Acetaminophen-induced antinociception via central 5-HT2A receptors

Acetaminophen is one of the most widely used analgesic drugs. Although the mechanism of analgesic action of acetaminophen is still not known, the involvement of the central serotonin (5-hydroxytryptamine: 5-HT) system is one possibility. In the present study, we examined the antinociceptive effect of acute and chronic intraperitoneally (i.p.) administered acetaminophen by tail flick latency measurements in the rat. A significantly increased tail flick latency was observed in acute and 15-day acetaminophen-treated rats, but not in 30-day acetaminophen-treated rats, at a dose of 400 mg/kg/day. To investigate the plasticity of receptors at postsynaptic membrane, we conducted a series of experiments by radioligand binding method on frontal cortex and brainstem membrane. The technique involved radioligand binding with [phenyl-4-³H]spiperone and ketanserin for studying 5-HT_2A receptor characteristics. A significant decrease in the maximum number of 5-HT_2A binding sites (B_max) was demonstrated in all treatment groups with acetaminophen 300 and 400 mg/kg on frontal cortex membrane, whereas the value of the dissociation equilibrium constant (K_d) remained unchanged. The down-regulation of 5-HT_2A binding sites in frontal cortex was of a lesser magnitude after 30 days of treatment and the tail flick latency was as in the control animals. These results suggest that down-regulation of 5-HT_2A receptor in response to 5-HT release is a major step in the mechanism underlying analgesia produced by this agent. On the contrary, chronic use of acetaminophen may result in 5-HT depletion, which in turn produces re-adaptation of postsynaptic 5-HT_2A receptors. These data provide further evidence for a central 5-HT-dependent antinociceptive effect of acetaminophen.     

Novel 3‐Oxo‐ and 3,24‐Dinor‐2,4‐secooleanane‐Type Triterpenes from Terminalia ivorensis A. Chev.

Two new oleanane‐type triterpenes named ivorengenin A (=3‐oxo‐2α,19α,24‐trihydroxyolean‐12‐en‐28‐oic acid; 1 ) and ivorengenin B (=4‐oxo‐19α‐hydroxy‐3,24‐dinor‐2,4‐secoolean‐12‐ene‐2,28‐dioic acid; 2 ), together with five known compounds, arjungenin, arjunic acid, betulinic acid, sericic acid, and oleanolic acid, were isolated from the barks of Terminalia ivorensis A. Chev . (Combretaceae). Their structures were established on the basis of 1D‐ and 2D‐NMR data, and mass spectrometry. A biogenetic pathway to the formation of these compounds from sericic acid, isolated as the major compound from this plant, was proposed. The antioxidant activities of different compounds were investigated by means of the 2,2‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) and 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) assays, and IC₅₀ values were calculated and compared with Trolox activity. Antiproliferative activities of the isolated compounds were also evaluated against MDA‐MB‐231, PC3, HCT116, and T98G human cancer cell lines, against which the compounds showed significant cytotoxic activities.     

Antagonism of morphine analgesia by CCK-8-S does not extend to all assays nor all opiate analgesics

The conditions under which CCK-8-S may block opiate-induced analgesia were examined in detail. A U-shaped dose-response relationship was observed for the ability of CCK-8-S to attenuate (by approximately 50%, at most) morphine-induced tail flick analgesia. The analgesic effects of morphine in the hot plate or acetic acid-induced stretching tests were not altered by CCK-8-S at doses that antagonized morphine in the tail flick test. Tail flick latency elevations induced by meptazinol, a putative mu-1 receptor agonist, were also attenuated by CCK-8-S according to a U-shaped dose-response relationship, but those induced by U-50,488, a kappa agonist, were not antagonized by CCK-8-S doses that attenuated morphine analgesia. Thus, the ability of CCK-8-S to antagonize opiate analgesia does not follow a conventional dose-response relationship, does not extend to all tests of analgesia and may not extend to all opioid drugs. Analgesia mediated by the mu-1 opioid receptor subtype may be more amenable to antagonism by CCK-8-S than that mediated by the kappa receptor subtype.     

