Biomedical subjects

Ikhlas A Khan

Publications and source records attributed to Ikhlas A Khan.

At least 19 recordsLinked to original sources

PubMed2006

Inhibition of NF-kappaB-mediated transcription and induction of apoptosis by melampolides and repandolides.

PURPOSE: Nuclear factor-kappaB (NF-kappaB) plays a crucial role in the regulation of inflammatory processes, cell proliferation, and apoptosis. Blocking NF-kappaB signaling may represent a therapeutic strategy in cancer and inflammation therapy. The aim of this study was to investigate the effects of sesquiterpenes isolated from Asteraceae, namely melampolides (enhydrin, tetraludin A) and repandolides (repandins A, B, D and E) on the activation of NF-kappaB, cell growth of cancer cells, cell cycle progression and apoptosis. In addition, their effects on the activity of cyclooxygenase-2 (COX-2) enzyme were also evaluated. METHODS: Cell-based reporter gene assay was conducted in SW1353 cells. COX-2 enzyme activity and cell growth inhibition was determined by enzyme immunoassay and MTT assay respectively. Cell cycle analysis was carried out by flow cytometry and apoptosis was observed by DAPI staining assay. RESULTS: In SW1353 cells, transcription mediated by NF-kappaB was inhibited by enhydrin, tetraludin A and repandins A, B, D and E, while Sp-1 mediated transcription was not affected. COX-2 enzyme activity was inhibited by enhydrin, repandin A and E, but not by tetraludin A, repandin B and D. These compounds were effective in inhibiting the growth of a panel of human tumor cell lines in a concentration-dependent manner. Cell cycle analysis and DAPI staining indicated cell cycle arrest in G(2)/M phase and induction of apoptosis. CONCLUSIONS: Enhydrin, tetraludin A and repandins A, B, D and E inhibited tumor cell growth and induced cell cycle arrest and apoptosis. These effects may be related to inhibition of NF-B activation.

Apoptosis↗

PubMed2006

9,10-seco-9,19-Cyclolanostane arabinosides from the roots of Actaea podocarpa.

Seven 9,10-seco-9,19-cyclolanostane arabinosides, named podocarpasides A-G (1-7), were isolated from the roots of Actaea podocarpa DC., a species closely related to black cohosh (a well known dietary supplement). Their structures were determined with the help of spectroscopic data including extensive 2D NMR spectroscopy. The isolates were found inactive, when tested for cytotoxic, estrogenic, and antioxidant activities in cell based assays. They were also tested for anticomplement activity against the classical pathway of complement system and only podocarpaside C (3) inhibited modest complement activity with an IC50 value of 200 microM.

Carbohydrate Conformation↗

PubMed2006

Quantitative and qualitative determination of six xanthones in Garcinia mangostana L. by LC-PDA and LC-ESI-MS.

A new method was developed for the simultaneous analysis of six naturally occurring xanthones (3-isomangostin, 8-desoxygartanin, gartanin, alpha-mangostin, 9-hydroxycalabaxanthone and beta-mangostin). The quantitative determination was conducted by reversed phase high performance liquid chromatography with photodiode array detector (LC-PDA). Separation was performed on a Phenomenex Luna C18(2) (150 mm x 3.00 mm, 5 microm) column. The xanthones were identified by retention time, ultraviolet (UV) spectra and quantified by LC-PDA at 320 nm. The precision of the method was confirmed by the relative standard deviation (R.S.D.), which was < or =4.6%. The recovery was in the range from 96.58% to 113.45%. A good linear relationship was established in over two orders of magnitude range. The limits of detection (LOD) for six xanthone compounds were < or =0.248 microg/mL. The identity of the peaks was further confirmed by high performance liquid chromatography with time-of-flight mass spectrometry (LC-TOF MS) system coupled with electrospray ionization (ESI) interface. The developed methods were applied to the determination of six xanthones in Garcinia mangostana products. The satisfactory results showed that the methods are effective for the analysis of real samples.

