone pinocembrin ( 1) was isolated as the most active principle. In a choice assay, compound 1 showed strong antifeedant activity against E. paenulata, Xanthogaleruca luteola and Spodoptera frugiperda with an AI% of 90, 94 and 91% ( p < 0.01) respectively, at 50 μg/cm 2. The dosages necessary for 50% feeding inhibition of the insects (ED 50) were 7.98, 6.13 and 8.86 μg/cm 2, respectively. The feeding inhibitory activity of 1 against E. paenulata was compared with the activity of other structurally related flavonoids like naringenin, which was inactive up to 100 μg/cm 2, catechin which was nearly 6 times less active than 1, and quercetin which was equally active as 1. The effect of these on the feeding behavior of E. paenulata was also studied.

Hepatoprotective activity of leaves of Rhododendron arboreum in CCl4 induced hepatotoxicity in rats

The study was designed to evaluate the hepatoprotective activity of pre-treatment with ethanolic extract of leaves of Rhododendron arboreum against carbon tetrachloride-induced hepatotoxicity in Wistar rat model. Liver damage was induced in experimental animals by administering CCl4. The ethanolic extract of R. arboreum (40, 60 and 100 mg/kg, po) was given for five days. Silymarin (100 mg/kg, po) was given as the reference drug. Hepatoprotective effect was studied by assaying the activities of serum marker enzymes like SGPT, SGOT, ALP, direct and total bilirubin, triglycerides, cholesterol and estimation of ascorbic acid in urine. The activities of all the marker enzymes registered a significant elevation in CCl4 treated rats, which were significantly recovered towards an almost normal level in animals co-administered with ethanolic extract of leaves of R. arboreum at a dose of 60 and 100 mg/kg. Ethanolic extract of leaves of R. arboreum prevented decrease in the excretion of ascorbic acid in CCl4 induced hepatotoxicity in rats. Histopathological analysis confirmed the biochemical investigations. The results indicate that leaves of R. arboreum possess hepatoprotective property possibly because of its reported anti-oxidant activity. This property may be attributed to the quercetin related flavonoids, saponins and phenolic compounds present in the leaves of R. arboreum.

Structure-spectrophotometric selectivity relationship in interactions of quercetin related flavonoids with double stranded and single stranded RNA

Interactions of five flavonoids with dsRNA and single stranded ssRNA were studied by UV/vis titrations. The results obtained supported the intercalative binding mode as a dominant interaction of studied flavonoids with dsRNA as well as major interaction with ssRNA. Furthermore, changes of the UV/vis spectra of flavonoids induced by addition of poly G or poly C, respectively, are significantly stronger than changes induced by double stranded poly G-poly C, pointing to essential role of the free poly G or poly C sequence (not hydrogen bonded in double helix). Exclusively poly G caused significant batochromic shift of the UV/vis maxima of all studied flavonoids, whereby the intensity of batochromic shift is nicely correlated to the number of OH groups of flavonoid. Unlikely to poly G, addition of poly A and poly U induced measurable changes only in the UV/vis spectra of flavonoids characterised by no OH (galangin) or three OH groups (myricetin) on the phenyl part of the molecule. Consequently, flavonoids with one- or two-OH groups on the phenyl part of the molecule (luteolin, fisetin, kaempferol) specifically differentiate between poly A, poly U (negligible changes in the UV/Vis spectra) and poly G (strong changes in the UV/Vis spectra) as well as poly C (moderate changes in the UV/Vis spectra).

Structural requirements for the flavonoid fisetin in inhibiting fibril formation of amyloid β protein

Fisetin (3,3′,4′,7-tetrahydroxyflavone) has been found to be neuroprotective, induce neuronal differentiation, enhance memory, and inhibit the aggregation of the amyloid β protein (Aβ) that may cause the progressive neuronal loss in Alzheimer's disease. The diverse collection of biological activities of this compound may lead to a new type of therapeutic drug for Alzheimer's disease. As the first step to design even more effective drugs based upon the structure of fisetin, the present study investigated the structural requirements for the anti-amyloidogenic activity of fisetin by comparing the effects of several structurally related flavonoids on Aβ fibril formation in vitro. Aβ1-42 (20 μM) and the flavonoids were incubated for 0–48 h at 37 °C, and fibril formation was quantitatively determined by the thioflavin T fluorescence assay. Among ten flavonoids tested, fisetin, 3′,4′,7-trihydroxylflavone, 3,3′,4′-trihydroxyflavone, luteolin, quercetin and myricetin inhibited Aβ fibril formation. On the other hand, 3,3′,7-trihydroxyflavone, 5-deoxykaempferol, chrysin and kaempferol enhanced Aβ fibril formation. These results suggest that the 3′,4′-dihydroxyl group, but not the 3- or 7-hydroxyl group, is essential for the inhibitory effect of fisetin on Aβ fibril formation.

