Natural insecticides fromHippocratea excelsa andHippocratea celastroides

Hippocratea excelsa andHippocratea celastroides have therapeutic and insecticide applications in Mexican traditional medicine. The toxicity ofH. excelsa root cortex has been previously demonstrated against the stored grain pest Sitophilus zeamais. To identify the active compounds, several extracts (petroleum ether, CH₂Cl₂, acetone, methanol, and water) and compounds were obtained from the roots, and tested (1% w/w) with a force-feeding assay againstS. zeamais. AllH. excelsa extracts showed high antifeedant activity, and elicited moderate mortality. The triterpenoid pristimerin and a mixture of sesquiterpene evoninoate alkaloids, isolated from the hexane and methanol extracts, respectively, strongly reduced the insect feeding capacity. Other triterpenoids (friedelin, β-sitosterol, canophyllol) isolated from the hexane extract, and the alditol galactitol obtained from the water extract, were innocuous or its activity was not statistically significant. The organic extracts fromH. celastroides only showed moderate antifeedant activity, while the water extract was innocuous. Galactitol was also obtained from this extract.     

Antioxidant,antibacterial, and antimutagenic activity of Piper nigrum seeds extracts

Piper nigrum is a widely used plant in traditional remedies and known for its numerous biological properties. However, fraction-based antioxidant activity and their antimutagenic potential are not yet fully investigated. Different extracts of the seeds P. nigrum were obtained by sequential extraction in different solvents. All extracts were evaluated for antibacterial and antioxidant activities using different methods. The most active fraction was analyzed for antimutagenic activity using the Ames Salmonella test. The antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) was found to be more prominent compared to ESβL producing Klebsiella pneumoniae isolates. The MIC values were found to be lower against MRSA than K. pneumoniae. The extract showing highest antioxidant activity (methanol extract) was further tested for antimutagenic activity both against direct and indirect-acting mutagens. A varying level of antimutagenic activity was shown by methanol extract at highest tested concentration (200 µg/plate). Alkaloids, phenols, and flavonoids were detected as major class of compounds in methanol extract. Gas chromatography-mass spectrometry (GC–MS) analysis showed the presence of various phytocompounds. Based on molecular docking of two major active phytocompounds (piperine and copaene), they were found to interact at the minor groove of DNA. Molecular dynamics (MD) simulation revealed that both the ligands were quite stable with DNA under physiological conditions. The ability of phytocompounds to interact with DNA might be reducing the interaction of mutagens and could be one of the possible mechanism of anti-mutagenic activity of P. nigrum extract. This study highlights the antioxidant and antimutagenic potential of Piper nigrum. The role of phytocompounds present in the bioactive extract is needed to be explored further for herbal drug research.     

Biological effects of active fraction isolated from Hydnocarpus pentandra (Bunch. –Ham.) Oken seeds against Helicoverpa armigera (Hub.) (Lepidoptera: Noctuidae)

Hexane, chloroform, ethyl acetate and methanol extracts of Hydnocarpus pentandra (Flacourtiaceae) seeds were tested for antifeedant, larvicidal, pupal mortality and adult deformations activities against Helicoverpa armigera. Crude extracts were screened at 0.5, 1.0, 1.5 and 2.0% concentrations. Bioassay-guided fractionation method was followed to isolate the active fraction from the crude extract. Active fraction was analysed by FT-IR, ¹H NMR, ¹³C NMR and GC-MS. Hexane extract presented the highest antifeedant (87.89%), pupal mortality (41.67%) and adult malformation activities at 2% concentration. Seven different fractions were isolated from hexane extract, among which fraction-2 showed the highest antifeedant (81.43%) activity and recorded the lowest LC₅₀ of 792.07 ppm. The fraction-2 contained two cyclopentenyl carboxylic acids, such as hydnocarpic acid (1) and chaulmoogric acid (2) in the ratio of 2:1. These compounds were major constituents in the active fraction of hexane extract of H. pentandra seeds. Fraction-2 can be used for agricultural pest management.     