Chromatography, Liquid↗

PubMed2006

Elemanolide sesquiterpenes and eudesmane sesquiterpene glycosides from Centaurea hierapolitana.

Two elemanolide sesquiterpenes and two eudesmane-type sesquiterpene glycosides named hierapolitanins A-D, were isolated, together with five known compounds, two flavones; hispidulin and jaceosidin, a flavon-C-glycoside, shaftoside, a flavonol glycoside, kaempferol-3-O-rutinoside and a neolignan, dehydrodiconiferyl alcohol from the aerial parts of Centaurea hierapolitana Boiss. (Asteraceae). Structure elucidations were based on spectroscopic evidence.

Centaurea↗

PubMed2006

Podocarpaside, a triterpenoid possessing a new backbone from Actaea podocarpa.

Podocarpaside (1), a novel arabinoside possessing a unique triterpene skeleton was isolated from Actaea podocarpa, a closely related species to black cohosh (dietary supplement used for menopausal disorders). Podocarpaside belongs to a new class of triterpenoids, for which the name "ranunculane" is proposed. Compound 1 possesses anticomplement activity. [structure: see text].

Actaea↗

PubMed2006

Antiprotozoal and antimicrobial activities of O-alkylated and formylated acylphloroglucinols.

In the present article, we examined the antileishmanial, antimalarial, antibacterial, and antifungal activities of several newly synthesized O-alkylated phloroglucinol compounds (11-19) which are analogues of the naturally occurring antimalarial compound 1. Analogues 12 and 16 exhibited antileishmanial activity against, Leishmania donovani promastigotes with IC(50)s of 5.3 and 4.2microg/mL, respectively. Naturally occurring monomeric formylated acylphloroglucinol compounds, grandinol (2), jensenone (3), and their analogues (29-37), were also synthesized and evaluated for antileishmanial, antimalarial, antibacterial, and antifungal activities. Amongst these, both grandinol and jensenone showed mild to moderate antibacterial, antifungal, and antileishmanial activities. Jensenone (3) was effective against Candida albicans with an IC(50) of 5.5microg/mL but was ineffective against Cryptococcus neoformans and methicillin-resistant Staphylococcus aureus. Among the analogues, 34 was the most active against C. albicans and C. neoformans with IC(50)s of 2.0 and 2.5microg/mL, respectively, and was fungicidal toward Candida albicans.

Animals↗

PubMed2006

Phytochemical study of actaea rubra and biological screenings of isolates.

A phytochemical study on the chemical constituents of the roots of Actaea rubra led to the isolation and characterization of eleven xylosides of 9,19-cyclolanostane type triterpenes including the new rubraside A (1) and a beta-sitosterol glucoside. The structures of the isolates were determined with the help of spectroscopic data including 2-dimensional NMR as well as comparison with reported data. The compounds were tested for cytotoxic, estrogenic, antioxidant, and anticomplement activities. They were found inactive in the tested assays, except for 4, which showed moderate anticomplement activity.

Actaea↗

PubMed2006

New constituents from noni (Morinda citrifolia) fruit juice.

Morinda citrifolia L. (Rubiaceae), known as noni, has a long history of traditional use in the Hawaiian and Tahitian islands. More recently, an array of commercial noni fruit juice products are gaining popularity as dietary supplements, with claims of anticancer and immunostimulant activities. The biologically active principles of noni are not fully known. In continuation of work on the isolation of markers from dietary supplements, this paper reports the isolation of three new markers, namely, 1-O-(3'-methylbut-3'-enyl)-beta-D-glucopyranose (1), 1-n-butyl-4-(5'-formyl-2'-furanyl)methyl succinate (2), and 4-epi-borreriagenin (3), together with the known iridoid glycosides asperulosidic acid (4) and deacetylasperulosidic acid (5) and a mixture of 1-n-butyl-4-methyl-2-hydroxysuccinate (6a) and 1-n-butyl-4-methyl-3-hydroxysuccinate (6b), as well as a mixture of alpha- and beta-glucopyranose from noni fruit juice obtained from Puerto Rico. The structures of compounds were based on 1H and 13C NMR, mainly 2D NMR COSY, HMQC, HMBC, and NOESY experiments, and HRMS. Furthermore, samples from fresh-squeezed noni fruit juice from Japan revealed the presence of scopoletin (7), in addition to compounds 1-6, indicating no significant differences in the marker constituents of noni collected from Atlantic and Pacific regions.

