Standardized Bioflavonoid Compositions as Analgesics 161 TABLE 2. Effect of UP446 on Formalin Test in Mice Groups Vehicle Ibuprofen UP446 0 100 100 N 12 12 12 Dose (mg/kg) Reaction Time (s) Inhibition (%) Reaction Time (s) Inhibition (%) (20–40) min (40–60) min 129.7 ± 7.9 35.2 ± 14.0 36.4 ± 6.4 – 72.9∗∗ 71.9∗∗ 72.5 ± 5.2 26.4 ± 9.6 30.9 ± 22.6 63.6∗ 57.4∗ Biphasic (early and inﬂammatory phase) nociceptive response was elicited in CD-1 mice (25–30 g; N = 12) by intraplantar injection of formalin (2.5%) half an hour after test article. Mice were treated with UP446 or ibuprofen at 100 mg/kg orally. Data are expressed as mean ± SD. ∗∗P ≤ .001; ∗ P ≤ .05 vs. vehicle. against vehicle control. During the late phase response, 20–40 min after injection of formalin, the duration of mentioned behavioral reactions was inhibited by 71.9% in animals pretreated with UP446 (Table 2). Ibuprofen attenuated the behavioral reaction to a similar extent of 72.9% (Table 2). No statistically significant difference in inhibition was observed when ibuprofen and UP446 data were compared (P = .91 for 20–40 min and P = .76 for 40–60 min). Visceral Pain Perception (Writhing Test) Intraperitoneal injection of acetic acid solution (0.7%, 10 ml/kg) resulted in 69.9 ± 18.7 abdominal contractions in a period of 30 min. Mice treated with a sin- gle oral dose of 100 mg/kg of UP446 showed 58.0% reduction in abdominal muscle constriction compared to vehicle-treated animals (Figure 2). Comparable inhibition was also observed for ibuprofen-treated animals (i.e., 64.1% reduction) (Figure 2). No statistically significant difference in inhibition was observed when ibuprofen and UP446 data were compared (P = .56). Vehicle Ibuprofen (100mg/kg) UP446(100mg/kg) Treatment Groups FIGURE 2. Effect of UP446 in Writhing’s test: CD-1 mice were treated orally with 100 mg/kg UP446, ibuprofen, or vehicle control 30 min before intraperitoneal administration of freshly made acetic acid (0.7% in 0.9% NaCl) at 10 ml/kg. Mice treated with a single oral dose of 100 mg/kg of UP446 showed 58.0% reduction in abdominal muscle constriction compared to vehicle-treated animals. Comparable inhibition, 64.1%, was also observed for ibuprofen- treated animals. Data are expressed as mean ± SD. ∗P ≤ .000001, §P ≤ .00001 vs. vehicle. 100 sec 90 /30 80 ion 70 t itrc 60 s con 50 lan 40 i om30 abd 20 fo 10 # 0 * §