Kinetic studies of the rich interaction of cannabinoids with oxygen-centered radicals and excited carbonyl compounds.

Laser flash photolysis techniques have been employed to measure absolute rate constants and transient spectra for reactions of alkoxyl radicals and ketone triplets with several cannabinoids, including tetrahydrocannabinol (THC) and cannabidiol (CBD) that show rich free radical chemistry as hydrogen atom donors towards alkoxyl radicals. Consistent with their proposed antioxidant activity, the reactive centers in these molecules are the phenoxyl groups. While these molecules also have allylic hydrogens, these seem to play a minor role in their free radical reactions.

Efficacy of Souroubea-Platanus Dietary Supplement Containing Triterpenes in Beagle Dogs Using a Thunderstorm Noise-Induced Model of Fear and Anxiety.

A novel botanical dietary supplement, formulated as a chewable tablet containing a defined mixture of spp. vine and spp. Bark, was tested as a canine anxiolytic for thunderstorm noise-induced stress (noise aversion).

Extract and Active Principal of the Neotropical Vine Gilg. Block Fear Memory Reconsolidation.

Gilg. is a neotropical vine native to Central America, investigated as part of a targeted study of the plant family Marcgraviaceae. Our previous research showed that extract of leaf and small branch extract had anxiolytic effects in animals and acts as an agonist for the GABA receptor at the benzodiazepine binding site.

Potent CYP3A4 Inhibitors Derived from Dillapiol and Sesamol.

Synthesis of 50 analogues of the natural insecticide synergists, dillapiol and sesamol, is reported. These were evaluated as potential insecticide synergists based on their inhibition of human CYP3A4. The most potent inhibitors have a relatively large hydrophobic substituent at either position 5 or 6 of these molecules.

Cannabidiol and the Remainder of the Plant Extract Modulate the Effects of Δ9-Tetrahydrocannabinol on Fear Memory Reconsolidation.

: Δ9-Tetrahydrocannabinol (THC, a CB1 receptor agonist) and Cannabidiol (CBD, a non-competitive antagonist of endogenous CB1 and CB2 ligands) are two primary components of species, and may modulate fear learning in mammals. The CB1 receptor is widely distributed throughout the cortex and some limbic regions typically associated with fear learning. Humans with posttraumatic disorder (PTSD) have widespread upregulation of CB1 receptor density and reduced availability of endogenous cannabinoid anandamide, suggesting a role for the endocannabinoid system in PTSD.

Safety evaluation of a new anxiolytic product containing botanicals spp. and spp. in dogs.

Separation anxiety and noise aversion are common behavioral problems in dogs. They elicit fear responses such as cowering, seeking out the owner, and attempting to escape. This can result in property damage, injury to the dog, and disruption of the owner-pet bond, possibly leading to pet abandonment or euthanasia.

New Botanical Anxiolytics for Use in Companion Animals and Humans.

As part of our ongoing research into botanical therapies for anxiety disorders, the neotropical vine Souroubea sympetala was chosen for study as a phytochemical discovery strategy focusing on rare Central American plant families. When orally administered to male Sprague-Dawley rats, the crude plant extract, its ethyl acetate fraction, supercritical carbon dioxide fraction, or its isolated triterpenes reduced anxiety and/or fear-related behavior in standardized behavioral models. Pharmacological studies showed that the extracts acted at the benzodiazepine GABA receptor and reduced corticosterone levels.

Comparison of anorectic and emetic potencies of deoxynivalenol (vomitoxin) to the plant metabolite deoxynivalenol-3-glucoside and synthetic deoxynivalenol derivatives EN139528 and EN139544.

The mycotoxin deoxynivalenol (DON) elicits robust anorectic and emetic effects in several animal species. However, less is known about the potential for naturally occurring and synthetic congeners of this trichothecene to cause analogous responses. Here we tested the hypothesis that alterations in DON structure found in the plant metabolite deoxynivalenol-3-glucoside (D3G) and two pharmacologically active synthetic DON derivatives, EN139528 and EN139544, differentially impact their potential to evoke food refusal and emesis.

Souroubea sympetala (Marcgraviaceae): a medicinal plant that exerts anxiolysis through interaction with the GABAA benzodiazepine receptor.

