Journal of Ethnopharmacology ∎ (∎∎∎∎) ∎∎∎–∎∎∎

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journal homepage: www.elsevier.com/locate/jep
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Analgesic, anti-inflammatory and antipyretic activities of the methanol
13 leaf extract of Dalbergia saxatilis Hook.F in rats and mice
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15 Q1 Hassan F. Ismail a,n, Abdulkadir U. Zezi a, Yaro A. Hamza b, Danmalam U. Habib c
16
a
17 Q2 b
Department of Pharmacology and Therapeutics, Ahmadu Bello University, Zaria, Nigeria
Department of Pharmacology, Bayero University, Kano, Nigeria
18 c
Department of Pharmacognosy and Drug Development, Ahmadu Bello University, Zaria, Nigeria
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art ic l e i nf o a b s t r a c t
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Article history: Ethnopharmacological relevance: The decoction of the leaves of Dalbegia saxatilis is used in Traditional
24 Received 5 January 2015 Medicine for various ailments such as cough, small pox, skin lesions, bronchial ailments and toothache.
25 Received in revised form The study is aimed at evaluating the analgesic, anti-inflammatory, and antipyretic effects of D. saxatilis to
26 2 March 2015
provide scientific basis for its use.
Accepted 5 March 2015
27 Materials and methods: Phytochemical screening and evaluation of oral median lethal dose was carried
28 out on the methanol leaf extract of the plant. Analgesic activity using acetic acid induced writhing and
29 Keywords: hot plate method in mice, anti-inflammatory activity using carrageenan induced paw oedema in rats, and
Dalbergia saxatilis antipyretic activity using Brewer's yeast induced pyrexia in rats were evaluated at 250 mg/kg, 500 mg/kg,
30
Analgesic
31 and 1000 mg/kg doses of the extract.
Anti-inflammatory
32 Results: The oral median lethal dose was found to be above 5000 mg/kg. The extract was found to
Antipyretic
contain alkaloids, flavonoids, tannins, saponins, cardiac glycosides, and triterpenes. The extract and the
33
standard drug (Aspirin) significantly decreased the number of writhes caused by acetic acid at p o0.001.
34
There was statistical significant increase in reaction time in standard group, extract 250 mg/kg, and
35 1000 mg/kg from 60 min at po 0.05 and po 0.01, from 30 min in 500 mg/kg group at po0.05 and
36 po 0.01 compared with 0 min. A statistical significant decreases in paw sizes at po 0.05 and po 0.01
37 compared to the peak increase in both standard and test groups was observed. Statistical significant
38 reduction in rectal temperatures was observed in standard group at 21 and 23 h, and in 500 mg/kg and
39 1000 mg/kg doses of the extract at 23 h at po 0.05 compared with the 19 h.
40 Conclusion: The results obtained indicated potential analgesic, anti-inflammatory and antipyretic effects
41 of the methanol leaf extract of D. saxatilis observed at doses tested which support the claim for the
42 traditional use of the plant in treatment of toothache.
& 2015 Published by Elsevier Ireland Ltd.
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45 67
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47 69
48 1. Introduction Majority of the world population depend on Traditional Med- 70
49 icine such as herbs for treatment of various ailments. Present day 71
50 Dalbergia is a large genus of trees, shrubs, lianas, and woody medicine was derived from herbal traditions (Ezeonwumelu et al., 72
51 climbers in the pea family also known as Fabaceae. It consists of 2012). Pain according to the International Association for the Study 73
52 over 200 species accepted and widely distributed in the tropical of Pain (IASP) is an unpleasant, sensory and emotional experience 74
53 and subtropical regions of the world (Saha et al., 2013; Vasudeva associated with actual or potential tissue damage, or described in 75
54 et al., 2009). Dalbergia saxatilis is an African shrub 2–3 m high, the terms of such damage (Merskey and Bogduk, 1994). It can also be 76
55 flowers are white or pink borne in loose axillary or terminal defined as the effect produced in consciousness by the arrival of 77
56 panicles, 15 cm and is widely distributed in northern Nigeria. nerve impulses generated by noxious stimuli in the brain (Mishra 78
57 Common parts used are the leaves, stem bark and root (Saha et al., 2011). Pain may vary in intensity, quality and duration from 79
58 et al., 2013). mild, moderate, or severe, sharp, burning or dull and transient, 80
59 intermittent, or persistent. It can also be superficial or deep, 81
60 localised or diffused (Woolf, 2004). Perception of pain can be 82
61 influenced by several psychological factors such as the processes of 83
62 n
Corresponding author. Tel.: þ 234 8034657833; fax: þ234 8050282202. attention, memory or learning, thought, beliefs, mood, behavioural 84
63 E-mail address: Pharm.fatee@yahoo.com (H.F. Ismail). responses, and ability to cope (Macintyre et al., 2010). 85
64 86
http://dx.doi.org/10.1016/j.jep.2015.03.007
65 87
0378-8741/& 2015 Published by Elsevier Ireland Ltd.
66 88

