Traditional Use, Phytochemical Profiles and Pharmacological Properties of Artemisia Genus from Central Asia.

The flora of Kazakhstan is characterized by its wide variety of different types of medicinal plants, many of which can be used on an industrial scale. The Traditional Kazakh Medicine (TKM) was developed during centuries based on the six elements of ancient Kazakh theory, associating different fields such as pharmacology, anatomy, pathology, immunology and food nursing as well as disease prevention. The endemic Artemisia L. species are potential sources of unique and new natural products and new chemical structures, displaying diverse bioactivities and leading to the development of safe and effective phytomedicines against prevailing diseases in Kazakhstan and the Central Asia region. This review provides an overview of Artemisia species from Central Asia, particularly traditional uses in folk medicine and the recent numerous phytochemical and pharmacological studies. The review is done by the methods of literature searches in well-known scientific websites (Scifinder and Pubmed) and data collection in university libraries. Furthermore, our aim is to search for promising and potentially active Artemisia species candidates, encouraging us to analyze Protein Tyrosine Phosphatase 1B (PTP1B), α-glucosidase and bacterial neuraminidase (BNA) inhibition as well as the antioxidant potentials of Artemisia plant extracts, in which endemic species have not been explored for their secondary metabolites and biological activities so far. The main result of the study was that, for the first time, the species Artemisia scopiformis Ledeb. Artemisia albicerata Krasch., Artemisia transiliensis Poljakov, Artemisia schrenkiana Ledeb., Artemisia nitrosa Weber and Artemisia albida Willd. ex Ledeb. due to their special metabolites, showed a high potential for α-glucosidase, PTP1B and BNA inhibition, which is associated with diabetes, obesity and bacterial infections. In addition, we revealed that the methanol extracts of Artemisia were a potent source of polyphenolic compounds. The total polyphenolic contents of Artemisia extracts were correlated with antioxidant potential and varied according to plant origin, the solvent of extraction and the analytical method used. Consequently, oxidative stress caused by reactive oxygen species (ROS) may be managed by the dietary intake of current Artemisia species. The antioxidant potentials of the species A. schrenkiana, A. scopaeformis, A. transiliensis and Artemisia scoparia Waldst. & Kitam. were also promising. In conclusion, the examination of details between different Artemisia species in our research has shown that plant materials are good as an antioxidant and eznyme inhibitory functional natural source.

Crosstalk of Cancer Signaling Pathways by Cyclic Hexapeptides and Anthraquinones from Rubia cordifolia.

The anticancer activities of Rubia cordifolia and its constituents have been reported earlier, but their influence on the crosstalk of complex cancer-related signaling metabolic pathways (i.e., transcription factors; TF) has not yet been fully investigated. In this study, R. cordifolia root extract was subjected to the cancer signaling assay based bioactivity-guided fractionation, which yielded the following compounds viz., three anthraquinones, namely alizarin (1), purpurin (2), and emodin (3); two lignans, namely eudesmin (4) and compound 5; and two cyclic hexapeptides, namely deoxybouvardin RA-V (6), and a mixture of 6+9 (RA-XXI). The structures of the isolated compounds were determined by NMR spectroscopy and HRESIMS. The isolated compounds 1, 2, 3, 6, and a mixture of 6+9 were tested against a panel of luciferase reporter genes that assesses the activity of a wide-range of cancer-related signaling pathways. In addition, reference anthraquinones viz., chrysophanol (11), danthron (12), quinizarin (13), aloe-emodin (14), and α-lapachone (15) were also tested. Among the tested compounds, the cyclic hexapeptide 6 was found to be very active against several signaling pathways, notably Wnt, Myc, and Notch with IC50 values of 50, 75, and 93 ng/mL, respectively. Whereas, the anthraquinones exhibited very mild or no inhibition against these signaling pathways. Compound 6 being the most active, we tested it for stability in simulated intestinal (SIF) and gastric fluids (SGF), since the stability in biological fluid is a key short-coming of cyclic hexapeptides. The anticancer activity of 6 was found to remain unchanged before and after the treatment of simulated gastric/intestinal fluids, indicating that RA-V was stable. As a result, it could be bioavailable when orally used in therapeutics and possibly a drug candidate for cancer treatment. The mechanism for the preferential inhibition of these pathways and the possible crosstalk effect with other previously reported signaling pathways has been discussed.

Involvement of the Benzodiazepine Site in the Anticonvulsant Activity of Tapinanthus globiferus against Pentylenetetrazole-induced Seizures in Mice.

