Anti-Inflammatory and Cytostatic Activities of a Parthenolide-Like Sesquiterpene Lactone from Cota palaestina subsp. syriaca.

A sesquiterpene lactone 1-ß,10-Epoxy-6-hydroxy-1,10H-inunolide (K100) was isolated through "bioassay-guided fractionation" from Cota palaestina subsp. syriaca, an Eastern Mediterranean endemic plant. K100 inhibited endotoxin- (ET-) induced proinflammatory markers: IL-6, MMP-9, and NO in normal mouse mammary SCp2 Cells. Molecular docking in silico suggested that K100, having highly analogous structure as parthenolide (PTL), an anticancer compound, could bind PTL target proteins at similar positions and with comparable binding affinities. Both compounds, K100 and PTL, inhibited the proliferation and prolonged the S-phase of the cell cycle of breast adenocarcinoma MDA-MB-231 cells grown in 2D cultures. Noncytotoxic concentrations of K100 and PTL decreased the proliferation rate of MDA-MB-231 and shifted their morphology from stellate to spherical colonies in 3D cultures. This was accompanied with a significant increase in the amount of small colonies and a decrease in the amount of large colonies. Moreover, K100 and PTL decreased cellular motility and invasiveness of MDA-MB-231 cells. In summary, these results suggest that K100 exhibits PTL-analogous anti-inflammatory, cytostatic, and antimetastatic effects.

Sesquiterpene lactones isolated from indigenous Middle Eastern plants inhibit tumor promoter-induced transformation of JB6 cells.

BACKGROUND: Sesquiterpene lactones (SL) are plant secondary metabolites that are known for their anti-fungal, anti-bacterial, anti-inflammatory, and anti-tumor properties. Considering that several SL-derived drugs are currently in cancer clinical trials, we have tested two SL molecules, 3-ß-methoxy-iso-seco-tanapartholide (ß-tan) isolated from Achillea falcata and salograviolide A (Sal A) isolated from Centaurea ainetensis, for their anti-tumor properties. We used the mouse epidermal JB6P + cells as a model for tumor promotion and cellular transformation. Key players that are involved in cellular transformation and tumorigenesis are the AP-1 and NF-κB transcription factors; therefore, we assessed how ß-tan and Sal A modulate their signaling pathways in JB6P + cells. METHODS: The effects of ß-tan and Sal A on the growth of normal and neoplastic keratinocytes and on the tumor promotion-responsive JB6P + cells were determined using the MTT assay. Anchorage-independent cell growth transformation assays were used to evaluate the anti-tumor promoting properties of these SL molecules in JB6P + cells and dual luciferase reporter assays and western blot analysis were used to investigate their effects on tumor promoter-induced AP-1 and NF-κB activities and protein levels of key AP-1 and NF-кB target genes. RESULTS: ß-tan and Sal A selectively inhibited tumor promoter-induced cell growth and transformation of JB6P + cells at concentrations that do not affect JB6P + and primary keratinocytes basal cell growth. In addition, both molecules reduced basal and tumor promoter-induced NF-κB transcriptional activities, differentially regulated basal and tumor promoter-induced AP-1 transcriptional activities, and modulated key players of the AP-1 and NF-κB signaling pathways. CONCLUSIONS: These results highlight the anti-tumor promoting properties of ß-tan and Sal A. These SL molecules isolated from two plant species native to the Middle East may provide opportunities for complementary medicine practices.

Perceived health and medicinal properties of six species of wild edible plants in north-east Lebanon.

OBJECTIVES: Wild edible plants (WEP) play the dual role of securing food diversity and promoting health in traditional societies. Current simplified dietary habits contribute to increasing population health risks. Since WEP are integral to the diet of traditional communities, identifying their significance as foods to people provides further evidence to conserve them and promote their consumption. Six species of WEP were identified as integral to the diet of rural Lebanese communities. We investigated their patterns of consumption and knowledge regarding their health and medicinal properties. DESIGN: An ethnobotanical survey, employing a qualitative questionnaire, was conducted among thirty informants. The identified species were Cichorium intybus, Eryngium creticum, Foeniculum vulgare, Malva sylvestris, Thymus syriacus and Gundelia tournifortii. RESULTS: Most informants consumed the six plants as a regular part of their diet. Seasonal variability in consumption was evident. C. intybus was renowned for its digestive and blood strengthening properties. F. vulgare was used as a digestive stimulant. M. sylvestris was distinguished for its anti-inflammatory qualities. T. syriacus was popular for its digestive and anti-poisonous properties. E. creticum was attributed less pronounced health benefits. G. tournifortii was considered a nutritious food. CONCLUSIONS: All six species were popular for their edible uses as well as their health and/or medicinal benefits. These properties are supported by scientific evidence. Our results highlight the importance of these plants for local people and support efforts for their conservation. However, we noticed a decline in indigenous knowledge. We encourage efforts to record it for other plants and in other communities.

