In vitro and in vivo antimalarial activity of the volatile oil of Cyperus articulatus (Cyperaceae)

SILVA, Nazaré Carneiro da; GONÇALVES, Suellen Ferreira; ARAÚJO, Luciana Silva de; KASPER, Aline Aparecida München; FONSECA, Amanda Luisa da; SARTORATTO, Adilson; CASTRO, Kelly Christina Ferreira; MORAES, Tânia Mara Pires; BARATTO, Leopoldo Clemente; VAROTTI, Fernando de Pilla; BARATA, Lauro Euclides Soares; MORAES, Waldiney Pires

doi:10.1590/1809-4392201804331

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Chemistry and Pharmacology • Acta Amaz. 49 (4) • Oct-Dec 2019 • https://doi.org/10.1590/1809-4392201804331 linkcopy

In vitro and in vivo antimalarial activity of the volatile oil of Cyperus articulatus (Cyperaceae)

Atividade antimalárica in vitro e in vivo do óleo essencial de Cyperus articulatus (Cyperaceae)

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Malaria is a disease of global tropical distribution, being endemic in more than 90 countries and responsible for about 212 million cases worldwide in 2016. To date, the strategies used to eradicate this disease have been ineffective, without specific preventive measures such as vaccines. Currently, the existing therapeutic arsenal is limited and has become ineffective against the expansion of artemisinin-resistant Plasmodium, demonstrating the need for studies that would allow the development of new compounds against this disease. In this context, we studied the volatile oil obtained from rhizomes of Cyperus articulatus (VOCA), a plant species commonly found in the Amazon region and popularly used as a therapeutic alternative for the treatment of malaria, in order to confirm its potential as an antimalarial agent by in vitro and in vivo assays. We cultured Plasmodium falciparum W2 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) strains in erythrocytes and exposed them to VOCA at different concentrations in 96-well microplates. In vivo antimalarial activity was tested in BALB/c mice inoculated with approximately 10⁶ erythrocytes infected with Plasmodium berghei. VOCA showed a high antimalarial potential against the two P. falciparum strains, with IC₅₀ = 1.21 μg mL^-1 for W2 and 2.30 μg mL^-1 for 3D7. VOCA also significantly reduced the parasitemia and anemia induced by P. berghei in mice. Our results confirmed the antimalarial potential of the volatile oil of Cyperus articulatus.

Keywords:
antiplasmodial; artemisinin resistance; chloroquine resistance; malaria; Plasmodium falciparum; Plasmodium berghei

t_R (min)	KI	Compound	% rel
5.77	933	α-pinene	5.37
6.29	953	thuja-2,4(10)-diene	0.42
6.93	977	β-pinene	3.07
8.39	1024	p-cymene	0.50
8.53	1028	limonene	0.60
12.13	1126	α-campholenal	0.31
12.68	1140	trans-pinocarveol	1.44
13.60	1162	pinocarvone	0.52
13.83	1168	p-mentha-1,5-dien-8-ol	0.60
15.01	1197	myrtenal	2.16
22.54	1376	α-copaene	4.42
23.48	1398	cyperene	1.70
23.74	1405	cis-thujupsadiene	1.18
25.08	1438	α-guaiene	0.72
25.89	1458	rotundene	0.88
26.45	1472	β-selinene	0.31
26.52	1474	4,5,9,10-dehydro-isolongifolene	0.54
26.63	1477	α-amorphene	1.04
27.04	1487	α-selinene	4.38
27.37	1495	eudesma-4(14),7(11)-diene	0.96
27.81	1506	α-bulnesene	2.16
29.26	1543	α-calacorene	1.16
30.50	1575	cedrene epoxide	2.53
30.73	1581	calamenene	1.32
30.82	1584	caryophylene oxide	3.73
31.00	1588	spathulenol	2.82
31.19	1593	β-copaen-4-α-ol	1.37
31.79	1609	humulene epoxide	1.27
32.84	1638	eudesma-3,11-dien-5-ol	1.56
33.51	1656	pogostol	2.54
34.44	1681	mustakone	9.91
34.56	1684	cyperol	2.55
34.96	1695	cyperotundone	2.79
35.51	1711	cis-thujopsenal	4.05
35.81	1719	14-hidroxi-α-humulene	0.55
36.98	1753	cyclocolorenone	7.42
37.63	1771	α-cyperone	0.59
Total identified (%)			79.44

Treatments	IC₅₀ (µg ml^-1)			SI
Treatments	W2	3D7	Wi 26VA-4	IC_{50Wi 26VA-4} / IC_50W2	IC_{50 Wi 26VA-4} / IC_{50 3D7}
VOCA	1.21 ± 0.05	2.30 ± 0.09	>100	>80	>40
Chloroquine	0.46 ± 0.08	0.21 ± 0.01	>100	>100	>200

	Control	VOCA concentration
	Control	5	50	300	2,000
Day 0	24.02 ± 1.28	24.08 ± 2.56	24.18 ± 3.77	25.03 ± 0.67	24.85 ± 0.57
Day 7	25.28 ± 2.51	26.02 ± 0.59	26.08 ± 1.27	27.20 ± 1.64	26.89 ± 1.03
Day 14	25.99 ± 2.96	26.36 ± 1.75	28.19 ± 0.89	28.71 ± 1.60	29.40 ± 1.31

Treatment	Erythrocytes (10⁶ µl^-1)	Hemoglobin (g dl^-1)	Hematocrit (%)
Group 1	9.48 ± 0.49	14.46 ± 1.21	49.50 ± 1.16
Group 2	3.28 ± 0.61***	6.16 ± 0.99***	20.92 ± 3.53***
Group 3	10.04 ± 2.03***	13.62 ± 2.50***	48.06 ± 8.3***
Group 4	8.04 ± 3.41**	14.77 ± 0.49**	43.03 ± 13.5**
Group 5	7.23 ± 2.60**	11.74 ± 2.59**	38.10 ± 11.44*
Group 6	3.60 ± 0.35	6.94 ± 0.85	25.34 ± 3.07

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[TFN1] Group1: control; Group 2: untreated malaria; Group 3: artemisinin 100 mg kg^-1; Groups 4, 5 and 6: VOCA 200, 100 and 10 mg kg^-1. Asterisks for Group 2 indicate significant differences in relation to Group 1. Asterisks for Groups 3, 4 and 5 indicate significant differences relative to Group 2. *p < 0.05; **p < 0.01; ***p < 0.001.