Constituents from the Polar Extract of Pisolithus arhizus and Their Anti-inflammatory Activity.

The phytochemical study of the Pisolithus arhizus fruiting body methanol extract led to the isolation of six new triterpenoids (1-6) and one new naphthalenoid pulvinic acid derivative (7), together with five known compounds, including norbadione A (8). Their structure was established from 1D and 2D NMR spectroscopy and HRESIMS analyses. The absolute configuration of the triterpenoids was determined by circular dichroism. The two pulvinic acid derivatives 7 and 8, showing the highest activity in modulating IL-6 secretion, were tested for their effect on COX-2, STAT3, and p-STAT3 proteins; both compounds were able to downregulate p-STAT3.

Caccinia macranthera Brand var. macranthera: Phytochemical analysis, phytotoxicity and antimicrobial investigations of essential oils with concomitant in silico molecular docking based on OPLS force-field.

This study was conducted to extract the essential oils (EOs) of Caccinia macranthera identify their phytochemicals, evaluate their phytotoxicity, antimicrobial activity and enzyme inhibition effects using in silico molecular docking technique. EOs of aerial parts, seeds, and roots of C. macranthera were extracted and analyzed via Gas chromatography-Mass Spectrometry. The antibacterial activity of EOs were determined on nine microorganisms via disk diffusion and microbroth dilution assays. In addition, the allelopathic properties of EOs were investigated by calculating the IC50s for inhibition of germination, seedling length and seedling weight growth of Cuscuta campestris seeds. In order to assess the possible inhibitory effect of major components of C. macranthera EOs on enzymes inhibiting germination and plant growth, molecular docking was employed against the glutamine synthetase (GS), acetohydroxyacid synthetase (AHAS), and 4-hydroxyphenyl pyruvate dioxygenase (HPPD) enzymes. The main compounds of EOs from aerial parts, seeds, and roots EOs were dihydrocarveol (29.5%), Trimethyl-2-Pentadecanone (13.6%), and Palmitic acid (16.8%), respectively. The maximum antibacterial effect was related to the aerial parts EO against Staphylococcus epidermidis. Phytotoxicity analysis exhibited a concentration-dependent increase (p ≤ 0.05) activity. The aerial parts EO demonstrated a substantial allelopathy effect, with IC50 values of 0.22 ± 0.026, 0.39 ± 0.021, and 0.20 ± 0.025 mg/mL, respectively, on inhibitory germination, seedling length and seedling weight growth of Cuscuta campestris seeds. Molecular docking analyzes showed that Oleic acid was suitable for dynamic stabilization of HPPD (-6.552 kJ/mol) and GS (-7.265 kJ/mol) and Eupatoriochromene had the inhibitory potential against AHAS, with docking score of -4.189 kJ/mol. The current research demonstrated that C. macranthera EOs from its aerial parts have an acceptable phytotoxic activity against Cuscuta campestris weed. The major components of EOs, Oleic acid and Eupatoriochromene, presented the strongest binding with HPPD, GS, and AHAS active sites causing disturbance in germination, photosynthesis and weed growth suggesting it as a natural herbicide for controlling the weeds.

New antiprotozoal sesquiterpene derivatives from Dorema glabrum Fisch & C.A.Mey.

Seven undescribed sesquiterpene derivatives, Azerins A-G (3-6, 8, 14 and 15), three known sesquiterpene phenols, kopetdaghin A (1), kopetdaghin B (2) and latisectin (7), together with five known sesquiterpene coumarins (9-13), were isolated from the roots of Dorema glabrum. The structures were elucidated by comprehensive 1D- and 2D-NMR spectral analysis as well as HR-ESI-MS. Compounds were assessed for their in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum. Cytotoxic potentials of the compounds were also tested on L6 rat skeletal myoblasts. Azerin G (15) showed a potent preferential growth inhibitory activity against T. b. rhodesiense with IC50 value of 0.01 µM and selectivity index of 329. Compounds 1, 4, 7 and 8 were also found as the most active compounds with selective growth inhibitory effects toward P. falciparum with selectivity indices ranging from 11.6 to 16.7 (IC50: 1.8-24.6 µM).

Sesquiterpene Lactones with Astrodaucane Skeleton from Astrodaucus orientalis.

