Standardized Bioflavonoid Compositions as Analgesics 163 Nociceptive behavior elicited by intraplantar injection of formalin in mice is a valued and reliable model in evaluating analgesic properties of plant extracts. UP446 inhibited the formalin nociception in late phase (inflammatory phase) by more than 50%. Consistent with our results, butanolic fraction of dried leaves of Acacia pennata (Mimosaceae), a similar class of A. catechu, tested on formalin mouse model, showed a significant inhibition in pain sensitivity induced by the phlogistic agent (Dongmo et al., 2005). The visceral pain inflicted by the intraperitoneal administration of acetic acid in mice has been employed as a tool for screening analgesic compounds. Imme- diately after injection, animals showed abdominal constrictions consisting of con- tractions of the abdominal muscle, which progressed posteriorly and ended with simultaneous flexor extension of both hind limbs with arching of the back. These behavioral responses observed for the duration of 30 min were reduced to 16.7 ± 12.7 and 21.8 ± 16.8 for UP446 and ibuprofen, respectively, to that of the vehi- cle control, i.e., 57.0 ± 19.4. Similar to the carrageenan and formalin models, both compounds showed a greater inhibition of nociception comparable to ibuprofen. However, the analgesic activity demonstrated in this model was not sufficient to indicate the central or peripheral activity of the compounds. Substantiating our findings, significant reduction in visceral pain perception was documented for Aca- cia karroo (Adedapo et al., 2008), Acacia pennata (Dongmo et al., 2005), gossypin (Viswanathan et al., 1984), myricitrin (Meotti et al., 2006), methoxy derivatives of flavone (Thirugnanasambantham et al., 1993) using acetic acid writhing mouse model. Since this is the first study in its kind to examine the antinociceptive effect of defined bioflavonoid composition from S. baicalensis and A. catechu in a range of behavioral tests, relative comparisons with the results of other published data are currently unavailable. Nevertheless, the antihyperalgesia and antiedema effects ex- hibited by UP446 pretreated animals in all the models were as expected provided that it is a dual inhibitor of COX and LOX enzymes. In conclusion, the results documented on carrageenan-induced mechanical hy- peralgesia, formalin-induced hind paw licking, and acetic acid-induced abdominal constriction show that UP446 was effective in attenuating pain perception caused by inflammation suggesting that the compound could possibly be used for its anal- gesic benefit supplementing its anti-inflammatory activity. At least in these models, UP446 has also shown comparable efficacy in pain inhibition to ibuprofen. How- ever, due to the complexity of peripheral pain perception and accompanied re- sponses exhibited in these animal models, a direct extrapolation of data to human usage needs to be proven in future human clinical trial. ACKNOWLEDGMENT The authors would like to express their best gratitude to Dr. Jifu Zhao for his in- calculable support for the completion of this research. Declaration of interest: The authors assure that the methods, results, and data depicted in this paper truly reflect the procedures used and raw data collected dur- ing the studies. The authors declare that they have no competing interests. All au- thors are employed by Unigen Pharmaceuticals, Inc which makes/markets UP446