The mode of action of the anxiolytic medicinal plant Souroubea sympetala was investigated to test the hypothesis that extracts and the active principle act at the pharmacologically important GABAA-benzodiazepine (GABAA-BZD) receptor. Leaf extracts prepared by ethyl acetate extraction or supercritical extraction, previously determined to have 5.54 mg/g and 6.

Synthesis and receptor binding in trans-CD ring-fused A-CD estrogens: comparison with the cis-fused isomers.

Ligands which selectively activate only one of the estrogen receptors, ERα or ERβ, are current pharmaceutical targets. Previously, we have reported on substituted cis A-CD ligands in which the B-ring of the steroidal structure has been removed and cis refers the stereochemistry of the CD ring junction as compared to trans in estradiol. These compounds often showed good potency and selectivity for ERβ.

Novel ligands balance estrogen receptor β and α agonism for safe and effective suppression of the vasomotor response in the ovariectomized female rat model of menopause.

Vasomotor thermo-dysregulation (hot flashes) are an often debilitating symptom of menopause. Effective treatment is achieved primarily through activation of the estrogen receptor (ER)α with estrogens but is also associated with increased risk for breast and uterine cancer. In this study, we have tested novel compounds lacking the B ring of 17-hydroxy-β-estradiol (E2) (A-CD compounds) with differing ratios of ERα:ERβ binding affinities for the ability to reduce diurnal/nocturnal tail-skin temperatures (TSTs) in the ovariectomized female rat menopausal hot flash model.

Effects of oral exposure to naturally-occurring and synthetic deoxynivalenol congeners on proinflammatory cytokine and chemokine mRNA expression in the mouse.

The foodborne mycotoxin deoxynivalenol (DON) induces a ribotoxic stress response in mononuclear phagocytes that mediate aberrant multi-organ upregulation of TNF-α, interleukins and chemokines in experimental animals. While other DON congeners also exist as food contaminants or pharmacologically-active derivatives, it is not known how these compounds affect expression of these cytokine genes in vivo. To address this gap, we compared in mice the acute effects of oral DON exposure to that of seven relevant congeners on splenic expression of representative cytokine mRNAs after 2 and 6h.

Preferential estrogen receptor β ligands reduce Bcl-2 expression in hormone-resistant breast cancer cells to increase autophagy.

Acquired resistance to selective estrogen receptor (ER) modulators (SERM) and downregulators (SERD) is a significant clinical problem in the treatment of estrogen (E2) receptor-positive (ER(+)) breast cancers. There are two ER subtypes, ERα and ERβ, which promote and inhibit breast cancer cell proliferation, respectively. Although ER(+) breast cancers typically express a high ratio of ERα to ERβ, the acquisition of SERM resistance in vitro and in vivo is associated with increased relative expression of the ERβ.

Ethnopharmacology of Souroubea sympetala and Souroubea gilgii (Marcgraviaceae) and identification of betulinic acid as an anxiolytic principle.

The neotropical lianas Souroubea gilgii and Souroubea sympetala (Marcgraviaceae) were chosen for study as part of a phytochemical discovery strategy focusing on rare plant families in Central America. In participatory research, Q'eqchi' healers in Belize reported the use of these plants to reverse psychological symptoms inflicted by witchcraft. Extracts of two Souroubea species showed significant anti-anxiety activity in the elevated plus maze, a standardized test paradigm.

Inhibition of bacterial quorum sensing and biofilm formation by extracts of neotropical rainforest plants.

Bacterial biofilms are responsible for many persistent infections by many clinically relevant pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. Biofilms are much more resistant to conventional antibiotics than their planktonic counterparts. Quorum sensing, an intercellular communication system, controls pathogenesis and biofilm formation in most bacterial species.

Experimental versus predicted affinities for ligand binding to estrogen receptor: iterative selection and rescoring of docked poses systematically improves the correlation.

The computational determination of binding modes for a ligand into a protein receptor is much more successful than the prediction of relative binding affinities (RBAs) for a set of ligands. Here we consider the binding of a set of 26 synthetic A-CD ligands into the estrogen receptor ERα. We show that the MOE default scoring function (London dG) used to rank the docked poses leads to a negligible correlation with experimental RBAs.

