Antiprotozoal and heme-binding activity of 13 aromatic and medicinal plants from Ahaggar, Algeria

Thirteen species from Ahaggar area were selected for antiprotozoal screening on the basis of ethnopharmacological uses and/or chemotaxonomy. Among the selected plants 10 Asteraceae, 2 Apiaceae and 1 Lamiaceae were collected in the Ahaggar National Park, in the Southern Sahara [1, 2]. Both antiplasmodial activity (P. falciparum, chloroquino-resistant FcB1/Colombia) and antileishmanial activity (promastigotes from L. amazonensis) were evaluated. 7 species exhibited a significant antileshmanial activity (IC₅₀ < 10 µg/ml) and 8 species showed significant antiplasmodial activity (IC₅₀ ≤1 µg/l), but no correlation between both activities was observed. As antiplasmodial activity could be associated with inhibition of heme degradation into hemozoin, with subsequent Plasmodium death, a combined heme-binding assay was carried out in order to identify stable heme-adducts [3]. Comparison of LC-MS spectra of crude extracts with or without heme allowed us to identify m/z values of compounds involved in the heme-adduct formation. Among all identified adducts, we found that two methoxyflavones isolated from P. monodiana can form adducts with heme.

Acknowledgements: Authors thanks the ChemBioFight European funding (FP7-people-2010-IRSES), Algerian government for PROFAS training financial support and Director of Ahaggar National Park.

Keywords: Ethnopharmacology, antiprotozoal, heme-binding, Ahaggar.

References:

[1] Ozenda P. Flore et végétation du Sahara, Ed. CNRS, 2004: 438

[2] Hammiche V, Maiza K. Traditional medicine in Central Sahara: Pharmacopoeia of Tassili N'ajjer. J Ethnopharmacol 2006; 105: 358 – 367

[3] Muñoz-Durango K, Maciuk A, Harfouche A, Torijano-Gutiérrez S, Jullian JC, Quintin J, Spelman K, Mouray E, Grellier P, Figadère B. Detection, characterization, and screening of heme-binding molecules by mass spectrometry for malaria drug discovery. Anal Chem 2012; 84: 3324 – 3329

Plant	Fraction	Antileishmania activity (IC50 µg/ml)	Antiplasmodial activity (IC50 µg/ml)	m/z values of compounds forming heme-adducts
Ammodaucus leucotrichus (fruit), Apiaceae	EtOAc	6.5	> 100	389 [M+H]+
	MeOH	-	79.3 ± 7.7	381 [M+H]+
Anvillea radiata (aerial part), Asteraceae	EtOAc	10.2	2.31 ± 0.86	277 [M+H]+, 287 [M+H]+, 344 [M+H]+
	MeOH	-	> 100	235 [M+H]+
Artemisia campestris ssp glutinosa (aerial part), Asteraceae	EtOAc	17.26	1.21 ± 0.16	315 [M+H]+, 330 [M+H]+ , 345 [M+H]+, 359 [M+Na]+
	MeOH	-	0.72 ± 0.27	355 [M+H]+
Artemisia judaica ssp saharensis (aerial part), Asteraceae	EtOAc	8.93	1.13 ± 0.19	314 [M+H]+, 344 [M+H]+, 420 [M+H]+
	MeOH	-	> 100	-
Cotula anthemoides (whole plant), Asteraceae	EtOAc	6.59	78.4 ± 15.6	250 [M+H]+, 264 [M+H]+
	MeOH	-	1.20 ± 0.32	250 [M+H]+, 395 [M+H]+
Deverra scoparia (aerial part)= Pituranthos scoparia, Apiaceae	EtOAc	32.54	4.60 ± 1.50	239 [M+H]+, 357 [M+Na]+, 451 [M+Na]+
	MeOH	-	20.4 ± 2.1	395 [M+Na]+
Deverra scoparia (root) = Pituranthos scoparia, Apiaceae	EtOAc	7.27	> 100	301 [M+H]+, 451 [M+H]+
	MeOH	-	0.99 ± 0.41	365 [M+H]+, 381 [M+H]+
Nauplius graveolens (aerail parts)= Asteriscus graveolens, Asteraceae	EtOAc	6.95	-	-
	MeOH	-	> 100	235 [M+H]+
Pentzia monodiana (aerial parts), Asteraceae	EtOAc	13.63	3.53 ± 1.08	359 [M+H]+, 389 [M+H]+
	MeOH	-	> 100	-
Pulicaria crispa (aerial parts)	EtOAc	14.93	36.2 ± 4.1	347 [M+H]+, 533 [M+H]+, 549 [M+H]+
	MeOH	-	8.80 ± 1.80	156 [M+H]+, 235 [M+H]+
Pulicaria incisa (aerial parts)	EtOAc	8.37	4.57 ± 1.23	329 [M+H]+, 353 [M+H]+
	MeOH	-	34.2 ± 8.1	-
Rhaponticum acaule (root)	EtOAc	14	4.7 ± 0.46	435 [M+H]+
	MeOH	-	> 100	365 [M+H]+
Rhaponticum acaule (aerial parts)	EtOAc	26	1.27 ± 0.49	385 [M+H]+, 445 [M+H]+, 585 [M+H]+
	MeOH	-	40.2 ± 4.93	434 [M+H]+
Salvia chudaei (leaves), Lamiaceae	EtOAc	-	> 100	329 [M+H]+, 369 [M+H]+
	MeOH	-	64.2 ± 40.5	399 [M+H]+