Oxyresveratrol possesses DNA damaging activity

Artocarpus lakoocha Wall. ex Roxb. (family: Moraceae) has been used as a traditional Thai medicine for the treatment of various parasitic diseases. This species has been reported to be the source of phytochemicals, which show potent biological activities. The objective of this study was to investigate the phytochemical profile of the extracts of the heartwood of A. lakoocha and their prooxidant activity in vitro. The heartwood was ground, extracted, and then chromatographic and spectroscopic analyses were carried out; oxyresveratrol was identified as the major component in the extracts. The pro-oxidant activity was investigated using DNA-nick, reactive oxygen species and reducing assays. The results showed that oxyresveratrol induced DNA damage dose-dependently in the presence of copper (II) ions. It was also found to generate reactive oxygen species (ROS) in a dose-dependent manner and reduce copper (II) to copper (I). It is concluded that oxyresveratrol is the most abundant stilbenoid in A. lakoocha heartwood. The compound exhibited pro-oxidant activity in the presence of copper (II) ions, which may be associated with its ability to act as an anticancer compound

ent-Clerodane Diterpenes from the Bark of Croton oligandrus Pierre ex. Hutch. and Assessment of their Cytotoxicity Against Human Cancer Cell Lines

New clerodane diterpenes, 12-epi-megalocarpodolide D (2) and an epimeric mixture of crotonolins A (3) and B (4), were isolated from the bark of Croton oligandrus following a bioassay-guided isolation protocol. Known compounds, megalocarpodolide D (1), 12-epi-crotocorylifuran (5), cluytyl-ferulate (6), hexacosanoyl- ferulate (7), vanillin (8), acetyl-aleuritolic acid (9) and lupeol (10), were also isolated. The structures of the isolated compounds (1-10) were elucidated by spectroscopic means. The cytotoxicity of compounds 1-10 was assessed against A549, MCF7, PC3 and PNT2 cell lines using the MTT assay. Compounds 1 and 2 showed moderate level of activity against both A549 and MCF7 cells with 1 being the most active with IC50 values of 63.8±13.8 and 136.2±22.7 µM against A549 and MCF7 cells, respectively. The epimeric mixture of 3 and 4 was moderately active against A549 and PC3 cells (IC50 = 128.6±31.0 and 111.2±2.9 µM, respectively)

Justicialosides A and B, two new flavone glycosides from the leaves of Ruspolia hypocrateriformis (Vahl) Milne-Redh. (Acanthaceae)

Two new flavone glycosides, luteolin 7-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside (1) and chrysoeriol 7-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside (2), along with five known compounds, luteolin 7-O-β-D-apiofuranosyl-(1→2)-β-D-xylopyranoside (3), grandulosides A and B (4 and 5), luteolin 7-O-[β-D-glucopyranosyl-(1→2)-α-L-rhamnosyl-(1→6)]-β-D-glucopyranoside (6) and 10H-quindoline (7) were isolated from the leaves of Ruspolia hypocrateriformis (Acanthaceae). Their structures were elucidated by spectroscopic means, including 1D and 2D NMR, HRESIMS and by comparison with published data

Zanthoamides G-I: Three new alkamides from Zanthoxylum zanthoxyloides

Three new alkamides, zanthoamides G-I (1-3), together with ten known compounds, araliopsine, skimmianine, N-methylplatydesminium cation, isoplatydesmine, myrtopsine, atanine, N-methylatanine, sesamin, hesperetin and hesperidin, were isolated from the fruits of Zanthoxylum zanthoxyloides. Their structures were elucidated by spectroscopic means. All isolated compounds were assessed for their cytotoxicity against A549, MCF7, PC3 and PNT2 cell lines. Among the alkamides, only zanthoamide G (1) showed low level of cytotoxicity against MCF7 cells

