Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions

Abstract

BackgroundIn traditional medicine whole plants or mixtures of plants are used rather than isolated compounds. There is evidence that crude plant extracts often have greater in vitro or/and in vivo antiplasmodial activity than isolated constituents at an equivalent dose. The aim of this paper is to review positive interactions between components of whole plant extracts, which may explain this.MethodsNarrative review.ResultsThere is evidence for several different types of positive interactions between different components of medicinal plants used in the treatment of malaria. Pharmacodynamic synergy has been demonstrated between the Cinchona alkaloids and between various plant extracts traditionally combined. Pharmacokinetic interactions occur, for example between constituents of Artemisia annua tea so that its artemisinin is more rapidly absorbed than the pure drug. Some plant extracts may have an immunomodulatory effect as well as a direct antiplasmodial effect. Several extracts contain multidrug resistance inhibitors, although none of these has been tested clinically in malaria. Some plant constituents are added mainly to attenuate the side-effects of others, for example ginger to prevent nausea.ConclusionsMore clinical research is needed on all types of interaction between plant constituents. This could include clinical trials of combinations of pure compounds (such as artemisinin + curcumin + piperine) and of combinations of herbal remedies (such as Artemisia annua leaves + Curcuma longa root + Piper nigum seeds). The former may enhance the activity of existing pharmaceutical preparations, and the latter may improve the effectiveness of existing herbal remedies for use in remote areas where modern drugs are unavailable.

Hypoglycemic and anti–hyperglycemic study of Gynura procumbens leaf extracts

“…It was noted earlier that the presence of a certain amount of water in an extraction solvent is necessary to enhance interaction of hydroxyl and/or carboxylic groups with water, to promote the dissolution of phenolics in the solvent [17] , but that as the amount of water is increased, the interaction is decreased by the benzene ring present in the structure hence restricting the solubility of phenolic compounds. Whole plant extracts are known to contain numerous compounds whose net observed pharmacological actions or inactions largely depend on synergistic or antagonistic interactions among these compounds [18] . These selective and non predictive interactions of compounds in the 25% extract of G. procumbens may have accounted for its potent anti-hyperglycemic effect, rather than the actual amount of phenolics or flavonoids.…”

In vitro antiplasmodial screening of ethnopharmacologically selected South African plant species used for the treatment of malaria

“…Investigations into treatments for malaria should therefore be directed at targeting the various stages of Plasmodium life-cycle and other clinical symptoms related to the disease state (Rasoanaivo et al, 2011).…”

Synergistic Interactions in Natural Products: Therapeutic Potential and Challenges

“…8,21,27,28 Adicionalmente, parece existir uma relação custo-benefício vantajosa na biossíntese de misturas de pequenas moléculas a partir de esqueletos simples, que se difundem facilmente, atingindo um maior número de alvos. 25 Estima-se que 90% das plantas medicinais descritas contenham misturas complexas de substâncias bioativas com atividade fraca ou moderada, ao invés de um restrito número de substâncias altamente ativas.…”

“…27,35 Para explicar este fato, propõe-se que flavonoides metoxilados atuem sinergisticamente potencializando a ação da artemisinina (2). 27 Conforme observado por Bilia et al 36 , esses flavonoides (16)(17)(18)(19) aumentam a velocidade de reação entre a artemisinina e a hemina, um produto da digestão parasitária da hemoglobina, levando à liberação de espécies reativas de oxigênio, responsáveis pela destruição dos plasmódios. Além disso, é possível que esses flavonoides tenham ação inibitória sobre bombas de efluxo da membrana celular, um mecanismo que permitiria aos extratos contornar o fenômeno da resistência.…”

“…Além disso, é possível que esses flavonoides tenham ação inibitória sobre bombas de efluxo da membrana celular, um mecanismo que permitiria aos extratos contornar o fenômeno da resistência. 27 As estruturas de alguns flavonoides presentes na espécie são mostradas na Figura 6. …”