Isolation and anti-inflammatory activity of colchicinoids from Gloriosa superba seeds

Gloriosa superba L. (Liliaceae) seeds, known as “kalihari” (Hindi), were phytochemically investigated for colchicine (well known for gout treatment) and other related alkaloid content. Colchicine, 2- demethylcolchicine, 3-demethylcolchicine, and N-formyl-N-deacetylcolchicine were alkaloids isolated from the seeds. The isolated samples have been standardized for their purity with respect to the reference standard using HPLC. The structures were confirmed by NMR spectroscopy and were analyzed by spiking them along with colchicine reference by HPLC. The purity of colchicine, 2- demethylcolchicine, 3- demethylcolchicine and N-formyl-N-deacetylcolchicine were 99.82, 96.78, 98.71, and 98.13% respectively. The compounds were subjected to an anti-inflammatory study by using the formaldehyde inflammagen-induced inflammation model. Oral administration of colchicine at 2, 4, and 6?mg/kg body weight resulted in 48.9, 68.7, and 79.1% inhibition respectively, while 30.9% inhibition was seen in the phenylbutazone 100?mg/kg treated group once daily for a period of 4 days. The results clearly indicated that the colchicine is more effective as an anti-inflammatory agent compared with phenylbutazone, the standard drug used in the study, whereas the oral administration of 6?mg/kg body weight of 2- demethylcolchicine, 3-demethylcolchicine and N-formyl-N-deacetylcolchicine showed very poor activity (41.6, 40.4, and 41.1% activity respectively).     

病毒清的抗炎解热与免疫增强作用

灌胃给予病毒清 (BingDuQing ,BDQ) 0 5 5、1 1 0、2 2 0 g/kg显著抑制小鼠二甲苯性耳肿胀 ,此剂量连续给药 7d ,能提高小鼠体内碳粒廓清能力和绵羊红细胞诱导的血清溶血素抗体水平。大鼠灌胃给予BDQ 0 4 0、0 80、1 60 g/kg能显著抑制角叉菜胶性足肿胀和干酵母性发热时体温的升高。家兔灌胃给予BDQ 0 2 0、0 4 0、0 80g/kg可降低伤寒菌苗致热时的体温     

Edematogenic activity of a sulfated galactan from the red marine algae Gelidium crinale

Context: The red algae Gelidium crinale (Turner) Gaillon (Gelidiaceae), encountered along the Southeast and Northeast Brazilian sea coast, contains a sulfated galactan presenting a similar saccharide backbone compared to λ carrageenan. Inflammatory effects of other galactans were reported, but not for that obtained from G. crinale (SG-Gc).

Objective: To investigate the in vivo edematogenic effect of SG-Gc in comparison to λ carrageenan.

Methods: SG-Gc was isolated by ion exchange chromatography. Paw edema was induced by subcutaneous (s.c.) intraplantar injection of SG-Gc or λ carrageenan and evaluated by hydroplethysmometry. Data were expressed as the increase in paw volume subtracted from the basal volume or area under curve-AUC. To investigate the participation of early and late-phase inflammatory mediators, rats were treated with pyrilamine, compound 48/80, indomethacin, NG-nitro-l-arginine methyl ester (l-NAME), or pentoxifylline before SG-Gc.

Results: SG-Gc edematogenic effect was initiated at 0.5 h, peaked at 2 h (1.26 ± 0.05 mL) and lasted until 6 h (0.21 ± 0.03 mL), whereas the carrageenan-induced edema started at 1 h. The first phase (1–3 h) of SG-Gc-induced edema was 176 ± 15 (AUC) versus carrageenan (114.5 ± 14), whereas the second phase (3–5 h) was 95 ± 12 (AUC) versus carrageenan (117.5 ± 11). Treatment with compound 48/80, pyrilamine, indomethacin, L-NAME, and pentoxifylline inhibited the effect of SG-Gc by 32, 40, 69, 72, and 49%, respectively.

Discussion and conclusion: SG-Gc and λ carrageenan induce different profile of inflammatory response in the paw edema model, that involves histamine, cytokines, prostaglandins, and nitric oxide (NO), but with different degree of participation.     

