Lignans of<Emphasis Type="Italic">Rosa multiflora</Emphasis> roots

Five known lignans, (+)-pinoresinol (1), (+)-8-hydroxypinoresinol (2), (-)-dehydrodiconiferyl alcohol (3), (+)-trans-dehydrodiconiferyl alcohol (4), and (-)-olivil (5), were isolated from the roots of Rosa multiflora for the first time. Their structures were determined using spectroscopic data.     

Free radical scavenging and antielastase activities of flavonoids from the fruits of <Emphasis Type="Italic">Thuja orientalis</Emphasis>

Bioassay-guided fractionation of the MeOH extract of Thuja orientalis fruits using a DPPH (2,2-diphenyl-1-picrylhydrazyl) assay led to the isolation of 9 flavonoids: cupressuflavone (1), amentoflavone (2), robustaflavone (3), afzelin (4), (+)-catechin (5), quercitrin (6), hypolaetin 7-O-β-xylopyranoside (7), isoquercitrin (8) and myricitrin (9). Their chemical structures were determined by spectroscopic analyses. The free radical scavenging and human neutrophil elastase (HNE) inhibitory activities were evaluated for the isolated compounds. By DPPH scavenging assay, compounds 5, 6, 7, 8 and 9 showed anti-oxidant activities with IC₅₀ values of 28.66, 31.19, 18.30, 26.63 and 15.10 μM, respectively. By ABTS [2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt] scavenging assay, these compounds also exhibited potent anti-oxidant activities with IC₅₀ values of 6.77, 13.96, 6.97, 22.79 and 9.96 μM, respectively. Of note, compounds 1, 2 and 3 showed significant HNE inhibitory activities with IC₅₀ values of 8.09, 1.27 and 1.33 μM, respectively.     

The radical scavenging effects of stilbene glucosides from<Emphasis Type="Italic">Polygonum multiflorum</Emphasis>

The extract of the root of Polygonum multiflorum exhibited a significant antioxidant activity assessed by the DPPH radical scavenging activity in vitro. The bioassay-guided fractionation of the extract yielded a stilbene glucoside, (E)-2,3,5,4'-tetrahydroxystilbene-2-O-beta-d-glucopyranoside (1) as an active constituent responsible for the antioxidant property. Compound 1 demonstrated a moderate DPPH radical scavenging activity (IC50, 40 microM), while the corresponding deglucosylated stilbene 2 exhibited a much higher activity (IC50, 0.38 microM).     

In vitro antioxidant and free radical scavenging activities of Garcinia kola seeds

Garcinia kola Heckel – a tropical plant which grows in moist forest, has found wide applications in traditional medicine especially in the West and Central African sub-region. The seeds have been demonstrated to possess numerous bioactivities but research is highly limited on the link between its fractions and the bioactivities. In this work, the methanolic extract of Garcinia kola seeds was subjected to silica gel column chromatography into five fractions ME1–ME5 and the free radical scavenging activities and antioxidant potentials were determined for each fraction using various in vitro models. The ME4 fraction possessed the greatest activities. It was also demonstrated that the ME4 fraction strongly inhibited nitric oxide production in lipopolysaccharide activated macrophage U937 cells. Chromatographic fractionation and spectroscopic analysis of the ME4 fraction revealed the presence of four compounds namely garcinia biflavonoids GB1 and GB2, garcinal and garcinoic acid. These findings show that these four compounds are partly responsible for the great antioxidant potential of Garcinia kola seeds. This gives further evidence to the nutraceutical and pharmaceutical potential of Garcinia kola.     

A new lignan glycoside from the fruits of <Emphasis Type="Italic">Cornus kousa</Emphasis> Burg.

A new lignan glycoside, (7'S, 8'R)-dihydrodehydrodiconiferyl alcohol-4'-O-beta-D-xylopyranoside (1), named cornuskoside A, was isolated from the fruits of Cornus kousa. The structure of the compound was determined by spectroscopy, including FABMS, UV, IR, (1)H-and 13C-NMR, DEPT and 2D-NMR (COSY, HSQC, and HMBC). This new lignan glycoside, along with its aglycone, (7'S, 8'R)-dihydrodehydrodiconiferyl alcohol (3), and another lignan with a similar skeleton, (-)-balanophonin (2), which have been previously isolated from this plant, were evaluated for cytotoxicity in human cancer cell lines such as HeLa, MCF-7, SK-MEL-5, and SK-OV-3. Compounds 2 and 3 showed cytotoxicity against HeLa [IC50 = 29.1 microM (2), 45.5 microM (3)], MCF-7 [IC50 = 29.2 microM (2), 28.2 microM (3)], SK-MEL-5 [IC50 = 31.3 microM (2), 32.3 microM (3)], and SK-OV-3 [IC50 = 33.4 microM (2), 43.4 microM (3)] cell lines.     

