Identification of Apocarotenoids as Chemical Markers of In Vitro Anti-Inflammatory Activity for Spirulina Supplements.

Identification of chemical markers in food additives and dietary supplements is crucial for quantitative assessment and standardization of their quality and efficacy. Arthrospira platensis, formerly Spirulina platensis and known colloquially as spirulina, has been widely investigated for its various biological effects, including anti-inflammation, antihypertension, antioxidant, and antiatherosclerosis. In this study, we utilized an approach involving a combination of bioassay-guided fractionation, synthesis, mass spectral molecular networking, principal component analysis (PCA), and correlation analysis to identify measurable chemical markers in spirulina products that can be used to evaluate the efficacy of commercial products in downregulating the expression level of the proinflammatory cytokines, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor α (TNFα). Consequently, we found that the apocarotenoids 3-hydroxy-ß-ionone (1) and apo-13-zeaxanthinones (2a/2b) significantly repressed expression of IL-1ß (9.5 ± 1.5 and 28.7 ± 0.6%, respectively) and IL-6 (10.1 ± 0.7 and 6.1 ± 0.4%, respectively) at 10 µg/mL (p < 0.05) using RAW 264.7 mouse macrophages. Notably, this is the first report of the isolation of these apocarotenoids from spirulina and their in vitro anti-inflammatory properties. Finally, we propose the use of our approach as a convenient way to establish markers in other dietary supplements.

Electrocardiographic effects of hawthorn (Crataegus oxyacantha) in healthy volunteers: A randomized controlled trial.

The objective of this study was to evaluate the electrocardiographic effects of hawthorn in healthy adult volunteers. It was double-blind cross-over trial randomized 20 healthy adult volunteers to receive either a single oral 160-mg dose of hawthorn or matching placebo. Triplicate 12-lead electrocardiograms were taken before treatment and at 1-, 2-, 4-, and 6-hr post-dose. Following at least a 7-day washout period, participants were crossed over to the opposing treatment arm and had the measurements repeated. The primary endpoint was the change in corrected (Fridericia) QT intervals (QTc I) at 4 and 6 hr. Maximum post-dose QTc I and changes in PR and QRS intervals were measured. No significant differences in 4- or 6-hr QTc I were seen between hawthorn and placebo. Maximum post-dose QTc I in the hawthorn and placebo groups were similar (346 ± 35 vs 346 ± 40 ms; p = .979). No significant adverse events were seen. In conclusion, a single dose of oral hawthorn had no effect on electrocardiographic parameters in healthy volunteers.

Current therapeutic role and medicinal potential of Scutellaria barbata in Traditional Chinese Medicine and Western research.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria barbata is a common herb in Traditional Chinese Medicine (TCM) most often used to treat cancer. S. barbata has been found to exhibit efficacy both in vitro and in vivo on a variety of cancer types. Similarly encouraging results have been shown in patients with metastatic breast cancer from Phase Ia and Ib clinical trials. This study aims to elucidate the current use of S. barbata by TCM practitioners and in current Western research. MATERIALS AND METHODS: Semi-structured interviews were conducted with fifteen TCM practitioners in Beijing and Nanjing, China to understand their clinical use of S. barbata. Practitioners were also asked to comment on the future development of TCM using Western research methods and the potential for integration of the two types of medicine in clinical therapy. Statistical analyses were conducted to compare use of S. barbata by disease and in conjunction with other herbs. RESULTS: Current Western research related to S. barbata is focused on cancer treatment, which corresponds to the most common use of S. barbata by TCM practitioners. Other common uses that practitioners reported included infection and inflammation, for which Beijing practitioners reported use of S. barbata more often than Nanjing practitioners (p<0.05). Hedyotis diffusa was found to be the most commonly cited herb to pair with S. barbata for cancer treatment (p<0.05). When compared to Western clinical trials of BZL101, an S. barbata extract, TCM practitioners reported using smaller doses of S. barbata in shorter durations, in combination with numerous other herbs with the goal to potentiate therapeutic efficacy and mitigate side effects. In addition, TCM practitioners repeatedly emphasized symptom differentiating as the key to achieving maximum therapeutic potential of S. barbata, a factor typically overlooked in Western research. CONCLUSION: Similarities and differences in diagnosis and treatment regimens between TCM practitioners and Western research have the potential to shed light on possible new avenues of research. Additional research may prove beneficial on possible synergistic effects of herbs commonly used with S. barbata, such as Hedyotis diffusa and Lobelia chinensis.

Natural compounds with aromatase inhibitory activity: an update.

