The protective effect of Tinospora cordifolia on various mast cell mediated allergic reactions

Figures & data

Table 1.  The effect of TC (125- 1000 mg/kg, p.o.) treatment on compound 48/80 induced lethality in rats.

Group	Dose (mg/kg)	Log dose	Compound 48/80 (0.75 mg/kg)	% Protection	ED50 (mg/kg)
Control	-	-	+	0	-
TC 125	125	2.097	+	10	517.81
TC 250	250	2.398	+	20
TC 500	500	2.699	+	40
TC 1000	1000	3.000	+	80
Cetirizine	0.3	-	+	70	-

Groups of rats (n = 10 per group) were treated with the test drugs 1 h before the compound 48/80 injection. Protection (%) within 1 h following compound 48/80 injection was represented as the number of survived rats × 100/total number of experimental rat.

Table 2.  The effect of TC (125- 1000 mg/kg, p.o.) treatment on histamine induced paw edema in mice.

Group	Dose (mg/kg)	Mean % increase in paw volume	% Inhibition	ED50 (mg/kg)
Control	-	27.2 ± 2.09
TC 125	125	21.43 ± 2.57 ^n.s.	21.22	672.32
TC 250	250	18.07 ± 3.39 ^n.s.	33.56
TC 500	500	14.48 ± 2.49**	46.78
TC 1000	1000	12.12 ± 2.67**	55.45
Cetirizine	0.25	7.19 ± 0.39***	73.58

Groups of mice (n = 10 per group) were treated with the test drugs 1 h before the compound 48/80 injection. Percentage increase in volume of paw was represented as the (left paw weight in mg – right paw weight in mg) × 100/ right paw weight in mg. Values are expressed as mean ± SEM. ***p < 0.001; **p < 0.01; *p < 0.05; n.s., not significant compared to control group.

Table 3.  The effect of TC (125- 1000 mg/kg, p.o.) treatment on anti-DNP IgE induced cutaneous reaction (vascular permeability of Evans blue) in rats.

Group	Dose (mg/kg)	Mean Evans blue concentration (μg/mL)	% Inhibition	ED50 (mg/kg)
Control	-	3.11 ± 0.44
TC 125	125	2.65 ± 0.04 ^n.s.	14.64	520.07
TC 250	250	2.16 ± 0.06*	30.45
TC 500	500	1.61 ± 0.12***	48.01
TC 1000	1000	1.01 ± 0.06***	67.61
Cetirizine	0.3	0.72 ± 0.06***	76.82

Groups of rats (n = 6 per group) were treated with the test drugs 1 h before the anti-DNP IgE injection. Values are expressed as mean ± SEM. ***p < 0.001; **p < 0.01; *p < 0.05; n.s., not significant compared to control group.

Table 4.  The effect of TC (125-1000 mg/kg, p.o.) treatment on compound 48/80 induced ear swelling response in mice.

Group	Dose (mg/kg)	Mean % increase in ear volume	% Inhibition	ED50 (mg/kg)
Control	-	50.48 ± 5.93
TC 125	125	40.93 ± 1.5 ^n.s.	18.93	423.93
TC 250	250	33.16 ± 3.49 ^n.s.	34.31
TC 500	500	22.9 ± 0.84***	54.63
TC 1000	1000	13.62 ± 2.95***	73.02
Cetirizine	0.25	23.39 ± 2.94***	53.68	-

Groups of mice (n = 10 per group) were treated with the test drugs 1 h before the compound 48/80 injection. % increase in volume of ear was represented as the (left ear weight in mg-right ear weight in mg) × 100/ right ear weight in mg. Values are expressed as mean ± SEM. ***p < 0.001; **p < 0.01; *p < 0.05; n.s., not significant compared to control group.

Table 5.  The effect of TC (125-1000 mg/kg, p.o.) or cetirizine (0.3 mg/kg) alone on allergic bronchoconstriction in guinea pigs.

Group	Dose (mg/kg)	Preconvulsive Breathing (min)	% Inhibition	ED50 (mg/kg)
CON	-	3 ± 0.26
TC 125	125	3.60 ± 0.2 ^n.s.	16.67	374.33
TC 250	250	4.88 ± 0.37 ^n.s.	38.52
TC 500	500	9.55 ± 0.61*	68.59
TC 1000	1000	9.99 ± 1.04**	69.97
CTZ 0.3	0.3	9.65 ± 1.97*	68.91	-

Groups of guinea pigs (n = 3 per group) were treated with the test drugs 1 h before the exposure of histamine aerosol. Values of preconvulsive breathing (min) are expressed as mean ± SEM. ***p < 0.001; **p < 0.01; *p < 0.05; n.s., not significant compared to control group.