Four sesquiterpene lactones, astrodaucanolide A - D (1: -4: ) with unique structures, toghether with two known phenylpropanoid esters (5: and 6: ) were isolated from a flower extract of Astrodaucus orientalis. The structures were established by 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HRESIMS), and the absolute configuration of 1: -4: was determined by electronic circular dichroism (ECD). Compounds 1: -4: novel architecture represents a new class of sesquiterpenes with new skeleton. A putative biosynthetic pathway for their scaffold is proposed with a germacryl cation as the precursor. The suggested biosynthesis pathway is similar to that of eudesmane sesquiterpenes with a different direction of protonation which then leads to the new skeleton, named astrodaucane by the 1,2-methyl migration.

Molecular networking based dereplication of AChE inhibitory compounds from the medicinal plant Vincetoxicum funebre (Boiss. & Kotschy).

Alzheimer's disease (AD) is a devastating neurodegenerative disease affecting 47 million people worldwide. While acetylcholinesterase (AChE) inhibitors such as donepezil and galantamine are leading drugs in the symptomatic treatment of AD, new AChE inhibitors continue to be explored for improved potency and selectivity. Herein, a molecular networking approach using high resolution (HR-MS) and tandem mass spectrometry (MS2) has been used for rapid chemical profiling of an extract of the medicinal plant Vincetoxicum funebre Boiss. & Kotschy (Apocynaceae family) that was active against AChE. A total of 44 compounds were identified by combining the MN with traditional natural product methods, including the isolation and identification of five known compounds (13, 41-44) and a novel C13-norisoprenoid (40). In addition, the potential inhibitory activity of all 44 compounds was evaluated against the AChE enzyme via molecular docking to provide further support to the proposed structures. The glycosylated flavonoid querciturone (31) exhibited the highest affinity with a docking score value of -13.43 kJ/mol. Another five compounds showed stronger docking scores against AChE than the clinically used donepezil including the most active isolated compound daucosterol (44), with a binding affinity of -10.11 kJ/mol towards AChE. These findings broaden our understanding of Vincetoxicum metabolites and highlight the potential of glycosylated flavonoids as AChE inhibitors.Communicated by Ramaswamy H. Sarma.

Two seco-norabietane diterpenoids with unprecedented skeletons from the roots of Salvia abrotanoides (Kar.) Sytsma.

Two seco-norabietane diterpenes with unique structures, namely abrotafuran and abrotacid, were isolated from the roots of Salvia abrotanoides (Kar.) Sytsma. The compounds were characterized by 1D and 2D NMR spectroscopic techniques, ECD, and HR-ESIMS experiments. Plausible biosynthetic pathways of abrotafuran and abrotacid were proposed. These compounds did not exhibit antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. However, the rearranged seco-norabietane abrotafuran showed antiproliferative activity on HeLa (cervical carcinoma) and Jurkat (T-cell leukemia) cell lines.

An analysis of variations in morphological characteristics, essential oil content, and genetic sequencing among and within major Iranian Juniper (Juniperus spp.) populations.

Junipers (Juniperus spp.) are important pharmaceutical plants, and they are commonly grown in the northern hemisphere because of the various medicinal properties attributed to the Juniperus genus. However, despite their pharmaceutical and also industrial importance, and despite plant diversity being a common topic of research among professional breeding programs, there is a relatively small body of work which focuses on diversity in juniper, and this is especially true of juniper species that are native to Iran. Thus, the present study set out to investigate juniper diversity via identifying any morphological, phytochemical, and genetic differences among and within three important species of Iranian junipers. The data revealed the terpenoid profiles of the investigated species to be distinct from one another, with α-pinene, ß-pinene, myrcene, sabinene, and limonene being the predominant terpenoids detected. Intriguingly, high levels of myrtenyl acetate were detected in the J. sabina tissue collected from the Ramsar site, and this terpenoid was not found in either of the other studied species, nor has it been noted in any other studies that focus on juniper. The genetic variation of Juniperus was analyzed using five ISSR markers and the molecular variance was computed using the GenAlEx software. The results revealed there to be a high degree of genetic diversity both among and within the studied populations. A dendrogram of the genetic data using the UPGMA method with the Dice coefficient divided the genotypes into two main groups. J. communis and J. excelsa were grouped together, while J. sabina was separated into its own group. In general, morphologically speaking, the leaf and cone types were found to be chiefly influential vis-à-vis separating the populations into their respective groups. Ultimately, it is our hope that the biochemical, genetic, and morphological diversity data collected from these species will contribute to the success of future juniper breeding and restoration programs.