Biochemical and genetic characterization of Arabidopsis flavanone 3β-hydroxylase

Flavanone 3beta-hydroxylase (F3H; EC 1.14.11.9) is a 2-oxoglutarate dependent dioxygenase that catalyzes the synthesis of dihydrokaempferol, the common precursor for three major classes of 3-hydroxy flavonoids, the flavonols, anthocyanins, and proanthocyanidins. This enzyme also competes for flux into the 3-deoxy flavonoid branch pathway in some species. F3H genes are increasingly being used, often together with genes encoding other enzymes, to engineer flavonoid synthesis in microbes and plants. Although putative F3H genes have been cloned in a large number of plant species, only a handful have been functionally characterized. Here we describe the biochemical properties of the Arabidopsis thaliana F3H (AtF3H) enzyme and confirm the activities of gene products from four other plant species previously identified as having high homology to F3H. We have also investigated the surprising "leaky" phenotype of AtF3H mutant alleles, uncovering evidence that two related flavonoid enzymes, flavonol synthase (EC 1.14.11.23) and anthocyanidin synthase (EC 1.14.11.19), can partially compensate for F3H in vivo. These experiments further indicate that the absence of F3H in these lines enables the synthesis of uncommon 3-deoxy flavonoids in the Arabidopsis seed coat.

Inhibition of Polymorphic Human Carbonyl Reductase 1 (CBR1) by the Cardioprotectant Flavonoid 7-monohydroxyethyl Rutoside (monoHER)

Carbonyl reductase 1 (CBR1) reduces the anticancer anthracyclines doxorubicin and daunorubicin into the cardiotoxic metabolites doxorubicinol and daunorubicinol. We evaluated whether the cardioprotectant monoHER inhibits the activity of polymorphic CBR1. We performed enzyme kinetic studies with monoHER, CBR1 (CBR1 V88 and CBR1 I88) and anthracycline substrates. We also characterized CBR1 inhibition by the related flavonoids triHER and quercetin. MonoHER inhibited the activity of CBR1 V88 and CBR1 I88 in a concentration-dependent manner. The IC(50) values of monoHER were lower for CBR1 I88 compared to CBR1 V88 for the substrates daunorubicin and doxorubicin (daunorubicin, IC(50)-CBR1 I88 = 164 microM vs. IC(50)-CBR1 V88 = 219 microM; doxorubicin, IC(50)-CBR1 I88 = 37 microM vs. IC(50)-CBR1 V88 = 59 microM; p < 0.001). Similarly, the flavonoids triHER and quercetin exhibited lower IC(50) values for CBR1 I88 compared to CBR1 V88 (p < 0.001). MonoHER acted as a competitive CBR1 inhibitor when using daunorubicin as a substrate Ki = 45 +/- 18 microM. MonoHER acted as an uncompetitive CBR1 inhibitor for the small quinone substrate menadione Ki = 33 +/- 17 microM. The cardioprotectant monoHER inhibits CBR1 activity. CBR1 V88I genotype status and the type of anthracycline substrate dictate the inhibition of CBR1 activity.

The flavonoid fisetin promotes nerve cell survival from trophic factor withdrawal by enhancement of proteasome activity

To explore the possibility that specific flavonoids can substitute for neurotrophic factors, we examined the ability of the flavonol fisetin and several related flavonoids to support the survival of low density, serum-free cultures of rat cortical neurons. Normally these cells die within 24 h in the absence of trophic factors but in the presence of fisetin and several related flavonoids the cells survive and produce long neurites. While the survival-promoting effect of several of the fisetin-related flavonoids was partially dependent on ERK activation, the effect of fisetin was not. Fisetin can enhance glutathione synthesis but the survival-promoting effect of fisetin was also not dependent on glutathione. However, proteasome inhibitors almost completely blocked the ability of fisetin to promote survival. Consistent with this observation, fisetin increased proteasome activity. Together these results demonstrate a new activity for fisetin and tie this activity to its neurotrophic effects.