Biological Effects of Caesalpinia crista Seed Extracts on Helicoverpa armigera (Lepidoptera: Noctuidae) and Its Predator,Coccinella septumpunctata (Coleoptera: Coccinellidae)

Caesalpinia crista seed extracts were investigated in the laboratory against Helicoverpa armigera (Hubner). The extracts exhibited powerful antifeedant and growth disruption activity. The toxic symptoms of the poisoned larvae included reduction in weight gain and mortality of larvae and pupae, larval-pupal intermediates and malformed adults. Maximum anti-feedance is caused by methanol extract (AI₅₀=0.0186%), followed by hexane extract (0.0212%), ethyl acetate extract (0.0416%), butanol extract (0.0767%) and aqueous extract (0.2199%). The larval mortality ranged from 10.00 to 70.00% in different extracts. The 50% larval growth inhibition recorded at 3DAT was statistically at par by methanol and hexane extract. The percent 150 values for inhibiting normal adult emergence were 0.0287, 0.0325, 0.0485, 0.0977 and 0.0547% for methanol, hexane, ethyl acetate, aqueous and butanol extract. The biosafety evaluation of these extracts carried out against the predator, Coccinella septumpunctata showed no mortality of the adults till nine days after treatment. Though the observation taken at 10 DAT, showed slight mortality of adults by methanol extract at both 5.0 and 1.0% concentration.     

Leishmanicidal effects of piperine, its derivatives, and analogues on Leishmania amazonensis

Leishmaniasis is a tropical disease caused by protozoan parasites of the genus Leishmania which affects 12 million people worldwide. The discovery of drugs for the treatment of leishmaniasis is a pressing concern in global health programs. The aim of this study aim was to evaluate the leishmanicidal effect of piperine and its derivatives/analogues on Leishmania amazonensis. Our results showed that piperine and phenylamide are active against promastigotes and amastigotes in infected macrophages. Both drugs induced mitochondrial swelling, loose kinetoplast DNA, and led to loss of mitochondrial membrane potential. The promastigote cell cycle was also affected with an increase in the G1 phase cells and a decrease in the S-phase cells, respectively, after piperine and phenylamide treatment. Lipid analysis of promastigotes showed that piperine reduced triglyceride, diacylglycerol, and monoacylglycerol contents, whereas phenylamide only reduced diacylglycerol levels. Both drugs were deemed non toxic to macrophages at 50 μM as assessed by XTT (sodium 2,3,-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-2H-tetrazolium inner salt), Trypan blue exclusion, and phagocytosis assays, whereas low toxicity was noted at concentrations higher than 150 μM. None of the drugs induced nitric oxide (NO) production. By contrast, piperine reduced NO production in activated macrophages. The isobologram analysis showed that piperine and phenylamide acted synergistically on the parasites suggesting that they affect different target mechanisms. These results indicate that piperine and its phenylamide analogue are candidates for development of drugs for cutaneous leishmaniasis treatment.     

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/cm². 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/cm². The dosages necessary for 50% feeding inhibition of the insects (ED₅₀) were 7.98, 6.13 and 8.86 μg/cm², 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/cm², 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.     

Toxicity and Detoxification Mechanism of Black Pepper and Its Major Constituent in Controlling <Emphasis Type="Italic">Rhynchophorus ferrugineus</Emphasis> Olivier (Curculionidae: Coleoptera)

The survival, feeding response, and detoxification mechanism of Rhynchophorus ferrugineus Olivier, a key pest responsible for destruction of date palm, was examined with different extracts of Piper nigrum and its major constituent (piperine) identified by GC-MS. In the present study, toxicity of different extracts of black pepper was evaluated by incorporating diffferent doses of extracts into the artificial diet of red palm weevil larvae. All extracts showed dose-dependent insecticidal activity to the tested eighth-instar red palm weevil larvae. Among all the extracts, maximum larvicidal activity was exhibited by chloroform (LD₅₀ = 342.62 mg/l), followed by dichloromethane (LD₅₀ = 357.78 mg/l), acetone (LD₅₀ = 372.57 mg/l), and ethanol (LD₅₀ = 408.88 mg/l). However, piperine, a major constituent of all black pepper extracts identified by GC-MS in the present work, was found to be the most potent treatment exhibiting the least LD₅₀ (219.88 mg/l). In addition, nutritional indices evaluated by calculating the efficiency of the conversion of ingested food (ECI) and digested food (ECD) at the same dose (219.88 mg/l) showed that there was maximum reduction in the ECI (49.90%) and ECD (62.21%) index of larvae fed diets incorporated with piperine. Larvae that were fed diets incorporated with different black pepper extracts experienced increases in the expression of detoxification genes (glutathione S-transferase and cytochrome P450), and this upregulation in detoxification genes (glutathione S-transferase, cytochrome P450 and esterase) was tremendously high in larvae fed diets incorporated with piperine. Results suggest that piperine is a promising bio-pesticide agent for the control of R. ferrugineus Olivier.     