A new furofuran lignan from <Emphasis Type="Italic">Isodon japonicus</Emphasis>

A new sesamin type furofuran lignan, (−)-sesamin-2,2′-diol (1), along with two known flavonoids (2 and 3) and three phenolic compounds (4–6) were isolated from the aerial parts of Isodon japonicus. The structures of these compounds were determined by analysis of spectroscopic data (1D-, 2D-NMR, HRMS and CD) and by comparison of the data with those of related metabolites.     

Appraisal of anti-inflammatory and free radical scavenging activities of ethanol extract of Ilex ficoidea Hemsl and Ilex centrochinensis S.Y. Hu

This study was to appraise the anti-inflammatory and free radical scavenging activities of ethanol extracts of Ilex ficoidea Hemsl (EIFH) and Ilex centrochinensis S.Y. Hu (EICC). Anti-inflammatory activities were evaluated using xylene-induced ear edema and the cotton pellet granuloma tests. Some antioxidants produced during chronic inflammation were quantitated and the DPPH, superoxide anion and hydroxyl free radicals scavenging activities in vitro were also investigated. EICC showed a significant anti-inflammatory effect during the acute inflammation and chronic inflammation without any acute oral toxicity. However, EIFH exhibited a negligible anti-acute inflammatory and a moderate anti-chronic inflammatory activity. EICC significantly inhibited the formation of MDA and markedly raised the activities of SOD, CAT and GSH-Px. EIFH could reduce the level of MDA and elevate the activity of SOD only at the high dose. The free radical scavenging activities of EICC are higher than that of EIFH. These results suggest that EICC possesses significant anti-inflammatory and free radical scavenging activities. The anti-inflammatory mechanism is attributed, in part, to enhance the activities of antioxidant enzymes.     

Free radical scavenging and antiatherogenic activities of Sesamum indicum seed extracts in chemical and biological model systems

An emerging consensus underscores the importance of oxidative events in vascular disease including excess production of reactive oxygen/nitrogen species (ROS/RNS), in addition to lipoprotein oxidation. Sesamum indicum has long been used extensively as a traditional food. The aim of present study was to evaluate antioxidant action of aqueous and ethanolic seed extracts from S. indicum using various in vitro ROS/RNS generated chemical and biological models. Results demonstrated that the graded-dose (25–1000 μg/ml) of aqueous and ethanolic extracts markedly scavenged the nitric oxide, superoxide, hydroxyl, 1,1-diphenyl-2-picrylhydrazyl and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and, showed metal chelating ability as well as reducing capacity in Fe³⁺/ferricyanide complex and ferric reducing antioxidant power assays. In biological models, both extracts were found to inhibit metal-induced lipid peroxidation in mitochondrial fractions, human serum and LDL oxidation models. In lipoprotein kinetics study, both extracts significantly (P < 0.05) increased lag phase time along with reduced oxidation rate and conjugated dienes production. Ethanolic extract of S. indicum showed higher amounts of total polyphenol and flavonoid content as compared to their counterpart. The IC₅₀ values of both extracts were compared with respective antioxidant standards. Overall, ethanolic extract of S. indicum possess strong antioxidant capacity and offering effective protection against LDL oxidation susceptibility.     

Antioxidant,free radical scavenging activities of Salvia brachyantha and its protective effect against oxidative cardiac cell injury

In this study, antioxidant and free radical scavenging activities of an endemic Salvia species (Salvia brachyantha (Bordz) probed. was assessed in vitro using 1,1-diphenyl-2-picryhydrazyl (DPPH) radical, β-carotene linoleic acid, superoxide anion radical, hydroxyl radical, and reducing power assays. Regarding our data, the plant extract exhibited antioxidant and radical scavenging activities at different magnitudes of potency. In addition, this study was undertaken to assess whether methanol extract of S. brachyantha could increase the endogenous antioxidant enzymes in cells, and where such increased cellular defences could provide protection against oxidative cell injury. Pre treatment of rat heart cell lines with 100 μg/ml of plant extract for 24 h significantly prevented cell damage and enhanced activity of antioxidant enzymes induced by a treatment with xanthine/xanthine oxidase. Increased reactive oxygen species and cell apoptosis induced by xanthine/xanthine oxidase was dose-dependently prevented when cells were pre treated for 24 h with plant extract. These results indicated that S. brachyantha could protect against cell injury via induction of the antioxidant enzyme defences. The extract of this plant might be valuable antioxidant natural sources and seemed to be applicable in both healthy medicine and food industry.     