Table 6.  The effect of TC (2.5-160 μg/mL) treatment on histamine induced contraction of guinea pig ileum in vitro.

Sr No.	Treatment	Dose	Mean contraction (mm)	% Inhibition of histamine response	EC50 (μg/mL)
1	Histamine	5.5 × 10^−7 M	45 ± 1.22	-	-
2	TC	2.5 μg/mL	32 ± 1***	28.89	13.48
3	TC	5 μg/mL	28 ± 0.92***	37.78
4	TC	10 μg/mL	25 ± 0.99***	44.44
5	TC	20 μg/mL	23 ± 0.8***	48.89
6	TC	40 μg/mL	18 ± 0.41***	60.
7	TC	80 μg/mL	10 ± 0.2***	77.78
8	TC	160 μg/mL	3 ± 0.2***	93.33
9	Cetirizine	1 nM	40 ± 1.11*	11.11	0.04
10	Cetirizine	5 nM	33 ± 0.9***	26.67
11	Cetirizine	25 nM	25 ± 0.43***	44.44
12	Cetirizine	125 nM	10 ± 0.8***	77.78
13	Cetirizine	625 nM	2 ± 0.2***	95.56

Each datum represents the mean ± SEM of 3 independent experiments. ***p < 0.001; **p < 0.01; *p < 0.05; n.s., not significant compared to control (Submaximal response of histamine) value.

Figure 1.  Effect of TC on dose-response curves for histamine- induced contraction of guinea pig ileum. Dose-response curves for histamine-induced contraction of guinea pig ileum were obtained in the absence of (•) or presence of 2.5 (▪), 5 (▴), 10 (□) and 20 (▾) mg/mL TC. Each point is the mean percentage of response (n = 4-5) at a given concentration of histamine with respect to the maximum contraction obtained in the control curve (•). pA₂ = 7.5.

Figure 2.  The effect of TC (0.01-10 mg/mL) and sodium chromoglycate (SC) treatment on compound 48/80-induced histamine release from mast cells. RPMC (2 × 10⁵ cells/mL) were preincubated with test samples at 37°C for 10 min prior to incubation with compound 48/80. Each data represents the mean ± SEM of 3 independent experiments. ***p < 0.001; **p < 0.01; *p < 0.05; n.s., not significant compared to saline value.

Figure 3.  The effect of TC (0.01-10 mg/mL) and cetirizine (Cet.) treatment on anti-DNP IgE antibody-induced TNF-α secretion from mast cells (MC). RPMC (3 × 10⁵ cells/mL) were sensitized with anti-DNP IgE (1 mg/mL) and incubated for 18 h in the absence or presence of test samples before the challenge with DNP-HSA (0.1 mg/mL). Each data represents the mean ± SEM of 3 independent experiments. ***p < 0.001; **p < 0.01; *p < 0.05; n.s., not significant compared to mast cell+ anti-DNP IgE+DNP-HSA group.

Figure 4.  Time-dependent effect of TC (1 mg/mL) on cAMP level of RPMC. RPMC (2 × 10⁵ cells/mL) were preincubated with test samples at 37°C for 10 min prior to incubation with compound 48/80 (5 mg/mL). Each datum represents the mean ± SEM of three independent experiments. ***p < 0.001; **p < 0.01; *p < 0.05; n.s., not significant compared to saline value.

Figure 5.  Effect of TC on the intracellular Ca²⁺ levels in RPMC. RPMC (2 × 10⁵ cells/mL) were preincubated with test samples at 37°C for 10 min before adding compound 48/80 (5 mg/mL) and then another 10 min with compound 48/80. Each data represents the mean ± SEM of 3 independent experiments. ***p < 0.001; **p < 0.01; *p < 0.05; n.s., not significant for the compound 48/80 value.

Figure 6.  Effect of TC on concentration-response relationships for intracellular reactive oxygen species. Concentration-response relationships for intracellular reactive oxygen species generation in the absence and presence of TC (0.01- 10 mg/mL) from rat peritoneal mast cells (2 × 10⁵ cells/mL) in response to compound 48/80. Each point is the mean ± SEM of six experiments. ***p < 0.001; **p < 0.01; *p < 0.05; n.s., not significant compared to saline value.