Purified compounds from marine organism sea pen induce apoptosis in human breast cancer cell MDA-MB-231 and cervical cancer cell Hela.

Marine organisms are an important source of chemical compounds which are appropriate for use as therapeutic agents. Among them, Sea pens produce valuable chemical compounds being used as anti-cancer drugs. The aim of this study was to investigate anti-cancer property of extracted and purified compounds from marine organism Sea pen and evaluate their effects on inducing of apoptosis. The extracts were prepared from dried colony of Virgularia gustaviana. The compounds (3ß)-Cholest,5en,3ol (cholesterol) (15 mg), Hexadecanoic acid (2.5 mg) and 2-Hexadecanol (10.7 mg) were identified by GC-MS and NMR. The cytotoxic effects of the compounds were evaluated on Hela and MDA-Mb-231 human cancer cell lines with MTT assay. Immunocytochemistry and Western Blot analyses were used to evaluate the expression of apoptosis related markers Caspase 3, Caspase 8, Bax and BCL2 in cancer cells after treating with three compounds. The purified compounds reduced viability of human breast cancer cell line MDA-MB-231 and human cervical cancer cell line Hela concentration-dependently. 2-Hexadecanol reduced significantly the viability of both cancer cell lines in comparison to the other purified compounds. Treatment of cancer cells with the three purified compounds increased the expression of caspase-3, caspase-8 and Bax proteins and decreased the relative Bcl-2/Bax ratio, demonstrating induction of apoptosis as possible mechanism of action. According to the results, three purified compounds inhibit the growth of cancer cells by inducing of apoptosis pathway; an effect which needs to be further investigated in the future studies.

Synthesis, in-vitro antiprotozoal activity and molecular docking study of isothiocyanate derivatives.

Novel isothiocyanate derivatives were synthesized starting from noscapine, bile acids, amino acids, and some aromatic compounds. Antiparasitic activities of the synthesized derivatives were tested against four unicellular protozoa, i.e., Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum. Interestingly, seven isothiocyanate analogues displayed promising antiparasitic activity against Leishmania donovani with IC50 values between 0.4 and 1.0 µM and selectivity index (SI) ranged from 7.8 to 18.4, comparable to the standard drug miltefosine (IC50 = 0.7 µM). Compound 7h demonstrated the best antileishmanial activity with an IC50 value of 0.4 µM. Seven products exhibited inhibition activity against T. brucei rhodesiense with IC50s below 2.0 µM and SI between 2.7 and 29.3. Four primary amine derivatives of noscapine and five isothiocyanate derivatives exhibited antiplasmodial activity with IC50s in the range of 1.1-2.7 µM and SI values between 1.1 and 14.5. The isothiocyanate derivative 7c showed against T. cruzi with an IC50 value of 1.9 µM and SI 4. Molecular docking and ADMET studies were performed to investigate the interaction between active ligands and T. brucei trypanothione reductase active site. The docking studies showed significant binding affinity of noscapine derivatives to enzyme active site and good compatibility with experimental data.

Experimental validation and computational modeling of anti-influenza effects of quercetin-3-O-α-L-rhamnopyranoside from indigenous south African medicinal plant Rapanea melanophloeos.