In vivo anti-inflammatory and antinociceptive effects of liriodendrin isolated from the stem bark of Acanthopanax senticosus

In the present study, liriodendrin isolated by activity-guided fractionation from the ethyl acetate (EtOAc) extracts of the stem bark of Acanthopanax senticosus, was evaluated for anti-inflammatory and antinociceptive activities. Liriodendrin (5, 10 mg/kg/day, p. o.) significantly inhibited the increase of vascular permeability induced by acetic acid in mice and reduced an acute paw edema induced by carrageenan in rats. When the analgesic activity was measured by the acetic acid-induced writhing test and hot plate test, liriodendrin showed a dose-dependent inhibition in animal models. In addition, syringaresinol, the hydrolysate of liriodendrin, more potently inhibited the LPS-induced production of NO, PGE 2 and TNF-alpha production of macrophages than liriodendrin. Consistent with these observations, the expression level of iNOS and COX-2 enzyme was decreased by syringaresinol in a concentration-dependent manner. These results suggest that the anti-inflammatory and antinociceptive effects of liriodendrin after oral administration were attributable to the in vivo transformation to syringaresinol, which may function as the active constituent.     

Analysis of the anti-inflammatory and chemopreventive potential and description of the antimutagenic mode of action of the Annona crassiflora methanolic extract

Context: Annona crassiflora Mart. (Annonaceae) is a medicinal plant that is widely used in folk medicine, which leads to its investigation as a potential source of new pharmacological principles.

Objective: This study describes the anti-inflammatory, antiallodynic, and antimutagenic/chemopreventive activities of the leaves A. crassiflora methanolic extract. Its antimutagenic mode of action was analyzed in a plant or animal experimental model.

Materials and methods: Total flavonoids were quantified by spectrophotometry at 415?nm and its composition was analyzed by ¹H NMR spectra. Animals received orally, 30, 100, and 300?mg/kg of extract in both tests, carrageenan-induced paw edema and myeloperoxidase activity. Animals were treated with 100 and 300?mg/kg, in all the analyzed tests, pleural cell migration and protein exudation, carrageenan-induced cell migration into the pouch, induction of joint inflammation and carrageenan-induced allodynia response in the mouse paw. To evaluate the antimutagenic/chemopreventive activity through the Allium cepa test, we used 5, 10, and 15?mg/L of extract, and for the micronucleus test in the peripheral blood, we used the dose of 15?mg/kg.

Results: The fractionation of the ethyl acetate (EA) fraction, resulting from the partition of the methanol extract of the A. crassiflora, afforded through chromatographic methods resulted in the isolation of kaempferol 3-O-β-glucoside and kaempferol 3-O-β-diglucoside. Oral treatment with 100 and 300?mg/kg of extract significantly inhibited the carrageenan-induced edema formation, with inhibitions of 53?±?7% and 47?±?10%; in MPO activity, the observed inhibitions were 60?±?7% for 100?mg/kg treatment and 63?±?7% for 300?mg/kg. The ACME reduced significantly the total leukocytes (an inhibition of 78?±?9% with 100?mg/kg and 90?±?7% with 300?mg/kg) and protein levels (approximately 100% inhibition with both doses) in the pleurisy model. In?carrageenan-induced leukocyte migration into the pouch, the extract inhibited leukocyte migration only when administered 300?mg/kg per dose (the reduction was 43?±?5%). Pretreatment with extract failed to reduce the zymosan-induced edema formation and did not inhibit the carrageenan-induced mechanical allodynia. Damage reduction in Allium cepa tested with different concentrations (5, 10, and 15?mg/L) was 66.17, 75.75, and 69.19% for the pre-treatment; 72.72, 33.33, and 22.22% for the simple simultaneous treatment; 100.50, 93.93, and 102.52% for the simultaneous treatment with pre-incubation; 89.39, 79.79, and 84.34%; for the post-treatment, and 86.36, 81.31, and 93.43% for the continuous treatment. The antimutagenic evaluation in the micronucleous test showed a damage reduction of 75.00 and 64.58% for the pre-treatment and simultaneous protocols, respectively. The post-treatment protocol increased the cyclophosphamide effects in 45.83%.

Conclusion: These results suggest that this medicinal plant has chemopreventive and anti-inflammatory therapeutic potential.     

Lipid peroxidation inhibitory activity of some constituents isolated from the stem bark ofEucalyptus globulus

Twelve compounds with lipid peroxidation inhibitory activity were isolated from the stem bark of E. globulus. Their structures were assigned as a new aromatic monoterpene (1) and eleven known compounds, pinoresinol (2), vomifoliol (3), 3,4,5-trimethoxyphenol 1-O-beta-D-(6'-O-galloyl)glucopyranoside (4), methyl gallate (5), rhamnazin (6), rhamnetin (7), eriodictyol (8), quercetin (9), taxifolin (10), engelitin (11), and catechin (12) on the basis of UV, mass, and NMR spectroscopic analyses. These compounds except vomifoliol significantly inhibited lipid peroxidation in rat liver microsome.     

