Antipyretic and antinociceptive effects of Nauclea latifolia root decoction and possible mechanisms of action

Figures & data

Table 1.  Phytochemical constituents of the decoction of the roots of Nauclea latifolia.

Constituents/test	Inference
Alkaloids	+
Flavonoids	+
Saponins	+
Tannins	+
Phenols	+
Anthraquinones	+
Cardiac glycosides	+
Glycosides	+
Bufadienolides	-
Lipids	-

+ Present; − Absent.

Table 2.  Acute toxicity of the decoction of the roots of Nauclea latifolia administered by intraperitoneal injection to mice.

Treatments	Dose (mg/kg)	Sex	D/T	Mortality latency (h)	Toxic symptoms
Control	-	Male Female	0/5 0/5	--	None None
N. latifolia	100	Male Female	0/5 0/5	--	None None
N. latifolia	250	Male Female	0/5 0/5	--	None None
N. latifolia	500	Male Female	0/5 0/5	--	None None
N. latifolia	1000	Male Female	0/5 0/5	--	None Hypoactivity, piloerection
N. latifolia	2000	Male Female	1/5 1/5	>36, <48 >36, <48	Hypoactivity, piloerection, salivation, asthenia Hypoactivity, piloerection, salivation, asthenia
N. latifolia	4000	Male Female	3/5 2/5	>24, <36 >24, <36	Hypoactivity, piloerection, salivation, syncope Hypoactivity, piloerection, salivation, syncope
N. latifolia	8000	Male Female	5/5 5/5	>24, <36 >24, <36	Asthenia, anorexia, salivation, syncope Asthenia, anorexia, salivation, syncope

D/T, the number of dead mice over the number of treated mice; None, no toxic symptoms during the observation period; mortality latency, time to death (in days) after the intraperitoneal injection. The decoction of the Nauclea latifolia was administered as a single intraperitoneal dose to groups of mice. Mice in each group were carefully examined for any signs of toxic (behavioral changes and mortality) for 14 days. Control group received distilled water (10 mL/kg, i.p.).

Table 3.  Influence of the decoction of the roots of Nauclea latifolia on body temperature.

Treatments	Dose (mg/kg)	Duration of study (h)
		t0b	t0a	0.5	1	2	3	24
Control	-	35.2 ± 0.3	35.4 ± 0.1	35.5 ± 0.2	35.3 ± 0.3	35.2 ± 0.1	35.0 ± 0.5	35.5 ± 0.3
N. latifolia	16	35.1 ± 0.2	35.1 ± 0.4	35.3 ± 0.2	34.5 ± 0.1	34.4 ± 0.1	34.1 ± 0.1*	35.3 ± 0.1
N. latifolia	40	35.1 ± 0.2	35.4 ± 0.3	35.3 ± 0,5	34.4 ± 0.2*	34.3 ± 0.1*	34.2 ± 0.1*	35.2 ± 0.1
N. latifolia	80	35.1 ± 0.3	35.2 ± 0.2	35.2 ± 0.2	34.3 ± 0.1**	34.2 ± 0.1**	34.1 ± 0.1*	35.1 ± 0.3
N. latifolia	160	35.2 ± 0.3	35.1 ± 0.3	35.1 ± 0.4	34.3 ± 0.1**	34.2 ± 0.1**	34 ± 0.1**	35.1 ± 0.1

Results are expressed as mean ± SEM. t₀b, initial body temperature; t₀a, body temperature after the administration of the different treatment, the changes in temperature were expressed as the difference between the reference point and the value of rectal temperature after the injection of the extract or distilled water; n = 6 each group; ^*P <0.05, ^*P <0.05, significantly different compared to the control group, data were analyzed by two-way ANOVA followed by Tukey’s (HSD) multicomparison test.

Table 4.  Influence of the decoction of the roots of Nauclea latifolia on Brewer’s yeast-induced pyrexia.

