In vitro antileishmanial effects of antibacterial diterpenes from two Ethiopian Premna species: P. schimperi and P. oligotricha

Pharmacognosy & Phytotherapy Research Laboratory, School of Chemical and Life Sciences, the University of Greenwich at Medway, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.
BMC Pharmacology (Impact Factor: 1.84). 07/2003; 3(1):6. DOI: 10.1186/1471-2210-3-6
Source: PubMed

ABSTRACT Three antibacterial diterpenes: (5R,8R,9S,10R)-12-oxo-ent-3,13(16)-clerodien-15-oic acid (1), 16-hydroxy-clerod-3,13(14)-diene-15,16-olide (2) and ent-12-oxolabda-8,13(16)-dien-15-oic acid (3) were previously isolated form Premna schimperi and P. oligotricha. Since andrographolide and other structurally related diterpenes were shown to have antileishmanial activity, the aim of the present study was to assess the in vitro effect of premna diterpenes against Leishmania aethiopica; the causative agent of cutaneous leishmaniasis in Ethiopia.
The diterpenes showed potent concentration-dependant suppressive effect on the viability of axenically cultured amastigotes of L. aethiopica. The clerodane diterpenes 1 and 2 were most active (LD50 values 1.08 and 4.12 microg/ml respectively) followed by andrographolide and 3. Compounds 1 and 2 appear to be over 20 and 10-times respectively more selective to leishmania amastigotes than the permissive host cell line, THP-1 cells or the promastigotes stage of the parasites.
The clerodane diterpenes (1, 2) which were more potent and selective than labdanes (andrographolide and 3) are promising for further studies and/or development.

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Available from: Solomon Habtemariam, Sep 29, 2015
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    • "Nature has been a source of medicinal agents for thousands of years. An impressive number of modern drugs has been isolated from medicinal plants including antimicrobial (Habtemariam 2003; Israr et al. 2012). It is also assumed that these plants-based antibacterial may possibly have the novel and different mechanism(s) of action and thus could be more effective especially in the reduction/prevention of antimicrobial resistance. "
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    ABSTRACT: The aim of this study was to explore the extract/fractions and compounds of Diospyros lotus against various Gram-positive and Gram-negative bacteria strain. The results showed marked susceptibility of extract and its fractions against test pathogens. Among them, chloroform fraction was most dominant and effective against all tested bacteria. The chloroform fraction was subjected to column chromatography which led to the isolation of lupeol (1), 7-methyljuglone (2), b-sitosterol (3), stigmasterol (4), betulinic acid (5), diospyrin (6) and 8-hydroxyisodiospyrin (7). Among the isolated compounds, betulinic acid (5) showed significant activity against most of the tested pathogen. In conclusion, our study validated the traditional uses of the plant in the treatment of infectious diseases which was also strongly supported by the isolated compound, betulinic acid (5).
    Natural Product Research 02/2015; DOI:10.1080/14786419.2015.1013957 · 0.92 Impact Factor
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    • "In vitro antileishmanial activity tests were carried out against the promastigote stage of L. aethiopica and L. major, and their toxicity was checked by measuring their hemolytic effect against sheep red blood cell (RBC). L. aethiopica and L. major isolates were grown in tissue culture flasks containing RPMI 1640 medium supplemented with 10% heat-inactivated fetal calf serum, 100 IU penicillin/mL and 100 μg/mL streptomycin solution at 22 °C for L. aethiopica (Habtemariam, 2003) and 26 °C for L. major (Ephros et al., 1999). "
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    ABSTRACT: Leishmaniasis is a major protozoal disease threatening the lives of 350 million people throughout the world. However, the therapeutic options for the disease are limited. In the present study, the antiprotozoal activity of the latex obtained from the Ethiopian plant Aloe calidophila Reynolds was evaluated by in vitro testing against Leishmania aethiopica and Leishmania major. It was found that the latex possesses moderate activity against both parasites with IC50 values of 64.05 and 82.29 µg/mL, respectively. Phytochemical investigation resulted in the isolation of three anthrones identified as aloinoside, aloin, and microdontin on the basis of IR, MS, 1H NMR, and 13C NMR spectral data. The isolated compounds showed strong antileishmanial activity with IC50 values ranging from 1.76 to 6.32 µg/mL against L. aethiopica and from 2.09 to 8.85 µg/mL against L. major. Although these values were higher than those of amphotericin B (IC50 = 0.109 and 0.067 µg/mL), the selectivity indices (813.35 and 694.90, respectively, against L. aethiopica and L. major) of aloinoside were much better than those of the standard drug (423.49 and 688.96). The results indicate that the isolated compounds have the potential to be used as a scaffold for the development of safe and cost-effective antileishmanial agents. Copyright © 2014 John Wiley & Sons, Ltd.
    Phytotherapy Research 07/2014; 28(12). DOI:10.1002/ptr.5204 · 2.66 Impact Factor
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    • "A 7:1 ratio proved to be optimal for the assay and used routinely. To enhance promastigote infectivity, the promastigote to PEM ratio was incubated at 31 °C ($skin temperature), 5% CO 2 and 95% relative humidity for 24 h (Habtemariam, 2003), extracellular parasites were removed by washing, and fresh medium containing serial concentrations of the four drugs was added. Plates were washed after 3 days of incubation, and replenished with fresh solutions of SSG, miltefosine, paromomycin and amphotericin B and incubated for additional 2 days. "
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    ABSTRACT: Cutaneous Leishmaniasis (CL) caused by Leishmania aethiopica is a public health and social problem with a sequel of severe and mutilating skin lesions. It is manifested in three forms: localized CL (LCL), mucosal CL (MCL) and diffuse CL (DCL). Unresponsiveness to sodium stibogluconate (SbV) is common in Ethiopian CL patients. Using the amastigote-macrophage in vitro model the susceptibility of 24 clinical isolates of L. aethiopica derived from untreated patients was investigated. Eight strains of LCL, 9 of MCL, and 7 of DCL patients together with a reference strain (MHOM/ET/82/117/82) were tested against four antileishmanial drugs: amphotericin B, miltefosine, SbV and paromomycin. In the same order of drugs, IC50 (μg/ml±SD) values for the 24 strains tested were 0.16±0.18, 5.88±4.79, 10.23±8.12, and 13.63±18.74. The susceptibility threshold of isolates originating from the 3 categories of patients to all 4 drugs was not different (p>0.05). Maximal efficacy was superior for miltefosine across all the strains. Further susceptibility test could validate miltefosine as a potential alternative drug in cases of sodium stibogluconate treatment failure in CL patients.
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