Please cite this article as: Ismail, H.F., et al., Analgesic, anti-inflammatory and antipyretic activities of the methanol leaf extract of
Dalbergia saxatilis Hook.F in rats and mice. Journal of Ethnopharmacology (2015), http://dx.doi.org/10.1016/j.jep.2015.03.007i
 2 H.F. Ismail et al. / Journal of Ethnopharmacology ∎ (∎∎∎∎) ∎∎∎–∎∎∎

1 Inflammation is a defensive mechanism of the body to remove absence of chemical constituents as detailed in the literature 67
2 injurious stimuli and initiate healing process for the tissue, but if it runs (Evans, 2002). 68
3 unchecked, it can lead to onset of certain diseases as vasomotor 69
4 rhinnorrhoea, rheumatoid arthritis, and atherosclerosis (Sharma et al., 2.6. Acute toxicity studies (LD50 determination) 70
5 2010). It is characterised by redness, swelling, heat and pain and a 71
6 times loss of function (Punchard et al., 2004). Fever is defined as the The median lethal dose of the extract was determined using 72
7 elevation of core body temperature above normal (Dalal and Lorke's method (1983). The study was carried out in two phases 73
8 Zhukovsky, 2006). In normal adults, average oral temperature is 37 1C and animals (both mice and rats) were deprived of food over night 74
9 (98.6 1F). Fever may be due to infection, inflammation, or any tissue prior to administration of the extract. In phase 1, three groups of 75
10 damage and disease state. It arises as a secondary impact of infection, three animals per group were used. The extract was administered 76
11 malignancy or other diseased states (Tirumalasetty et al., 2012). orally in geometrically increasing doses (10 mg/kg, 100 mg/kg and 77
12 D. saxatilis is native to Angola, Cameroon, Gabon, Ghana, 1000 mg/kg). The treated animals were observed for four hours 78
13 Guinea, Guinea Bissau, Ivory Coast, Liberia, Nigeria, Senegal, Sierra post administration for signs of toxicity. After 24 h, when no death 79
14 Leone and Zaire, and is used as a decoction in Traditional Medicine occurred, phase 2 was initiated. In phase 2, three groups of one 80
15 for various ailments such as cough, small pox, skin lesions, animal each were given the extract orally in geometrically increas- 81
16 bronchial ailments and toothache (Saha et al., 2013; Okwute et ing doses (1600 mg/kg, 2900 mg/kg and 5000 mg/kg). The animals 82
17 al., 2009). The study is aimed at evaluating the analgesic, anti- were then observed for signs of toxicity for the first 4 h and 83
18 inflammatory, and antipyretic effects of D. saxatilis to provide mortality for 24 h. 84
19 scientific basis for its use. 85
20 2.7. Analgesic studies 86
21 87
22 2. Materials and methods 2.7.1. Acetic acid induced writhing in mice 88
23 Acetic acid induced writhing method described by (Koster et al., 89
24 2.1. Drugs and chemicals 1959) was adopted for evaluation of analgesic activity. Writhing is 90
25 defined as a stretch, tension to one side, extension of hind legs, 91
26 Glacial acetic acid, methanol, 10% v/v formalin solution, Carra- contraction of the abdomen so that the abdomen of mice touches the 92
27 geenan (Sigma Aldrich, Germany), Aspirin (Abcam Inc., Cambridge, floor, turning of trunk (Mishra et al., 2011). Thirty Swiss albino mice 93
28 MA), morphine (Martindale Pharmas, Essex, United Kingdom), of both sexes were divided into five groups, 1 and 2 served as 94
29 Brewer's yeast (Merck, Germany). negative control (distilled water 10 ml/kg) and positive control 95
30 (Aspirin 300 mg/kg), while groups 3, 4, and 5 received 250, 500, 96
31 2.2. Experimental animals and 1000 mg/kg of the extract, respectively. All the drugs were 97
