Prophylactic and curative anti-ulcerative colitis activity and the possible mechanisms of action of some desert plants

Figures & data

Figure 1. Curative effect of investigated plant extracts on acetic acid-induced colitis in rats. The figure shows % protection of control colitis for 22 groups of animals (n = 6), treated with alcohol extract of investigated plant extracts (125, 250, and 500 mg/kg) and dexamesathone (0.1 mg/kg) for 5 successive days after ulcerative colitis induction. The colitis was induced by slowly infusion of 2 ml (4%, v/v) acetic acid in saline into the colon through the catheter. *Significantly different from control colitis at p < 0.05. @Significantly different from dexamesathone at p < 0.05.

Table 1. Prophylactic effect of the investigated extracts on acetic acid-induced colitis in rats.

Groups	Dose mg/kg	Lesion score (0–5)	Ulcer area (mm^2)	Ulcer index	Wet W/L (g/8 cm)
Normal control	–	0.0 ± 0.0	0.0 ± 0.0	0.0 ± 0.0	0.38 ± 0.05
Control colitis	–	4.00 ± 0.89	35.71 ± 1.21	39.74 ± 1.86	0.96 ± 0.09
Dexamethasone	0.1	1.50* ± 0.55	11.20* ± 1.17	12.70* ± 1.03	0.51* ± 0.09
Conyza dioscoridis	125	2.30* ± 0.52	10.70* ± 0.82	13.00* ± 0.89	0.71*@ ± 0.09
	250	2.00* ± 0.63	10.21* ± 0.75	12.20* ± 0.75	0.58* ± 0.07
	500	1.20* ± 0.41	5.21*@ ± 0.81	6.50*@ ± 0.84	0.46* ± 0.10
Euphorbia hirta	125	2.70*@ ± 0.52	16.50*@ ± 0.55	19.20*@ ± 0.98	0.80*@ ± 0.08
	250	1.50* ± 0.55	7.71*@ ± 0.82	9.20*@ ± 0.98	0.66*@ ± 0.07
	500	1.81* ± 0.75	5.20*@ ± 0.75	7.00*@ ± 0.63	0.63*@ ± 0.08
Origanum syriacum	125	2.30*@ ± 0.52	16.50*@ ± 0.55	19.20*@ ± 0.98	0.80*@ ± 0.08
	250	2.20*@ ± 0.41	10.7* ± 0.82	13.00* ± 0.75	0.65*@ ± 0.06
	500	1.70* ± 0.82	3.50*@ ± 1.05	5.20*@ ± 0.75	0.52* ± 0.07
Salvia lanigera	125	2.20* ± 0.98	8.80*@ ± 0.98	11.00* ± 1.67	0.61* ± 0.10
	250	2.00* ± 0.89	8.30*@ ± 1.03	10.30*@ ± 1.21	0.54* ± 0.07
	500	1.50* ± 0.55	3.30*@ ± 1.20	4.80*@ ± 0.75	0.50* ± 0.06
Sisymbrium irio	125	2.30*@ ± 0.82	17.20*@ ± 1.47	19.50*@ ± 1.76	0.71*@ ± 0.12
	250	2.50*@ ± 0.55	8.50*@ ± 1.38	11.00*@ ± 1.26	0.67*@ ± 0.11
	500	1.80* ± 0.98	6.20*@ ± 1.20	8.00*@ ± 1.79	0.60* ± 0.09
Solanum nigrum	125	2.80 ± 1.00	21.00*@ ± 0.90	23.80*@ ± 1.33	0.79*@ ± 0.07
	250	2.80 ± 1.17	20.20*@ ± 1.60	23.00*@ ± 1.90	0.78*@ ± 0.07
	500	2.50*@ ± 0.55	19.80* ± 1.17	22.30*@ ± 1.63	0.72*@ ± 0.16
Solenostemma arghel	125	2.30*@ ± 0.52	13.70*@ ± 0.82	16.00*@ ± 0.89	0.65*@ ± 0.09
	250	1.20* ± 0.75	3.70*@ ± 1.03	4.80*@ ± 1.47	0.48* ± 0.08
	500	1.00* ± 0.89	3.30*@ ± 1.21	4.30*@ ± 1.97	0.41* ± 0.05

Groups of 6 received different doses of the investigated extracts, standard and vehicle orally for 5 successive days. Two hour after the last dose, ulcerative colitis was induced by acetic acid. Two days later, animals were sacrificed, colonic segments were excised, opened and were used for macroscopic scoring. All values were expressed as mean ± S.D.