Bioactivity of semisynthetic eugenol derivatives against Spodoptera frugiperda (Lepidoptera: Noctuidae) larvae infesting maize in Colombia

The anti-acetylcholinesterase, larvicidal, antifeedant activities and general toxicity of 15 semisynthetic eugenol derivatives based on clove oil (including the own oil), were evaluated against the maize armyworm, Spodoptera frugiperda (J.E. Smith). Therefore, promising eugenol molecules were classified with larvicidal, anti-acetylcholinesterase and antifeedant activities for controlling this pest. During structure–activity relationship studies and physicochemical profile analysis, it was found that among tested molecules 1–15, eugenol 1, prenyl eugenol 4, isoeugenol 8 and isoeugenol acetate 11 exhibited lethal effects LD₅₀ at concentrations <1 mg/g of insect. On the other hand, eugenol 1, metallyl eugenol 3, isoeugenol 8 and isoeugenol acetate 11 showed a good antifeedant activity (CE₅₀ = 158–209 µg/mL) with a high antifeedant index (70–78%) at concentration 1000 µg/mL, possessing a weak anti-acetylcholinesterase activity (IC₅₀ = 21–31 μg/mL). According to their ecotoxicological profiles (LC₅₀ = 2033.1–6303.8 µg/mL on Artemia salina larvae), isoeugenol 8 and its acetate derivative 11 could be potential used in control of the growth, feeding, or reproduction of S. frugiperda larvae, acting as moderate insecticidal acetylcholinesterase inhibitors and/or antifeedant molecules. Such structure–activity relationship studies could stimulate the identification of lead structures from natural sources for the development of larvicidal and deterrent products against S. frugiperda and related insect pests.     

In vitro anti-cancer activities of Job’s tears (Coix lachryma-jobi Linn.) extracts on human colon adenocarcinoma

The whole seed (W), endosperm (E) and hull (H) of five cultivars of Job’s tears (Coix lachryma-jobi Linn. var. ma-yuen Stapf) including Thai Black Phayao, Thai Black Loei, Laos Black Loei, Laos White Loei and Laos Black Luang Phra Bang were processed before solvent extraction by non-cooking, roasting, boiling and steaming Each part of the Job’s tears was extracted by the cold and hot process by refluxing with methanol and hexane. The total of 330 extracts included 150 methanol extracts and 180 hexane extracts were investigated for anti-proliferative activity on human colon adenocarcinoma cell line (HT-29) by the sulforhodamine B (SRB) assay. The extracts which gave high anti-proliferative activity were tested for apoptotic activity by acridine orange and ethidium bromide double staining and anti-oxidative activities including free radical scavenging and lipid peroxidation inhibition activities. The extract from the hull of Thai Black Loei roasted before extracting by hot methanol (M-HTBL-R2) showed the highest anti-proliferative activity on HT-29 with the IC₅₀ values of 11.61 ± 0.95 μg/ml, while the extract from the non-cooked hull of Thai Black Loei by cold methanol extraction (M-HTBL-N1) gave the highest apoptosis (8.17 ± 1.18%) with no necrosis. In addition, M-HTBL-R2 and M-HTBL-N1 indicated free radical scavenging activity at the SC₅₀ values of 0.48 ± 0.12 and 2.47 ± 1.15 mg/ml, respectively. This study has demonstrated the anti-colorectal cancer potential of the M-HTBL-R2 and M-HTBL-N1 extracts.     

Insect Antifeedants,Pterocarpans and Pterocarpol,in Heartwood of Pterocarpus macrocarpus Kruz.

The insect antifeedant activities of pterocarpans and a sesquiterpene alcohol from the dichloromethane extract of Pterocarpus macrocarpus Kruz. (Leguminosae) were evaluated against the common cutworm, Spodoptera litura F. (Noctuidae), and the subterranean termite, Reticulitermes speratus (Kolbe)(Rhinotermitidae). Three pterocarpans, (?)-homopterocarpin (1), (?)-pterocarpin (2), and (?)-hydroxyhomopterocarpin (3) and the sesquiterpene alcohol, (+)-pterocarpol (5), were isolated from the dichloromethane extract of the heartwood of P. macrocarpus under guidance by a biological assay. Among these natural products, the most active insect antifeedant against both S. litura and R. speratus was 1. On the other hand, sesquiterpene alcohol 5 showed less insect antifeedant activity than the other pterocarpans against both insect species. While its methylated derivative, (?)-methoxyhomopterocarpin (4), showed high biological activity, 3 showed less insect antifeedant activity in this study. Interestingly, racemic 1 did not show insect antifeedant activity against S. litura. However, all of the test pterocarpans and isoflavones showed antifeedant activity against the test termites. Additionally, since these compounds were major constituents of P. macrocarpus, these antifeedant phenolics may act as chemical defense factors in this tree. In Thailand, lumber made from this tree is used to make furniture and in building construction due to its resistance to termite attack.     

Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer

In this work, the natural piperine moiety was utilised to develop two sets of piperine-based amides (5a–i) and ureas (8a–y) as potential anticancer agents. The anticancer action was assessed against triple negative breast cancer (TNBC) MDA-MB-231, ovarian A2780CP and hepatocellular HepG2 cancer cell lines. In particular, 8q stood out as the most potent anti-proliferative analogue against TNBC MDA-MB-231 cells with IC₅₀ equals 18.7 µM, which is better than that of piperine (IC₅₀ = 47.8 µM) and 5-FU (IC₅₀ = 38.5 µM). Furthermore, 8q was investigated for its possible mechanism of action in MDA-MB-231 cells via Annexin V-FITC apoptosis assay and cell cycle analysis. Moreover, an in-silico analysis has proposed VEGFR-2 as a probable enzymatic target for piperine-based derivatives, and then has explored the binding interactions within VEGFR-2 active site (PDB:4ASD). Finally, an in vitro VEGFR-2 inhibition assay was performed to validate the in silico findings, where 8q showed good VEGFR-2 inhibitory activity with IC₅₀ = 231 nM.     

Antifeedant and oviposition-deterring activity of total ginsenosides against Pieris rapae

The purpose of this study was to evaluate the antifeedant and oviposition-deterring activity of total ginsenosides against P. rapae. Total ginsenosides exhibited increased antifeedant effects against P. rapae. The highest nonselective and selective antifeedant activity were observed at 2.0% concentration where ginsenosides caused antifeedant percentages of 86.09 and 88.90, respectively. The total ginsenosides showed significantly oviposition-deterring activity of 77.78% against oviposition of P. rapae at 1.0% concentration. Total ginsenosides had antifeeding activity against P. rapae and inhibitory effects on its oviposition. Ginsenosides could be used as an agent to prepare botanical new pesticidal formulations.     

Bis- and mono-substituted Chalcones exert anti-feedant and toxic effects on fall armyworm Spodoptera frugiperda

Spodoptera frugiperda is a highly polyphagous migratory lepidopteran pest species. It causes infestation in crops leading to the severe crop losses. Being a new invasive parasite, its susceptibility to insecticides needs to be explored; and therefore, there is an urgent need to develop the potent insecticides for the effective control of this insect pest. To attain the crop sustainability, the antifeedant, toxicity and nutritional effects on larvae of Spodoptera frugiperda were studied with six mono- and eight bis- substituted chalcones. The antifeedant activity was calculated when 50% of the larvae control ate 50% of the diet through the FR factor. Toxicity was assessed through larval, pupal mortality and the emergence of adults and nutritional effects with consumption rates (IC), growth (GR) and consumption efficiency (EIC). The bis-chalcones 6b, 6e, 6f and 6h caused lethal effect on S. frugiperda in the first larval stages, being 6b the most toxic (85%). Adults who survived showed malformations and decreased size, which led to death. The larvae fed with aggregate in the bis-chalcones diet: 6b, 6e and 6f had the highest percentage of intake and the poorest conversion of nutrient absorption (ECI), which suggests that the larva metabolizes food for energy and results in a decrease of growth and death in early stages. Bis-chalcones showed more toxicity than mono-chalcones and 6b causes the most toxic and dietary change.     

Several Antifeedants from Neem Oil,Azadirachta indica A. Juss., against Reticulitermes speratus Kolbe (Isoptera: Rhinotermitidae)

A methanol extract of neem oil indicated antifeedant activity at 200 μg/disc by a no-choice bioassay against Reticulitermes speratus Kolbe. The extract was purified by recycling HPLC to isolate 11 compounds of variable termite antifeedant potency. Deacetylgedunin was the most active compound (95% protective concentration or PC₉₅ = 113.7 μg/disc). This was followed by salannin, gedunin, 17-hydroxyazadiradione, nimbandiol, azadiradione, deacetylsalannin, and deacetylnimbin, with PC₉₅ estimates of 203.3, 218.4, 235.6, 245.4, 827.5, 1373.1, and 1581.2 μg/disc, respectively. Epoxyazadiradione, 17-epiazadiradione, and nimbin were not active (PC₉₅ estimates were beyond the bioassay limits). It could be presumed, by comparing their structures and activities, that the furan ring, αβ-unsaturated ketone and hydroxyl group each played an important role in determining the antifeedant activity.     