BACKGROUND: Influenza A virus (IAV) is still a major health threat. The clinical manifestations of this infection are related to immune dysregulation, which causes morbidity and mortality. The usage of traditional medication with immunomodulatory properties against influenza infection has been increased recently. Our previous study showed antiviral activity of quercetin-3-O-α-L-rhamnopyranoside (Q3R) isolated from Rapanea melanophloeos (RM) (L.) Mez (family Myrsinaceae) against H1N1 (A/PR/8/34) infection. This study aimed to confirm the wider range of immunomodulatory effect of Q3R on selective pro- and anti-inflammatory cytokines against IAV in vitro, to evaluate the effect of Q3R on apoptosis pathway in combination with H1N1, also to assess the physical interaction of Q3R with virus glycoproteins and RhoA protein using computational docking. METHODS: MDCK cells were exposed to Q3R and 100CCID50/100 µl of H1N1 in combined treatments (co-, pre- and post-penetration treatments). The treatments were tested for the cytokines evaluation at RNA and protein levels by qPCR and ELISA, respectively. In another set of treatment, apoptosis was examined by detecting RhoA GTPase protein and caspase-3 activity. Molecular docking was used as a tool for evaluation of the potential anti-influenza activity of Q3R. RESULTS: The expressions of cytokines in both genome and protein levels were significantly affected by Q3R treatment. It was shown that Q3R was much more effective against influenza when it was applied in co-penetration treatment. Q3R in combination with H1N1 increased caspase-3 activity while decreasing RhoA activation. The molecular docking results showed strong binding ability of Q3R with M2 transmembrane, Neuraminidase of 2009 pandemic H1N1, N1 and H1 of PR/8/1934 and Human RhoA proteins, with docking energy of - 10.81, - 10.47, - 9.52, - 9.24 and - 8.78 Kcal/mol, respectively. CONCLUSIONS: Quercetin-3-O-α-L-rhamnopyranoside from RM was significantly effective against influenza infection by immunomodulatory properties, affecting the apoptosis pathway and binding ability to viral receptors M2 transmembrane and Neuraminidase of 2009 pandemic H1N1 and human RhoA cellular protein. Further research will focus on detecting the detailed specific mechanism of Q3R in virus-host interactions.

Taxonomically Informed Scoring Enhances Confidence in Natural Products Annotation.

Mass spectrometry (MS) offers unrivalled sensitivity for the metabolite profiling of complex biological matrices encountered in natural products (NP) research. The massive and complex sets of spectral data generated by such platforms require computational approaches for their interpretation. Within such approaches, computational metabolite annotation automatically links spectral data to candidate structures via a score, which is usually established between the acquired data and experimental or theoretical spectral databases (DB). This process leads to various candidate structures for each MS features. However, at this stage, obtaining high annotation confidence level remains a challenge notably due to the extensive chemodiversity of specialized metabolomes. The design of a metascore is a way to capture complementary experimental attributes and improve the annotation process. Here, we show that integrating the taxonomic position of the biological source of the analyzed samples and candidate structures enhances confidence in metabolite annotation. A script is proposed to automatically input such information at various granularity levels (species, genus, and family) and complement the score obtained between experimental spectral data and output of available computational metabolite annotation tools (ISDB-DNP, MS-Finder, Sirius). In all cases, the consideration of the taxonomic distance allowed an efficient re-ranking of the candidate structures leading to a systematic enhancement of the recall and precision rates of the tools (1.5- to 7-fold increase in the F1 score). Our results clearly demonstrate the importance of considering taxonomic information in the process of specialized metabolites annotation. This requires to access structural data systematically documented with biological origin, both for new and previously reported NPs. In this respect, the establishment of an open structural DB of specialized metabolites and their associated metadata, particularly biological sources, is timely and critical for the NP research community.

N-substituted noscapine derivatives as new antiprotozoal agents: Synthesis, antiparasitic activity and molecular docking study.

Novel N-substituted noscapine derivatives were synthesized by a three-component Strecker reaction of cyclic ether of N-nornoscapine with varied aldehydes, in the presence of cyanide ion. Moreover, the corresponding amides were synthesized by the oxidation of cyanide moieties in good yields. The in vitro antiprotozoal activity of the products was also investigated. Interestingly, some analogues did put on display promising antiparasitic activity against Trypanosoma brucei rhodesiense with IC50 values between 2.5 and 10.0 µM and selectivity index (SI) ranged from 0.8 to 13.2. Eight compounds exhibited activity against Plasmodium falciparum K1 strain with IC50 ranging 1.7-6.4 µM, and SI values between 2.8 and 10.5 against L6 rat myoblast cell lines. Molecular docking was carried out on trypanothione reductase (TbTR, PDB ID: 2WOW) and UDP-galactose 4' epimerase (TbUDPGE PDB: 1GY8) as targets for studying the envisaged mechanism of action. Compounds 6j2 and 6b2 displayed excellent docking scores with -8.59 and -8.86 kcal/mol for TbTR and TbUDPGE, respectively.