Beverages↗

PubMed2006

HPLC assisted chemobiological standardization of alpha-glucosidase-I enzyme inhibitory constituents from Piper longum Linn-An Indian medicinal plant.

Formulations of traditional medicines are usually made up of complex mixture of herbs. However, effective quality control methods in order to select right quality materials are lacking. Though Piper longum is a widely used herb in several Ayurvedic formulations prescribed for various diseases, there is no analytical method in the literature so far which can help in selecting the right quality material with proper proportions of the active ingredients (alpha-glucosidase-I enzyme inhibitory principles). We employed a systematic bioassay guided fractionation method and isolated pipataline, pellitorine, sesamin, brachystamide B and guineensine as active principles. A reversed-phase high-performance liquid chromatography method was developed to quantify these active principles in the plant material, which can serve as an effective quality control tool. The separation was carried out using a Discovery HS F5 C-18 (ODS) column and the solvent system used was a gradient comprising of (A) acetonitrile and (B) water with a flow rate of 1 ml/min. The detection was performed using a PDA detector. Regression equation pertaining to all the bioactive isolates revealed a linear relationship (r2 > 0.9995). The detection limits (S/N = 3) ranged from 0.005 to 0.001 microg/ml. Of all the active isolates, sesamin was identified to be present in maximum quantities (0.91%) where as brachystamide B was found in minimum quantity (0.01%).

Calibration↗

PubMed2006

Frequency and timing of leaf removal affect growth and podophyllotoxin content of Podophyllum peltatum in full sun.

Podophyllotoxin is a pharmaceutical compound found in leaves and rhizomes of American mayapple (P. peltatum L.), a species being investigated as an alternative to that of the Indian mayapple (P. emodi). Leaves alone can serve as a renewable source of podophyllotoxin (and other lignans) leaving rhizomes undisturbed to produce leaf biomass in subsequent years. It is not known, however, how frequently or severely plants can be defoliated without adversely affecting future plant growth, lignan content, or podophyllotoxin yield (g.m(-2)). This study compared harvest strategies that were mild to severe in frequency and timing of leaf removal. A wild population in full sun was subjected to leaf removal treatments of varying frequency (every year, every 2nd or 3rd year) and timing (early or late). Control plots not previously harvested were included every year. Plots were 1.0 m2 and established during spring of 2001. Duration of the study was four years. P. peltatum plants did not tolerate the most severe harvest treatment: annual harvest frequency in combination with early harvest time. Early annual harvests reduced total leaf dry mass and total leaf area in a consistent and linear manner. In contrast, plants tolerated annual harvests when conducted late in the growing season and tolerated early harvests when conducted every 2nd or 3rd year. The number of sexual shoots was reduced to zero by early annual harvests. Podophyllotoxin content was 2.7 to 6.5 times greater in leaves harvested early compared to those harvested late, though content was significantly greater in only two out of four years. In conclusion, we can recommend leaf removal every year from well-established P. peltatum populations grown in full sun if harvests are conducted late in the growing season. This harvest strategy ensures maximum podophyllotoxin yield without jeopardizing future leaf biomass yield. Leaves harvested early appear to have greater podophyllotoxin content, but we discourage early harvest every year. Instead, our results indicate that leaves can be harvested early every other year without reducing long-term performance of P. peltatum populations.

Agriculture↗

PubMed2006

Gas chromatographic-mass spectrometric analysis of essential oils from Pimpinella species gathered from Central and Northern Turkey.