Effect of mdr1a P-glycoprotein gene disruption, gender, and substrate concentration on brain uptake of selected compounds

Purpose. This study assessed the influence of mdr1a P-glycoprotein (P-gp) gene disruption, gender and concentration on initial brain uptake clearance (Cl _up) of morphine, quinidine and verapamil. Methods. Cl _up of radiolabeled substrates was determined in P-gp-competent and deficient [mdr1a(–/–)] mice by in situ brain perfusion. Brain:plasma distribution of substrates after i.v. administration was determined in both strains. Results. Genetic disruption of mdr1a P-gp resulted in 1.3-, 6.6- and 14-fold increases in Cl _up for morphine, verapamil and quinidine, respectively. With the exception of small differences for verapamil, gender did not affect Cl _up. Saturable transport of verapamil and quinidine was observed only in P-gp-competent mice, with apparent IC ₅₀ values for efflux of 8.6 ± 2.3 M and 36 ± 2 M, respectively. VerapamilCl _up was 50% higher in mdr1a(+/–) vs. mdr1a(+/+) mice; no such difference was observed for quinidine. In P-gp-competent mice, uptake of verapamil and quinidine was unaffected by organic vehicles. Plasma decreased VER Cl _up to a greater extent in the presence of P-gp. The influence of P-gp in situ was lower than, but correlated with, the effect in vivo. Conclusions. P-gp decreases Cl _up of morphine, verapamil and quinidine in situ with little or no influence of gender, but this effect cannot fully account for the effects of P-gp in vivo. P-gp is the only saturable transport mechanism for verapamil and quinidine at the murine blood-brain barrier. The influence of protein binding on Cl _up may be enhanced by P-gp-mediated efflux.     

A new stilbene glucoside gallate from the roots of Polygonum multiflorum

A new stilbenoid (1) was isolated from the root extract of Polygonum multiflorum together with eight known constituents (2∼9). The chemical structure of 1 was established as the 6″-O-monogalloyl ester of (E)-2,3,4′,5-β-tetrahydroxystilbene-2-β-D-glucopyranoside based on physicochemical and spectroscopic analyses, particularly by NMR spectroscopic data, i.e., COSY, HMQC and HMBC. Compound 1 weakly inhibited acetylcholinesterase in vitro.     

Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines

Background  Although man’s first encounters with hallucinogens predate written history, it was not until the rise of the sister disciplines of organic chemistry and pharmacology in the nineteenth century that scientific studies became possible. Mescaline was the first to be isolated and its chemical structure determined. Since then, additional drugs have been recovered from their natural sources and synthetic chemists have contributed many more. Given their profound effects upon human behavior and the need for verbal communication to access many of these effects, some see humans as ideal subjects for study of hallucinogens. However, if we are to determine the mechanisms of action of these agents, establish hypotheses testable in human subjects, and explore the mechanistic links between hallucinogens and such apparently disparate topics as idiopathic psychosis, transcendental states, drug abuse, stress disorders, and cognitive dysfunction, studies in animals are essential. Stimulus control by hallucinogens has provided an intuitively attractive approach to the study of these agents in nonverbal species. Objective  The intent of this review is to provide a brief account of events from the time of the first demonstration of hallucinogen-induced stimulus control to the present. In general, the review is limited to lysergic acid diethylamide (LSD) and the hallucinogenic derivatives of phenethylamine and tryptamine. Results  The pharmacological basis for stimulus control by LSD and hallucinogenic phenethylamines and tryptamines is serotonergic in nature. The 5-HT_2A receptor appears to be the primary site of action with significant modulation by other serotonergic sites including 5-HT_2C and 5-HT_1A receptors. Interactions with other neurotransmitters, especially glutamate and dopamine, are under active investigation. Most studies to date have been conducted in the rat but transgenic mice offer interesting possibilities. Conclusions  Hallucinogen-induced stimulus control provides a unique behavioral tool for the prediction of subjective effects in man and for the elucidation of the pharmacological mechanisms of the action of these agents.     