32 administered orally. Sixty minutes after treatment, the mice received 98
33 Wistar rats and mice of both sexes weighing 100–150 g and 0.6% v/v acetic acid (10 ml/kg) interperitoneally to induce pain. 5 min 99
34 20–25 g respectively were obtained from the Animal house of the after acetic acid injection, the animals were observed and number of 100
35 Department of Pharmacology and Therapeutics, Ahmadu Bello writhes by each mouse was counted for 15 min. Percentage inhibi- 101
36 University, Zaria. The animals were allowed free access to standard tion was calculated using the following formula: 102
37 feed and water ad libitum. They were kept in clean cages filled 103
Average number of writhesðcontrolÞ–Average number of writhesðtestÞ
38 % inhibition ¼ 104
with saw dust, which was replaced every three days. The study Average number of writhesðcontrolÞ
39 was conducted according to ethical guidelines on laboratory 105
40 animal use and care policy, which is in compliance with Ahmadu 106
41 Bello University Research Policy (Revised, 2010). 2.7.2. Hot plate method 107
42 This method was carried out as described by Eddy and 108
43 Leimback (1953). The paws of mice and rats are very sensitive to 109
2.3. Plant material
44 heat at temperatures which are not damaging to the skin. The 110
45 responses are jumping, withdrawal of the paws and licking of the 111
The leaves of D. saxatilis was collected in June, 2013 at
46 paws. The temperature of the hot plate was set at 5571 1C 112
Galadimawa, Giwa Local Government Area, Kaduna state. The
47 (Mishra et al., 2011). Thirty Swiss Albino mice of both sexes used 113
plant was identified and authenticated in the Herbarium of the
48 were fasted 12 h prior to the experiment, and divided into five 114
Biological Science Department of Ahmadu Bello University, Zaria
49 groups, 1 and 2 served as negative control (distilled water 10 ml/ 115
by Mallam Umar S. Gallah and was compared with a previously
50 kg) and positive control (Morphine 10 mg/kg), while groups 3, 4, 116
deposited voucher specimen number of 717.
51 and 5 received 250 mg/kg, 500 mg/kg, and 1000 mg/kg of the 117
52 extract respectively. The test and standard drugs were adminis- 118
53 2.4. Preparation of plant extract tered orally. The animals were individually placed on the hot plate 119
54 and the time until either licking or jumping occurred was recorded 120
55 The leaves collected were air-dried for two weeks and size by a stop-watch, 30, 60, 90 and 120 min after treatment. 121
56 reduced with mortar and pestle. This was extracted by cold macera- 122
57 tion using absolute methanol. 200 g of the powder was added into 2.8. Anti-inflammatory studies 123
58 Erlnmeyer Flask with 1000 ml of the solvent and kept for 48 h with 124
59 intermittent shaking, then filtered. The extract was evaporated to 2.8.1. Carrageenan induced rat paw oedema model 125
60 dryness in an evaporator under reduced pressure and controlled The anti-inflammatory study was carried out using the method 126
61 temperature (40–60 1C). described by Winter et al. (1963). Thirty wistar rats were divided into 127
62 five groups, 1 and 2 served as negative control (distilled water 10 ml/ 128
63 2.5. Phytochemical screening kg) and positive control (Aspirin 300 mg/kg), while groups 3, 4, and 129
64 5 received 250, 500, and 1000 mg/kg of the extract respectively. 130
65 Phytochemical screening was carried out on the methanol leaf Treatments were administered 1 h before carrageenan injection. 131
66 extract using simple chemical tests to detect the presence or Carrageenan was prepared as 1% w/v solution in 0.9% w/v NaCl and 132