Essential oils from 15 Pimpinella species were analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. One species, Pimpinella anisum, in which only fruits were evaluated, was also included in the study. A total of 140 different compounds were identified and significant qualitative and quantitative differences were observed among the samples. Pimpinella essential oils were characterized as having mono-, sesqui- and trinorsesquiterpenoids, propenylphenols, and pseudoisoeugenols. Trinorsesquiterpenoids and phenylpropanoids appear to be chemical markers of Pimpinella species analyzed thus far. Essential oils obtained from Pimpinella roots share the same principal compound, epoxypseudoisoeugenyl-2-methylbutyrate at concentrations from 20 to 82.6%.

Gas Chromatography-Mass Spectrometry↗

PubMed2006

Issues related to botanicals.

Herbal product studies cannot be considered scientifically valid if the product tested was not authenticated and characterized in order to ensure reproducibility in the manufacturing of the product in question. Many studies refer to the use of standardized material, but in reality they are referring to chemical standardization. While chemical standardization is important, its utility is limited when the starting material is not well characterized botanically. Although the resulting studies are sound with respect to the actual product tested, adequate authentication of the product cannot be compared to other products on the market. Also, a comparison of one study to another cannot be made due to inconsistencies in the identity of the botanical matrix. The tools needed for authentication of the field plant material also depend on the plant and process involved. This could be as straightforward as botanical/morphological identification or as elaborate as genetic or chemical profiling. Authenticated raw material is the basic starting point for the development of a botanical product. However, harvesting, storing, processing and formulating methods may dramatically affect the quality and consistency of the final product by altering the desired marker components or by increasing the possibility of unwanted contaminants. Thus, validated methods to ensure quality control in manufacturing and storage are required tools for optimal efficacy and safety of the products. These controls are also critical for the evaluation of pharmacological, toxicological and clinical studies of the botanical supplements.

Drug Industry↗

PubMed2006

Schisandrene, a dibenzocyclooctadiene lignan from Schisandra chinensis: structure-antioxidant activity relationships of dibenzocyclooctadiene lignans.

Phytochemical investigation of the fruits of Schisandra chinensis led to the isolation of 13 lignans including schisandrene (13), a new lignan based on a dibenzocyclooctadiene backbone with an exocyclic double bond. Its structure and absolute configuration were established using NMR, MS, and CD data. Antioxidant activity of the lignans was evaluated using a DCFH-DA cellular-based assay. The structure-activity relationships of the dibenzocyclooctadiene lignans showed that the exocyclic methylene functionality was essential for antioxidant activity, with the benzoyloxy group probably enhancing such effects.

Antioxidants↗

PubMed2006

Antimicrobial principle from Aframomum longifolius.

Antimicrobial activity-directed fractionation of the seeds of Aframomum longifolius (Zingiberaceae) afforded two new labdane-type diterpenoids, 15-hydroxy-15-methoxylabda-8(17), 12( E)-dien-16-al (aframolin A) ( 1) and 8beta(17)-epoxy-15,15-dimethoxylabd-12( E)-en-16-al (aframolin B) ( 2), together with the known diterpenes labda-8(17),12( E)-diene-15,16-dial ( 3) and aframodial ( 4). Their structures were determined by spectroscopic methods. Compound 4 showed significant antimicrobial activity against Cryptococcus neoformans, Staphylococcus aureus and methicillin-resistant S. aureus (MRS) while 1, 2 and 3 were found to be inactive.

Anti-Infective Agents↗

PubMed2006

The use of polymerase chain reaction (PCR) for the identification of ephedra DNA in dietary supplements.

As part of a continuing research effort to develop chemical and genetic authentication profiles of botanicals, an investigation was performed with the goal to detect, identify and verify Ephedra sinica Stapf DNA in dietary supplements such as plant mixtures and tablets/capsules. We amplified and sequenced the chloroplast psbA-trnH spacer from 21 Ephedra spp. and from two of their closest relatives, Gnetum gnemon L. and Welwitschia mirabilis Hook. Based on sequence comparisons, we identified regions unique to all of the Ephedra spp. samples analyzed. We concluded that the psbA-trnH spacer sequence could be used as a molecular marker. Based on this spacer sequence, we designed Ephedra spp.-specific primers that can help to identify Ephedra spp. DNA in plant mixtures containing as little as 1/1,000 part of Ephedra spp. tissue. We used a DNA extraction method that allows for quick DNA isolation from plant mixtures for PCR analysis.