Phytochemical and Biological Activities of Pseudocalymma elegans: A False Garlic

Evaluation of phytochemical constituents and antioxidant and antimicrobial activities of hexane (PELH), dichloromethane (PELDCM), ethyl acetate (PELEA), and MeOH (PELM) extracts of young leaves of Pseudocalymma elegans have been carried out. Moreover, extracts have also been explored for the presence of sulphur containing compounds, 1,2‐dithiolane ( 33 ), diallyl disulfide ( 35 ), 3‐vinyl‐1,2‐dithiacyclohex‐5‐ene ( 37 ), and diallyl trisulfide ( 38 ) responsible for the garlic like smell of P. elegans. All the extracts were found to be antioxidant and showed potent inhibition with IC₅₀ values of 0.168 ± 0.001, 0.128 ± 0.002, 0.221 ± 0.011, and 0.054 ± 0.001, respectively, as compared to standard drugs ascorbic acid (AA) and butylated hydroxytoluene (BHT). The ethyl acetate extract (PELE) showed excellent activities against few Gram‐positive and Gram‐negative bacteria and some fungi as compared with standard drug ceftriaxone (3rd generation cephalosporin) and nystatin, respectively. Chemical constituents of hexane, dichloromethane, and ethyl acetate extracts were identified by gas chromatography‐mass spectrometry and mass spectral library search. Over all 55 chemical constituents were first time identified from the leaves which included branched and n‐hydrocarbons, fatty acids, fatty acid methyl esters, fatty alcohols, terpenes, alkaloid, vitamins, glycosides, aromatic compounds, and sulfur containing compounds. Two known chemical constituents, ursolic acid ( 1 ) and β‐amyrin ( 2 ), were also purified for the first time from the MeOH extract. To elucidate the structures of these compounds, UV, IR, EI‐MS, ¹H‐ and ¹³C‐NMR spectroscopy were used.     

Three new cytochalasins from the marine-derived fungus Spicaria elegans KLA03 by supplementing the cultures with L- and D-tryptophan

Three new cytochalasins Z₂₁–Z₂₃ ( 1 – 3 , resp.), together with five analogs, 4 – 8 , were isolated from Spicaria elegans KLA03 by the OSMAC (one strain‐many compounds) approach with adding L ‐ and D ‐tryptophan during its cultivation. The structures of new cytochalasins were elucidated on the basis of comprehensive 1D‐ and 2D‐NMR and HR‐ESI‐MS analyses. Cytochalasins Z₂₁ and Z₂₂ ( 1 and 2 , resp.), and compound 5 showed cytotoxic activities against A‐549 cell lines with IC₅₀ values of 8.2, 20.0, and 3.1 μM , respectively.     

Lappaconitine and N-deacetyllappaconitine potentiate footshock-induced analgesia in rats

The effects of lappaconitine (LA) and N-deacetyllappaconitine (DLA) on footshock-induced analgesia (FSIA) were studied by the rat tail flick test. Rats subjected to 90 s nonescaping footshock had a significant increase in tail flick latency. Naloxone (4 micrograms, i.c.v.) partially antagonized the FSIA. After 5 consecutive exposures to footshock, rats developed a complete tolerance to the FSIA. The rats tolerant to FSIA showed a cross-tolerance to morphine- but not LA- and DLA-induced analgesia. Administrations of subanalgesic doses of LA and DLA potentiated the FSIA in both intact and adrenalectomized rats.     

Inhibitory Effects of Constituents of an Endophytic Fungus Hypoxylon investiens on Nitric Oxide and Interleukin‐6 Production in RAW264.7 Macrophages

Three new compounds, hypoxyloamide ( 1 ), 8‐methoxynaphthalene‐1,7‐diol ( 2 ), and hypoxylonol ( 3 ), together with seven compounds isolated from nature for the first time, investiamide ( 4 ), hypoxypropanamide ( 5 ), hypoxylonol A ( 6 ), investienol ( 7 ), 2‐heptylfuran ( 8 ), (3S)‐5‐methyl‐8‐O‐methylmellein ( 9 ), (4R)‐O‐methylsclerone ( 10 ), along with 19 known compounds, 11 – 29 , were isolated from the culture broth of Hypoxylon investiens BCRC 10F0115, a fungal endophyte residing in the stems of an endemic Formosan plant Litsea akoensis var. chitouchiaoensis. The structures of the new compounds were established by spectroscopic methods, including UV, IR, HR‐ESI‐MS, and extensive 1D‐ and 2D‐NMR techniques. Of these isolates, 2 , 8‐methoxynaphthalen‐1‐ol ( 15 ), and 1,8‐dimethoxynaphthalene ( 16 ) showed nitric oxide (NO) inhibitory activity with IC₅₀ values of 11.8±0.9, 17.8±1.1, and 13.3±0.5 μM , respectively, stronger than the positive control quercetin (IC₅₀ 36.8±1.3 μM ). Compounds 2, 15 , and 16 also showed interleukin‐6 (IL‐6) inhibitory activity with IC₅₀ values of 9.2±1.7, 18.0±0.6, and 2.0±0.1 μM , stronger than the positive control quercetin (IC₅₀ 31.3±1.6 μM ). To the best of our knowledge, this is the first report on guaiane sesquiterpene metabolites, 3, 6 , and 7 , from the genus Hypoxylon.     