Treatments	Dose (mg/kg)	Duration of study (h)
		t0b	t0a	0.5	1	2	3	4	5	6
Control	-	35.0 ± 0.1	37.3 ± 0.1	38.1 ± 0.1	38.2 ± 0.1	38.3 ± 0.2	38.4 ± 0.1	38.4 ± 0.1	38.6 ± 0.1	38.2 ± 0.1
N. latifolia	16	35.1 ± 0.1	37.2 ± 0.1	38.0 ± 0.3	38.0 ± 0.3	37.9 ± 0.3*	37.5 ± 0.2*	37.2 ± 0.2*	37.1 ± 0.3*	36.8 ± 0.5**
N. latifolia	40	35.0 ± 0.2	37.2 ± 0.1	38.1 ± 0.1	38.0 ± 0.2	37.4 ± 0.2*	37.0 ± 0.1*	36.6 ± 0.2**	36.1 ± 0.1**	36.0 ± 0.2**
N. latifolia	80	35.1 ± 0.1	37.1 ± 0.1	38.1 ± 0.1	37.8 ± 0.1	37.2 ± 0.1*	36.8 ± 0.1**	36.0 ± 0.2***	35.9 ± 0.2***	35.6 ± 0.3***
N. latifolia	160	35.0 ± 0.1	7.1 ± 0.1	38.0 ± 0.1	37.7 ± 0.2*	37.2 ± 0.1*	36.7 ± 0.2**	35.3 ± 0.1***	35.4 ± 0.3***	35.2 ± 0.3***
Aspirin	300	35.1 ± 0.1	37.1 ± 0.1	37.9 ± 0.1	37.4 ± 0.3*	36.3 ± 0.2***	36.1 ± 0.1***	35.6 ± 0.1***	35.4 ± 0.1***	34.9 ± 0.3***

Results are expressed as mean ± SEM; t₀b, initial body temperature prior to injection of Brewer’s yeast; t₀a, body temperature 18 h after injection of brewer’s yeast; n = 6 each group; ^*P <0.05, ^**P <0.01, ^***P <0.001, significantly different compared to the control groups, data were analyzed by two-way ANOVA, followed by Tukey’s (HSD) multicomparison test.

Table 5.  Influence of the decoction of the roots of Nauclea latifolia on acetic acid-induced writhing.

Treatments	Dose (mg/kg)	Number of contractions	Inhibition (%)
Control		78.0 ± 4.3	-
N. latifolia	16	56.7 ± 1.3	27.3*
N. latifolia	40	46.2 ± 1.2	40.8*
N. latifolia	80	36.8 ± 2.2	52.8**
N. latifolia	160	29.8 ± 4.1	61.7***
Aspirin	150	35.7 ± 2.4	54.3**
Morphine	5	26.3 ± 1.3	66.2***
N. latifolia + naloxone	160 + 1	62.7 ± 4.1	19.6*

Results are expressed as mean ± SEM, the statistical analysis was performed on absolute data, the extract at all doses used began manifesting its assuaging effect on the writing reflex 1 h following administration; n = 6; ^*P<0.05, ^**P<0.01, ^***P<0.001, significantly different compared to the control groups; data were analyzed by two-way ANOVA, followed by Tukey’s (HSD) multicomparison test.

Table 6.  Influence of the decoction of the roots of Nauclea latifolia on formalin-induced pain.

Treatments	Dose (mg/kg)	Licking time (s)		Inhibition (%)
		Early phase(0-5 min)	Late phase (15-30 min)	Early phase	Late phase
Control		73.3 ± 1.8	69.3 ± 2.9	-	-
N. latifolia	16	57.3 ± 3.7	55.2 ± 1.9	21.8*	20.4*
N. latifolia	40	48.2 ± 3.2	45.7 ± 1.3	34.3*	34.1*
N. latifolia	80	33.7 ± 2.3	33.3 ± 2.5	54.1**	51.9**
N. latifolia	160	28.8 ± 1.2	24.8 ± 2.1	60.7**	64.2***
Indomethacin	10	70.2 ± 1.5	22.8 ± 2.2	4.3	67.1***
Morphine	5	35.8 ± 2.2	18.7 ± 1.0	64.8***	73.1***
Theophylline + N. latifolia	5 + 160	28.0 ± 1.6	25.2 ± 1.5	61.8***	63.7***
Glibenclamide + N. latifolia^#	8 + 160	71.5 ± 1.8	68.5 ± 1.6	2.5	1.2
Naloxone + N. latifolia^#	2 + 160	71.3 ± 4.0	68.2 ± 2.5	2.7	1.7
l-NAME + N. latifolia^#	10 + 160	68.2 ± 1.8	68.5 ± 1.8	7.0	1.2

Results are expressed as mean ± SEM; the amount of time spent licking and biting the injected paw was indicative of pain and was recorded in 0-5 min (first phase) and 15-30 min (second phase); n = 6; ^*P <0.05, ^**P <0.01, ^***P <0.001, significantly different compared to the control group, data were analyzed by two-way ANOVA, followed by Tukey’s (HSD) multicomparison test. l-NAME: N_ω-l-nitro-arginine methyl ester. ^#P < 0.01: control is Nauclea latifolia at the dose of 160 mg/kg.