The effects of linkage disequilibrium in large scale SNP datasets for MDR

<p>Abstract</p> <p>Background</p> <p>In the analysis of large-scale genomic datasets, an important consideration is the power of analytical methods to identify accurate predictive models of disease. When trying to assess sensitivity from such analytical methods, a confounding factor up to this point has been the presence of linkage disequilibrium (LD). In this study, we examined the effect of LD on the sensitivity of the Multifactor Dimensionality Reduction (MDR) software package.</p> <p>Results</p> <p>Four relative amounts of LD were simulated in multiple one- and two-locus scenarios for which the position of the functional SNP(s) within LD blocks varied. Simulated data was analyzed with MDR to determine the sensitivity of the method in different contexts, where the sensitivity of the method was gauged as the number of times out of 100 that the method identifies the correct one- or two-locus model as the best overall model. As the amount of LD increases, the sensitivity of MDR to detect the correct functional SNP drops but the sensitivity to detect the disease signal and find an indirect association increases.</p> <p>Conclusions</p> <p>Higher levels of LD begin to confound the MDR algorithm and lead to a drop in sensitivity with respect to the identification of a direct association; it does not, however, affect the ability to detect indirect association. Careful examination of the solution models generated by MDR reveals that MDR can identify loci in the correct LD block; though it is not always the functional SNP. As such, the results of MDR analysis in datasets with LD should be carefully examined to consider the underlying LD structure of the dataset.</p

Four new neo-clerodane diterpenes from the stem bark of Croton oligandrus.

Four new neo-clerodanes, crotonolins C-F (3-6), were isolated from the stem bark of Croton oligandrus together with the known clerodane crotonzambefuran A, the abietanes 7-β-hydroxydehydroabietic acid and 7-oxodehydroabietic acid, and ferulic acid. Their structures were elucidated by spectroscopic analyses including 1D and 2D NMR and HRESIMS and by comparison with previously reported data. The cytotoxicity of the isolated compounds against A549, MCF7, PC3 and PNT2 cells was evaluated using the MTT assay. Only 7-β-hydroxydehydroabietic acid showed a moderate level of activity against PC3 cells with an IC50 value of 68.9 ± 6.6 μM

Therapeutic potential of Leea indica (Vitaceae)

Background: Leea indica (Burm. f.) Merr. (fam. Vitaceae), commonly known as ‘bandicoot berry’, is a Thai medicinal plant, and distributed widely in the far-east and south-east Asian countries, and in some parts of northern Australia. In Thailand, this plant has traditionally been used for the treatment of diarrhoea, pain, gastric ulcer, viral infections and some forms of cancers. Aims: To review published findings on medicinal properties of L. indica and to critically appraise its therapeutic potential. Methods: A comprehensive literature search was performed utilizing several databases, notably, Web of Science, PubMed and Google Scholar, and other relevant published materials. The keywords used in the search, individually as well as in combinations, were Leea indica, Vitaceae and traditional medicine. Results: In vitro assays and in vivo animal studies displayed efficacy of the extracts and fractions of L. indica as an analgesic, antidiabetic, anti-inflammatory, antimicrobial, antioxidant and antiproliferative agent and indicated their therapeutic potential. Phytochemical studies revealed the presence of alkaloids, flavonoids, polyphenolics and terpenoids as major bioactive components in L. indica. Conclusion: Preliminary bioactivity studies on L. indica provided some scientific basis for its traditional therapeutic applications. The presence of certain bioactive compounds in this plant could further support its therapeutic potential and traditional medicinal uses

Improving health and well-being through community health champions: a thematic evaluation of a programme in Yorkshire and Humber.