Characterization and Influence of Green Synthesis of Nano‐Sized Zinc Complex with 5‐Aminolevulinic Acid on Bioactive Compounds of Aniseed

A new water soluble zinc‐aminolevulinic acid nano complex (n[Zn(ALA)₂]), which was characterized by TEM, IR, and EDX spectra, has been prepared via sonochemical method under green conditions in water. In the current study, the effectiveness of foliar Zn amendment using synthetic Zn‐ALA nano complex, as a new introduced Zn‐fertilizer here, was evaluated. As the model plant, Pimpinella anisum, the most valuable spice and medicinal plant grown in warm regions, was used. By using zinc nano complex, further twenty compounds were obtained in the essential oil of anise plants. Application of 0.2% (w/v) Zn‐ALA nano complex increased the levels of (E)‐anethole, β‐bisabolene, germacrene D, methyl chavicol, and α‐zingiberene in the essential oil. Nano Zn complex at the rate of 0.2% induced considerable high phenolic compounds and zinc content of shoots and seeds. Chlorogenic acid had the highest level between four detected phenolic compounds. The maximum antioxidant activity was monitored through the application of Zn nano complex. According to the results, nanoscale nutrients can be provided with further decreased doses for medicinal plants. Using Zn‐ALA nano complex is a new and efficient method to improve the pharmaceutical and food properties of anise plants.     

Piptadenin,a Novel 3,4‐Secooleanane Triterpene and Piptadenamide,a New Ceramide from the Stem Bark of Piptadeniastrum africanum (Hook.f.) Brenan

Piptadenin ( 1 ), a new triterpene along with piptadenamide ( 10 ), a new ceramide, have been isolated from the AcOEt‐soluble fraction of the MeOH extract of the stem bark of Piptadeniastrum africanum along with nine known compounds, 1‐O‐[(3β,22β)‐3,22‐dihydroxy‐28‐oxoolean‐12‐en‐28‐yl]‐β‐d ‐glucopyranose ( 2 ), 22β‐hydroxyoleanic acid ( 3 ), oleanic acid ( 4 ), lupeol ( 5 ), betulinic acid ( 6 ), 5α‐stigmasta‐7,22‐dien‐3β‐ol ( 7 ), 5α‐stigmasta‐7,22‐dien‐3‐one ( 8 ), (3β)‐stigmast‐5‐en‐3‐yl β‐d ‐glucopyranoside ( 9 ) and 2,3‐dihydroxypropyl hexacosanoate ( 11 ). Except for compound 11 , all the isolated compounds are reported for the first time from this plant. The structures of the isolated compounds were elucidated by spectroscopic data including 1D and 2D NMR. The pure compounds 1 – 11 were subjected to the pharmacological screening and compounds 2 , 5 – 7 and 9 exhibited potent urease inhibitory activity with IC₅₀ value of 25.8, 28.9, 30.1, 31.8 and 32.7 μm , respectively, whereas compound 1 showed moderate activity (IC₅₀ = 98.7 μm ). The potent urease inhibitory activity supplemented the previous literature reports and medicinal uses of this plant.     