Evaluation of the Radioprotective Effects of Propolis and Flavonoids in Gamma-Irradiated Mice: The Alkaline Comet Assay Study

The radioprotective effects of water-soluble derivate of propolis (WSDP) collected in Croatia, and single flavonoids, caffeic acid, chrysin and naringin in the whole-body irradiated CBA mice were investigated. Irradiation was performed using a gamma-ray source ((60)Co), and absorbed doses were 4 and 9 Gy. The efficiency of test components was evaluated when given intraperitoneally (i.p.) at dose of 100 mg kg(-1) for 3 consecutive days before and/or after irradiation. Moreover, possible genotoxic effects of all test components were assessed on non-irradiated animals. The higher efficiency of test components was observed when given preventively. The results suggest that propolis and related flavonoids given to mice before irradiation protected mice from lethal effects of whole-body irradiation and diminish primary DNA damage in their white blood cells as detected by the alkaline comet assay.

Acetylcholinesterase-Inhibitory Activity of Linarin from Buddleja davidii, Structure-Activity Relationships of Related Flavonoids, and Chemical Investigation of Buddleja nitida

In order to find some medicinal value for invasive neophytes, inhibition of acetylcholinesterase of Reynoutria sachalinensis F. Schmidt ex Maxim. (Polygonaceae), Polygonum cuspidatum Siebold. & Zucc. (Polygonaceae), Heracleum mantegazzianum Sommier & Levier (Apiaceae), Buddleja davidii Franch. (Buddlejaceae), and Ambrosia artemisiifolia L. (Asteraceae) was prescreened by a bioautographic TLC assay. Activity was found in the methanol extract of the leaves of the common ornamental bush B. davidii. Its fractionation by centrifugal partition chromatography led to the isolation of linarin as the most active compound. While extracts of Buddleja nitida Benth. (Buddlejaceae) from Panama were inactive, some constituents were identified on the basis of a comparison with B. davidii by HPLC-MS/MS. Structure-activity relationships of linarin and related flavonoids were investigated. For this purpose, fortunellin and tilianin were prepared by methylation reactions. It appears that the structural elements important for acetylcholinesterase inhibition are not only the 4′ -OMe group, but also the 7-substituted sugar and the pattern of substitution on the B-ring.

Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: Lack of association between antioxidant and lipoxygenase inhibitory activity

Dietary flavonoids are thought to have health benefits possibly due to antioxidant and anti-inflammatory properties. Many previous in vitro studies examining the bioactivity of flavonoids have failed to consider the effects of metabolic transformation on flavonoid activity. In this study we examined the effect of quercetin and its major metabolites on the production of pro-inflammatory eicosanoids by human leukocytes. Studies comparing free radical scavenging, antioxidant activity and eicosanoid production demonstrate that there are different structural requirements for antioxidant and anti-inflammatory activity. We also investigated the effect of metabolic transformation on flavonoid bioactivity by comparing the activity of quercetin and its major metabolites to inhibit inflammatory eicosanoid production from human leukocytes. Quercetin was a potent inhibitor of leukotriene B 4 formation in leukocytes (IC 50 ∼ 2 μM), and its activity was dependent on specific structural features, particularly the 2,3-double bond of the C-ring. Functionalisation of the 3′-OH group with either methyl or sulfate reduced inhibitory activity up to 50% while a glucuronide substituent at the 3-OH effectively removed the LTB 4 inhibitory activity. The major quercetin metabolite quercetin-3′- O-sulfate retained considerable lipoxygenase inhibitory activity (IC 50 ∼ 7 μM) while quercetin-3- O-glucuronide maintained antioxidant activity but had no lipoxygenase inhibitory activity at physiological concentrations. In conclusion, we have found that structural modification of quercetin due to metabolic transformation had a profound effect on bioactivity, and that the structural features required for antioxidant activity of quercetin and related flavonoids were unrelated to those required for inhibition of inflammatory eicosanoids.