Studies on cytotoxic, hydroxyl radical scavenging and topoisomerase inhibitory activities of extracts of Tabernaemontana divaricata (L.) R.Br. ex Roem. and Schult

In the present investigation, the cytotoxic, hydroxyl radical scavenging and topoisomerase inhibition activities of Tabernaemontana divaricata (Apocynaceae) were evaluated. The extracts from leaves of the plant were prepared with different solvents viz. chloroform, methanol, ethyl acetate and hexane. In, in vitro cytotoxicity assay, with cell lines viz HCT-15 (Colon), HT-29 (Colon), 502713 (Colon), MCF-7 (Breast), PC- 3 (Prostrate), it was observed that the ethyl acetate extract was effective against only one colon cell line (502713) at the lowest dose i.e. 10 micro g/ml, whereas the chloroform extract was effective against all the three colon cancer cell lines, at 30 microg/ ml. In order to evaluate the mechanism of cytotoxicity of these extracts, they were assessed for their ability to scavenge hydroxyl radicals in plasmid nicking assay with pBR322. It was observed that all the extracts effectively inhibited the unwinding of supercoiled DNA except hexane extract, which showed the least effect. Since the expression of topo enzymes is linked with cell proliferation so the extracts were also checked for topo I and topo II inhibitory activities. It was noticed that ethyl acetate extract selectively showed inhibition of topo II in topoisomerase II relaxation assay.     

In vitro screening of essential oil from young and mature leaves of Artemisia scoparia compared to its major constituents for free radical scavenging activity

The present study investigated the chemical characterization, and antioxidant activity of essential oil hydrodistilled from young and mature leaves of Artemisia scoparia. GC–MS analyses revealed a monoterpenoid nature (64–67%) with 44 and 31 constituents in young and mature leaves oil, respectively. The oil from young leaf contained greater amount of oxygenated compounds. β-Myrcene (24.13%) and p-cymene (27.06%) were the major constituents in young and mature leaves oil, respectively. A. scoparia leaf oils (25–200 μg/ml) exhibited a strong 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity and antioxidant activity against hydroxyl radical and hydrogen peroxide. However, the activities of major constituent monoterpenes, β-myrcene and p-cymene, were less. In general, the DPPH radical scavenging and antioxidant activity was in the order: mature leaf oil > young leaf oil > β-myrcene > p-cymene.     

Effect of interaction between phenolic compounds and copper ion on antioxidant and pro-oxidant activities

Phenolic compounds are widely used in food and cosmetics to prevent undesirable oxidation. On the other hand, phenolic compounds are also strong reducing agents and under in vitro conditions and in the presence of copper ion, they can act as pro-oxidants. In this study, we conducted electron spin resonance (ESR) measurements for the increase in reactive oxygen species (ROS) in relation to their structure and interaction with transition metals. Moreover, the antioxidant activity was assessed with the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, and the pro-oxidant effect of phenolic compounds on DNA damage was assessed by measuring 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is effectively formed during oxidative damage. In conclusion, ortho-dihydroxyl groups that can chelate with Cu²⁺ induce the greatest pro-oxidant activity. Moreover, the interaction between phenolic compounds and copper induced to H₂O₂. The obtained results indicated that ROS participated in oxidative DNA damage induced by phenolic compounds in the presence of Cu²⁺.     

元胡生物碱的化学研究 Ⅵ.元胡叔胺生物碱的反相高效液相色谱法测定

用反相高效液相色谱法分离了元胡块茎中6个主要叔胺生物碱即(—)-四氢非洲防己胺(A),(±)-四氢巴马亭(B),(+)-紫堇碱(C),(—)-四氢小檗碱(D),四氢黄连碱(E),(+)-海罂栗碱(F)。并用外标法测定了这些生物碱在元胡生药样品及醋制品中的含量。本法用Nucleosil10 C₁₈层析柱(2.6mm×25 cm),甲醇—水(70:30)为流动相,紫外λ280 nm检测,流速0.8ml/min。方法简便、快速,准确,重现性好。     

Antagonism by haloperidol and its metabolites of mechanical hypersensitivity induced by intraplantar capsaicin in mice: role of sigma-1 receptors