A new tricyclic abietane diterpenoid from Salvia chloroleuca and evaluation of cytotoxic and apoptotic activities

Abstract In this study, sahandone (1) and a new diterpenoid named sahandol II (2) were isolated from the roots of Salvia chloroleuca Rech. f. & Aellen, Lamiaceae. The absolute configurations of compounds 1 and 2 were assigned by comparison of experimental electronic circular dichroism spectra and comparing with published data. Cytotoxic and apoptotic evaluation of the isolated compounds and the methanol crude extract and its subfractions including petroleum ether, dichloromethane, ethyl acetate, n-butanol and aqueous fraction on two human prostate cancer cell lines and a breast cancer cell lines, showed that non-polar and semi-polar subfractions had the potent cytotoxic effect on PC3 cells with the IC50 values of 24.19, 33.59, and 47.15 µg/ml, respectively. Sub-G1 peak in flow cytometry histogram of cells treated with petroleum ether, dichloromethane and ethyl acetate subfractions showed the induction of apoptosis. Change in the Bax/Bcl-2 ratio and cleavage of poly ADP-ribose polymerase were observed.

Tracking leading anti-Candida compounds in plant samples; Plumbago europaea.

BACKGROUND AND OBJECTIVES: Due to the importance of finding new and more effective antifungal and antibacterial compounds against invasive vaginitis strains, this study was conducted for fast screening of plant samples. MATERIALS AND METHODS: Thirty Iranian plant samples were successively extracted by n-hexane, ethyl acetate and methanol to obtain a total of 90 extracts. Each extract was prepared in six concentrations and evaluated for antifungal activity via a micro-broth dilution method. Further phytochemical study of the aerial parts of Plumbago europaea, as the most promising source of anti-Candida compounds (with minimum inhibitory concentration of about 7µg/ml), was carried out and antifungal activity in the ethyl acetate extract was tracked using a combination of HPLC time-based fractionation and Thin Layer Chromatography-Bioautography via a bioassay-guided fractionation procedure. The compounds in the active region of the chromatogram were purified by a combination of column chromatography and preparative TLC, and then structure elucidation was achieved by 1D and 2D NMR, mass spectrometry and UV spectra. RESULTS: Seven compounds were isolated and identified: (1) plumbagin, (2) isoplumbagin, (3) 5, 8-dihydroxy-2-methyl-[1, 4] naphthoquinone, (4) droserone, (5) 7-methyljuglone, (6) Isozeylanone, and (7) methylene-3, 3'-diplumbagin. Antimicrobial activity of the purified compounds were also evaluated against C. albicans (MIC values ranging from 2 to 2500 µM) and Gardnerella vaginalis (MIC values ranging from 20 to 2500 µM). CONCLUSION: These naphthoquinone compounds could be surveyed for finding new and more effective anti-vaginitis agents via drug design approaches.

The activity of Levisticum officinale W.D.J. Koch essential oil against multidrug-resistant Mycobacterium tuberclosis.

BACKGROUND AND OBJECTIVES: Essential oils are used for controlling and preventing human diseases and the application of those can often be quite safe and effective with no side effect. The essential oils have been found to have antiparasitic, antifungal, antiviral, antioxidant and especially antibacterial activity including antibacterial activity against tuberculosis. In this study the chemical composition and anti-TB activity of essential oil extracted from Levisticum officinale has been evaluated. MATERIALS AND METHODS: The essential oil of L. officinale was obtained by the hydro distillation method and the oil was analyzed by GC-FID and GC-MS techniques. The antibacterial activity of essential oil was evaluated through Minimum Inhibitory Concentration (MIC) assay using micro broth dilution method against multidrug-resistant Maycobacterium tuberculosis. The molecular modeling of major compounds was evaluated through molecular docking using Auto Dock Vina against-2-trans-enoyl-ACP reductase (InhA) as key enzyme in M. tuberclosis cell wall biosynthesis. RESULTS: The hydrodistillation on aerial parts of L. officinale yielded 2.5% v/w of essential oil. The major compounds of essential oil were identified as α-terpinenyl acetate (52.85%), ß- phellandrene (10.26%) and neocnidilide (10.12%). The essential oil showed relatively good anti-MDR M. tuberculosis with MIC = 252 µg/ml. The results of Molecular Docking showed that affinity of major compounds was comparable to isoniazid. CONCLUSION: The essential oil of aerial parts extracted from L. officinale was relatively active against MDR M. tuberculosis, and molecular docking showed the major compounds had high affinity to inhibit 2-trans-enoyl-acyl carrier protein reductase (InhA) as an important enzyme in M. tuberculosis cell wall biosynthesis.