Two New Antioxidant Phenylpropanoids from Lindelofia stylosa

Two new phenylpropanoids were isolated from Lindelofia stylosa (Kar . and Kir .) and characterized as 4‐hydroxy‐N‐{4‐[(E)‐3‐(4‐hydroxy‐3‐methoxyphenyl)prop‐2‐enamido]butyl}benzamide ( 1 ) and 2‐[3‐hydroxy‐4‐(4‐hydroxyphenoxy)phenyl]‐1‐(methoxycarbonyl)ethyl (E)‐3‐(3,4‐dihydroxyphenyl)prop‐2‐enoate ( 2 ). Four known compounds, i.e. two phenylpropanoids, p‐coumaric acid (=(E)‐3‐(4‐hydroxyphenyl)prop‐2‐enoic acid; 3 ) and ferulic acid (=(E)‐3‐(4‐hydroxy‐3‐methoxyphenyl)prop‐2‐enoic acid; 4 ), and two naphthalene glycosides, 8‐O‐β‐D ‐glucopyranosyltorachrysone ( 5 ) and 8‐O‐β‐D ‐glucopyranosyl‐6‐demethoxytorachrysone ( 6 ), were also isolated for the first time from the plant. Compounds 1 – 6 were subjected to various antioxidant assays, including DPPH radical‐ and superoxide anion‐scavenging, and Fe²⁺‐chelation assays. Compound 2 was found to be most active in all assays with potency nearly similar to that of propyl gallate. Besides 2 , compounds 1 and 5 were also found to be active in DPPH radical‐scavenging standard assay.     

Two Antiproliferative Triterpene Saponins from Nematostylis anthophylla from the Highlands of Central Madagascar

Investigation of the endemic Madagascan plant Nematostylis anthophylla (Rubiaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the known triterpene saponin randianin ( 1 ), and the two new bioactive triterpene saponins 2″‐O‐acetylrandianin ( 2 ) and 6″‐O‐acetylrandianin ( 3 ). The structures of the two new compounds were elucidated based on analysis of their 1D‐ and 2D‐NMR spectra, and mass spectrometric data. The three isolated triterpene saponins displayed moderate but selective antiproliferative activities, with IC₅₀ values of 1.2, 1.7, and 2.2 μM , respectively, against the A2780 ovarian cancer, but only weak inhibitions of the proliferation of A2058 melanoma and the H522 lung cancer cell lines.     

A New Phenolic Constituent and a Cyanogenic Glycoside from Balanophora involucrata (Balanophoraceae)

Balanophora involucrata Hook .f. & Thomson (Balanophoraceae) is a parasite plant often growing on the roots of leguminous plants. The whole herb has been used medicinally for the treatment of irregular menstruation, cough, hemoptysis, traumatic injury and bleeding, dizziness and gastralgia in Yunnan Province, China. The 2,2‐diphenyl‐2‐picrylhydrazyl (DPPH) assay on the 60% aq. acetone extract of the fresh whole plant of B. involucrata showed considerable radical‐scavenging activity (SC₅₀ 15.3 μg/ml). Further purification on the extract led to the isolation of one new phenolic glycoside, sieboldin‐3′‐ketocarboxylic acid ( 1 ), and one new cyanogenic glycoside, proacacipetalin 6′‐O‐β‐D ‐glucopyranoside ( 2 ), together with 26 known compounds including three 4″‐O‐galloyl and 2″,3″‐O‐(S)‐hexahydroxydiphenoyl (HHDP) derivatives of dihydrochalcone glucosides, seven hydrolyzable tannins, and alkane glycosides. The cyanogenic compound isolated from the Balanophoraceae family for the first time might be a signal molecule between B. involucrata and its hosts. The free‐radical‐scavenging activity of the isolated compounds was also examined by DPPH assay.     

Isolation and identification of neo‐clerodane diterpenes from Ajuga remota by high‐performance liquid chromatography

In order to explore the suitability of reversed‐phase HPLC for the rapid isolation, identi?cation and semipreparative fractionation of neo‐clerodane diterpenes from Ajuga remota, an extract from aerial parts of the plant was examined using a C₁₈ column with UV detection and gradient elution with water:methanol. In addition to the known diterpenes ajugarins I, II, IV and V and clerodin, the presence and chromatographic behaviours of ajugapitin, dihydroajugapitin, dihydroclerodin and deacetylajugarin IV, not previously isolated from A. remota, were established. Presence of the epimeric mixture of 14‐hydro‐15‐hydroxyclerodin (scutecyprol A) was also demonstrated together with that of 14‐hydro‐15‐hydroxyajugapitin, the latter only in trace amounts. The structures of all isolated diterpenes were determined from NMR data. The anti‐feedant activities of the isolated compounds against Spodoptera littoralis are also reported here. Copyright © 2005 John Wiley & Sons, Ltd.     