Please cite this article as: Ismail, H.F., et al., Analgesic, anti-inflammatory and antipyretic activities of the methanol leaf extract of
Dalbergia saxatilis Hook.F in rats and mice. Journal of Ethnopharmacology (2015), http://dx.doi.org/10.1016/j.jep.2015.03.007i
 H.F. Ismail et al. / Journal of Ethnopharmacology ∎ (∎∎∎∎) ∎∎∎–∎∎∎ 3

1 0.1 ml was injected underneath the planter region of the rat's paw. analysis of variance (ANOVA) followed by Dunnett t-test and 67
2 The paw size was then measured with digital vernier calliper at 0, 1, repeated measures ANOVA followed by Bonferroni test for multi- 68
3 2, 3, 4, and 5 h after carrageenan injection (Sharma et al., 2010). ple comparison. Results were considered significant at p o0.05. 69
4 70
5 2.9. Antipyretic studies 71
6 3. Results 72
7 2.9.1. Brewer's yeast induced pyrexia model 73
8 The antipyretic activity was evaluated using Brewer's yeast- Percentage yield of the methanolic leaf extract of D. saxatilis 74
9 induced pyrexia in rats as described by (Kumar et al., 2009). Fever was 22.8% w/w. Phytochemical screening revealed the presence of 75
10 was induced by administering 20 ml/kg of 20% aqueous suspension alkaloids, flavonoids, cardiac glycosides, tannins, triterpenes, and 76
11 of Brewer's yeast in normal saline subcutaneously 18 h before saponins, while anthraquinones were found absent as reported by 77
12 treatment. Thirty wistar rats of both sexes were divided into five Okwute and Fatokun, 2014. 78
13 groups, 1 and 2 served as negative control (distilled water 10 ml/kg) 79
14 and positive control (Aspirin 300 mg/kg), while groups 3, 4, and 3.1. Acute toxicity studies 80
15 5 received 250, 500, and 1000 mg/kg of the extract respectively. All 81
16 drugs were administered orally. Rectal temperatures were taken by The oral median lethal dose in both mice and rats was found to 82
17 the use of digital thermometer (Mediklin, China) before yeast be greater than 5000 mg/kg; this is because no death occurred in 83
18 injection, 19 h after the injection, and at 1, 2, 3, and 4 h after drug both phases of the experiment. 84
19 administration. 85
20 86
21 3.2. Analgesic studies 87
2.10. Statistical analysis
22 88
23 3.2.1. Effect of methanol leaf extract of D. saxatilis on acetic acid 89
Results were expressed as mean 7standard error of mean and induced writhing in mice
24 presented as graphs and tables. Data were analysed using one way 90
25 The extract significantly decreased the number of writhes 91
26 caused by acetic acid in a dose independent manner at po 0.001 92
Table 1 (Table 1). The effects observed at 250 mg/kg and 1000 mg/kg were
27 Effect of methanol leaf extract of Dalbergia saxatilis on acetic acid induced writhing 93
28 in mice.
more than that of 500 mg/kg of the extract. The effect observed in 94
29 1000 mg/kg group was comparable to that of the standard drug. 95
Treatment Dose (mg/kg) Mean number of writhes Inhibition (%)
30 96
31 Distilled water 10 ml/kg 28.3373.84 – 3.2.2. Effect of methanol leaf extract of D. saxatilis on hot plate 97
32 Aspirin 300 4.6771.45a 83.5 induced pain in mice 98
33 Extract 250 9.50 73.13a 66.5 The methanol leaf extract significantly increased the reaction 99
Extract 500 11.50 73.66a 59.4
34 time at different doses at p o0.05 (Fig. 1). 0 min in each group was 100
Extract 1000 4.6771.56a 83.5
35 taken as control and compared to other time intervals. At 30 min, 101
36 Values are Mean 7SEM., n¼6. there was significant increase in reaction time in the 500 mg/kg 102
37 a
Denotes significant difference from control group F {(4, 22) ¼ 9.53; po 0.001}. and 1000 mg/kg groups of the extract. At 60, 90, and 120 min, 103
38 One way ANOVA followed by Dunnett's test. there was significant increase in reaction time in both the standard 104
39 105
40 7 106
41 107
42 108
43 b 109
6
44 110
45 b 111
b Distilled
Mean reaction time in seconds

46 b 112
5 b b water
47 ab 10ml/kg 113
b morphine
48 a 114
49 10mg/kg 115
4 a a b
50 Extract 250 116
51 mg/kg 117
52 118
3 Extract 500
53 119
mg/kg
54 120
55 Extract 121
2 1000mg/kg
56 122
57 123
58 124
59 1 125
60 126
61 127
62 0 128
0min 30mins 60mins 90mins 120mins
63 129
64 Time interval 130
65 Fig. 1. Effect of the methanol extract of Dalbergia saxatilis on hot plate induced pain in mice. Values are Mean 7 SEM, n¼ 6, a and b denotes significant difference from control 131
66 group F {(4, 25) ¼2.88; p o0.05, (4, 25) ¼ 6.83; p o 0.01}. Repeated measures ANOVA followed by Bonferroni test. 132

Please cite this article as: Ismail, H.F., et al., Analgesic, anti-inflammatory and antipyretic activities of the methanol leaf extract of
Dalbergia saxatilis Hook.F in rats and mice. Journal of Ethnopharmacology (2015), http://dx.doi.org/10.1016/j.jep.2015.03.007i
 4 H.F. Ismail et al. / Journal of Ethnopharmacology ∎ (∎∎∎∎) ∎∎∎–∎∎∎