Nematicidal effects of piperine on the pinewood nematode Bursaphelenchus xylophilus

The plant-parasitic nematode Bursaphelenchus xylophilus is a notorious forest pest and the cause of pine-wilt disease which is becoming a serious issue in Asia and Europe. Few available pesticides or nematicides effectively kill B. xylophilus and the topic is the subject of on-going research. This study describes the killing effects of three constituents (piperine, piperlongumine, and piperonal) of the long pepper on the pinewood nematode juveniles. Piperine at 50 µg/mL achieved killing of B. xylophilus juveniles in 6 h, and uniquely, the pattern of killing involved rapid curling (1 h), aggregation (2 h), and death (6 h). Also, piperine adversely affected the fecundity and locomotor traits in B. xylophilus while piperine had marginal effect on the growth of plant seed germination. Computational studies showed piperine interacts with the Gln²¹⁹ residue of glutamate gated chloride ion channel (GluCl) receptor, a residue associated with receptor activation. Furthermore, the mode of action of piperine resembled that of ivermectin in in silico studies. These results suggest that piperine (the major component of peppers) be regarded a potential nematicide for pinewood nematodes and warrant further field investigations.     

Leishmania donovani pteridine reductase 1: comparative protein modeling and protein–ligand interaction studies of the leishmanicidal constituents isolated from the fruits of Piper longum

Visceral leishmaniasis or kala-azar is caused by the dimorphic parasite Leishmania donovani in the Indian subcontinent. Treatment options for kala-azar are currently inadequate due to various limitations. Currently, drug discovery for leishmaniases is oriented towards rational drug design; the aim is to identify specific inhibitors that target particular metabolic activities as a possible means of controlling the parasites without affecting the host. Leishmania salvages pteridin from its host and reduces it using pteridine reductase 1 (PTR1, EC 1.5.1.33), which makes this reductase an excellent drug target. Recently, we identified six alkamides and one benzenoid compound from the n-hexane fraction of the fruit of Piper longum that possess potent leishmanicidal activity against promastigotes as well as axenic amastigotes. Based on a homology model derived for recombinant pteridine reductase isolated from a clinical isolate of L. donovani, we carried out molecular modeling and docking studies with these compounds to evaluate their binding affinity. A fairly good agreement between experimental data and the results of molecular modeling investigation of the bioactive and inactive compounds was observed. The amide group in the conjugated alkamides and the 3,4-methylenedioxystyrene moiety in the benzenoid compound acts as heads and the long aliphatic chain acts as a tail, thus playing important roles in the binding of the inhibitor to the appropriate position at the active site. The remarkably high activity of a component containing piperine and piperine isomers (3.36:1) as observed by our group prompted us to study the activities of all four isomers of piperine—piperine (2E,4E), isopiperine (2Z,4E), isochavicine (2E,4Z), and chavicine (2Z,4Z)—against LdPTR1. The maximum inhibitory effect was demonstrated by isochavicine. The identification of these predicted inhibitors of LdPTR1 allowed us to build up a stereoview of the structure of the binding site in relation to activity, affording significant information that should prove useful during the structure-based design of leishmanicidal drugs.     

Castor and camphor essential oils alter hemocyte populations and induce biochemical changes in larvae of Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae)