Table 7.  Influence of the decoction of the roots of Nauclea latifolia on tail flick response in mice after immersion in a water bath at 55°C.

Treatments	Dose (mg/kg)	Duration of study (min)
		0	15	30	60
Control	-	4.4 ± 0.6	4.1 ± 0.6 (-8.6)	4.3 ± 0.5 (-2.8)	4.1 ± 0.1 (-7.1)
N. latifolia	16	4.4 ± 0.6	4.9 ± 0.7 (10.3)	5.1 ± 0.8 (14.9)	5.2 ± 0.8 (17.6)*
N. latifolia	40	4.6 ± 0.4	4.9 ± 0.1 (8.9)	6.2 ± 0.7 (36.5)**	6.5 ± 0.5 (43.3)**
N. latifolia	80	4.3 ± 0.6	5.2 ± 0.4 (20.0)**	6.9 ± 0.7 (62.1)***	7.8 ± 0.5 (81.1)***
N. latifolia	160	4.4 ± 0.8	6.3 ± 0.5 (44.6)***	7.7 ± 0.5 (75.4)***	8.0 ± 0.3 (83.3)***
Aspirin	150	5.9 ± 0.3	6.1 ± 0.3 (2.3)	6.1 ± 0.6 (2.5)	6.0 ± 0.3 (1.8)
Morphine	5	4.1 ± 0.6	6.2 ± 0.4 (51.8)***	8.3 ± 0.5 (103.4)***	8.1 ± 0.5 (98.2)***
N. latifolia + naloxone	160 + 1	4.4 ± 0.3	5.7 ± 0.4 (30.6)**	6.4 ± 0.3 (47.3)**	6.8 ± 0.3(55.9)**

Results are expressed as mean ± SEM and units are in seconds; percentage of protection against thermally induced pain by warm water are in parentheses; n = 6; ^*P <0.05, ^**P <0.01, ^***P <0.001, significantly different compared to the control group; data were analyzed by two-way ANOVA, followed by Tukey’s (HSD) multicomparison test.

Table 8.  Influence of the decoction of the roots of Nauclea latifolia on hot-plate-induced pain in mice.

Treatments	Dose (mg/kg)	Duration of study (h)
		0	0.5	1	2	3	4	5	6
Control	-	19.5 ± 0.9	19.3 ± 0.9 (-1.0)	19.1 ± 0.6 (0.2)	19.4 ± 0.9 (0.2)	19.3 ± 0.6 (-0.9)	20.1 ± 0.8 (3.1)	21 1 ± 0.9 (7.9)	20.1 ± 1.0 (3.3)
N. latifolia	16	17.1 ± 1.2	17.3 ± 1.1 (2.0)	20.3 ± 1.4 (30.4)**	22.2 ± 0.7 (30.4)**	25.3 ± 1.3 (48.6)**	21.4 ± 1.6 (25.6)**	20.7 ± 1.2 (21.8)**	19.6 ± 1.0 (15.3)*
N. latifolia	40	18.2 ± 0.8	18.8 ± 1.1 (3.3)	22.2 ± 1.3 (31.0)**	23.9 ± 1.2 (31.0)**	26.8 ± 0.9 (46.9)**	22.3 ± 1.4 (22.4)**	20.8 ± 0.9 (14.2)**	20.1 ± 0.8 (10.5)*
N. latifolia	80	17.1 ± 1.0	17.8 ± 0.9 (4.0)	22.9 ± 1.6 (75.6)***	29.7 ± 1.5 (73.6)***	35.4 ± 4.5 (106.7)***	31.6 ± 3.5 (84.8)***	30.1 ± 2.5 (75.7)***	28.3 ± 1.2 (65.6)***
N. latifolia	160	16.9 ± 1.9	17.8 ± 1.6 (5.0)	26.2 ± 1.3 (172.4)***	46.1 ± 3.5 (172.4)***	56.1 ± 3.9 (230.5)***	47.2 ± 1.7 (178.8)***	46.7 ± 2.5 (175.4)**	45.4 ± 4.3 (167.8)***
Aspirin	150	18.9 ± 1.3	18.9 ± 0.9 (-0.3)	19.3 ± 0.8 (2.8)	19.5 ± 2.5 (2.9)	19.2 ± 1 (1.5)	19.5 ± 1.1 (3.2)	19.2 ± 0.6 (1.6)	19.1 ± 1.2 (0.5)
Morphine	5	18.7 ± 1.6	19.6 ± 1.5 (4.7)	31.6 ± 2.8 (190.0)***	54.2 ± 5.9 (189.9)***	60.1 ± 2.2 (220.9)***	62.7 ± 1.9 (235.3)***	60.6 ± 2.3 (223.8)***	57.9 ± 2.9 (208.3)***
N. latifolia + naloxone	160 + 1	19.7 ± 1.2	20.6 ± 1.2 (4.7)	24.2 ± 0.7 (44.1)**	28.3 ± 1.3 (44.1)**	30.5 ± 1.3 (55.3)***	26.5 ± 1,5 (34.6)**	27.5 ± 1.0 (39.8)**	28.3 ± 1.8 (44.1)**