AIMS: The contribution that lay people can make to the public health agenda is being increasingly recognised in research and policy literature. This paper examines the role of lay workers (referred to as 'community health champions') involved in community projects delivered by Altogether Better across Yorkshire and Humber. The aim of the paper is to describe key features of the community health champion approach and to examine the evidence that this type of intervention can have an impact on health. METHODS: A qualitative approach was taken to the evaluation, with two strands to gathering evidence: interviews conducted with different stakeholder groups including project leads, key partners from community and statutory sectors and community workers, plus two participatory workshops to gather the views of community health champions. Seven projects (from a possible 12) were identified to be involved in the evaluation. Those projects that allowed the evaluation team to explore fully the champion role (training, infrastructure, etc.) and how that works in practice as a mechanism for empowerment were selected. In total, 29 semi-structured interviews were conducted with project staff and partners, and 30 champions, varying in terms of age, gender, ethnicity and disability, took part in the workshops. RESULTS: Becoming a community health champion has health benefits such as increased self-esteem and confidence and improved well-being. For some champions, this was the start of a journey to other opportunities such as education or paid employment. There were many examples of the influence of champions extending to the wider community of family, friends and neighbours, including helping to support people to take part in community life. Champions recognised the value of connecting people through social networks, group activities, and linking people into services and the impact that that had on health and well-being. Project staff and partners also recognised that champions were promoting social cohesiveness and helping to integrate people into their community. CONCLUSIONS: The recent public health White Paper suggested that the Altogether Better programme is improving individual and community health as well as increasing social capital, voluntary activity and wider civic participation. This evaluation supports this statement and suggests that the community health champion role can be a catalyst for change for both individuals and communities

Composition of Amesiodendron chinense(Merr.) Hu Seed Oil and Assessment of Its Nrf2/ARE Induction Activity in AREc32 Cells

Background: Amesiodendron chinense (Merr.) Hu (family: Sapindaceae) is a Thai medicinal plant. The seed oil of this species has been used by folk healers and local people in southern Thailand for the treatment of wounds, skin disorders and common hair problems. This study aimed at the GC-MS-based determination of the chemical composition of the seed oil of this plant, and evaluation of its Nrf2/ARE induction activity in AREc32 cells (modified human breast cancer cell line MCF-7) using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and luciferase reporter gene assays. Results: GC-MS analysis identified 9-(E)-octadecenoic acid (84.82%) as the main component of this seed oil. TLC-based qualitative DPPH (2,2-diphenyl-1-picrylhydrazyl) assay revealed the DPPH radical-scavenging activity of the seed oil and its chromatographic fractions. A low-level DPPH-scavenging activity was observed in the quantitative assay, but no IC50 value could be determined even with the highest tested concentration (10 mg/mL). Neither the oil nor its chromatographic fractions showed any significant Nrf2/ARE induction in AREc32 cells. The seed oil was noncytotoxic against the AREc32 cells. Conclusions: A. chinense seed oil and its fractions had a low level of free-radical scavenging property but no significant Nrf2/ARE induction activity in AREc32 cells. However, as the oil did not show any cytotoxicity at test concentrations in the MTT assay, this oil might potentially be safe to use in cosmetic formulations or as a vehicle for the dermal delivery of drug molecules

Chalcones: Synthetic Chemistry Follows Where Nature Leads

Chalcones belong to the flavonoid class of phenolic compounds. They form one of the largest groups of bioactive natural products. The potential anticancer, anti-inflammatory, antimicrobial, antioxidant, and antiparasitic properties of naturally occurring chalcones, and their unique chemical structural features inspired the synthesis of numerous chalcone derivatives. In fact, structural features of chalcones are easy to construct from simple aromatic compounds, and it is convenient to perform structural modifications to generate functionalized chalcone derivatives. Many of these synthetic analogs were shown to possess similar bioactivities as their natural counterparts, but often with an enhanced potency and reduced toxicity. This review article aims to demonstrate how bioinspired synthesis of chalcone derivatives can potentially introduce a new chemical space for exploitation for new drug discovery, justifying the title of this article. However, the focus remains on critical appraisal of synthesized chalcones and their derivatives for their bioactivities, linking to their interactions at the biomolecular level where appropriate, and revealing their possible mechanisms of action