Onopordum cynarocephalum induces apoptosis and protects against 1,2 dimethylhydrazine-induced colon cancer.

The potential chemopreventive properties of the crude extract of Onopordum cynarocephalum were evaluated. Growth inhibition was investigated in FHs74Int human normal intestinal cells and ModeK mouse normal intestinal cell line and in two human colon cancer cells HCT-116 (p53+/+) and HT-29 (p53+/-). The extract was not cytotoxic to FHs74Int cells at concentrations 2-fold higher than the IC50 of HCT-116 cells. The extract inhibited dose-dependently the growth of HCT-116 cells (IC50=0.18 mg/ml) to a greater extent than HT-29 cells (IC50=1.8 mg/ml). The p53 wild-type HCT-116 cells were more sensitive than p53 mutant HT-29 cells to the pro-apoptotic effects of the plant extract; five times lower concentrations were needed to induce apoptosis in HCT-116 cells. Apoptosis induction by the extract was associated with an increase in the expression of pro-apoptotic proteins such as p53 and Bax, and a significant inhibition of the anti-apoptotic protein Bcl-2. Significant decrease in cyclin D1 protein and increase in p21 protein was observed in extract-treated HCT-116 cells. In vivo, the crude extract injected intra-peritoneally reduced the number of tumors by 64% (p<0.0001) and decreased the mean size of aberrant crypt foci in the DMH model of colon cancer. These data collectively suggest that O. cynarocephalum has potential anti-colon cancer effects.

Evaluation of homeopathy in broiler chickens exposed to live viral vaccines and administered Calendula officinalis extract.

BACKGROUND: In this study it was determined that a Calendula officinalis water extract can reduce the immune response to three different viruses in broiler chickens, associated with improvement in body weights. MATERIAL/METHODS: The experiment was conducted on broiler chickens divided into two groups of 105 birds each. The first group received a Calendula officinalis water extract orally, while the second group received drinking water only. All birds in the two groups were similarly exposed to three different live vaccine viruses. Quantitative assessment of humoral immunity to each of the 3 viruses and records of bursal and thymus weight indices were taken. Performance, as observed in weight records at 21 and 41 days of age, feed conversion, and% mortality up to market age, was also evaluated. RESULTS: There was a reduction in immune response to IB virus at 42 days of age, to ND virus at 29 and 42 days of age, and to IBD virus at 14, 29, and 42 days of age in the Calendula officinals-treated birds in comparison with controls. This immune reduction in Calendula officinalis-treated birds was associated with insignificant reduction in the bursal weight index at 42 days of age and an improvement in mean weights at 21 and 41 days of age; the feed conversion and mortality rates were similar in the two groups (P>0.05). CONCLUSIONS: Calendula officinalis had an immunomodulation effect against three different live viruses in broiler chickens.

Screening of selected indigenous plants of Lebanon for antimicrobial activity.

The objective of this study is to test in vitro the antimicrobial efficacy of 39 water and 39 methanol extracts derived from different parts of 27 indigenous wild plant species that have been commonly used in Lebanese folk medicine. The antimicrobial efficacy was determined using the single disk diffusion method, with 10 and 20 microl load extract volume per disc. Nine test microorganisms were used namely, Escherichia coli, Proteus sp., Pseudomonas aeruginosa, Shigella dysenteria, Salmonella enteritidis, Salmonella typhi, Staphylococcus aureus, Streptococcus faecalis, and Candida albicans. Only one water extract out of 39 derived from whole plant of Alchemilla diademata showed an antimicrobial activity against Staphylococcus aureus. The percentage of test organisms that were susceptible to 10 most efficacious methanol plant extracts (20 microl/disc) were as follows: Achillea damascena whole plant (88.8%), Anthemis scariosa flower (88.8%), Cirsium sp. whole plant (88.8%), Centaurea ainetensis flowers (88.8%), Hieracium sp. whole plant (88.8%), Origanum libanoticum whole plant (99.9%), Ranunculus myosuroudes whole plant (88.8%), Nepata curviflora leaf (88.8%), Nepata curviflora stem, and Verbascum leptostychum flower (99.9%). The minimum inhibitory concentration (MIC) was determined on plant extracts that showed high efficacy against the test organisms. The chance to find antimicrobial activities was more apparent in methanol rather than water extracts of the same indigenous plants of Lebanon, with higher antimicrobial activities in 20 microl methanol extract-discs in comparison to that present in the 10 microl discs (P < 0.05).