Study of Antimalarial Activity of Chemical Constituents from Diospyros quaesita

Bioassay‐directed fractionation led to the isolation of seven compounds from a sample of the dried leaves, twigs, and branches of Diospyros quaesita Thw . (Ebenaceae). One of the isolates, betulinic acid 3‐caffeate ( 1 ), showed in vitro antimalarial activity against Plasmodium falciparum clones D₆ (chloroquine‐sensitive) and W₂ (chloroquine‐resistant) with IC₅₀ values of 1.40 and 0.98 μM , respectively. Evaluation of compound 1 in the human oral epidermoid (KB) cancer cell line revealed cytotoxicity at ED₅₀ of 4.0 μM . In an attempt to reduce the cytotoxicity of 1 , the acetylated derivative 1a and betulinic acid ( 1b ) were prepared. Of the seven isolates, diospyrosin ( 2 ) was determined to be a new neolignan. In addition to 1 , other known compounds isolated in this study were pinoresinol, lariciresinol, N‐benzoyl‐L ‐phenylalaninol, scopoletin, and poriferast‐5‐en‐3β,7α‐diol. The structure of 2 was elucidated based on spectroscopic data analysis including 1D‐ and 2D‐NMR, and HR‐ESI‐MS.     

Role of peripheral and central opioid activity in analgesia induced by restraint stress

Rats subjected to prolonged restraint showed an increase in tail flick latency which outlasted the period of restraint by 15 min. This restraint could be blocked but not reversed by 1 mg/kg of naltrexone hydrochloride given subcutaneously. Naltrexone methobromide, administered subcutaneously in doses of 10 or 25 mg/kg, did not block the analgesia indicating that peripheral opioid receptors were probably not involved. Naltrexone hydrochloride was shown to have no effect on brain tryptophan uptake in restrained rats, a neurochemical event which had previously been shown to be critical to restraint-induced analgesia.     

HPTLC Autography Based Screening and Isolation of Mushroom Tyrosinase Inhibitors of European Plant Species

In the course of this project, 133 plants were evaluated on their ability to inhibit tyrosinase, a key enzyme in melanogenesis. The screening was performed by means of a HPTLC autographic assay, resulting in the selection of three plants, Asplenium trichomanes, Pinus uncinata, and Scutellaria altissima, with promising tyrosinase inhibiting activities. With the aid of the HPTLC assay, it was not only possible to select the most interesting plant extracts, but also to monitor the activity‐guided fractionation which, in a relatively short time period, led to the isolation of active principles. Benzoic acid, roseoside, and dihydrovomifoliol‐O‐β‐d ‐glucopyranoside could be identified as tyrosinase inhibitors present in P. uncinata. Globularin turned out to be the active principle of S. altissima, and 4‐ethenylphenyl 6‐O‐(6‐deoxy‐α‐l ‐mannopyranosyl)‐β‐d ‐glucopyranoside was detected as tyrosinase inhibitor of A. trichomanes. The pure compounds were tested also in a 96 well‐plate assay in order to determine their IC₅₀ values. The lowest IC₅₀ value (42 μm ) could be obtained for globularin, whereas the other compounds, e. g., benzoic acid exhibited a rather high IC₅₀ value (IC₅₀=552 μm ). This stood in clear contrast to the autographic assay, but is has to be taken into account that the outcome of the autography assay is not only depending on the IC50 value of a compound, but also on the content of the respective constituent in the extract.     

Chemical composition and antidiabetic activity of Opuntia Milpa Alta extracts

Three new compounds, 1 – 3 , and 20 known compounds were isolated from the AcOEt and BuOH extract of edible Opuntia Milpa Alta. The petroleum ether extract was examined by GC and MS. A total of 26 compounds were identified, representing 95.6% of the total extract, phytosterol (36.03%) being the most abundant component, and polyunsaturated fatty acids (18.57%) represented the second largest group, followed by phytol (12.28%), palmitic acid, palmitate (13.54%), vitamin E (4.51%), and other compounds (7.47%). The effects of various extracts from edible Opuntia Milpa Alta (petroleum ether extract, AcOEt extract, BuOH extract, aqueous extract, H₂O parts) and the positive control (received dimethylbiguanide) were tested on streptozotocin (STZ)‐induced diabetic mice. The results indicated that all the treatment groups could significantly decrease blood glucose levels in STZ‐induced diabetic mice compared to the model control group (P<0.01), except the aqueous extract group (P<0.05). Especially, the petroleum ether extract group and the positive control group showed remarkable decrease of blood glucose levels. Taken together, the results indicate that the petroleum ether extract is the major hypoglycemic part in edible Opuntia Milpa Alta, which may be developed to a potential natural hypoglycemic functional ingredient.     

