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In vitro, in silico and in vivo studies of ursolic acid as an anti-filarial agent.

Kalani K, Kushwaha V, Sharma P, Verma R, Srivastava M, Khan F, Murthy PK, Srivastava SK - PLoS ONE (2014)

Bottom Line: The selectivity index (SI) of UA for the parasites was found safe.Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug.To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

View Article: PubMed Central - PubMed

Affiliation: Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015 (U.P.) India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, New Delhi, 110 001, India.

ABSTRACT
As part of our drug discovery program for anti-filarial agents from Indian medicinal plants, leaves of Eucalyptus tereticornis were chemically investigated, which resulted in the isolation and characterization of an anti-filarial agent, ursolic acid (UA) as a major constituent. Antifilarial activity of UA against the human lymphatic filarial parasite Brugia malayi using in vitro and in vivo assays, and in silico docking search on glutathione-s-transferase (GST) parasitic enzyme were carried out. The UA was lethal to microfilariae (mf; LC100: 50; IC50: 8.84 µM) and female adult worms (LC100: 100; IC50: 35.36 µM) as observed by motility assay; it exerted 86% inhibition in MTT reduction potential of the adult parasites. The selectivity index (SI) of UA for the parasites was found safe. This was supported by the molecular docking studies, which showed adequate docking (LibDock) scores for UA (-8.6) with respect to the standard antifilarial drugs, ivermectin (IVM -8.4) and diethylcarbamazine (DEC-C -4.6) on glutathione-s-transferase enzyme. Further, in silico pharmacokinetic and drug-likeness studies showed that UA possesses drug-like properties. Furthermore, UA was evaluated in vivo in B. malayi-M. coucha model (natural infection), which showed 54% macrofilaricidal activity, 56% female worm sterility and almost unchanged microfilaraemia maintained throughout observation period with no adverse effect on the host. Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug. To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

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The schematic extraction and fractionation of UA from the leaves of E. tereticornis.$Washed with water and the solvent was dried over anhydrous Na2SO4. *Solvent was completely removed under vacuum at 35°C on a Buchi Rota vapour.
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pone-0111244-g001: The schematic extraction and fractionation of UA from the leaves of E. tereticornis.$Washed with water and the solvent was dried over anhydrous Na2SO4. *Solvent was completely removed under vacuum at 35°C on a Buchi Rota vapour.

Mentions: The air dried leaves of E. tereticornis (1.3 kg) were powdered and defatted with n-hexane. The defatted leaves were further extracted with MeOH (4×5 L) (Figure 1).The combined MeOH extract was dried under vacuum at 40°C. The MeOH extract so obtained was dissolved in distilled water (2L) and successively fractionated with n-hexane, CHCl3 and n-BuOH (saturated with H2O) [12], [13]. All the fractions were evaluated for anti-filarial activity, of which CHCl3 fraction (35.0 g) was found active hence subjected for chromatographic separation over VLC-1 using silica gel H (260 g). The gradient elution of VLC was carried out with mixture of hexane, CHCl3 and MeOH in increasing order of polarity.


In vitro, in silico and in vivo studies of ursolic acid as an anti-filarial agent.

Kalani K, Kushwaha V, Sharma P, Verma R, Srivastava M, Khan F, Murthy PK, Srivastava SK - PLoS ONE (2014)

The schematic extraction and fractionation of UA from the leaves of E. tereticornis.$Washed with water and the solvent was dried over anhydrous Na2SO4. *Solvent was completely removed under vacuum at 35°C on a Buchi Rota vapour.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222910&req=5

pone-0111244-g001: The schematic extraction and fractionation of UA from the leaves of E. tereticornis.$Washed with water and the solvent was dried over anhydrous Na2SO4. *Solvent was completely removed under vacuum at 35°C on a Buchi Rota vapour.
Mentions: The air dried leaves of E. tereticornis (1.3 kg) were powdered and defatted with n-hexane. The defatted leaves were further extracted with MeOH (4×5 L) (Figure 1).The combined MeOH extract was dried under vacuum at 40°C. The MeOH extract so obtained was dissolved in distilled water (2L) and successively fractionated with n-hexane, CHCl3 and n-BuOH (saturated with H2O) [12], [13]. All the fractions were evaluated for anti-filarial activity, of which CHCl3 fraction (35.0 g) was found active hence subjected for chromatographic separation over VLC-1 using silica gel H (260 g). The gradient elution of VLC was carried out with mixture of hexane, CHCl3 and MeOH in increasing order of polarity.

Bottom Line: The selectivity index (SI) of UA for the parasites was found safe.Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug.To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

View Article: PubMed Central - PubMed

Affiliation: Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015 (U.P.) India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, New Delhi, 110 001, India.

ABSTRACT
As part of our drug discovery program for anti-filarial agents from Indian medicinal plants, leaves of Eucalyptus tereticornis were chemically investigated, which resulted in the isolation and characterization of an anti-filarial agent, ursolic acid (UA) as a major constituent. Antifilarial activity of UA against the human lymphatic filarial parasite Brugia malayi using in vitro and in vivo assays, and in silico docking search on glutathione-s-transferase (GST) parasitic enzyme were carried out. The UA was lethal to microfilariae (mf; LC100: 50; IC50: 8.84 µM) and female adult worms (LC100: 100; IC50: 35.36 µM) as observed by motility assay; it exerted 86% inhibition in MTT reduction potential of the adult parasites. The selectivity index (SI) of UA for the parasites was found safe. This was supported by the molecular docking studies, which showed adequate docking (LibDock) scores for UA (-8.6) with respect to the standard antifilarial drugs, ivermectin (IVM -8.4) and diethylcarbamazine (DEC-C -4.6) on glutathione-s-transferase enzyme. Further, in silico pharmacokinetic and drug-likeness studies showed that UA possesses drug-like properties. Furthermore, UA was evaluated in vivo in B. malayi-M. coucha model (natural infection), which showed 54% macrofilaricidal activity, 56% female worm sterility and almost unchanged microfilaraemia maintained throughout observation period with no adverse effect on the host. Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug. To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

Show MeSH
Related in: MedlinePlus