Научная статья на тему 'Exploiting in vitro synergistic interactions between the constituent plants of some anti-malarial polyherbals to improve therapeutic selectivity'

Exploiting in vitro synergistic interactions between the constituent plants of some anti-malarial polyherbals to improve therapeutic selectivity Текст научной статьи по специальности «Фундаментальная медицина»

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Текст научной работы на тему «Exploiting in vitro synergistic interactions between the constituent plants of some anti-malarial polyherbals to improve therapeutic selectivity»

INVESTIGATION OF THREE TANACETUM L. TAXA FROM TURKEY ON THE PROLIFERATION OF HUMAN PROSTATE CANCER CELLS AND EXPRESSION OF DETOXIFICATION ENZYME ACTIVITIES

© Zekiye Ceren Arituluk1, Emre Evin2, Serdar Karakurt3, Nurten Ezer1, Orhan Adah2, Ay§e Mine Gengler-Özkan4

1 Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Botany, Ankara, Turkey;

2 Middle East Technical University, Department of Biological Sciences, Joint Graduate Program in Biochemistry, Ankara, Turkey;

3 Selcuk University, Faculty of Science, Department of Biochemistry, Konya, Turkey;

4Ankara University, Faculty of Pharmacy, Department of Pharmaceutical Botany, Ankara, Turkey

The genus Tanacetum L. belonging to Asteraceae family have been used traditionally as herbal remedies in the treatment of various health problems and the members of this genus are rich in essential oils, sesquiterpenes and phenolic compounds which are responsible for their biological activities such as anti-inflammatory, cytotoxic, insecticidal [1]. Aim of this study is to investigate in vitro cytotoxic effects of methanol extracts obtained from the aerial parts of T. parthenium (L.) Schultz. Bip., T. argenteum (Lam.) Willd. subsp. canum (C.Koch) Grierson var. pumilum Grierson, and T. argenteum (Lam.) Willd. subsp. flabellifolium (Boiss. & Heldr.) Grierson on human prostate cancer cells; PC-3 (Androgen-independent) and LNCaP (Androgen-dependent) cells with Alamar Blue assay. Besides, modulatory role of those plant extracts on detoxification Phase II enzymes; glutathione-S-transferases (GST) and NAD(P)H: quinone oxidoreductase (NQO1) activities were also evaluated via spectrophotometrically.Extracts

of T. parthenium, T. argenteum subsp. canum var. pumilum and T. argenteum subsp. flabellifolium showed dose-dependent inhibition of proliferation of PC-3 cells with IC50 values of 134 |ig/mL, 72 |ig/mL, and 162 |ig/mL, respectively. Furthermore, the proliferation of LNCaP cells was also inhibited with IC50 values of 81 |ig/mL, 84 ^g/mL, and 147 ^g/mL, respectively. Interestingly, all plant extracts with IC50 value activated NQO1 enzyme activity in both PC-3 and LNCaP cells.

The results of this study have shown that methanol extracts of T. parthenium, T. argenteum subsp. canum var. pumilum andT. argenteum subsp. flabellifolium may modulate the Phase II enzymes and influence the metabolic activation of xenobiotics mediated by these enzymes.

References:

1. Gören N. et al., 2002. Stud Nat Prod Chem. 547-658.

EXPLOITING IN VITRO SYNERGISTIC INTERACTIONS BETWEEN THE CONSTITUENT PLANTS OF SOME ANTI-MALARIAL POLYHERBALS TO IMPROVE THERAPEUTIC SELECTIVITY

© Tarkang P.A.12, Appiah-Opong R.2, Ofori M.F.2, Ayong L.S.3, Nyarko A.K.24

11nstitute of Medical Research and Medicinal Plants Studies, Yaounde, Cameroon;

2 Noguchi Memorial Institute for Medical Research, Accra, Ghana;

3 Centre Pasteur du Cameroun, Yaounde, Cameroon;

4 School of Pharmacy, University of Ghana, Accra, Ghana

The low structural diversity of currently available anti-malarial drugs and the increasing ability of malaria parasites to quickly develop resistance to new anti-malarial drug molecules underscores the need to explore new therapeutic strategies. Combination therapyimproves efficacy by synergistic effects and slows down parasite resistance [1]. Hence, the potential of combiningplant extracts and/or introducing these into conventional treatment regimens are tools to be systematically explored. Our objective was to exploitin vitro synergistic interactions between the constituent

plant aqueous and ethanol extracts of six selected polyherbals (PNF, PFC, PFH, PFA, PFT, PFS), to explore strategies of improving their therapeutic selectivity.An accelerated solvent extraction (ASE) method was used to generate a 96 plants solvent extract library. In vitro antiplasmodial activities of polyherbal constituents were evaluated on multidrug resistant P. falciparum strain [2], followed by cytotoxicity screening [3]. Extract interactions were analyzed using an equipotency ratio drug combination approach [4]. The 50% fractional inhibitory concentration (FIC50) and combination indices

Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy]

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(CI) for each pair were calculated from determined EC50 values.ASEobtained yields were 1-5% for nonpolar and20-25% for polar solvents. Eighteen of theseextracts exhibited good antiplasmodial selectivity indices (SI >250). Exhibited fold increases in activity of aqueous and ethanol extracts of the polyherbals: PNF (5; 3), PFC (8; 0.8), PFH (6; 39), PFA (4; 0.3), PFT (1.3; 12.6), PFS (5.7; 0.2), indicating improved therapeutic selectivity, potential efficacy and safety for fold increases > 4. Out of 120 paired extracts, 21 aqueous and 16 ethanol extracts exhibited synergism with

CI < 0.8. Identified synergistic pairs informedconditions for improving therapeutic selectivity. The outcomes are likely to substantially advance phytotherapy and the future of medicine.

References:

1. Deshpande, Kuppast,. 2016. Med Chem., 6:1.

2. Izumiyama et al., 2009. Exp Parasitol. 121(2):144-150.

3. Nociari et al. 1998. JImmunol Meth, 213(2):157-167.

4. Ohrt et al. 2002. Antimicrob Agent Chemother., 46(8): 2518-2524.

INVESTIGATION OF THE INFLUENCE OF GLYCOSYLATED POLYPEPTIDE OF SEA URCHINS ON LPS-INDUCED PHOSPHORYLATION OF P38 MAP-KINASES IN U937 CELL CULTURE

© Baditch S.P., Malysheva I.A., Pozharitskaya O.N., Shikov A.N.

Saint Petersburg Institute of Pharmacy, Leningrad region, Vsevolozhsky district, 188663, Kuzmolovo P 245, Russia

The test object is a substance glycosylated polypeptide (GPP) 3.5 kDa. Peptide was isolated from the internal organs of the green sea urchins Strongylocentrotus droebachiensis (O.F. Müller, 1776) by original technology. It is proposed to use GPP for the treatment of postinflammatory conditions, in which the inflammatory process plays a key role. The parameters of the number of phosphorylated forms of MAP kinases and the total number of MAP kinases in U937 cell culture were evaluated by the immunoblot method [1, 2]. The aim of the study is to study the effect of the glycosylated polypeptide on LPS-induced phosphorylation of p38 MAP kinases

in U937 cell culture. To study the effect of GPP, the cell culture was incubated with lipopolysaccharide (LPS), then a specific inhibitor SB 203580 (Sigma) of human p38 MAP kinase and the test substance were added at various concentrations. An estimate of the number of phosphorylated forms of p38 MAP kinase in the model showed that the threshold concentration at which the inhibitory effect begins to appear is 25 ng/ml. Direct concentration dependence was observed in the range from 0.41 ng/ml to 2.50 ng/ml (Table 1). This action had the character of direct concentration dependence.

The IC50 of the GLP substance was 1.33 ng/ml.

Table 1. Effect of GPP on the level of phosphorylated forms of p38 MAP kinase in U937 cell culture stimulated by LPS (LPS stimulated cells without inhibitors were used as a negative control), M ± m

Samples, concentration, ng/ml Quantity of phospho-MAPKs p38 (% from control), M ± m

Intact group 39.4±2.6 (n = 12)

Negative control (stimulation of LPS) 100 (n = 12)

Positive control (specific inhibitor), 1880 26.3±1.6 (n = 12)

GPP, 2.50 26.4±1.4 (n = 9)

GPP, 1.25 48.6±2.1 (n = 9)

GPP, 0.63 64.9±1.8 (n = 12)

GPP, 0.41 72.5±1.7 (n = 6)

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Figure 1. Effect of GPP on the level of phosphorylated forms of p38 MAP kinase: 1 - intact cells; 2 - cells + LPS; 3 - cells + LPS + + SB; 4 - cells + LPS + GPP 50 ng/ml; 5 - cells + LPS + GPP 50 ng/ml; 6 - cells + LPS + GPP 25 ng/ml; 7 - cells + LPS + GPP 25 ng/ml; 8 - cells + LPS + GPP 10 ng/ml; 9 - cells + LPS + GPP 2,5 ng/ml; 10 - cells + LPS + GPP 1,25 ng/ml; 11 - cells + LPS + + GPP 0,63 ng/ml; 12 - cells + LPS + GPP 0,41 ng/ml; 13 - cells + LPS + GPP 0,41 ng/ml; 14 - cells + LPS + GPP 0,16 ng/ml

Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy] vol. 15/2017/suppLement 1

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