Rationale  We evaluated the effects of haloperidol and its metabolites on capsaicin-induced mechanical hypersensitivity (allodynia) and on nociceptive pain induced by punctate mechanical stimuli in mice. Results  Subcutaneous administration of haloperidol or its metabolites I or II (reduced haloperidol) dose-dependently reversed capsaicin-induced (1 μg, intraplantar) mechanical hypersensitivity of the hind paw (stimulated with a nonpainful, 0.5-g force, punctate stimulus). The order of potency of these drugs to induce antiallodynic effects was the order of their affinity for brain sigma-1 (σ₁) receptor ([³H](+)-pentazocine-labeled). Antiallodynic activity of haloperidol and its metabolites was dose-dependently prevented by the selective σ₁ receptor agonist PRE-084, but not by naloxone. These results suggest the involvement of σ₁ receptors, but discard any role of the endogenous opioid system, on the antiallodynic effects. Dopamine receptor antagonism also appears unlikely to be involved in these effects, since the D₂/D₃ receptor antagonist (−)-sulpiride, which had no affinity for σ₁ receptors, showed no antiallodynic effect. None of these drugs modified hind-paw withdrawal after a painful (4 g force) punctate mechanical stimulus in noncapsaicin-sensitized animals. As expected, the control drug gabapentin showed antiallodynic but not antinociceptive activity, whereas clonidine exhibited both activities and rofecoxib, used as negative control, showed neither. Conclusion  These results show that haloperidol and its metabolites I and II produce antiallodynic but not antinociceptive effects against punctate mechanical stimuli and suggest that their antiallodynic effect may be due to blockade of σ₁ receptors but not to dopamine receptor antagonism.     

Identification of the main volatile compounds in the leaf and flower of <Emphasis Type="Italic">Tithonia diversifolia</Emphasis> (Hemsl) Gray

The composition of the essential oils of the leaves and flowers of Tithonia diversifolia (Hemsl) A. Gray, Mexican sunflower, are reported. The oils were obtained by hydrodistillation in an all-glass Clevenger-type apparatus and analyzed by GC–MS. The leaf oil was comprised of an abundance of α-pinene (32.9%), β-caryophyllene (20.8%), germacrene D (12.6%), β-pinene (10.9%) and 1, 8-cineole (9.1%). Germacrene D (20.3%), β-caryophyllene (20.1%) and bicyclogermacrene (8.0%) characterized the oil of the flower. A number of aliphatic fatty acids and a diterpenoid compound, sandaracopimaradiene, that were present in the flower, could not be detected in the leaf oil.     

Biotransformation of glycyrrhizin by human intestinal bacteria and its relation to biological activities

The relationship between the metabolites of glycyrrhizin (18beta-glycyrrhetinic acid-3-O-beta-D-glucuronopyranosyl-(1-->2)-beta-D-glucuronide, GL) and their biological activities was investigated. By human intestinal microflora, GL was metabolized to 18beta-glycyrrhetinic acid (GA) as a main product and to 18beta-glycyrrhetinic acid-3-O-beta-D-glucuronide (GAMG) as a minor product. The former reaction was catalyzed by Eubacterium L-8 and the latter was by Streptococcus LJ-22. Among GL and its metabolites, GA and GAMG had more potent in vitro anti-platelet aggregation activity than GL. GA also showed the most potent cytotoxicity against tumor cell lines and the potent inhibitory activity on rotavirus infection as well as growth of Helicobacter pylori. GAMG, the minor metabolite of GL, was the sweetest.     

Anti-oxidative and anti-inflammatory activities of some isolated constituents from the stem bark of Allanblackia monticola Staner L.C (Guttiferae)

Stem bark of Allanblackia monticola has been used in association with others plant in the Cameroonian folk medicine for the treatment of various diseases such amoebic dysentery, diarrhoea, lung infections, and skin diseases. The methylene chloride fraction, its isolated compounds like α-mangostin, lupeol and acid betulinic were screened for antioxidant activity using free radical scavenging method. These isolated compounds were further tested for anti-inflammatory properties using carrageenan-induced model. Methylene chloride fraction, showed concentration-dependent radical scavenging activity, by inhibiting 1,1-diphenyl-1-picryl-hydrazyl radical (DPPH) with an IC₅₀ value of 14.60 μg/ml. α-Mangostin and betulinic acid (500 μg/ml), showed weak radical scavenging activity with a maximum inhibition reaching 38.07 μg/ml and 26.38 μg/ml, respectively. Betulinic acid, lupeol and α-mangostin (5 mg/kg and 9.37 mg/kg) showed anti-inflammatory activity with a maximum inhibition of 57.89%, 57.14% and 38.70%, respectively. Methylene chloride fraction of Allanblackia monticola and some derivatives, have antioxidant and anti-inflammatory activities. Received 7 July 2008; accepted 7 October 2008