*Significantly different from control colitis at p < 0.05.

@Significantly different from dexamesathone at p < 0.05.

Table 2. Curative effect of the investigated extracts on acetic acid-induced colitis in rats.

Groups	Dose mg/kg	Lesion score (0–5)	Ulcer area (mm^2)	Ulcer index	Wet W/L (g/8 cm)
Normal control	–	0.0 ± 0.0	0.0 ± 0.0	0.0 ± 0.0	0.41 ± 0.03
Control colitis	–	4.20 ± 0.75	36.21 ± 1.47	40.23 ± 1.75	1.04 ± 0.09
Dexamethasone	0.1	1.80* ± 1.17	9.71* ± 1.03	11.50* ± 1.87	0.51* ± 0.08
Conyza dioscoridis	125	3.00* ± 0.63	16.30*@ ± 1.63	19.30*@ ± 1.37	0.88*@ ± 0.1
	250	2.70* ± 0.52	13.31*@ ± 1.51	16.00*@ ± 1.90	0.86*@ ± 0.07
	500	2.50* ± 0.55	11.70*@ ± 0.52	14.21*@ ± 0.98	0.81*@ ± 0.07
Euphorbia hirta	125	3.20* ± 0.75	16.50*@ ± 0.55	19.70*@ ± 1.03	0.87*@ ± 0.12
	250	3.00* ± 0.89	14.70*@ ± 1.51	17.70*@ ± 1.21	0.84*@ ± 0.11
	500	2.80* ± 0.41	14.00*@ ± 1.26	16.80*@ ± 1.17	0.76*@ ± 0.14
Origanum syriacum	125	3.00* ± 0.89	21.30*@ ± 1.97	24.30*@ ± 1.51	0.91*@ ± 0.08
	250	2.50* ± 0.84	18.50*@ ± 1.05	21.00*@ ± 1.10	0.86*@ ± 0.09
	500	2.20* ± 1.17	15.50*@ ± 0.55	17.70*@ ± 1.51	0.81*@ ± 0.14
Salvia lanigera	125	2.30* ± 0.82	7.80*@ ± 0.75	10.20* ± 0.75	0.81*@ ± 0.11
	250	2.00* ± 0.98	7.30*@ ± 0.80	9.30*@ ± 1.03	0.79*@ ± 0.08
	500	1.70* ± 0.52	5.70*@ ± 2.8	7.30*@ ± 2.34	0.75*@ ± 0.12
Sisymbrium irio	125	2.30* ± 0.52	10.70* ± 0.82	23.00*@ ± 0.89	0.71*@ ± 0.09
	250	2.50* ± 0.55	18.00*@ ± 1.79	20.50*@ ± 1.76	0.86*@ ± 0.11
	500	2.00* ± 0.89	16.5*@ ± 1.00	18.50*@ ± 0.84	0.80* ± 0.08
Solanum nigrum	125	3.30* ± 1.00	26.50*@ ± 1.40	29.80*@ ± 1.94	0.93*@ ± 0.09
	250	3.30* ± 0.82	25.80*@ ± 1.50	29.20*@ ± 1.47	0.88*@ ± 0.08
	500	3.00* ± 1.10	22.50*@ ± 1.22	25.50*@ ± 2.07	0.81*@ ± 0.10
Solenostemma arghel	125	2.30* ± 0.52	13.70*@ ± 0.82	16.00*@ ± 0.89	0.89*@ ± 0.05
	250	2.00* ± 0.63	13.30*@ ± 1.21	15.30*@ ± 1.21	0.85*@ ± 0.06
	500	1.80* ± 0.75	12.00*@ ± 1.10	13.80*@ ± 1.47	0.77*@ ± 0.07

Groups of 6 received different doses of the investigated extracts, standard and vehicle orally for 5 successive days after one hour of ulcerative colitis induced by acetic acid. Two days later, animals were sacrificed, colonic segments were excised, opened and were used for macroscopic scoring. All values were expressed as mean ± S.D.