Phytochemical constituents of Sarracenia purpurea L. (pitcher plant).

From the leaves of Sarracenia purpurea, collected in Mistissini, Quebec, Canada, four goodyerosides and three phenolics and nine known compounds, were isolated. The structures of the compounds were determined by mass spectrometry, including HRMS, and by 1D and 2D NMR spectroscopy.

Potent anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R. Br. ex Cass., a Q'eqchi' Maya traditional medicine.

The widespread use of Neurolaena lobata (L.) R. Br.

BC-spiro-estradiols. Synthesis and estrogen receptor binding affinity of four new estradiol isomers.

The synthesis of four new isomers of estradiol in which the ring A to ring C planes are perpendicular to each other as a result of a spiro BC ring junction is described. Heterocyclic analogs and carbocyclic homologs of these compounds are also reported. Estrogen receptor binding studies show that the spiro compounds with the natural stereochemistry at C9 bind almost as strongly as estradiol but with greater β to α selectivity.

Antibacterial properties of a glycolipid-rich extract and active principle from Nunavik collections of the macroalgae Fucus evanescens C. Agardh (Fucaceae).

This study investigated the antibacterial activity of glycolipid-rich extracts of the brown macroalga Fucus evanescens in cell culture. Accessions were collected on the Arctic coast of Ungava Bay, Nunavik, Quebec. The crude ethyl acetate extract of these accessions showed strong antibacterial activity (≥4 log(10) cfu) against Hemophilus influenzae , Legionella pneumophila , Propionibacterium acnes (ATCC and clinical isolate), and Streptococcus pyogenes at 100 µg/mL.

A-CD estrogens. I. Substituent effects, hormone potency, and receptor subtype selectivity in a new family of flexible estrogenic compounds.

Long-term use of estrogen supplements by women leads to an increased risk of breast and uterine cancers. Possible mechanisms include metabolism of estradiol and compounds related to tumor-initiating quinones, and ligand-induced activation of the estrogen receptors ERα and ERβ which can cause cancer cell proliferation, depending on the ratio of receptors present. One therapeutic goal would be to create a spectrum of compounds of variable potency for ERα and ERβ, which are resistant to quinone formation, and to determine an optimum point in this spectrum.

Bioassay-guided isolation of the antidiabetic principle from Sorbus decora (Rosaceae) used traditionally by the Eeyou Istchee Cree First Nations.

Bioassay-guided fractionation of a crude extract (80% EtOH in H(2)O) of stem bark of Sorbus decora led the isolation of three new pentacycle triterpenes (compounds 1-3). The structures of 1-3 were established on the basis of spectroscopic methods (IR, HREIMS, 1D and 2D NMR) as 23,28-dihydroxyursan-12-ene-3β-caffeate, 23,28-dihydroxylupan-20(29)-ene-3β-caffeate, and 3β,23,28-trihydroxy-12-ursene, respectively. Compound 2 significantly enhanced glucose uptake in C2C12 cells, but compounds 1 and 3 did not.

Anxiolytic activity of a supercritical carbon dioxide extract of Souroubea sympetala (Marcgraviaceae).

The purpose of this work was to develop an extraction technique to yield a betulinic acid-(BA) enriched extract of the traditional anti-anxiety plant Souroubea sympetala Gilg (Marcgraviaceae). Five extraction techniques were compared: supercritical carbon dioxide extraction (SCE), conventional solvent extraction with ethyl acetate (EtOAc), accelerated solvent extraction (ASE), ultrasonic assisted extraction (UAE) and soxhlet extraction (Sox). The EtOAc and SCE extraction methods resulted in BA-enriched extracts, with BA concentrations of 6.

Triterpenoids from the bark of Ruptiliocarpon caracolito.

Five spirocaracolitone triterpenoids were isolated from the dichloromethane-soluble fraction of the bark of Ruptiliocarpon caracolito, and their structures were determined mainly by application of 1D and 2D NMR spectroscopy. Two known CD-spirotriterpenoids were also isolated from the same source. This brings the total number of known CD-spirotriterpenoids from this source to 17.