Antinociceptive and anti-inflammatory effects of the ethyl acetate stem bark extract of Bridelia scleroneura (Euphorbiaceae)

Bridelia scleroneura is a member of the Euphorbiaceae family. In folk medicine in Cameroon, the stem bark of this plant is used for relieving abdominal pain, contortion, arthritis and inflammation. In this study, the antinociceptive and anti-inflammatory activities of the ethyl acetate stem bark extract have been evaluated. The putative analgesic effect of the plant extract was examined in abdominal constriction, hot plate, formalin and on pain using tail immersion mouse models and in carrageenan-induced paw edema in rats. The extract (150–600 mg/kg) exhibited a dose-dependent analgesic effect (46.27–78.97%) in acetic acid-induced abdominal constriction in mice. B. scleroneura extract increased the pain latency of nociceptive response to thermal stimuli at the higher dose of 600 mg/kg. B. scleroneuna induced significant dose-dependent reduction of the nociception in both early and late phases of the formalin test. The extract at the dose of 300 mg/kg, increased significantly, by 63.70% and 52.01% the tail-immersion latency time, 1 and 2 h post-dosing. In the carrageenan test, B. scleroneura (150–600 mg/kg, p.o) had dose-dependent and significant effects at different time intervals. This behaviour was similar to indometacin (10 mg/kg) used as a standard drug. These results show that the ethyl acetate stem bark extract of B. scleroneura possesses peripheral and central analgesic properties as well as anti-inflammatory activity against acute inflammation processes, in support of the folk medicinal use of the plant.     

Antimalarial activity and cytotoxicity of (-)-roemrefidine isolated from the stem bark of Sparattanthelium amazonum.

(-)-Roemrefidine, an aporphine alkaloid isolated from Sparattanthelium amazonum Martius (Hernandiaceae) a vine from Bolivia, has been found to be active against both resistant and sensitive strains of Plasmodium falciparum in vitro and against P. berghei in mice. The compound demonstrated no cytotoxic activity against three cell lines (KB, HEp-2 and HeLa).     

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     

Anti-Helicobacter pylori effect of costunolide isolated from the stem bark ofMagnolia sieboldii

Helicobacter pylori (H. pylori) infection is now established as the major pathogenic factor in chronic gastritis and peptic ulcer disease. In addition, there is accumulating evidence thatH. pylori plays an important role in the process of gastric carcinogenesis. On the other hand, oriental traditional medicines have been used for stomach disease for thousands of years. In the present study, methanol extract from the stem bark ofMagnolia sieboldii (M. sieboldii) and its components were investigated on their inhibitory effects against urease activity and growth ofH. pylori in vitro. The methanol extract ofM. sieboldii significantly inhibited the growth ofH. pylori ATCC 43504 at 5 mg/ml. From the further fractionation, the chloroform fraction inhibited the bacterial growth dose-dependently. Among four fractions separated from the chloroform fraction by silica gel column chromatography, MS-C-2 was the most potent. Costunolide was isolated from the MS-C-2 subfraction by preparative TLC and recrystallization using n-hexane. Anti-H. pylori effect of costunolide was investigated using one commercial strain (H. pylori ATCC 43504) and three clinical strains (H. pylori 4, 43, 82548). Costunolide exhibited potent anti-H. pylori activity, and the MIC was around 100–200 μg/ml. However, costunolide had no inhibitory effect ofH. pylori urease activity at the concentration used for the growth inhibition assay. From these results, we conclude that costunolide inhibits the growth ofH. pylori by the independent manner ofH. pylori urease inhibition.     

Essential moiety for antimutagenic and cytotoxic activity of hederagenin monodesmosides and bisdesmosides isolated from the stem bark of Kalopanax pictus

For the elucidation of the antimutagenic and cytotoxic principles from the stem bark of Kalopanax pictus, seven isolated components of this crude drug were tested in the Ames test and the MTT test. Hederagenin and its monodesmosides, kalopanaxsaponin A and I in addition to its bisdesmosides, kalopanaxsaponin B and H, showed potent antimutagenic activities against aflatoxin B1 (AFB1). However, they had no inhibitory effects on mutagenicity induced by the direct mutagen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). This suggested that hederagenin glycosides might effectively prevent the metabolic activation of AFB1 or scavenge the electrophilic intermediate capable of inducing mutation. Hederagenin was found to be an essential moiety for the exhibition of antimutagenicity. Moreover, hederagenin and its 3-O-glycosides were found to be cytotoxic on various tumor cell lines, P-388, L-1210, U-937, HL-60, SNU-5 and HepG2, while 3,28-di-O-glycosides of hederagenin were not cytotoxic. Hence, hederagenin and its 3-O-glycosides could be suitable for cancer treatment chemopreventive drugs.     