1 and all doses of the extract as shown in Fig. 1 at p o0.05 and 250 mg/kg group, the peak increase was observed in the third 67
2 p o0.01 respectively. hour which was also statistically significant. In the 500 mg/kg 68
3 group, the peak increase in paw size was observed in the first hour 69
4 at po 0.05, while in the 1000 mg/kg group, there was statistical 70
5 3.3. Anti-inflammatory studies significant increase in paw size in all the hours when compared to 71
6 the zero hour. 72
7 3.3.1. Effect of methanol leaf extract of D. saxatilis on carrageenan 73
8 induced paw oedema in rats 74
9 The extract decreased the rat paw size at different doses 3.4. Antipyretic studies 75
10 though not statistically significant as shown in (Fig. 2). Zero hour 76
11 in each group was taken as control and compared to other times. 3.4.1. Effect of methanol leaf extract of D. saxatilis on Brewer's yeast 77
12 There was statistical significant increase in paw size at the second induced pyrexia in rats 78
13 hour compared to the first hour; a significant reduction was seen The effect of the extract on Brewer's yeast induced pyrexia in 79
14 in the fourth and fifth hour compared to the second hour (peak rats is shown in Fig. 3. Statistical significant reduction in rectal 80
15 increase) in the distilled water group. There was no statistical temperature was observed in the group treated with aspirin 81
16 significant increase or decrease in paw size when time zero was 300 mg/kg at po 0.05 from the 21 h to the 23 h compared to the 82
17 compared to the other times in the positive control group. In the 19 h. There was reduction in rectal temperature in the groups 83
18 84
19 0.5 85
20 a 86
0.45 Distille
21 d water 87
22 0.4 10ml/k 88
23 a g 89
Mean paw diameter

24 0.35 a a Aspirin 90
** a* *
25 300 91
0.3 b c ** a mg/kg
26 92
27 0.25 93
Extract
28 250 94
0.2
29 mg/kg 95
30 0.15 96
31 Extract 97
0.1 500
32 98
mg/kg
33 0.05 99
34 100
35 0 101
0hr 1hr 2hrs 3hrs 4hrs 5hrs
36 102
37 Time interval 103
38 Fig. 2. Effect of methanol leaf extract of Dalbergia saxatilis on carrageenan-induced rat paw oedema model. Values are Mean7 SEM, n ¼6, a, b and c denotes significant 104
39 difference from control group F {(4, 25) ¼ 3.46; p o 0.05, (4, 25) ¼4.95; po 0.01, (4, 25) ¼6.1; p o 0.001}. Repeated measures ANOVA followed by Bonferroni test. 105
40 106
41 107
42 39 108
43 109
44 110
45 38 111
46 112
47 Distilled 113
water
Rectal temperature °C

48 114
37 10ml/kg
49 Aspirin 115
a
50 300 116
51 a mg/kg 117
36 Extract
52 118
a a a 250
53 119
mg/kg
54 Extract 120
55 35 500 121
56 mg/kg 122
Extract
57 1000 123
58 mg/kg 124
34
59 125
60 126
61 127
62 33 128
0hr 19hrs 20hrs 21hrs 22hrs 23hrs
63 129
64 Time interval 130
65 Fig. 3. Effect of the methanol leaf extract of Dalbergia saxatilis on Brewer's yeast induced pyrexia in rats. Values are Mean 7SEM, n¼ 6, a, b and c denotes significant 131
66 difference from control group F {(4, 25) ¼ 5.1; po 0.05}. Repeated measures ANOVA followed by Bonferroni test. 132

Please cite this article as: Ismail, H.F., et al., Analgesic, anti-inflammatory and antipyretic activities of the methanol leaf extract of
Dalbergia saxatilis Hook.F in rats and mice. Journal of Ethnopharmacology (2015), http://dx.doi.org/10.1016/j.jep.2015.03.007i
 H.F. Ismail et al. / Journal of Ethnopharmacology ∎ (∎∎∎∎) ∎∎∎–∎∎∎ 5

1 treated with 250 mg/kg, 500 mg/kg and 1000 mg/kg of the extract properties at doses tested. This gives support to the claim for the 60
2 at 20–23 h, though not statistically significant. There was statistical traditional use of the plant in the treatment of toothache. 61
3 significant reduction in the 500 mg/kg group and 1000 mg/kg 62
4 groups of the extract at the 23 h at p o0.05. 63
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Please cite this article as: Ismail, H.F., et al., Analgesic, anti-inflammatory and antipyretic activities of the methanol leaf extract of
Dalbergia saxatilis Hook.F in rats and mice. Journal of Ethnopharmacology (2015), http://dx.doi.org/10.1016/j.jep.2015.03.007i