*Significantly different from control colitis at p < 0.05.

@Significantly different from dexamesathone at p < 0.05.

Figure 2. Prophylactic effect of investigated plant extracts on acetic acid-induced colitis in rats. The figure shows % protection of control colitis for 22 groups of animals (n = 6), pretreated with alcohol extract of investigated plant extracts (125, 250, and 500 mg/kg) and dexamesathone (0.1 mg/kg) for 5 successive days before ulcerative colitis induction. The colitis was induced by slow infusion of 2 ml (4%, v/v) acetic acid in saline into the colon through the catheter. *Significantly different from control colitis at p < 0.05. @Significantly different from dexamesathone at p < 0.05.

Table 3. Effects of the alcohol extracts of the investigated plants on scavenging DPPH radical.

	Radical scavenging activity %
Extracts	2 mg/ml	4 mg/ml	6 mg/ml	8 mg/ml	10 mg/ml
Conyza dioscoridis	42.70 ± 1.01	79.50 ± 0.95	83.70 ± 1.00	85.80 ± 0.87	91.40 ± 1.09
Euphorbia hirta	15.20 ± 1.20	17.00 ± 1.04	19.20 ± 0.98	20.70 ± 1.01	22.10 ± 1.04
Origanum syriacum	20.20 ± 0.90	34.40 ± 1.01	42.60 ± 1.10	49.20 ± 0.90	65.60 ± 0.95
Salvia lanigera	30.50 ± 0.75	45.70 ± 0.90	50.90 ± 0.87	58.20 ± 0.84	62.30 ± 0.73
Sisymbrium irio	27.90 ± 0.98	30.10 ± 0.87	45.60 ± 1.02	49.60 ± 1.17	55.70 ± 0.99
Solanum nigrum	10.70 ± 1.07	12.40 ± 1.09	15.70 ± 1.20	17.90 ± 1.09	19.80 ± 1.20
Solenostemma arghel	22.00 ± 0.45	34.70 ± 1.21	53.90 ± 0.75	65.80 ± 1.11	85.30 ± 1.03

Different concentrations 2, 4, 6, 8 and 10 mg/ml from each investigated extracts were tested for their scavenging activity towards DPPH radical. Absorbance were recorded at 517 nm and the radical scavenging activity (%) was calculated. Each experiment was performed at least 3 times and data were expressed as mean ± S.D.

Table 4. Effect of Salvia lanigera L. and Solenostemma arghel (Del.) Hayne. on colonic thiobarbituric acid reactive substance (MDA) content on acetic acid-induced ulcerative colitis in rats.

Group	MDA (nmol/mg tissue)	% Change of control colitis
Normal control	59.01 ± 2.89	–
Control colitis	115.20 ± 3.05	–
Dexamesathone 0.1 mg/kg	70.30* ± 4.10	39.00
Salvia lanigera 250 mg/kg	64.90* ± 5.03	43.66
Salvia lanigera 500 mg/kg	62.60* ± 2.35	45.66
Solenostemma arghel 250 mg/kg	69.40* ± 2.89	39.76
Solenostemma arghel 500 mg/kg	65.30* ± 3.01	43.32

Total alcohol extracts of S. lanigera and S. arghel (250 and 500 mg/kg), dexamesathone (0.1 mg/kg) and vehicle were orally administrated to groups of 6 for 5 consecutive days. Two hour after the last dose, ulcerative colitis was induced by acetic acid. Two days later, animals were sacrificed, colonic segments were excised, homogenized and malondialdehyde contents were measured. All values were expressed as mean ± S.D.

