Pharmacological Analysis of the Anti-inflammatory and Antiallodynic Effects of Zinagrandinolide e from Zinnia grandiflora in Mice

Zinagrandinolide E (1, ZGE) is an elemanolide with antinociceptive action isolated from Zinnia grandiflora (Asteraceae), valued in North México and southwestern United States for pain relief. Herein, we report the anti-inflammatory and antiallodynic action of ZGE (1) in carrageenan-induced inflammation and tactile allodynia in mice and in a neuropathic pain model in hyperglycemic mice. Local peripheral administration of ZGE (1-30 μg/paw) induced dose-dependent acute anti-inflammatory and antiallodynic effects. The anti-inflammatory effect was comparable to diclofenac (30 μg/paw). Intrathecal (i.t.) administration of ZGE (30 μg) in acute experiments did not affect carrageenan-induced inflammation but significantly reduced tactile allodynia in a dose-dependent fashion. In long-term experiments (15 or 6 days), using two different scheme treatments (pretreatment or post-treatment), ZGE (3-30 μg/paw) showed antiallodynic but not anti-inflammatory action. Local peripheral (3-30 μg/paw) or intrathecal (3-30 μg) administration of ZGE partially reversed tactile allodynia in hyperglycemic mice, better or comparable, respectively, with those of pregabalin (30 μg/paw or 30 μg i.t.). The effects were dose-dependent. According to the pharmacological tools employed, the anti-inflammatory and antiallodynic activities of ZGE are multitarget; these involve the opioidergic, serotoninergic, and GABAergic systems, as well as the NO-cGMP-ATP-sensitive K⁺channel signaling pathway.