New 2‐Oxoimidazolidine Derivatives: Design,Synthesis and Evaluation of Anti‐BK Virus Activities in Vitro

A series of novel 2‐oxoimidazolidine derivatives were synthesized and their antiviral activities against BK human polyomavirus type 1 (BKPyV) were evaluated in vitro. Bioassays showed that the synthesized compounds 1‐{[(4E)‐5‐(dichloromethylidene)‐2‐oxoimidazolidin‐4‐ylidene]sulfamoyl}piperidine‐4‐carboxylic acid ( 5 ) and N‐Cyclobutyl‐N′‐[(4E)‐5‐(dichloromethylidene)‐2‐oxoimidazolidin‐4‐ylidene]sulfuric diamide ( 4 ) exhibited moderate activities against BKPyV (EC₅₀=5.4 and 5.5 μm , respectively) that are comparable to the standard drug Cidofovir. Compound 5 exhibited the same cytotoxicity in HFF cells and selectivity index (SI₅₀) as Cidofovir. The selectivity index of compound 4 is three times less than that of Cidofovir due to the higher toxicity of this compound. Hence, these compounds may be taken as lead compound for further development of novel ant‐BKPyV agents.     

A novel lipid transfer protein from the dill Anethum graveolens L.: isolation,structure, heterologous expression,and functional characteristics

A novel lipid transfer protein, designated as Ag‐LTP, was isolated from aerial parts of the dill Anethum graveolens L. Structural, antimicrobial, and lipid binding properties of the protein were studied. Complete amino acid sequence of Ag‐LTP was determined. The protein has molecular mass of 9524.4 Da, consists of 93 amino acid residues including eight cysteines forming four disulfide bonds. The recombinant Ag‐LTP was overexpressed in Escherichia coli and purified. NMR investigation shows that the Ag‐LTP spatial structure contains four α ‐helices, forming the internal hydrophobic cavity, and a long C‐terminal tail. The measured volume of the Ag‐LTP hydrophobic cavity is equal to ~800 A³, which is much larger than those of other plant LTP1s. Ag‐LTP has weak antifungal activity and unpronounced lipid binding specificity but effectively binds plant hormone jasmonic acid. Our results afford further molecular insight into biological functions of LTP in plants. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.     

Antibacterial Flavonoids and Other Compounds from the Aerial Parts of Vernonia guineensis Benth. (Asteraceae)

An extensive phytochemical study of the aerial parts of Vernonia guineensis Benth. (Asteraceae) led to the isolation of a new flavone, vernoguinoflavone and a naturally isolated glycerol ester, eicosanoic acid 2‐hydroxy‐1,3‐propanediyl ester, together with eighteen known secondary metabolites including quercetin, luteolin, vernopicrin, vernomelitensin, β‐amyrin, oleanolic acid, ursolic acid, lupeol, betulinic acid, β‐carotene, a mixture of stigmasterol and β‐sitosterol, β‐sitosterol‐3‐O‐β‐D‐glucoside, 2,3‐dihydroxypropyl heptacosanoate, pentacosanoic acid, docosan‐1‐ol, tritriacontan‐1‐ol, and heptatriacontan‐1‐ol. Eleven compounds are reported herein for the first time from this species. The structures of these compounds were elucidated on the basis of extensive spectroscopic analyses, particularly 1D and 2D NMR, and HR‐ESI‐MS and by comparison of their data with those reported in the literature. The crude extract, fractions and some isolated compounds were evaluated for their antibacterial activity against Gram‐negative bacteria: Escherichia coli (ATCC 25922), Shigella flexineri (NR 518), Salmonella muenchen, Salmonella typhimurium and Salmonella typhi (ATCC 19430). All the tested compounds demonstrated inhibitory activities against the tested enteric bacteria with MIC values ranging from 3.12 to 100 μg/ml. Three flavonoids isolated from the most active fraction demonstrated the best bioactivities against Escherichia coli, Salmonella muenchen and Salmonella typhimurium with MIC values ranging from 3.12 to 25 μg/mL.