Differential apoptotic effect of wogonin and nor‐wogonin via stimulation of ROS production in human leukemia cells

We investigate the roles of methoxyl (OCH(3)) and hydroxyl (OH) substitutions at C8 of flavonoids on their apoptosis-inducing activities. Wogonin (Wog) and nor-wogonin (N-Wog) are structurally related flavonoids, and respectively contain an OH and OCH(3) at C8. In leukemia HL-60 cells, N-Wog exhibited more-potent cytotoxicity than Wog according to the MTT and LDH release assays, and the IC(50) values of Wog and N-Wog in HL-60 cells were 67.5 +/- 2.1 and 21.7 +/- 1.5 microM, respectively. Apoptotic characteristics including DNA ladders, apoptotic bodies, and hypodiploid cells accompanied by the induction of caspase 3 protein processing appeared in Wog- and N-Wog-treated HL-60 cells. Interestingly, an increase in intracellular peroxide production was detected in N-Wog- but not Wog-treated HL-60 cells by the DCHF-DA assay, and the reduction of intracellular peroxide by catalase (CAT) induced by N-Wog significantly reduced the N-Wog- but not the Wog-induced cytotoxic effect according to the MTT assay in accordance with the blocking of DNA ladder formation and caspase 3 and PARP protein processing elicited by N-Wog. We further analyzed the effect of six structurally related compounds, including 5-OH, 7-OH, 5,7-diOH, 5,7-diOCH(3), 7,8-diOCH(3), and 7-OCH(3)-8-OH flavones, on apoptosis induction in HL-60 cells. Results suggested that OH at C5 and C7 is essential for both the apoptosis-inducing activity of flavonoids, and OH at C8 may contribute to apoptosis induction ability. Evidence to support a distinct structure-activity relationship in apoptosis induction of flavonoids is provided for the first time in this study.

Myricitrin as a substrate and inhibitor of myeloperoxidase: Implications for the pharmacological effects of flavonoids

Flavonoids are increasingly being ingested by the general population as chemotherapeutic and anti-inflammatory agents. They are potentially toxic because of their conversion to free radicals and reactive quinones by peroxidases. Little detailed information is available on how flavonoids interact with myeloperoxidase, which is the predominant peroxidase present at sites of inflammation. This enzyme uses hydrogen peroxide to oxidize chloride to hypochlorous acid, as well as to produce an array of reactive free radicals from organic substrates. We investigated how the flavonoid myricitrin is oxidized by myeloperoxidase and how it affects the activities of this enzyme. Myricitrin was readily oxidized by myeloperoxidase in the presence of hydrogen peroxide. Its main oxidation product was a dimer that underwent further oxidation. In the presence of glutathione, myricitrin was oxidized to a hydroquinone that was conjugated to glutathione. When myeloperoxidase oxidized myricitrin and related flavonoids it became irreversibly inactivated. The number of hydroxyl groups in the B ring of the flavonoids and the presence of a free hydroxyl m-phenol group in the A ring were important for the inhibitory effects. Less enzyme inactivation occurred in the presence of chloride. Neutrophils also oxidized myricitrin to dimers in a reaction that was partially dependent on myeloperoxidase. Myricitrin did not affect the production of hypochlorous acid by neutrophils. We conclude that myricitrin will be oxidized by neutrophils at sites of inflammation to produce reactive free radicals and quinones. It is unlikely to affect hypochlorous acid production by neutrophils.

Flavonoids Affect Actin Functions in Cytoplasm and Nucleus

Based on the identification of actin as a target protein for the flavonol quercetin, the binding affinities of quercetin and structurally related flavonoids were determined by flavonoid-dependent quenching of tryptophan fluorescence from actin. Irrespective of differences in the hydroxyl pattern, similar K d values in the 20 μM range were observed for six flavonoids encompassing members of the flavonol, isoflavone, flavanone, and flavane group. The potential biological relevance of the flavonoid/actin interaction in the cytoplasm and the nucleus was addressed using an actin polymerization and a transcription assay, respectively. In contrast to the similar binding affinities, the flavonoids exert distinct and partially opposing biological effects: although flavonols inhibit actin functions, the structurally related flavane epigallocatechin promotes actin activity in both test systems. Infrared spectroscopic evidence reveals flavonoid-specific conformational changes in actin which may mediate the different biological effects. Docking studies provide models of flavonoid binding to the known small molecule-binding sites in actin. Among these, the mostly hydrophobic tetramethylrhodamine-binding site is a prime candidate for flavonoid binding and rationalizes the high efficiency of quenching of the two closely located fluorescent tryptophans. The experimental and theoretical data consistently indicate the importance of hydrophobic, rather than H-bond-mediated, actin-flavonoid interactions. Depending on the rigidity of the flavonoid structures, different functionally relevant conformational changes are evoked through an induced fit.