Identification and Mode of Action of a Plant Natural Product Targeting Human Fungal Pathogens.

Candida albicans is a major cause of fungal diseases in humans, and its resistance to available drugs is of concern. In an attempt to identify novel antifungal agents, we initiated a small-scale screening of a library of 199 natural plant compounds (i.e., natural products [NPs]). In vitro susceptibility profiling experiments identified 33 NPs with activity against C. albicans (MIC50s ≤ 32 µg/ml). Among the selected NPs, the sterol alkaloid tomatidine was further investigated. Tomatidine originates from the tomato (Solanum lycopersicum) and exhibited high levels of fungistatic activity against Candida species (MIC50s ≤ 1 µg/ml) but no cytotoxicity against mammalian cells. Genome-wide transcriptional analysis of tomatidine-treated C. albicans cells revealed a major alteration (upregulation) in the expression of ergosterol genes, suggesting that the ergosterol pathway is targeted by this NP. Consistent with this transcriptional response, analysis of the sterol content of tomatidine-treated cells showed not only inhibition of Erg6 (C-24 sterol methyltransferase) activity but also of Erg4 (C-24 sterol reductase) activity. A forward genetic approach in Saccharomyces cerevisiae coupled with whole-genome sequencing identified 2 nonsynonymous mutations in ERG6 (amino acids D249G and G132D) responsible for tomatidine resistance. Our results therefore unambiguously identified Erg6, a C-24 sterol methyltransferase absent in mammals, to be the main direct target of tomatidine. We tested the in vivo efficacy of tomatidine in a mouse model of C. albicans systemic infection. Treatment with a nanocrystal pharmacological formulation successfully decreased the fungal burden in infected kidneys compared to the fungal burden achieved by the use of placebo and thus confirmed the potential of tomatidine as a therapeutic agent.

HPLC-Based Activity Profiling for GABAA Receptor Modulators in Extracts: Validation of an Approach Utilizing a Larval Zebrafish Locomotor Assay.

Gamma-aminobutyric acid type A (GABAA) receptors are major inhibitory neurotransmitter receptors in the central nervous system and a target for numerous clinically important drugs used to treat anxiety, insomnia, and epilepsy. A series of allosteric GABAA receptor agonists was identified previously with the aid of HPLC-based activity profiling, whereby activity was tracked with an electrophysiological assay in Xenopus laevis oocytes. To accelerate the discovery process, an approach has been established for HPLC-based profiling using a larval zebrafish (Danio rerio) seizure model induced by pentylenetetrazol (PTZ), a pro-convulsant GABAA receptor antagonist. The assay was validated with the aid of representative GABAergic plant compounds and extracts. Various parameters that are relevant for the quality of results obtained, including PTZ concentration, the number of larvae, the incubation time, and the data analysis protocol, were optimized. The assay was then translated into an HPLC profiling protocol, and active compounds were tracked in extracts of Valeriana officinalis and Magnolia officinalis. For selected compounds the effects in the zebrafish larvae model were compared with data from in silico blood-brain barrier (BBB) permeability predictions, to validate the use for discovery of BBB-permeable natural products.

Cancer chemopreventive activity of compounds isolated from Waltheria indica.

