Mechanisms Underlying the Antinociceptive, Antiedematogenic, and Anti-Inflammatory Activity of the Main Flavonoid from Kalanchoe pinnata

Kalanchoe pinnata (KP) is popularly used for treating inflammatory diseases. This study investigated the antinociceptive, antiedematogenic, and anti-inflammatory potential of the subcutaneous administration of KP flower aqueous extract (KPFE), its ethyl acetate (EtOAcF) and butanol (BuOHF) fractions, and the main KP flavonoid [quercetin 3-O-alpha-L-arabinopyranosyl (1 -> 2)alpha-L-rhamnopyranoside] (KPFV) in mice, as well as its possible mechanisms of action. KPFE (30-300mg/kg) and KPFV (110mg/kg) inhibited the acetic acid-induced writhing (ID50 = 164.8 and 9.4mg/kg, resp.). KPFE (300mg/kg), EtOAcF (12mg/kg), BuOHF (15mg/kg), or KPFV (0.3-3.0mg/kg) reduced leukocyte migration on carrageenan-induced pleurisy (ID50 = 2.0mg/kg for KPFV). KPFE (3-30 mg/kg) and KPFV (0.3-3.0 mg/kg) reduced the croton oil-induced ear edema (ID50 = 4.3 and 0.76mg/kg, resp.). KPFE and KPFV reduced the TNF-alpha concentration in the pleural exudates on carrageenan-induced pleurisy test. Moreover, KPFV inhibited COX-1 (IC50 = 22.1 mu g/mL) and COX-2 (IC50 > 50 mu g/mL). The selectivity index (COX-1 IC50 /COX-2 IC50) was < 0.44. These results indicate that KPFE and KPFV produced antinociceptive, antiedematogenic, and anti-inflammatory activities through COX inhibition and TNF-alpha reduction, revealing that the main flavonoid in KP flowers and leaves plays an important role in the ethnomedicinal use of the plant.