Antidiarrheal activity of extracts and compound from Trilepisium madagascariense stem bark

Objective:

The present study was performed to evaluate the preventive and curative antidiarrheal effects of the methanol extract, fractions and compound from the stem bark of Trilepisium madagascariense in rats.

Materials and Methods:

The methanol extract from the stem bark of T. madagascariense, its fractions (n-hexane, ethyl acetate, n-butanol and aqueous residue) and compound (obtained from further column chromatography of the ethyl acetate fraction) were evaluated for the antidiarrheal activity in rats. These test samples (at 100, 200 and 400 mg/kg for the extract and fractions and 2.5 mg/kg for compound) were assayed on the latent periods, purging indices and fecal frequencies in castor oil-induced diarrhea. Gastrointestinal transit and castor oil-induced enteropooling assays were conducted. Shigella-induced diarrhea was assayed. Blood chemistry and fecal Shigella load were examined.

Results:

The fractionation of the ethyl acetate fraction from the methanol extract of T. madagascariense afforded a known compound [isoliquiritigenin (1)]. Compound 1 increased the latent period of diarrhea induction (179.40 min) compared to the saline control (60.80 min). The purging indices, fecal frequencies and intestinal enteropooling decreased with an increase in the dose of test samples. The blood cell counts, sera creatinine and fecal Shigella load decreased significantly (P ≤ 0.05) in the plant extract-treated rats compared to the saline control.

Conclusion:

The results of our study, being reported for the first time, provide clear evidence that the methanol extract, fractions and isoliquiritigenin from T. madagascariense stem bark possess antidiarrheal activities.     

Analgesic and anti-inflammatory effects of the methanol stem bark extract of Prosopis africana

Prosopis africana (Guill. & Perr.) Taub. (Mimosoideae) is a shrub used for menstrual and general body pain in Nupe land in north central Nigeria. In this study, the methanol extract of the stem bark of Prosopis africana (at doses of 62.5, 125, and 250?mg/kg) was evaluated for analgesic and anti-inflammatory activities using acetic acid-induced writhing assay and carrageenan-induced inflammation in rats. The extract significantly (P <0.05) attenuated the acetic acid-induced writhing with the highest activity observed at the highest dose, 250?mg/kg (76.89%) comparable to that of piroxicam (83.16%) the standard agent used. In the carrageenan-induced inflammation assay, the extract showed significant anti-inflammatory activity (P <0.001) from the third hour. The preliminary phytochemical screening revealed the presence of flavonoids, saponins, carbohydrates, cardiac glycosides, tannins, and alkaloids. The oral median lethal dose was found to be 3807.9?mg/kg in mice and > 5000?mg/kg in rats. This study supports the folkloric claim of the use of Prosopis africana in the management of pain.     

Anti-complement activity of norlignans and terpenes from the stem bark of Styrax japonica

A new norlignan, styraxlignolide A (1), and two new terpenes, styraxosides A (2) and B (3), were isolated from the MeOH-soluble fraction of Styrax japonica Sieb. et Zucc. (Styracaceae) stem bark, together with two known compounds, egonol (4) and masutakeside I (5). The new compounds were determined as 5-(3'-hydroxypropyl)-7-methoxy-2-(3',4'-dimethoxyphenyl)-benzofuran 3'- O-[beta-D-xylopyranoside-(1-->6)-beta- D-glucopyranoside] (1), 3beta,7beta-dihydroxy-4alpha,4beta,8beta,10beta,14alpha-pentamethyl-5alpha-gon-16-en-2-one 3-O-[beta-D-glucopyranoside-(1-->2)-beta-D-glucopyranoside] (2), and 3beta,17beta-dihydroxy-28-norolean-12-en-16-one 3-O-[alpha-L-rhamopyranoside-(1-->2)-beta-D-glucuronopyranoside] (3) by spectroscopic means including 2D-NMR. The five compounds were tested in vitro for anti-complement activity against the complement system. Compounds 1, 3, 4, and 5 displayed inhibitory activity in the anti-complement assay, with IC50 values of 123, 65, 33, and 166 microM, respectively. Compound 1a and camellenodiol (3a), obtained from acid hydrolysis of 1 and 3, respectively, did not affect the hemolytic activity of human serum against sensitized erythrocytes. This shows that a sugar seems to play a role of enhancing significantly anti-complement activity.     

Scyphocephalione A isolated from the stem bark of Scyphocephalium ochocoa (Myristicaceae) attenuate acute and chronic pain through the antiinflammatory activity

Inflammopharmacology - In the treatment of cancer, patients that receive anti-cancer drugs such as Vincristine develop peripheral neuropathic pain. Scyphocephalione A is a new bioactive compound...     