ETHNOPHARMACOLOGICAL RELEVANCE: Waltheria indica L. is traditionally used in several countries against inflammatory related diseases and cancer, mainly as a decoction of the aerial parts. AIM OF THE STUDY: The transcription factor NF-κB is known to induce tumor promotion and progression and is considered a major player in inflammation-driven cancers. Therefore, inhibitors of this pathway possess cancer chemopreventive and chemotherapeutic activities. This study aimed first to confirm the use of Waltheria indica as a traditional anti-inflammatory remedy by assessing the NF-κB inhibitory activity and then to identify the major bioactive compounds. The isolated compounds were also tested for their QR inducing property, a complementary strategy in cancer chemoprevention able to target tumor initiation. Finally, the relevance of in vitro results was examined by investigating the occurrence of the active compounds in traditional preparations. MATERIALS AND METHODS: Compounds were isolated from the dichloromethane extract of the aerial parts using flash chromatography and semi-preparative HPLC. NF-κB inhibitory activity of pure compounds from Waltheria indica was assessed using a luciferase reporter assay in HEK293 cells. Their QR inducing activity was also assessed in Hepa1c1c7 cells. RESULTS: Twenty-nine compounds, of which 5 are new, were obtained from the dichloromethane extract and tested for their cancer chemoprevention activity. Eleven compounds inhibited NF-κB and/or induced QR in the low to mid µM range. Chrysosplenol E (20) was active in both tests. Two of the most potent NF-κB inhibitors, waltherione A (4) and waltherione C (5), as well as 20 were found in the traditional decoction, in which 4 and 5 were major compounds. CONCLUSION: The presence of potent NF-κB inhibitors and QR inducing compounds in the decoction of the aerial parts of Waltheria indica supports its traditional use in inflammatory-related diseases and cancer chemoprevention.

Securigenin glycosides as hypoglycemic principles of Securigera securidaca seeds.

Seeds of Securigera securidaca (Fabaceae) are used in Iranian folk medicine as an antidiabetic treatment. In this study, the antihyperglycemic activity of chloroform and methanol fractions (CF and MF) from S. securidaca seed extract was investigated and their bioactive constituents were identified. The antidiabetic effects of fractions were assessed by streptozocin-induced diabetic Naval Medical Research Institute mice. The hypoglycemic activity of MF at 100 mg/kg and CF at 400 mg/kg was comparable with glibenclamide (3 mg/kg). MF at 400 mg/kg and CF at 600 mg/kg showed equal hypoglycemic responses to 12.5 IU/kg insulin (P > 0.05). Three cardiac glycosides were isolated as active constituents responsible for the hypoglycemic activity. Securigenin-3- O -ß-glucopyranosyl-(1 â†’ 4)-ß-xylopyranoside (1) was a major compound in seeds. Securigenin-3- O -inositol-(1 â†’ 3)-ß-glucopyranosyl-(1 â†’ 4)-ß-xylopyranoside (2) and securigenin-3- O -α-rhamnopyranosyl-(1 â†’ 4)-α-glucopyranoside (3) were found as new natural products. When 1-3 were tested at 10 mg/kg there was a significant reduction of blood glucose levels in diabetic mice, comparable to that of 3 mg/kg glibenclamide (P > 0.05). The hypoglycemic effect was due to an increase in insulin secretion; the insulin levels in the diabetic mice significantly improved and were comparable with those in healthy animals (P > 0.05). Compounds responsible for the hypoglycemic properties of S. securidaca seeds were identified as cardiac glycosides and were found to act via an increase of insulin levels in a diabetic mouse model.

Gastroprotective effects of hydroethanolic root extract of Arrabidaea brachypoda: Evidences of cytoprotection and isolation of unusual glycosylated polyphenols.

The hydroethanolic root extract of Arrabidaea brachypoda, from Bignoniaceae family, a Brazilian medicinal plant, demonstrated significant in vivo gastroprotective effects using different in vivo assays. The activity was evaluated in several models of experimental gastric ulcer in rats (absolute ethanol, glutathione depletion, nitric oxide depletion, non-steroidal anti-inflammatory drugs, pylorus ligation and acetic acid). Using 300 mg/kg (p.o.) the extract significantly reduced gastric injury in all models. In depth phytochemical investigation of this extract led to the isolation of two previously undescribed phenylethanoid glycosides derivatives and seven unusual glycosylated dimeric flavonoids. The structures were elucidated using UV, NMR and HRMS analysis. Absolute configuration of the dimeric flavonoids was performed by electronic circular dichroism (ECD) spectroscopy.