Base Sequence↗

PubMed2006

LC-MS-(TOF) analysis method for benzodiazepines in urine samples from alleged drug-facilitated sexual assault victims.

In recent years there has been an increase in the number of reports in the U.S. of the use of drugs to commit sexual assault. In 1994, a nationwide urine testing program was developed to assess the incidence of the use of drugs to facilitate sexual assault and provide information for use in the investigation of these crimes. Urine samples were collected from victims of suspected drug-induced sexual assault by law enforcement agencies, emergency rooms, and rape crisis centers. The most implicated drug class was benzodiazepines, either alone or in combination with alcohol. In this report, a procedure was developed for the screening of 22 benzodiazepines in human urine by liquid chromatography-time of flight-mass spectrometry [LC-MS-(TOF)]. The limit of quantitation for all benzodiazepines ranged from 2 to 10 ng/mL, and the limit of detection was 0.5 to 3.0 ng/mL. These results suggest that the method sensitivity is suitable to screen for all 22 benzodiazepines in human urine at low levels. The method was used to analyze samples previously reported to have screened positive for benzodiazepines by immunoassay at 50 ng/mL cut off but failed to confirm by a gas chromatography-MS method. The results of reanalysis of these samples using this LC-MS method are reported.

Benzodiazepines↗

PubMed2006

Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P450-2C9 substrate.

The effect of Ginkgo biloba on the activity of CYP2C9, the isoform responsible for S-warfarin clearance, was assessed in 11 healthy volunteers who received single 100-mg doses of flurbiprofen, a probe substrate for CYP2C9. Subjects also received either a standardized G biloba leaf preparation (Ginkgold, 3 doses of 120 mg) or matching placebo in a randomized, double-blind, 2-way crossover study. Mean kinetic variables for flurbiprofen with either placebo or G biloba were elimination half-life, 3.9 versus 3.5 hours; total AUC, 57 versus 55 microg/mL h; and oral clearance, 32.9 versus 31.6 mL/min. None of these differences was significant. Based on highperformance liquid chromatography analysis, each 60-mg Ginkgold tablet contained 6.6 mug of amentoflavone and 61.2 microg of quercetin, both previously identified as CYP2C9 inhibitors. These amounts were apparently too low to inhibit CYP2C9 function in vivo. The results confirm previous controlled clinical studies showing no effect of ginkgo on the kinetics or dynamics of warfarin.

Adult↗

PubMed2005

Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities of euglobals and their analogues.

In the present communication, naturally occurring phloroglucinol-monoterpene adducts, euglobals G1-G4 (3b/a and 4a/b) and 16 new analogues (13a/b-18a/b and 19-22) were synthesized by biomimetic approach. These synthetic compounds differ from natural euglobals in the nature of monoterpene and acyl functionality. All of these compounds were evaluated for their antibacterial, antifungal, antileishmanial and antimalarial activities. Analogue 17b possessed good antibacterial activity against methicillin-resistant Staphylococcus aureus, while analogues 19-22 possessed potent antifungal activity against Candida glabrata with IC50s ranging from 1.5 to 2.5 microg/mL. Euglobals along with all synthesized analogues exhibited antileishmanial activity. Amongst these, euglobal G2 (3a), G3 (4a) and analogues 13a and 14a showed potent antileishmanial activity with IC50s ranging from 2.8 to 3.9 microg/mL. Analogue 16a possessed antimalarial activity against chloroquine sensitive D6 clone of Plasmodium falciparum. None of the compounds showed toxicity against mammalian kidney fibroblasts (vero cells) upto the concentration of 4.76 microg/ml.

Animals↗