Tapinanthus globiferus is often referred to as an all-purpose herb for the treatment of stroke and epilepsy. The present study investigates the anticonvulsant effect of methanolic leaf extract, active fractions, and lupeol (isolate) of Tapinanthus globiferus in mice as well as the underlying mechanisms. Following phytochemical studies of T. globiferus, preliminary assays were performed to evaluate MLE-induced toxic effect and behavioral changes. The pentylenetetrazol (70 mg/kg, i. p.)-induced seizure was evaluated in mice that were pretreated orally with vehicle 10 mL/kg, MLE (4, 20, or 100 mg/kg), fractions (F1 to F6), lupeol 10 mg/kg or diazepam (3 mg/kg). Methanolic leaf extract preserved neuron viability as well as the relative organ weight, and hematological and biochemical parameters. The behavioral endpoints, neuromuscular coordination, and sensory response parameters revealed a dose-dependent effect of methanolic leaf extract. This extract, active fractions, lupeol, and diazepam potentiated the hypno-sedative effect of the barbiturate and attenuated PTZ-induced acute seizure. This antiseizure effect was completely reversed by flumazenil 2 mg/kg (benzodiazepine site antagonist). Altogether, the benzodiazepine site-mediated anticonvulsant effects of methanolic leaf extract, active fractions, and lupeol corroborate traditional application of T. globiferus against epilepsy.

4-O-Methylhonokiol Influences Normal Cardiovascular Development in Medaka Embryo.

Although 4-O-Methylhonokiol (MH) effects on neuronal and immune cells have been established, it is still unclear whether MH can cause a change in the structure and function of the cardiovascular system. The overarching goal of this study was to evaluate the effects of MH, isolated from Magnolia grandiflora, on the development of the heart and vasculature in a Japanese medaka model in vivo to predict human health risks. We analyzed the toxicity of MH in different life-stages of medaka embryos. MH uptake into medaka embryos was quantified. The LC50 of two different exposure windows (stages 9⁻36 (0⁻6 days post fertilization (dpf)) and 25⁻36 (2⁻6 dpf)) were 5.3 ± 0.1 µM and 9.9 ± 0.2 µM. Survival, deformities, days to hatch, and larval locomotor response were quantified. Wnt 1 was overexpressed in MH-treated embryos indicating deregulation of the Wnt signaling pathway, which was associated with spinal and cardiac ventricle deformities. Overexpression of major proinflammatory mediators and biomarkers of the heart were detected. Our results indicated that the differential sensitivity of MH in the embryos was developmental stage-specific. Furthermore, this study demonstrated that certain molecules can serve as promising markers at the transcriptional and phenotypical levels, responding to absorption of MH in the developing embryo.

Antileishmanial Carbasugars from Geosmithia langdonii.

Two new carbasugar-type metabolites, (1 S,2 R,3 R,4 R,5 R)-2,3,4-trihydroxy-5-methylcyclohexyl-2',5'-dihydroxybenzoate (1) and (1 S,2 S,3 S,4 R,5 R)-4-[(2',5'-dihydroxybenzyl)oxy]-5-methylcyclohexane-1,2,3-triol (2), were isolated from the filamentous fungus Geosmithia langdonii isolated from cotton textiles from Assiut, Egypt. The structures of 1 and 2 were elucidated based on comprehensive 1D and 2D NMR and MS data. Compounds 1 and 2 showed antileishmanial activity against Leishmania donovani with IC50 values of 100 and 57 µM, respectively. The (1 S,2 R,3 R,4 R,5 R) absolute configuration of carbasugar 1 was assigned via 2D NMR and experimental and calculated electronic circular dichroism (ECD) data. Similarly, the tentative structure of compound 2 was shown to possess a (1 S,2 S,3 S,4 R,5 R) absolute configuration via comparing its experimental ECD data and the specific rotation with 1 as well as examining the energy-minimized 3D computational models of compounds 1 and 2.

Significance of endangered and threatened plant natural products in the control of human disease.

One in five of the world's plant species is threatened with extinction according to the 2010 first global analysis of extinction risk. Tilman et al. predicted a massive ecological change to terrestrial plants within the next 50-100 y, accompanied by an increase in the number of global plant species facing extinction [Tilman D, et al. (2001) Proc Natl Acad Sci USA 98(10):5433-5440]. Most of the drug-producing plant families contain endangered species never previously studied for their utility to human health, which strongly validates the need to prioritize protection and assessment of these fragile and endangered groups [Zhu F, et al. (2011) Proc Natl Acad Sci USA 108(31):12943-12948]. With little prior attention given to endangered and rare plant species, this report provides strong justification for conservation of the rare plant Diplostephium rhododendroides Hieron., as well as other potential drug-producing endangered species in this and other groups.

Antileishmanial metabolites from Geosmithia langdonii.

Antileishmanial bioassay guided fractionation of Geosmithia langdonii has resulted in the isolation and identification of two new compounds (1 and 2) together with 10 known compounds (3-12). The structures of the isolated metabolites were elucidated based on comprehensive 1D and 2D NMR spectroscopic data as well as mass spectrometry. The absolute configuration at C4, C5, and C6 of 2 was determined as R using a modified Mosher esterification method and NOESY correlations. The extracts and the isolated metabolites were evaluated for their antileishmanial activities. Compounds 3, 9, 11, and 12 were found to be active against Leishmania donovani with IC50 values of 6.9, 3.3, 8.5, and 9.2 µM, respectively, while compounds 1, 5, and 10 showed lower activities against L. donovani with IC50 values of 13.0, 47.3, and 34.0 µM, respectively.