*Significantly different from the control colitis at p < 0.05.

^@Significantly different from dexamesathone at p < 0.05.

Table 5. Effect of Salvia lanigera L. and Solenostemma arghel (Del.) Hayne. on plasma TNF-α (Tumor Necrosis Factor-alpha) level on acetic acid-induced ulcerative colitis rats.

Groups	TNF-α (pg/ml)	% Protection of control colitis
Control colitis	14.67 ± 1.21	–
Dexamesathone 0.1 mg/kg	6.78* ± 1.08	55.78
Salvia lanigera 250 mg/kg	6.90* ± 0.89	52.96
Salvia lanigera 500 mg/kg	5.50*@ ± 1.08	62.51
Solenostemma arghel 250 mg/kg	7.05* ± 1.03	51.94
Solenostemma arghel 500 mg/kg	6.08*@ ± 1.55	58.55

Total alcohol extracts of S. lanigera and S. arghel (250 and 500 mg/kg), dexamesathone (0.1 mg/kg) and vehicle were orally administrated to groups of 6 for 5 consecutive days. Two hour after the last dose, ulcerative colitis was induced by acetic acid. Two days later, blood samples were collected, sera were separated and TNF-α was measured. All values were expressed as mean ± S.D.

*Significantly different from the control colitis at p < 0.05.

@Significantly different from dexamesathone at p < 0.05.

Figure 3. Inhibition of sPLA2 activity. The figure shows % inhibition of the catalytic activity of the pro-inflammatory hG-IIA and phospholipase A2 activity of DrG-IB for the seven investigated plant extracts in vitro.

Table 6. Inhibition of sPLA₂ activity.

	sPLA2 inhibitory activity (%)
Extract	DrGIB	hGIIA
Conyza dioscoridis	9.33 ± 0.58	31.67 ± 1.50
Euphorbia hirta	6.33 ± 1.15	20.67 ± 2.08
Origanum syriacum	11.33 ± 1.15	56.67 ± 4.16
Salvia lanigera	5.33 ± 0.58	44.67 ± 3.00
Sisymbrium irio	10.67 ± 1.15	26.00 ± 3.60
Solanum nigrum	5.90 ± 1.01	16.04 ± 1.90
Solenostemma arghel	10.67 ± 0.58	66.00 ± 1.73

Figure 4. Inhibition of protease activity. The figure shows % inhibition of the protease activity for the seven investigated plant extracts in vitro.

Table 7. Inhibition of protease activity.

Extract	Protease inhibitory activity (%)
Conyza dioscoridis	44.67 ± 3.51
Euphorbia hirta	40.00 ± 2.64
Origanum syriacum	72.33 ± 3.51
Salvia lanigera	29.33 ± 4.04
Sisymbrium irio	31.00 ± 2.64
Solanum nigrum	25.00 ± 3.51
Solenostemma arghel	75.00 ± 5.00

Table 8. Effect of Salvia lanigera L. and Solenostemma arghel (Del.) Hayne. on liver and kidney functions.

	Liver function (U/l)		Kidney function (mg/dl)
Treatment	AST	ALT	Blood urea	Serum creatinine
Normal control	65.11 ± 2.62	144.62 ± 5.39	32.16 ± 1.83	0.36 ± 0.03
Salvia lanigera	67.39 ± 4.26	146.50 ± 4.27	33.40 ± 1.96	0.37 ± 0.03
Solenostemma arghel	65.72 ± 3.82	146.30 ± 4.30	30.85 ± 1.83	0.38 ± 0.02

Three groups of animals (n = 10) orally administrated the total alcohol extracts (500 mg/kg) of S. lanigera and S. arghel daily for four weeks in addition to control group received water orally. After the treatment period, blood samples were collected, sera were separated and different parameters were measured.

All values were expressed as mean ± S.D.