Inhibitory Effects of Cissus quadrangularis L. Derived Components on Lipase, Amylase and α-Glucosidase Activity in vitro

The stems of Cissus quadrangularis L (Vitaceae) have been consumed for centuries throughout Asia and Africa as a culinary vegetable. The aqueous extract of C. quadrangularis stems and leaves contains flavonoids and stilbenes, which inhibit lipase, amylase and α-glucosidase and, therefore, might be, at least in part, related to the claimed anti-obesity activity of the plant. The enzyme inhibition activity is outlined of a novel flavonoid (3- O-α-L-rhamnopyranosylkaempferol) (2) and stilbene (3-(4-hydroxybenzylidene)-2-(2,5-dihydroxyphenyl)-1-(4-hydroxyphenyl)indane-4,6-diol) (7), four known structurally related flavonoids, and one stilbene isolated from the extract.

Inhibition of lipid peroxidation in UVA‐treated skin fibroblasts by luteolin and its glucosides

AbstractUltraviolet A (UVA) radiation causes oxidative damage to human skin cells. This damage may be reduced or prevented using plant compounds as photoprotectants. To investigate the relationship between chemical structure and UVA‐protective activity, three structurally related flavonoids, namely luteolin, luteolin‐7‐O‐glucoside (both present in artichoke) and luteolin‐4'‐O‐glucoside (present in wild carrot), were studied. Human skin fibroblasts exposed to UVA (250 and 500 kJ/m2) were treated with each flavonoid (30 µM) for 18 h prior to irradiation. The extent of lipid peroxidation in the cellular extracts was assessed as lipid peroxides and malondialdehyde (MDA). Luteolin and luteolin‐7‐O‐glucoside both prevented a significant increase in lipid peroxides at 250 kJ/m2, but at 500 kJ/m2 their effectiveness was clearly attenuated. Contrastingly, luteolin‐4'‐O‐glucoside was pro‐oxidant at both radiation doses. Measurements of MDA levels highlighted that luteolin was clearly more effective than the two glucosides at both 250 and 500 kJ/m2. Overall, these results show clear differences between the three flavonoids and suggest that the B ring 3',4'‐dihydroxy group, lacking in luteolin‐4'‐O‐glucoside, may be particularly important. Flavonoid: transition metal ion chelation studies confirmed the influence of the 3',4'‐dihydroxy group, which is also relevant to the quenching of singlet oxygen. These features as well as the greater lipophilic nature of luteolin together explain the superior activity of this flavonoid which may be potentially useful as a supplement in photoprotective skin preparations.

Isovitexin‐2″‐O‐β‐[6‐O‐E‐p‐coumaroylglucopyranoside] from UV‐B irradiated Leaves of Rice, Oryza sativa L. Inhibits Fertility of Helicoverpa armigera

UV-B irradiated rice leaves (Oryza sativa L.) contained four closely related flavonoids, with either an isoorientin or isovitexin aglycone. These flavonoids have previously been purified and characterized, and were added to artificial diets of the African bollworm (Helicoverpa armigera Hübner) at 0.1x concentration found in irradiated rice leaves. Consumption of different diets had relatively small effects on laval, pupal and adult duration, weight and survival, indicating the insects lived near normal life cycles on all diets. However, one of the compounds, flavonoid IIa, isovitexin-2''-O-beta-[6-O-E-p-coumaroylglucopyranoside], dramatically reduced the number of fertile eggs laid to 7% of control insects (P<0.001) when added to insect diets at 18 nmol gFW(-1) (14 ppm). A similar antifertility effect was observed when only the male partner consumed diet containing flavonoid IIa, indicating that the reduced fertility may be male specific. In contrast, the fecundity and fertility of insects eating diets containing the closely related flavonoids, isoorientin-2''-O-beta-[6-O-E-p-coumaroylglucopyranoside] or isoorientin-2''-O-beta-[6-O-E-p-feruloylglucopyranoside], were not significantly different to control diets.