Income inequality and environmental degradation in Egypt: evidence from dynamic ARDL approach.

Over the past four decades, the Egyptian economy has suffered from both income inequality and environmental degradation. This dual problem raises the question about the nature of the relationship between inequality and the environment in a developing country like Egypt. In this regard, the study aims to examine the impact of income inequality on carbon emissions during the period 1975-2017. The analysis considers the ability of the political economy approach compared to the Keynesian trade-off approach to explain the inequality-environment relationship in Egypt. To do this, the novel dynamic autoregressive distributed lags approach is employed to capture the short-run and long-run relationships and to overcome the complications associated with the structure of the widely used autoregressive distributive lags model. The findings show that the relationship between inequality and CO2 emissions is not a trade-off. Rather, inequality leads to environmental deterioration in the long run, but there is no significant effect in the short run. In the long run, a 1% rise in the Gini coefficient increases CO2 emissions by 2.28%. These results support the political economy approach in explaining the inequality-environment nexus. Hence, the economic development policies adopted in Egypt during the past four decades have led to a negative impact on the environment. The study advises economic policy makers in Egypt to adopt income redistribution policies to reduce the severity of income inequality. Improving income distribution has a positive effect on the environment in Egypt.

The environmental impact of remittance inflows in developing countries: evidence from method of moments quantile regression.

Despite the importance of remittance inflows as potential source of incomes for recipient households and one of main contributors to the development process in various developing countries, their environmental effects have been largely neglected in empirical literature. To fill this gap, the current study proposes an extension of the conventional environmental Kuznets curve by performing a modified version based on remittance inflows in both low- and middle-income countries from 1980 to 2014. Using the novel method of moments quantile regression with fixed effect, the outcomes provide evidence of an inverted N-shaped Kuznets curve for remittances at higher carbon dioxide emitters in lower middle-income countries, proving that remittances allow recipient households to shift toward clean energy pattern (production/consumption). We find U-shaped curve for remittances from the 40th to 80th quantiles in upper middle-income countries along with monotonic negative effect on carbon dioxide emissions at highest quantiles (90th and 95th). No significant effect on environment has been outlined at lower carbon dioxide emitters for all panels. Regarding economic growth, an inverted N-shaped curve has been observed across all quantiles in upper middle-income countries and from lower to middle quantiles in low-income countries. Finally, financial development, as control variable, exerts significant mixed effect on carbon dioxide emissions, swung between positive at all quantiles in low- and upper middle-income countries and negative at lower quantiles in low-income countries. Some recommendations were further built in the present study.

Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and Enterococcus faecium active dimeric isobutyrylphloroglucinol from Ivesia gordonii.

Bioassay-guided fractionation of the chloroform soluble fraction of stem, leaf, and flower extracts of the American plant Ivesia gordonii led to the isolation of a new dimeric acylphloroglucinol, 3,3'-diisobutyryl-2,6'-dimethoxy-4,6,2',4'-tetrahydroxy-5,5'dimethyldiphenyl methane (1), to which we have assigned the trivial name ofivesinol (1), together with a known monomeric acylphloroglucinol, 1,5-dihydroxy-2-(2'-methylpropionyl)-3-methoxy-6-methylbenzene (2). The structures of the isolated compounds were characterized using 1D- and 2D- NMR spectroscopy, including COSY, HMQC, HMBC, and ROESYexperiments, as well as mass spectrometry. Ivesinol (1) showed potent activity against Staphylococcus aureus (SA) and methicillin-resistant S. aureus (MRSA) with IC50/MIC/MBC values of 0.10/1.25/>20 microg/mL and 0.05/0.31/>20 microg/mL, respectively (vs. IC50/MIC/MBC 0.13/0.5/1.0 microg/mL and 0.13/0.5/1.0 microg/mL of ciprofloxacin), while the corresponding monomer 2 was found to be less active. Compound 1 also demonstrated strong activity against vancomycin-resistant Enterococcus faecium (VRE) with IC50/MlC/MBC values of 0.22/1.25/>20 microg/mL, whereas the reference standard ciprofloxacin was found to be inactive against this strain. In addition, compound 2 showed moderate activity against two species of Candida and Cryptococcus neoformans, while 1 was inactive against these fungi. In order to evaluate the influence of the acyl group(s) in phloroglucinol (3) as a ligand, the mono- (4) and diacetylphloroglucinol (5) were prepared from 3, and evaluated for their in vitro SA, MRSA, and VRE activities; 2,4-diacetylphloroglucinol (5) showed potent activity, like 1, against SA, MRSA, and VRE (ATCC 700221) with IC50/MIC values of 0.3/2.5, 0.23/2.5, and 0.86/2.5 microg/mL, respectively, while 4 was inactive.