Two plant essential oils; camphor and castor were tested for insecticidal and antifeedant activity against the 4th instar larvae of Spodoptera littoralis, a serious pest on cotton in Egypt. Also the impact of LC₁₀ of both oils on some physiological parameters in larvae was studied by using leaf dipping technique. Analysis of both oils using GC–MS revealed several insecticidal and antifeedant compounds. Our results showed higher insecticidal activity and antifeedant index of camphor oil against S. littoralis. The LC₅₀ and the antifeedant indices were 163.1, 246.8?mg/ml and 12.69, 6.62% for camphor and castor bean oil, respectively. The total hemocyte count (THC) and differential hemocyte count (DHC) were reduced significantly after 48?h of treatment compared to controls. Both oils reduced all types of hemocytes except plasmatocytes which were reduced only by castor oil. Camphor oil decreased total proteins and carbohydrates while castor oil targeted only carbohydrate content. Both oils didn't affect the amount of total lipids. Lipase, α-amylase and glucose-6-phosphate dehydrogenase (G6PD) enzyme activities were increased significantly in larvae treated with camphor oil than other treatments. These results clearly indicate that castor and camphor oils can affect the nutritional status in S. littoralis larvae, thereby changing the internal metabolic processes in the larvae which make them as potential control agents in IPM programs against S. littoralis.     

Host plant defenses of black (Solanum nigrum L.) and red nightshade (Solanum villosum Mill.) against specialist Solanaceae herbivore Leptinotarsa decemlineata (Say)

Black nightshade (Solanum nigrum, S. nigrum L.) and red nightshade ( Solanum villosum, S. villosum Mill.) are medicinal plants from the Solanaceae family that synthesize glycoalkaloids and other secondary metabolites. To recognize the potential insecticide activity of these compounds, leaf extracts (containing glycoalkaloid and methanol fractions) were tested for enzyme inhibition, antifeedant activity and toxicity. For in‐vitro glutathione S‐transferase (GST) inhibition activity, we used insecticide‐resistant Colorado potato beetle, Leptinotarsa decemlineata ( L. decemlineata; Say) midgut and fat‐body homogenate. In‐vivo toxicity and the antifeedant activity were performed using larval bioassays. The methanol extracts had greater GST inhibitory activity compared to the glycoalkaloids, as well as greater 2nd instar larvae mortality and antifeedant activity. Furthermore, the green leaf volatile compound, cis‐hex‐3‐enyl acetate, at the concentration of 5 ppm, caused 50% mortality of 2nd instar larvae. Our findings suggest the potential usefulness of S. nigrum and S. villosum extracts to control L. decemlineata.     

Anticonvulsant mechanisms of piperine,a piperidine alkaloid

Piperine, a natural compound isolated from the fruits of Piper, is known to modulate several neurotransmitter systems such as serotonin, norepinephrine, and GABA, all of which have been linked to the development of convulsions. Fruits of Piper species have been suggested as means for managing seizure disorders. The present study was designed to elucidate the anticonvulsant effect of piperine and its mechanisms of action using in-silico, in-vivo and in-vitro techniques.PASS software was used to determine its possible activity and mechanisms. Furthermore the latency for development of convulsions and mortality rate was recorded in different experimental mouse models of epilepsy (pentylenetetrazole, maximal electroshock, NMDA, picrotoxin, bicuculline, BAYK-8644, strychnine-induced convulsions) after administration of various doses of piperine (5, 10 and 20 mg/kg, i.p.). Finally, the effect of piperine on Na⁺ and Ca²⁺ channels were evaluated using the whole cell patch clamp techniqueOur results revealed that piperine decreased mortality in the MES-induced seizure model. Moreover, piperine (10 mg/kg) delayed the onset of tonic clonic convulsions in the pentylenetetrazole test and reduced associated mortality. Furthermore, an anticonvulsant dose of piperine also delayed the onset of tonic clonic seizures in strychnine, picrotoxin and BAY K-8644. Complete protection against mortality was observed in BAYK-8644 induced convulsions. Finally, whole cell patch clamp analysis suggested an inhibitory effect of piperine on Na⁺ channels. Together, our data suggest Na⁺ channel antagonist activity as a contributor to the complex anticonvulsant mechanisms of piperine.     

Insect growth‐reducing and antifeedant activity in Eastern North America hardwood species and bioassay‐guided isolation of active principles from Prunus serotina

1 Thirty extracts of wood and bark of hardwood trees from Eastern North America were examined for insect growth‐reducing activity in a bioassay with European corn borer, Ostrinia nubilalis, and an antifeedant bioassay with the rice weevil, Sitophilus oryzae. 2 Nine of the bark extracts and four of the wood extracts showed significant growth reducing effects at 0.5% in meridic diets, whereas only two bark extracts and one wood extract showed significant antifeedant effect at the same concentration. 3 Slower growing tree species were more biologically active than fast growing ones. Isolation of the bioactive compounds in one of the active species, Prunus serotina, showed that naringenin, its derivative methoxynaringenin, and eriodictyol were responsible for the antifeedant effects.