Results are expressed as mean ± SEM and units are in seconds, percentage of protection against thermally induced pain by hot-plate are in parentheses; n = 6; ^*P <0.05, ^**P <0.01, ^***P <0.001, significantly different compared to the control group; data were analyzed by two-way ANOVA, followed by Tukey’s (HSD) multicomparison test.

Figure 1.  Effects of acute Nauclea latifolia decoction (16, 40, 80, 160 and 320 mg/kg) or diazepam (1 mg/kg) treatment on motor co-ordination of mice on the Rota-rod, Acquisition process of the Rota-rod performance as expressed by means ± SEM of performance time, ^ap <0.05, ^bp <0.01, ^cp <0.001, significantly different compared to the control; data were analyzed by two-way ANOVA, followed by Tukey’s (HSD) multicomparison test; n = 6 animals per group.

Table 9.  Influence of the decoction of the roots of Nauclea latifolia on bicuculline induced-behavioral excitation in 1 h.

Treatments	Dose (mg/kg)	Behavioral aspects
		Crossing number	Duration (s)
			Rearing	Grooming	Immobility	Sedation
Control 1	-	17.7 ± 0.8	992.2 ± 12.2	31.2 ± 1.8	106.5 ± 4.8	61.7 ± 2.9
Control 2	-	81.8 ± 5.1	2676.7 ± 93.3	73.2 ± 6.2	173.7 ± 3.7	11.8 ± 1.9
N. latifolia	16	68.2 ± 4.5 * (16.7)	2110.8 ± 25.3* (21.1)	70.7 ± 3.7 (3.4)	147.2 ± 4.8* (15.2)	26.7 ± 5.3* (55.6)
N. latifolia	40	65.3 ± 4.8* (20.2)	2124.2 ± 6.2* (20.6)	56.8 ± 3.2** (22.3)	142.3 ± 2.8* (18.0)	33.8 ± 4.2* (65.0)
N. latifolia	80	39.2 ± 3.2** (52.1)	1243.8 ± 49.5*** (53.5)	52.3 ± 5.3** (28.5)	130.3 ± 3.1* (24.9)	43.8 ± 4.1** (73.0)
N. latifolia	160	28.3 ± 4.7*** (65.4)	1209.5 ± 55.3*** (54.8)	47.8 ± 3.2** (34.6)	130.3 ± 2.3* (24.9)	65.8 ± 5.8*** (82.0)
Diazepam	3	20.3 ± 1.3*** (75.1)	1116.3 ± 66.4*** (58.3)	37.8 ± 1.8*** (48.3)	119.2 ± 2.2** (31.4)	73.2 ± 5.2*** (83.8)

Results are expressed as mean ± SEM; changes in the behavioral state of mice were evaluate in terms of changes in number of crossings and duration of rearing, grooming, immobility and sedation, n = 6, ^*P <0.05, ^**P <0.01, ^***P <0.001, significantly different compared to the control group (control 2), data were analyzed by two-way ANOVA, followed by Tukey’s (HSD) multicomparison test. Control 1 did not receive bicuculline.