Several synthetic aromatase inhibitors are currently in clinical use for the treatment of postmenopausal women with hormone-receptor positive breast cancer. However, these treatments may lead to untoward side effects and so the search for new aromatase inhibitors continues, especially those for which the activity is promoter-specific, targeting the breast-specific promoters I.3 and II. Recently, numerous natural compounds have been found to inhibit aromatase in noncellular, cellular, and IN VIVO studies. These investigations, covering the last two years, as well as additional studies that have focused on the evaluation of natural compounds as promoter-specific aromatase inhibitors or as aromatase inducers, are described in this review.

Bioactive 5,6-dihydro-alpha-pyrone derivatives from Hyptis brevipes.

Six new 5,6-dihydro-alpha-pyrone derivatives (1-6), namely, brevipolides A-F, together with seven known compounds, including a 5,6-dihydro-alpha-pyrone derivative (7), three flavonoids, a steroid glycoside, and two triterpenoids, were isolated from the entire plant of Hyptis brevipes. Compounds 1-7 were assigned with the absolute configuration 5R, 6S, 7S, and 9S, as elucidated by analysis of data obtained from their CD spectra and by Mosher ester reactions. Compounds 2, 6, and 7 exhibited ED(50) values of 6.1, 6.7, and 3.6 microM against MCF-7 cells, and compounds 1, 2, 6, and 8 (the known 5,6,3'-trihydroxy-3,7,4'-trimethoxyflavone) gave ED(50) values of 5.8, 6.1, 7.5, and 3.6 microM against HT-29 cells, respectively. However, no significant cytotoxicity was found against Lu1 cells for any of the compounds isolated. When these compounds were subjected to evaluation in a panel of mechanism-based in vitro assays, compound 7 was found to be active in an enzyme-based ELISA NF-kappaB assay, with an ED(50) value of 15.3 microM. In a mitochondrial transmembrane potential assay, compounds 3, 7, and 8 showed ED(50) values of 8.5, 75, and 310 nM, respectively. No potent activity was found in a proteasome inhibition assay for any of the isolated compounds.

Natural products as aromatase inhibitors.

With the clinical success of several synthetic aromatase inhibitors (AIs) in the treatment of postmenopausal estrogen receptor-positive breast cancer, researchers have also been investigating the potential of natural products as AIs. Natural products from terrestrial and marine organisms provide a chemically diverse array of compounds not always available through current synthetic chemistry techniques. Natural products that have been used traditionally for nutritional or medicinal purposes (e.g., botanical dietary supplements) may also afford AIs with reduced side effects. A thorough review of the literature regarding natural product extracts and secondary metabolites of plant, microbial, and marine origin that have been shown to exhibit aromatase inhibitory activity is presented herein.

Xanthones from the botanical dietary supplement mangosteen (Garcinia mangostana) with aromatase inhibitory activity.

Twelve xanthone constituents of the botanical dietary supplement mangosteen (the pericarp of Garcinia mangostana) were screened using a noncellular, enzyme-based microsomal aromatase inhibition assay. Of these compounds, garcinone D (3), garcinone E (5), alpha-mangostin (8), and gamma-mangostin (9) exhibited dose-dependent inhibitory activity. In a follow-up cell-based assay using SK-BR-3 breast cancer cells that express high levels of aromatase, the most potent of these four xanthones was gamma-mangostin (9). Because xanthones may be consumed in substantial amounts from commercially available mangosteen products, the consequences of frequent intake of mangosteen botanical dietary supplements require further investigation to determine their possible role in breast cancer chemoprevention.

Drug discovery from natural sources.

Organic compounds from terrestrial and marine organisms have extensive past and present use in the treatment of many diseases and serve as compounds of interest both in their natural form and as templates for synthetic modification. Over 20 new drugs launched on the market between 2000 and 2005, originating from terrestrial plants, terrestrial microorganisms, marine organisms, and terrestrial vertebrates and invertebrates, are described. These approved substances, representative of very wide chemical diversity, together with several other natural products or their analogs undergoing clinical trials, continue to demonstrate the importance of compounds from natural sources in modern drug discovery efforts.

Drug discovery from medicinal plants.

Current research in drug discovery from medicinal plants involves a multifaceted approach combining botanical, phytochemical, biological, and molecular techniques. Medicinal plant drug discovery continues to provide new and important leads against various pharmacological targets including cancer, HIV/AIDS, Alzheimer's, malaria, and pain. Several natural product drugs of plant origin have either recently been introduced to the United States market, including arteether, galantamine, nitisinone, and tiotropium, or are currently involved in late-phase clinical trials. As part of our National Cooperative Drug Discovery Group (NCDDG) research project, numerous compounds from tropical rainforest plant species with potential anticancer activity have been identified. Our group has also isolated several compounds, mainly from edible plant species or plants used as dietary supplements, that may act as chemopreventive agents. Although drug discovery from medicinal plants continues to provide an important source of new drug leads, numerous challenges are encountered including the procurement of plant materials, the selection and implementation of appropriate high-throughput screening bioassays, and the scale-up of active compounds.