Antiepileptic activity of total triterpenes isolated from Poria cocos is mediated by suppression of aspartic and glutamic acids in the brain

Context: Triterpenes from Poria cocos Wolf (Polyporaceae) have been used to treat various diseases in traditional Chinese medicine. However, the antiepileptic effects and mechanism are not fully understood.

Objective: The objective of this study is to investigate the antiepileptic properties of total triterpenes (TTP) from the whole P. cocos.

Materials and methods: The ethanol extract TTP was identified by HPLC fingerprint analysis. Male ICR mice were gavaged (i.g.) with TTP (5, 20, 80 or 160?mg/kg) or reference drugs twice a day for 7 d. Antiepileptic activities of TTP were evaluated by maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizures in mice for 30 and 60?min, respectively. Locomotor activity and Rota-rod tests were performed for 60?min and 5?min, respectively. The levels of glutamic acid (Glu), aspartic acid (Asp), γ-aminobutyric acid (GABA) and glycine (Gly) in convulsive mice were estimated. The chronic epileptic model of Wistar rats was built to measure expressions of glutamate decarboxylase 65 (GAD65) and GABA_A in rat brain after TTP treatment.

Results: The LC₅₀ of TTP (i.g.) was above 6?g/kg. TTP (5–160?mg/kg) protected mice against MES- and PTZ-induced convulsions at 65.0% and 62.5%, respectively, but have no effect on rota-rod treadmill; TTP (20–160?mg/kg) significantly reduced the locomotor activities, shortened the onset of pentobarbital sodium-induced sleep; TTP decreased Glu and Asp levels in convulsive mice, but increased the GAD65 and GABA_A expressions in chronic epileptic rats at doses usage.

Discussion and conclusion: TTP extracted from P. cocos possessed potential antiepileptic properties and is a candidate for further antiepileptic drug development.     

Triterpenes and xanthones from the stem bark of Garcinia tetralata

A new compound, 3β,18,19β-trihydroxylupane, was isolated from Garcinia tetralata, along with five known compounds, garcinexanthone B, morolic acid acetate, toxyloxanthone A, 6,11-dihydroxy-2,2-dimethylpyrano[3,2-c]xanthen-7(2H)-one, and 1,4-dihydroxy-5,6-dimethoxy-xanthone. The structure of the new compound was established by extensive spectroscopic techniques.     

Inhibition of chitin synthase 2 and antifungal activity of lignans from the stem bark of Lindera erythrocarpa

Potent chitin synthase 2 inhibitors, methyllinderone (1), linderone (2) and kanakugiol (3) were isolated from the stem bark of L. erythrocarpa Makino (Lauraceae). These compounds inhibited chitin synthase 2 with IC(50) values of 23.3, 21.4 and 23.8 microg/mL, respectively. Methyllinderone (1) and linderone (2) exhibited no inhibitory activities for chitin synthases 1 and 3 from S. cerevisiae, and chitin synthase 1 from Candida albicans up to the concentration of 280 microg/mL, while kanakugiol (3) exhibited very weak activity against chitin synthase 1 of C. albicans with an IC(50) of 160 microg/mL. All of the compounds showed moderate to weak antifungal activities against various pathogenic fungi (MIC: 8 - >128 microg/mL) including Cryptococcus neoformans, Aspergillus fumigatus, and Colletotrichum lagenarium. The results indicate that these compounds are specific inhibitors of chitin synthase 2 and can potentially serve as antifungal agents.     

Potential anti-tumor promoting activity of lupane-type triterpenoids from the stem bark of Glochidion zeylanicum and Phyllanthus flexuosus

Four known lupane-type triterpenoids, glochidonol (1), glochidiol (2), lup-20(29)-ene-1beta,3beta-diol (3) and glochidone (3) were isolated from the stem bark of Glochidion zeylanicum. Previously, lupeol (5), lup-20(29)-ene-3beta,24-diol (6) and betulin (7) were isolated from the stem bark of Phyllanthus flexuosus. This study reports the assays of these lupane-type triterpenoids: all isolates 1-7 and synthetic analogues, glochidonyl acetate (1a), lup-20(29)-ene-1,3-dione (1b) and lup-20(29)-ene 3beta,24-diacetate (6a) were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). Among them, the effects of compounds 2 (IC50 = 290 mol ratio/32 pmol TPA) and 3 (IC50 = 300) were stronger than the others. In addition, compound 2 exhibited a strong inhibitory effect on mouse skin tumor promotion in an in vivo mouse two-stage carcinogenesis test.