Azadirachta indica extract-artesunic acid combination produces an increased cure rate of Plasmodium berghei-infected mice

Pharm Biol. 2014 Jul;52(7):883-9. doi: 10.3109/13880209.2013.872153. Epub 2014 Feb 7.

Abstract

Context: Available artemisinin-combination therapies (ACTs) are expensive. Various traditional herbal remedies for malaria involve plants, proven scientifically to have antiplasmodial effects, e.g., Azadirachta indica A. Juss. (Meliaceae).

Objective: Combination of an artemisinin-based compound and a medicinal herb extract will provide an indigenous alternative/herb-based ACT.

Materials and methods: The in vivo schizontocidal activity of the crude aqueous extract of 100, 500, and 1000 mg/kg of A. indica fresh leaves (NCE) and 6, 15, and 20 mg/kg of artesunic acid were determined, alone and in combination, while keeping the dose of artesunic acid constant at 15 mg/kg, using the Peter's 4-day suppressive test and Swiss albino mice. The ED50 was calculated from the dose-response relationships. Percentage survival and cure were also determined.

Results: The average yield of two extractions of NCE was 8.33 ± 1.67%. Combination of 1000 mg/kg of NCE and 15 mg/kg of artesunic acid, produced a significant reduction of parasitemia (96.87%), compared to 20 mg/kg of artesunic acid alone (68.14%). The combination had an ED50 of 0.58 mg/kg while that of artesunic acid alone was 8.814 mg/kg. The combinations of NCE with artesunic acid produced a cure, although the artesunic acid did not produce a cure in 30 d.

Discussion: NCE increased the activity of artesunic acid in terms of reduction in parasitemia, and increased survival time and cure rate.

Conclusion: The combination of an artemisinin and aqueous extract of neem leaf is possible, providing a potentiated reduction of parasitemia, and increased cure rate.

Keywords: Artemisinin-based combination therapy; drug resistance; malaria parasites.

MeSH terms

  • Animals
  • Antimalarials / pharmacology
  • Antimalarials / therapeutic use*
  • Artemisinins / administration & dosage
  • Artemisinins / pharmacology
  • Artemisinins / therapeutic use*
  • Azadirachta / chemistry*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Malaria / drug therapy*
  • Malaria / parasitology
  • Mice
  • Parasitemia / drug therapy
  • Parasitemia / parasitology
  • Phytotherapy*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Leaves / chemistry
  • Plasmodium berghei / drug effects*
  • Schizonts / drug effects
  • Succinates / administration & dosage
  • Succinates / pharmacology
  • Succinates / therapeutic use*

Substances

  • Antimalarials
  • Artemisinins
  • Plant Extracts
  • Succinates
  • artesunic acid